Sample records for accelerated wound closure

  1. Topical naltrexone accelerates full-thickness wound closure in type 1 diabetic rats by stimulating angiogenesis.

    PubMed

    McLaughlin, Patricia J; Immonen, Jessica A; Zagon, Ian S

    2013-07-01

    Delays in wound healing often result in infection, chronic ulceration, and possible amputation of extremities. Impaired wound healing is a major complication of the 23 million people in the USA with diabetes, and financial and medical burdens are demanding new treatments for wound healing. Previous studies have demonstrated that topical application of the opioid antagonist naltrexone (NTX) dissolved in moisturizing cream reverses delays in wound closure in rats with streptozotocin-induced type 1 diabetes. A target of NTX's action is DNA synthesis and cell proliferation. In this study, granulation tissue was evaluated to ascertain the specific cellular targets that were impaired in diabetic wounds, as well as those that were enhanced following NTX application. Mast cell number as well as the number of new blood vessels immunoreactive to fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), and alpha smooth muscle actin (α-SMA) antibodies were recorded at 3, 5, 8, 10, 15, and 20 days following creation of full-thickness dorsal cutaneous wounds in normal and type 1 diabetic rats. Diabetic rats displayed delays in wound closure as well as a reduction in the number of mast cells responding to the injury, and delays in the spatial and temporal expression of FGF-2, VEGF, and α-SMA in capillaries. Topical NTX accelerated the rate of wound closure and stimulated expression of angiogenic factors within granulation tissue of diabetic rats relative to control animals receiving saline in moisturizing cream. These data support observations that a novel biological pathway is impaired under diabetic conditions and can be modulated by topical NTX to enhance proliferative events in wound healing.

  2. Economic comparison of methods of wound closure: wound closure strips vs. sutures and wound adhesives.

    PubMed

    Zempsky, William T; Zehrer, Cindy L; Lyle, Christopher T; Hedbloom, Edwin C

    2005-09-01

    Our objective was to review and assess the treatment of low-tension wounds and evaluate the cost-effectiveness of wound closure methods. We used a health economic model to estimate cost/closure of adhesive wound closure strips, tissue adhesives and sutures. The model incorporated cost-driving variables: application time, costs and the likelihood and costs of dehiscence and infection. The model was populated with variable estimates derived from the literature. Cost estimates and cosmetic results were compared. Parameter values were estimated using national healthcare and labour statistics. Sensitivity analyses were used to verify the results. Our analysis suggests that adhesive wound closure strips had the lowest average cost per laceration ($7.54), the lowest cost per infected laceration ($53.40) and the lowest cost per laceration with dehiscence ($25.40). The costs for sutures were $24.11, $69.91 and $41.91, respectively; the costs for tissue adhesives were $28.77, $74.68 and $46.68, respectively. The cosmetic outcome for all three treatments was equivalent. We conclude adhesive wound closure strips were both a cost-saving and a cost-effective alternative to sutures and tissue adhesives in the closure of low-tension lacerations.

  3. Scalp Wound Closure with K wires: An alternative easier method to scalp wound closure.

    PubMed

    Ramesh, S; Ajik, S

    2012-12-01

    Scalp defects and lacerations present a reconstructive challenge to plastic surgeons. Many methods have been described from the use of skin grafting to rotation flaps. Here we present a method of closure of a contaminated scalp wound with the use of Kirschner wires. In our case, closure of scalp laceration was made possible with the use of 1.4 Kirschner wires and cable tie/ zip tie fasteners. The duration to closure of wound was 10 days. In reconstructing the scalp defect, this method was found to adhere to principles of scalp reconstruction. There were no post operative complications found from the procedure. On initial application on the edge of the wound, tension applied caused the K wires to cut through the wound edge. On replacement of K wires 1cm away from wound edge the procedure was not plagued by any further complication. In conclusion we find scalp closure with Kirschner wires are a simple and effective method for scalp wound closure.

  4. Closure of skin incisions in rabbits by laser soldering: I: Wound healing pattern.

    PubMed

    Simhon, David; Brosh, Tamar; Halpern, Marisa; Ravid, Avi; Vasilyev, Tamar; Kariv, Naam; Katzir, Abraham; Nevo, Zvi

    2004-01-01

    Temperature-controlled tissue laser soldering is an innovative sutureless technique awaiting only solid experimental data to become the gold-standard surgical procedure for incision closure. The goals of the current study were: (1) to define the optimal laser soldering conditions, (2) to explore the immediate skin reparative healing events after sealing the wound, and (3) to determine the long-term trajectory of skin wound healing. Skin incisions were generated over rabbit dorsa and were closed using different wound-closure interventions, in three groups: (a) closure, using a temperature-controlled infrared fiberoptic CO2 laser system, employing 47% bovine serum albumin as a solder; (b) wound closure by cyanoacrylate glues; and (c) wound closure by sutures. The reparative outcomes were evaluated macroscopically and microscopically, employing semi-quantitative grading indices. Laser soldering of incisions at T = 65 degrees C emerged as the optimal method achieving immediate wound sealing. This in turn induced accelerated reparative events characterized by a reduced inflammatory reaction, followed by minimal scarring and leading to a fine quality healing. Temperature-controlled laser soldering offers an accelerated wound reparative process with numerous advantages over the conventional methods. Further investigations may reveal additional benefits in the spectrum of advantages that this innovative surgical technology has to offer. This can introduce new scientific insight that will pave the way for clinical use.

  5. Management of hidradenitis suppurativa wounds with an internal vacuum-assisted closure device.

    PubMed

    Chen, Y Erin; Gerstle, Theodore; Verma, Kapil; Treiser, Matthew D; Kimball, Alexandra B; Orgill, Dennis P

    2014-03-01

    Hidradenitis suppurativa is a chronic, debilitating disease that is difficult to treat. Once medical management fails, wide local excision offers the best chance for cure. However, the resultant wound often proves too large or contaminated for immediate closure. The authors performed a retrospective chart review of hidradenitis cases managed surgically between 2005 and 2010. Data collected included patient characteristics, management method, and outcomes. Approximately half of the patients received internal vacuum-assisted closure therapy using the vacuum-assisted closure system and delayed closure and half of the patients received immediate primary closure at the time of their excision. Delayed closure consisted of closing the majority of the wound in a linear fashion following internal vacuum-assisted closure while accepting healing by means of secondary intention for small wound areas. Patients managed with internal vacuum-assisted closure had wounds on average four times larger in area than patients managed without internal vacuum-assisted closure. In both groups, all wounds were eventually closed primarily. Healing times averaged 2.2 months with internal vacuum-assisted closure and 2.7 months without. At an average follow-up time of 2.3 months, all patients with internal vacuum-assisted closure had no recurrence of their local disease. Severe hidradenitis presents a treatment challenge, as surgical excisions are often complicated by difficult closures and unsatisfactory recurrence rates. This study demonstrates that wide local excision with reasonable outcomes can be achieved using accelerated delayed primary closure. This method uses internal vacuum-assisted closure as a bridge between excision and delayed primary closure, facilitating closure without recurrence in large, heavily contaminated wounds. Therapeutic, III.

  6. Mechanics of Wound Closure: Emerging Tape-Based Wound Closure Technology vs. Traditional Methods.

    PubMed

    Levi, Kemal; Ichiryu, Kei; Kefel, Pelin; Keller, Juergen; Grice, Jon; Belson, Ori; Storne, Eric; Safa, Bauback

    2016-10-12

    To date, there is still a lack of understanding of how wound closure methods perform comparatively under daily bodily movement during the course of healing and how they affect the mechanics of healing. The present study is a first step in understanding and objectively quantifying the gap. The study provides both a new method of metrology for noninvasive evaluation of skin mechanics at the onset of wound healing and an emerging tape-based wound closure technology. The latter shows better performance with respect to commonly used staples and sutures, holding the wound intact and providing uniform mechanical support across the incision.

  7. Frequent Application of the New Gelatin-Collagen Nonwoven Accelerates Wound Healing.

    PubMed

    Schiefer, Jennifer L; Rath, Rebekka; Held, Manuel; Petersen, Wiebke; Werner, Jan-Ole; Schaller, Hans-Eberhard; Rahmanian-Schwarz, Afshin

    2016-02-01

    Mortality after chronic wounds is high. Thus, proper and effective therapy is of critical importance. Adult mammalian skin cannot regenerate spontaneously. It heals under scar formation in a process of repair. In general, wound closure is achieved through a combination of contraction, scar formation, and regeneration. To enhance wound healing, research groups are continuously inventing and evaluating novel skin replacement products. A single application of a new gelatin-collagen nonwoven accelerates wound closure of full-thickness skin defects. Therefore, the authors' objective was to evaluate the effect of a higher application frequency of the nonwoven on wound closure in a minipig model. Four full-thickness skin defects were created surgically on the dorsum of 12 Göttingen minipigs. Next, 3 wounds were treated randomly with a novel gelatin-collagen nonwoven in different thicknesses, while the fourth wound was left untreated and served as the control wound. Moreover, 6 minipigs achieved multiple applications of the wound dressing. During the experimental period of 21 days, a close-up photographic documentation was performed. Finally, the areas of the initial wounds were excised and examined histologically. More frequent application of the nonwoven achieved accelerated wound healing and better epidermis quality compared with a single application. Mean time until wound closure of all wounds treated with a multiple application of the nonwoven was 11.0 (± 1.2) days, compared with a single application of the nonwoven with 12.4 (± 1.26) days and control wounds with 13.5 (± 1.19) days. Furthermore, the epidermal thickness of all wounds treated with multiple applications of the nonwoven was increased by 10.67 μm (31.89 ± 8.86 μm, P = .0007) compared with a single application of the nonwoven and by 6.53 μm (27.75 ± 7.24 μm, P = .0435) compared with the control group. Multiple applications of the gelatin-collagen nonwoven may be an appropriate treatment for

  8. Primary closure versus delayed closure for non bite traumatic wounds within 24 hours post injury.

    PubMed

    Eliya-Masamba, Martha C; Banda, Grace W

    2013-10-22

    Acute traumatic wounds are one of the common reasons why people present to the emergency department. Primary closure has traditionally been reserved for traumatic wounds presenting within six hours of injury and considered 'clean' by the attending surgeon, with the rest undergoing delayed primary closure as a means of controlling wound infection. Primary closure has the potential benefit of rapid wound healing but poses the potential threat of increased wound infection. There is currently no evidence to guide clinical decision-making on the best timing for closure of traumatic wounds. To determine the effect on time to healing of primary closure versus delayed closure for non bite traumatic wounds presenting within 24 hours post injury. To explore the adverse effects of primary closure compared with delayed closure for non bite traumatic wounds presenting within 24 hours post injury. In May 2013, for this first update we searched the Cochrane Wounds Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions with respect to language, date of publication or study setting. Randomised controlled trials comparing primary closure with delayed closure of non bite traumatic wounds. Two review authors independently evaluated the results of the searches against the inclusion criteria. No studies met the inclusion criteria for this review. Since no studies met the inclusion criteria, neither a meta-analysis nor a narrative description of studies was possible. There is currently no systematic evidence to guide clinical decision-making regarding the timing for closure of traumatic wounds. There is a need for robust research to investigate the effect of primary closure compared with delayed closure for non bite traumatic wounds presenting within 24 hours of injury.

  9. The TopClosure® 3S System, for skin stretching and a secure wound closure.

    PubMed

    Topaz, Moris; Carmel, Narin-Nard; Silberman, Adi; Li, Ming Sen; Li, Yong Zhong

    2012-07-01

    The principle of stretching wound margins for primary wound closure is commonly practiced and used for various skin defects, leading at times to excessive tension and complications during wound closure. Different surgical techniques, skin stretching devices and tissue expanders have been utilized to address this issue. Previously designed skin stretching devices resulted in considerable morbidity. They were invasive by nature and associated with relatively high localized tissue pressure, frequently leading to necrosis, damage and tearing of skin at the wound margins. To assess the clinical effectiveness and performance and, to determine the safety of TopClosure® for gradual, controlled, temporary, noninvasive and invasive applications for skin stretching and secure wound closing, the TopClosure® device was applied to 20 patients for preoperative skin lesion removal and to secure closure of a variety of wound sizes. TopClosure® was reinforced with adhesives, staples and/or surgical sutures, depending on the circumstances of the wound and the surgeon's judgment. TopClosure® was used prior to, during and/or after surgery to reduce tension across wound edges. No significant complications or adverse events were associated with its use. TopClosure® was effectively used for preoperative skin expansion in preparation for dermal resection (e.g., congenital nevi). It aided closure of large wounds involving significant loss of skin and soft tissue by mobilizing skin and subcutaneous tissue, thus avoiding the need for skin grafts or flaps. Following surgery, it was used to secure closure of wounds under tension, thus improving wound aesthetics. A sample case study will be presented. We designed TopClosure®, an innovative device, to modify the currently practiced concept of wound closure by applying minimal stress to the skin, away from damaged wound edges, with flexible force vectors and versatile methods of attachment to the skin, in a noninvasive or invasive manner.

  10. Randomized clinical trial of intestinal ostomy takedown comparing pursestring wound closure vs conventional closure to eliminate the risk of wound infection.

    PubMed

    Camacho-Mauries, Daniel; Rodriguez-Díaz, José Luis; Salgado-Nesme, Noel; González, Quintín H; Vergara-Fernández, Omar

    2013-02-01

    The use of temporary stomas has been demonstrated to reduce septic complications, especially in high-risk anastomosis; therefore, it is necessary to reduce the number of complications secondary to ostomy takedowns, namely wound infection, anastomotic leaks, and intestinal obstruction. To compare the rates of superficial wound infection and patient satisfaction after pursestring closure of ostomy wound vs conventional linear closure. Patients undergoing colostomy or ileostomy closure between January 2010 and February 2011 were randomly assigned to linear closure (n = 30) or pursestring closure (n = 31) of their ostomy wound. Wound infection within 30 days of surgery was defined as the presence of purulent discharge, pain, erythema, warmth, or positive culture for bacteria. Patient satisfaction, healing time, difficulty managing the wound, and limitation of activities were analyzed with the Likert questionnaire. The infection rate for the control group was 36.6% (n = 11) vs 0% in the pursestring closure group (p < 0.0001). Healing time was 5.9 weeks in the linear closure group and 3.8 weeks in the pursestring group (p = 0.0002). Seventy percent of the patients with pursestring closure were very satisfied in comparison with 20% in the other group (p = 0.0001). This study was limited by the heterogeneity in the type of stoma in both groups. The pursestring method resulted in the absence of infection after ostomy wound closure (shorter healing time and improved patient satisfaction).

  11. HoxD3 accelerates wound healing in diabetic mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hansen, Scott L.; Myers, Connie A.; Charboneau, Aubri

    Poorly healing diabetic wounds are characterized by diminished collagen production and impaired angiogenesis. HoxD3, a homeobox transcription factor that promotes angiogenesis and collagen synthesis, is up-regulated during normal wound repair whereas its expression is diminished in poorly healing wounds of the genetically diabetic (db/db) mouse. To determine whether restoring expression of HoxD3 would accelerate diabetic wound healing, we devised a novel method of gene transfer, which incorporates HoxD3 plasmid DNA into a methylcellulose film that is placed on wounds created on db/db mice. The HoxD3 transgene was expressed in endothelial cells, fibroblasts, and keratinocytes of the wounds for up tomore » 10 days. More importantly, a single application of HoxD3 to db/db mice resulted in a statistically significant acceleration of wound closure compared to control-treated wounds. Furthermore, we also observed that the HoxD3-mediated improvement in diabetic wound repair was accompanied by increases in mRNA expression of the HoxD3 target genes, Col1A1 and beta 3-integrin leading to enhanced angiogenesis and collagen deposition in the wounds. Although HoxD3-treated wounds also show improved re-epithelialization as compared to control db/db wounds, this effect was not due to direct stimulation of keratinocyte migration by HoxD3. Finally, we show that despite the dramatic increase in collagen synthesis and deposition in HoxD3-treated wounds, these wounds showed normal remodeling and we found no evidence of abnormal wound healing. These results indicate that HoxD3 may provide a means to directly improve collagen deposition, angiogenesis and closure in poorly healing diabetic wounds.« less

  12. Wound closure in flexion versus extension following total knee arthroplasty: a systematic review.

    PubMed

    Smith, Toby O; Davies, Leigh; Hing, Caroline B

    2010-06-01

    Optimising knee range of motion following total knee arthroplasty (TKA) is important for patient satisfaction, functional outcome and early rehabilitation to promote accelerated discharge. Historically, wound closure following TKA has been performed in extension. It has been suggested that knee position during wound closure may influence range of motion and clinical outcomes following TKA. The purpose of this study was to determine whether TKA wounds should be closed in flexion or extension. An electronic search of MEDLINE, EMBASE, CINAHL and AMED databases was made in addition to a review of unpublished material. All included papers were critically appraised using a modified PEDro (Physiotherapy Evidence Database) critical appraisal tool. Three papers were eligible, assessing 237 TKAs. On analysis, patients with TKA wounds closed in flexion had greater flexion range of motion and required less domiciliary physiotherapy compared to those with wounds closed in full extension. The specific degree of knee flexion used when closing total knee replacement wounds may be an important variable to clinical outcome. However, the present evidence-base is limited in both size and methodological quality.

  13. [Non-invasive assessment of the perfusion of wounds using power Doppler imaging: vacuum assisted closure versus direct wound closure].

    PubMed

    Jungius, K P; Chilla, B K; Labler, L; Teodorovic, N; Marincek, B

    2006-10-01

    The goal of our study was to assess the perfusion in wounds treated by vacuum assisted closure (VAC) compared to primary wound closure. Power Doppler Ultrasound (PDUS) was carried out under standardised conditions in 15 VAC-treated and 10 primarily closed wounds as well as on altogether 25 intraindividual reference areas. All data were sent to a work station for post-processing to determine the perfused area. Statistical data analysis was performed with the Mann-Whitney test. Both VAC-treated wounds and primarily closed wounds showed a significant increase of the perfusion when compared to the intraindividual reference area (p < 0.0001). In VAC-treated wounds, a markedly increased perfusion was measured compared to the wounds closed primarily (p < 0.0001). Perfusion decreased during treatment, but in two VAC-treated wounds, an initial increase of the perfusion was observed. Both these wounds were grossly infected. PDUS allows the quantification of the differences in wound perfusion. This can be helpful in the detection of progressive local wound infections.

  14. Cutaneous Wound Closure Materials: An Overview and Update

    PubMed Central

    Al-Mubarak, Luluah; Al-Haddab, Mohammed

    2013-01-01

    Introduction: On a daily basis, dermasurgeons are faced with different kinds of wounds that have to be closed. With a plethora of skin closure materials currently available, choosing a solution that combines excellent and rapid cosmetic results with practicality and cost-effectiveness can be difficult, if not tricky. Objectives: We aimed to review the available skin closure materials over the past 20 years and the scientific claims behind their effectiveness in repairing various kinds of wounds. Materials and Methods: The two authors independently searched and scrutinised the literature. The search was performed electronically using Pub Med, the Cochrane Database, Google Scholar and Ovid as search engines to find articles concerning skin closure materials written since 1990. Conclusion: Many factors are involved in the choice of skin closure material, including the type and place of the wound, available materials, physician expertise and preferences, and patient age and health. Evidence-based main uses of different skin closure materials are provided to help surgeons choose the appropriate material for different wounds. PMID:24470712

  15. Closure of abdominal wounds by adhesive strips: a clinical trial.

    PubMed Central

    Webster, D J; Davis, P W

    1975-01-01

    In a randomized trial of wound closure in 512 abdominal wounds, wounds were closed with either reinforced Steristrip skin closures or interrupted silk sutures. Comparisons were made of wound pain and discomfort, wound infection, discharge, redness, width, and skin reaction. The causes of peeling of the tapes were assessed. The results showed that tapes were significantly more comfortable and that patients preferred them to sutures (P less than 0.01), but wide scars occurred more often. There was no difference in rates of wound infection and no case of allergy to the tapes was seen. Closure of abdominal wounds by these tapes is a satisfactory procedure that could be used more extensively. PMID:1100188

  16. Time to wound closure in trauma patients with disorders in wound healing is shortened by supplements containing antioxidant micronutrients and glutamine: a PRCT.

    PubMed

    Blass, Sandra C; Goost, Hans; Tolba, René H; Stoffel-Wagner, Birgit; Kabir, Koroush; Burger, Christof; Stehle, Peter; Ellinger, Sabine

    2012-08-01

    : We hypothesize that wound closure in trauma patients with disorders in wound healing is accelerated by supplementation of antioxidant micronutrients and glutamine. In a randomized, double-blind, placebo-controlled trial, 20 trauma patients with disorders in wound healing were orally supplemented with antioxidant micronutrients (ascorbic acid, α-tocopherol, β-carotene, zinc, selenium) and glutamine (verum) or they received isoenergetic amounts of maltodextrine (placebo) for 14 days. Plasma/serum levels of micronutrients, glutamine, and vascular endothelial growth factor-A (VEGF-A) were determined before and after supplementation. In the wound, several parameters of microcirculation were measured. Time from study entry to wound closure was recorded. Micronutrients in plasma/serum did not change except for selenium which increased in the verum group (1.1 ± 0.2 vs. 1.4 ± 0.2 μmol/l; P = 0.009). Glutamine decreased only in the placebo group (562 ± 68 vs. 526 ± 55 μmol/l; P = 0.047). The prevalence of hypovitaminoses and the concentration of VEGF-A did not change. Considering microcirculation, only O(2)-saturation decreased in the placebo group (56.7 ± 23.4 vs. 44.0 ± 24.0 [arbitrary units]; P = 0.043). Wound closure occurred more rapidly in the verum than in the placebo group (35 ± 22 vs. 70 ± 35 d; P = 0.01). Time to wound closure can be shortened by oral antioxidant and glutamine containing supplements in trauma patients with disorders in wound healing. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  17. Predictors of Postoperative Wound Necrosis Following Primary Wound Closure of Open Ankle Fractures.

    PubMed

    Ovaska, Mikko T; Madanat, Rami; Mäkinen, Tatu J

    2016-04-01

    Most open malleolar ankle fracture wounds can be closed primarily after meticulous debridement. However, the development of wound necrosis following operative treatment of open malleolar ankle fractures can have catastrophic consequences. The aim of this study was to identify risk factors predisposing to postoperative wound necrosis following primary wound closure of open malleolar ankle fractures. A total of 137 patients with open malleolar ankle fractures were identified. The open fracture wound was primarily closed in 110 of 137 (80%) patients, and postoperative wound necrosis occurred in 18 (16%) of these patients. These patients were compared to the open fracture patients without wound necrosis. Twenty possible risk factors for the development of wound necrosis were studied with logistic regression analysis. The variables that were independently associated with an increased risk for postoperative wound necrosis included ASA class ≥2, Gustilo grade III open injury, and the use of pulsatile lavage at index surgery. Our study showed that ASA class ≥2, Gustilo grade III open injury, and the use of pulsatile lavage at index surgery were the most important factors predisposing to postoperative wound necrosis following primary wound closure of open malleolar ankle fractures. The findings warrant a further study specifically comparing primary and delayed wound closure in patients with Gustilo grade III open malleolar ankle fractures and different ASA classes. Also, the role of pulsatile lavage should be re-evaluated. Level III, retrospective comparative series. © The Author(s) 2016.

  18. Simple Skin-Stretching Device in Assisted Tension-Free Wound Closure.

    PubMed

    Cheng, Li-Fu; Lee, Jiunn-Tat; Hsu, Honda; Wu, Meng-Si

    2017-03-01

    Numerous conventional wound reconstruction methods, such as wound undermining with direct suture, skin graft, and flap surgery, can be used to treat large wounds. The adequate undermining of the skin flaps of a wound is a commonly used technique for achieving the closure of large tension wounds; however, the use of tension to approximate and suture the skin flaps can cause ischemic marginal necrosis. The purpose of this study is to use elastic rubber bands to relieve the tension of direct wound closure for simultaneously minimizing the risks of wound dehiscence and wound edge ischemia that lead to necrosis. This retrospective study was conducted to evaluate our clinical experiences with 22 large wounds, which involved performing primary closures under a considerable amount of tension by using elastic rubber bands in a skin-stretching technique after a wide undermining procedure. Assessment of the results entailed complete wound healing and related complications. All 22 wounds in our study showed fair to good results except for one. The mean success rate was approximately 95.45%. The simple skin-stretching design enabled tension-free skin closure, which pulled the bilateral undermining skin flaps as bilateral fasciocutaneous advancement flaps. The skin-stretching technique was generally successful.

  19. Simple skin-stretching device in assisted tension-free wound closure

    PubMed Central

    Cheng, Li-Fu; Lee, Jiunn-Tat; Hsu, Honda; Wu, Meng-Si

    2017-01-01

    Background Numerous conventional wound reconstruction methods such as wound undermining with direct suture, skin graft, and flap surgery can be used to treat large wounds. The adequate undermining of the skin flaps of a wound is a commonly used technique for achieving the closure of large tension wounds; however, the use of tension to approximate and suture the skin flaps can cause ischemic marginal necrosis. The purpose of this study is to use elastic rubber bands to relieve the tension of direct wound closure for simultaneously minimizing the risks of wound dehiscence and wound edge ischemia that lead to necrosis. Materials and Methods This retrospective study was conducted to evaluate our clinical experiences with 22 large wounds, which involved performing primary closures under a considerable amount of tension by using elastic rubber bands in a skin-stretching technique following a wide undermining procedure. Assessment of the results entailed complete wound healing and related complications. Results All 22 wounds in our study showed fair to good results except for one. The mean success rate was approximately 95.45%. Conclusion The simple skin-stretching design enabled tension-free skin closure, which pulled the bilateral undermining skin flaps as bilateral fasciocutaneous advancement flaps. The skin-stretching technique was generally successful. PMID:28195891

  20. Smad4 disruption accelerates keratinocyte reepithelialization in murine cutaneous wound repair.

    PubMed

    Yang, Leilei; Li, Wenlong; Wang, Shaoxia; Wang, Lijuan; Li, Yang; Yang, Xiao; Peng, Ruiyun

    2012-10-01

    Keratinocyte reepithelialization is a rate-limiting event in cutaneous wound repair, which involves the migration and proliferation of keratinocytes to cover the denuded dermal surface. Transforming growth factor-β1 (TGF-β1) has the ability to induce epithelial cell migration while inhibiting proliferation, and controversial results have been generated regarding the effect of TGF-β signaling on reepithelialization. In this study, full-thickness skin wounds were made in keratinocyte-specific Smad4 knockout and the control mice. The wound closure, reepithelialization, keratinocyte proliferation, myofibroblast numbers and collagen deposition of were assessed. The results showed that the proliferation of keratinocytes increased, which accelerated the reepithelialization, and led to faster wound repair in the epidermis of Smad4 mutant mice. Upregulation of keratin 17, 14-3-3 sigma and phosphorylated AKT in the hyperproliferative epidermis may be correlated with the accelerated reepithelialization. We conclude that Smad4 plays an inhibitory role in the keratinocyte-mediated reepithelialization of wound healing.

  1. PED/PEA-15 Controls Fibroblast Motility and Wound Closure by ERK1/2-Dependent Mechanisms

    PubMed Central

    Buonomo, Roberta; Giacco, Ferdinando; Vasaturo, Angela; Caserta, Sergio; Guido, Stefano; Pagliara, Valentina; Garbi, Corrado; Mansueto, Gelsomina; Cassese, Angela; Perruolo, Giuseppe; Oriente, Francesco; Miele, Claudia; Beguinot, Francesco; Formisano, Pietro

    2012-01-01

    Cell migration is dependent on the control of signaling events that play significant roles in creating contractile force and in contributing to wound closure. We evaluated wound closure in fibroblasts from mice overexpressing (TgPED) or lacking ped/pea-15 (KO), a gene overexpressed in patients with type 2 diabetes. Cultured skin fibroblasts isolated from TgPED mice showed a significant reduction in the ability to recolonize wounded area during scratch assay, compared to control fibroblasts. This difference was observed both in the absence and in the presence of mytomicin C, an inhibitor of mitosis. In time-lapse experiments, TgPED fibroblasts displayed about twofold lower velocity and diffusion coefficient, as compared to controls. These changes were accompanied by reduced spreading and decreased formation of stress fibers and focal adhesion plaques. At the molecular level, TgPED fibroblasts displayed decreased RhoA activation and increased abundance of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2). Inhibition of ERK1/2 activity by PD98059 restored RhoA activation, cytoskeleton organization and cell motility, and almost completely rescued wound closure of TgPED fibroblasts. Interestingly, skin fibroblasts isolated from KO mice displayed an increased wound closure ability. In vivo, healing of dorsal wounds was delayed in TgPED and accelerated in KO mice. Thus, PED/PEA-15 may affect fibroblast motility by a mechanism, at least in part, mediated by ERK1/2. J. Cell. Physiol. 227: 2106–2116, 2012. © 2011 Wiley Periodicals, Inc. PMID:21780113

  2. PDGF-BB Does Not Accelerate Healing in Diabetic Mice with Splinted Skin Wounds

    PubMed Central

    Shah, Nihar M.; Teixeira, Leandro; Motta, Monica J.; Covert, Jill; Dubielzig, Richard; Schurr, Michael; Isseroff, Roslyn Rivkah; Abbott, Nicholas L.; McAnulty, Jonathan; Murphy, Christopher J.

    2014-01-01

    Topical application of platelet-derived growth factor-BB (PDGF-BB) is considered to accelerate tissue repair of impaired chronic wounds. However, the vast literature is plagued with conflicting reports of its efficacy in animal models and this is often influenced by a wide array of experimental variables making it difficult to compare the results across the studies. To mitigate the confounding variables that influence the efficacy of topically applied PDGF-BB, we used a controlled full thickness splinted excisional wound model in db/db mice (type 2 diabetic mouse model) for our investigations. A carefully-defined silicone-splinted wound model, with reduced wound contraction, controlled splint and bandage maintenance, allowing for healing primarily by reepithelialization was employed. Two splinted 8 mm dorsal full thickness wounds were made in db/db mice. Wounds were topically treated once daily with either 3 µg PDGF-BB in 30 µl of 5% PEG-PBS vehicle or an equal volume of vehicle for 10 days. Body weights, wound contraction, wound closure, reepithelialization, collagen content, and wound bed inflammation were evaluated clinically and histopathologically. The bioactivity of PDGF-BB was confirmed by in vitro proliferation assay. PDGF-BB, although bioactive in vitro, failed to accelerate wound healing in vivo in the db/db mice using the splinted wound model. Considering that the predominant mechanism of wound healing in humans is by re-epeithelialization, the most appropriate model for evaluating therapeutics is one that uses splints to prevent excessive wound contraction. Here, we report that PDGF-BB does not promote wound closure by re-epithelialization in a murine splinted wound model. Our results highlight that the effects of cytoactive factors reported in vivo ought to be carefully interpreted with critical consideration of the wound model used. PMID:25121729

  3. A homeopathic remedy from arnica, marigold, St. John's wort and comfrey accelerates in vitro wound scratch closure of NIH 3T3 fibroblasts.

    PubMed

    Hostanska, Katarina; Rostock, Matthias; Melzer, Joerg; Baumgartner, Stephan; Saller, Reinhard

    2012-07-18

    Drugs of plant origin such as Arnica montana, Calendula officinalis or Hypericum perforatum have been frequently used to promote wound healing. While their effect on wound healing using preparations at pharmacological concentrations was supported by several in vitro and clinical studies, investigations of herbal homeopathic remedies on wound healing process are rare. The objective of this study was to investigate the effect of a commercial low potency homeopathic remedy Similasan® Arnica plus Spray on wound closure in a controlled, blind trial in vitro. We investigated the effect of an ethanolic preparation composed of equal parts of Arnica montana 4x, Calendula officinalis 4x, Hypericum perforatum 4x and Symphytum officinale 6x (0712-2), its succussed hydroalcoholic solvent (0712-1) and unsuccussed solvent (0712-3) on NIH 3T3 fibroblasts. Cell viability was determined by WST-1 assay, cell growth using BrdU uptake, cell migration by chemotaxis assay and wound closure by CytoSelect ™Wound Healing Assay Kit which generated a defined "wound field". All assays were performed in three independent controlled experiments. None of the three substances affected cell viability and none showed a stimulating effect on cell proliferation. Preparation (0712-2) exerted a stimulating effect on fibroblast migration (31.9%) vs 14.7% with succussed solvent (0712-1) at 1:100 dilutions (p < 0.001). Unsuccussed solvent (0712-3) had no influence on cell migration (6.3%; p > 0.05). Preparation (0712-2) at a dilution of 1:100 promoted in vitro wound closure by 59.5% and differed significantly (p < 0.001) from succussed solvent (0712-1), which caused 22.1% wound closure. Results of this study showed that the low potency homeopathic remedy (0712-2) exerted in vitro wound closure potential in NIH 3T3 fibroblasts. This effect resulted from stimulation of fibroblasts motility rather than of their mitosis.

  4. Closure of logging wounds after 10 years

    Treesearch

    H. Clay Smith; Gary W. Miller; Thomas M. Schuler

    1994-01-01

    Closure of logging wounds on 96 sample trees was evaluated after 2, 5, and 10 years for Appalachian hardwood trees in north-central West Virginia. For yellow-poplar, northern red oak, black cherry, and white oak, many small wounds, 1 to 50 square inches in size, closed between 5 and 10 years after logging. For larger wounds, 50 to 200 square inches, it appears that...

  5. Momordica charantia ointment accelerates diabetic wound healing and enhances transforming growth factor-β expression.

    PubMed

    Hussan, F; Teoh, S Lin; Muhamad, N; Mazlan, M; Latiff, A A

    2014-08-01

    Transforming growth factor-β (TGF-β) plays an important role in wound healing. Delayed wound healing is a consequence of diabetes, leading to high morbidity and poor quality of life. Momordica charantia (MC) fruit possesses anti-diabetic and wound healing properties. This study aimed to explore the changes in TGF-β expression in diabetic wounds treated with topical MC fruit extract. Fifty-six male Sprague-Dawley rats were divided into a normal control group and five diabetic groups of ten rats each. Intravenous streptozotocin (50mg/kg) was given to induce diabetes in the diabetic groups. Full thickness excision wounds were created on the thoracodorsal region of the animals, and these wounds were then treated with vehicle, MC powder, MC ointment and povidone ointment or ointment base for ten days. Wound healing was determined by the rate of wound closure, total protein content and TGF-β expression in the wounds, and histological observation. Diabetic groups showed delayed wound closure rates compared to the control group. The wound closure rate in the MC ointment group was significantly faster than that of the untreated diabetic group (p<0.05). The MC ointment group also showed intense TGF-β expression and a high level of total protein content. MC ointment has a promising potential for use as an alternative topical medication for diabetic wounds. This work has shown that it accelerates wound healing in diabetic rats, and it is suggested here that this occurs by enhancing TGF-β expression. Further work is recommended to explore this effect.

  6. Sinonasal Epithelial Wound Resealing in an In Vitro Model: Inhibition of Wound Closure with IL-4 Exposure

    PubMed Central

    Wise, Sarah K.; Den Beste, Kyle A.; Hoddeson, Elizabeth K.; Parkos, Charles A.; Nusrat, Asma

    2013-01-01

    Background Prolonged healing and persistent inflammation following surgery for rhinosinusitis impacts patient satisfaction and healthcare resources. Cytokines interleukin (IL)-4, 5, and 13 are important mediators in Th2 inflammatory rhinosinusitis. Decreased wound healing has been demonstrated with Th2 cytokine exposure, but this has not been extensively studied in sinonasal epithelium. We hypothesized that in vitro exposure of primary sinonasal epithelial cell cultures to Th2 inflammatory cytokine IL-4 and IL-13 would impair wound resealing and decrease expression of annexin A2 at the wound edge. Methods Following 24-hour exposure to IL-4, 5, or 13 versus controls, sterile linear mechanical wounds were created in primary sinonasal epithelial cultures (n = 12 wounds per condition). Wounds were followed for 36 hours or until complete closure and residual wound areas were calculated by image analysis. Group differences in annexin A2 were assessed by immunofluorescence labeling, confocal microscopy, and Western blots. Results Significant wound closure differences were identified across cytokine exposure groups (p<0.001). Mean percentage wound closure at the completion of the 36-hour timecourse was 98.41% ± 3.43% for control wounds versus 85.02% ± 18.46% for IL-4 exposed wounds. IL-13 did not significantly impair sinonasal epithelial wound resealing in vitro. Annexin A2 protein levels were decreased in IL-4 treated wounds when compared to control wounds (p<0.01). Conclusions Th2 cytokine IL-4 decreases sinonasal epithelial wound closure in vitro. Annexin A2 is also diminished with IL-4 exposure. This supports the hypothesis that IL-4 exposure impairs sinonasal epithelial wound healing and may contribute to prolonged healing in Th2 inflammatory rhinosinusitis. PMID:23468432

  7. Assessment of Severe Extremity Wound Bioburden at the Time of Definitive Wound Closure or Coverage: Correlation With Subsequent Postclosure Deep Wound Infection (Bioburden Study).

    PubMed

    Bosse, Michael J; Murray, Clinton K; Carlini, Anthony R; Firoozabadi, Reza; Manson, Theodore; Scharfstein, Daniel O; Wenke, Joseph C; Zadnik, Mary; Castillo, Renan C

    2017-04-01

    Infection remains the most common and significant complication after high-energy fractures. The Bioburden Study is a multicenter, prospective, observational cohort study of wound bacterial bioburden and antibiotic care in severe open lower extremity fractures. The aims of this study are to (1) characterize the contemporary extremity wound "bioburden" at the time of definitive wound closure; (2) determine the concordance between polymerase chain reaction results and hospital microbiology; (3) determine, among those who develop deep infections, the concordance between the pathogens at wound closure and at deep infection; and (4) compare the probability of deep infection between those who did and did not receive an appropriate course of antibiotics based on bioburden at the time of wound closure. To address these aims, sites collected tissue samples from severe lower extremity injuries at the time of wound closure and at first surgery for treatment of a deep infection, nonunion, flap failure, amputation, or other complications (because these surgeries may be due to undetected infection). Otherwise, if no further surgical treatment occurred, participants were followed for 12 months. The study was conducted at 38 US trauma centers and has enrolled 655 participants aged 18-64 years. This is the first large multi-institutional study evaluating the wound bioburden of severe open tibia fractures and correlating this bioburden with the risk of wound complications after definitive soft tissue closure.

  8. Teaching advanced wound closure techniques using cattle digits.

    PubMed

    Khalil, Philipe N; Kanz, Karl-Georg; Siebeck, Matthias; Mutschler, Wolf

    2011-03-01

    To evaluate a model used to impart advanced wound closure skills because available models do not meet the necessary requirements to a substantial degree. Seventy-one residents were asked to evaluate a 75-minute-long skills course using cadaveric cattle digits to learn Z-plasty, V-Y-plasty, and oval-shaped rotational flaps. A short film and the course instructor demonstrated each technique first. A Likert rating scale ranging from 1 to 6 was used for questions in the survey given to the residents. There was strong agreement among residents (1.65 ± 1.17 years of experience) that advanced wound closure training courses are necessary (5.73 ± 0.73), which corresponded to the residents' low level of knowledge and self-assessment of practical skills and present experience (2.84 ± 1.01). The course was evaluated with high acceptance, even though it was found to be demanding for the trainees (5.84 ± 0.40). This might also be related to the high rating of the model itself, which was found to be a suitable method for teaching advanced wound closure techniques (5.50 ± 0.71) that was easily comprehensible (5.73 ± 0.53). Skills training courses for young trainees are warranted to impart advanced wound closure techniques. The curriculum using cattle digits presented here is recommended. The authors have indicated no significant interest with commercial supporters. © 2011 by the American Society for Dermatologic Surgery, Inc.

  9. Comparison of V-Loc™ 180 wound closure device and Quill™ PDO knotless tissue-closure device for intradermal closure in a porcine in vivo model: evaluation of biomechanical wound strength.

    PubMed

    Gingras, Kristen; Zaruby, Jeffrey; Maul, Don

    2012-05-01

    The objective of this study was to compare the biomechanical strength of two barbed suture devices: V-Loc™ 180 Wound Closure Device and Quill™ PDO Knotless Tissue-Closure Device following primary cosmetic skin closures in a porcine dermal model. This prospective randomized, controlled in vivo trial compared size 3/0 V-Loc™ 180 device to size 2/0 Quill™ PDO device. Both products were tested for dermal closure in adult porcine models and evaluated at five timepoints. At postoperative days 0, 3, 7, 14, and 28 sutured tissue regions were excised post mortem and tested for intradermal wound holding strength. Wounds closed with V-Loc™ 180 device were stronger than Quill™ PDO device at days 0, 3, 7, and 14 with these differences being significant (p < 0.05) at days 3 and 7. At day 3, the average maximum load of V-Loc™ 180 was 13.53 kgf and Quill™ PDO was 10.38 kgf (p = 0.002). At day 7, the average maximum load of V-Loc™ 180 was 10.4 kgf and Quill™ PDO was 7.56 kgf (p = 0.001). Throughout the duration of the study, there was no suture extrusion or tissue distortion and all wounds healed with no major complications. In this study, V-Loc™ 180 device was significantly stronger than Quill™ PDO device during the critical phases of wound healing in skin. Copyright © 2012 Wiley Periodicals, Inc.

  10. Hydrogel Microencapsulated Insulin-Secreting Cells Increase Keratinocyte Migration, Epidermal Thickness, Collagen Fiber Density, and Wound Closure in a Diabetic Mouse Model of Wound Healing.

    PubMed

    Aijaz, Ayesha; Faulknor, Renea; Berthiaume, François; Olabisi, Ronke M

    2015-11-01

    Wound healing is a hierarchical process of intracellular and intercellular signaling. Insulin is a potent chemoattractant and mitogen for cells involved in wound healing. Insulin's potential to promote keratinocyte growth and stimulate collagen synthesis in fibroblasts is well described. However, there currently lacks an appropriate delivery mechanism capable of consistently supplying a wound environment with insulin; current approaches require repeated applications of insulin, which increase the chances of infecting the wound. In this study, we present a novel cell-based therapy that delivers insulin to the wound area in a constant or glucose-dependent manner by encapsulating insulin-secreting cells in nonimmunogenic poly(ethylene glycol) diacrylate (PEGDA) hydrogel microspheres. We evaluated cell viability and insulin secretory characteristics of microencapsulated cells. Glucose stimulation studies verified free diffusion of glucose and insulin through the microspheres, while no statistical difference in insulin secretion was observed between cells in microspheres and cells in monolayers. Scratch assays demonstrated accelerated keratinocyte migration in vitro when treated with microencapsulated cells. In excisional wounds on the dorsa of diabetic mice, microencapsulated RIN-m cells accelerated wound closure by postoperative day 7; a statistically significant increase over AtT-20ins-treated and control groups. Histological results indicated significantly greater epidermal thickness in both microencapsulated RIN-m and AtT-20ins-treated wounds. The results suggest that microencapsulation enables insulin-secreting cells to persist long enough at the wound site for a therapeutic effect and thereby functions as an effective delivery vehicle to accelerate wound healing.

  11. The use of a silicon sheet for gradual wound closure after fasciotomy.

    PubMed

    Walker, Tobias; Gruler, Miriam; Ziemer, Gerhard; Bail, Dorothee H L

    2012-06-01

    We present a silicon sheet for temporary wound covering and gradual wound closure after open fasciotomy. Fasciotomy was performed in a total of 70 limbs with compartment syndrome (CS). The main etiology of CS was predominantly vascular. All patients were treated with a silicon sheet to cover the soft tissue defect and gradually reapproximate the skin margins. In 53% of the patients, a delayed final wound closure was achieved after a mean of 11.9 days. This method allows final closure of fasciotomy wounds without scar contractures, marginal necrosis, infection, or significant pain. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  12. Extended negative pressure wound therapy-assisted dermatotraction for the closure of large open fasciotomy wounds in necrotizing fasciitis patients

    PubMed Central

    2014-01-01

    Background Necrotizing fasciitis (NF) is a rapid progressive infection of the subcutaneous tissue or fascia and may result in large open wounds. The surgical options to cover these wounds are often limited by the patient condition and result in suboptimal functional and cosmetic wound coverage. Dermatotraction can restore the function and appearance of the fasciotomy wound and is less invasive in patients with comorbidities. However, dermatotraction for scarred, stiff NF fasciotomy wounds is often ineffective, resulting in skin necrosis. The authors use extended negative pressure wound therapy (NPWT) as an assist in dermatotraction to close open NF fasciotomy wounds. The authors present the clinical results, followed by a discussion of the clinical basis of extended NPWT-assisted dermatotraction. Methods A retrospective case series of eight patients with NF who underwent open fasciotomy was approved for the study. After serial wound preparation, dermatotraction was applied in a shoelace manner using elastic vessel loops. Next, the extended NPWT was applied over the wound. The sponge was three times wider than the wound width, and the transparent covering drape almost encircled the anatomical wound area. The negative pressure of the NPWT was set at a continuous 100 mmHg by suction barometer. The clinical outcome was assessed based on wound area reduction after treatment and by the achievement of direct wound closure. Results After the first set of extended NPWT-assisted dermatotraction procedures, the mean wound area was significantly decreased (658.12 cm2 to 29.37 cm2; p = 0.002), as five out of eight patients achieved direct wound closure. One patient with a chest wall defect underwent latissimus dorsi musculocutaneous flap coverage, with primary closure of the donor site. Two Fournier’s gangrene patients underwent multiple sets of treatment and finally achieved secondary wound closure with skin grafts. The patients were followed up for 18.3 months on

  13. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Geiger, Adolf, E-mail: ageiger@dreirosen-pharma.com; Walker, Audrey, E-mail: awalker@dreirosen-pharma.com; Nissen, Erwin, E-mail: enissen@dreirosen-pharma.com

    Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-β1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo.more » Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers. - Highlights: • Fibrocytes have shown potent wound healing properties in vitro and in vivo. • Their clinical use is precluded by low numbers and antigen-presenting function. • We isolated exosomes with no immunogenicity potential from human fibrocytes. • Their cargo included microRNAs and proteins that are known healing promoters. • They accelerated wound closure in diabetic mice in a dose-dependent manner.« less

  14. A homeopathic remedy from arnica, marigold, St. John’s wort and comfrey accelerates in vitro wound scratch closure of NIH 3T3 fibroblasts

    PubMed Central

    2012-01-01

    Background Drugs of plant origin such as Arnica montana, Calendula officinalis or Hypericum perforatum have been frequently used to promote wound healing. While their effect on wound healing using preparations at pharmacological concentrations was supported by several in vitro and clinical studies, investigations of herbal homeopathic remedies on wound healing process are rare. The objective of this study was to investigate the effect of a commercial low potency homeopathic remedy Similasan® Arnica plus Spray on wound closure in a controlled, blind trial in vitro. Methods We investigated the effect of an ethanolic preparation composed of equal parts of Arnica montana 4x, Calendula officinalis 4x, Hypericum perforatum 4x and Symphytum officinale 6x (0712–2), its succussed hydroalcoholic solvent (0712–1) and unsuccussed solvent (0712–3) on NIH 3T3 fibroblasts. Cell viability was determined by WST-1 assay, cell growth using BrdU uptake, cell migration by chemotaxis assay and wound closure by CytoSelect ™Wound Healing Assay Kit which generated a defined “wound field”. All assays were performed in three independent controlled experiments. Results None of the three substances affected cell viability and none showed a stimulating effect on cell proliferation. Preparation (0712–2) exerted a stimulating effect on fibroblast migration (31.9%) vs 14.7% with succussed solvent (0712–1) at 1:100 dilutions (p < 0.001). Unsuccussed solvent (0712–3) had no influence on cell migration (6.3%; p > 0.05). Preparation (0712–2) at a dilution of 1:100 promoted in vitro wound closure by 59.5% and differed significantly (p < 0.001) from succussed solvent (0712–1), which caused 22.1% wound closure. Conclusion Results of this study showed that the low potency homeopathic remedy (0712–2) exerted in vitro wound closure potential in NIH 3T3 fibroblasts. This effect resulted from stimulation of fibroblasts motility rather than of their mitosis. PMID:22809174

  15. Vacuum assisted closure for the treatment of sternal wounds: the bridge between débridement and definitive closure.

    PubMed

    Song, David H; Wu, Liza C; Lohman, Robert F; Gottlieb, Lawrence J; Franczyk, Mieczyslawa

    2003-01-01

    A method to refine the treatment of sternal wounds using Vacuum Assisted Closure (V.A.C.) therapy as the bridge between débridement and delayed definitive closure is described. A retrospective review of 35 consecutive patients with sternal wound complications over a 2-year period (March of 1999 to March of 2001) was performed. The treatment of sternal wounds with traditional twice-a-day dressing changes was compared with the treatment with the wound V.A.C. device. An analysis of the number of days between initial débridement and closure, number of dressing changes, number and types of flaps needed for reconstruction, and complications was performed. Eighteen patients were treated with traditional twice-a-day dressing changes and 17 patients were treated with V.A.C. therapy alone. The two groups were similar regarding age, sex, type of cardiac procedure, and type of sternal wound. The V.A.C. therapy group had a trend toward a shorter interval between débridement and closure, with a mean of 6.2 days, whereas the dressing change group had mean of 8.5 days. The V.A.C. therapy group had a significantly lower number of dressing changes, with a mean of three, whereas the twice-a-day dressing change group had a mean of 17 (p < 0.05). Reconstruction required an average of 1.5 soft-tissue flaps per patient treated with traditional dressing changes versus 0.9 soft-tissue flaps per patient for those treated with V.A.C. therapy (p < 0.05). Before closure, there was one death among patients undergoing dressing changes and three in the V.A.C. therapy group, all of which were unrelated to the management of the sternal wound. Patients with sternal wounds who have benefited from V.A.C. therapy alone have a significant decrease in the number of dressing changes and number of soft-tissue flaps needed for closure. Finally, the V.A.C. therapy group had a trend toward a decreased number of days between débridement and closure.

  16. Serpina3n accelerates tissue repair in a diabetic mouse model of delayed wound healing.

    PubMed

    Hsu, I; Parkinson, L G; Shen, Y; Toro, A; Brown, T; Zhao, H; Bleackley, R C; Granville, D J

    2014-10-09

    Chronic, non-healing wounds are a major complication of diabetes and are characterized by chronic inflammation and excessive protease activity. Although once thought to function primarily as a pro-apoptotic serine protease, granzyme B (GzmB) can also accumulate in the extracellular matrix (ECM) during chronic inflammation and cleave ECM proteins that are essential for proper wound healing, including fibronectin. We hypothesized that GzmB contributes to the pathogenesis of impaired diabetic wound healing through excessive ECM degradation. In the present study, the murine serine protease inhibitor, serpina3n (SA3N), was administered to excisional wounds created on the dorsum of genetically induced type-II diabetic mice. Wound closure was monitored and skin wound samples were collected for analyses. Wound closure, including both re-epithelialization and contraction, were significantly increased in SA3N-treated wounds. Histological and immunohistochemical analyses of SA3N-treated wounds revealed a more mature, proliferative granulation tissue phenotype as indicated by increased cell proliferation, vascularization, fibroblast maturation and differentiation, and collagen deposition. Skin homogenates from SA3N-treated wounds also exhibited greater levels of full-length intact fibronectin compared with that of vehicle wounds. In addition, GzmB-induced detachment of mouse embryonic fibroblasts correlated with a rounded and clustered phenotype that was prevented by SA3N. In summary, topical administration of SA3N accelerated wound healing. Our findings suggest that GzmB contributes to the pathogenesis of diabetic wound healing through the proteolytic cleavage of fibronectin that is essential for normal wound closure, and that SA3N promotes granulation tissue maturation and collagen deposition.

  17. Bulge Hair Follicle Stem Cells Accelerate Cutaneous Wound Healing in Rats.

    PubMed

    Heidari, Fatemeh; Yari, Abazar; Rasoolijazi, Homa; Soleimani, Mansoureh; Dehpoor, Ahmadreza; Sajedi, Nayereh; Joulai Veijouye, Sanaz; Nobakht, Maliheh

    2016-04-01

    Skin wound healing is a serious clinical problem especially after surgery and severe injury of the skin. Cell therapy is an innovative technique that can be applied to wound healing. One appropriate source of stem cells for therapeutic use is stem cells from the adult bulge of hair follicles. This study examined the effects of adult bulge hair follicle stem cells (HFSC) in wound healing. Hair follicle stem cells were obtained from rat vibrissa and labeled with DiI (Invitrogen, Carlsbad, CA), then special markers were detected using flow cytometry. A full-thickness excisional wound model was created and DiI-labeled HFSC were injected around the wound bed. Wound healing was recorded with digital photographs. Animals were sacrificed at 3, 7, or 14 days after surgery, and were used for the following histological analyses. Flow cytometry analysis showed that HFSC were CD34 positive and nestin positive, but K15 negative. Morphological analysis of HFSC-treated wounds exhibited accelerated wound closure. Histological analysis of hematoxylin and eosin stained and Masson's trichrome-stained photomicrographs showed significantly more re-epithelialization and dermal structural regeneration in HFSC-treated wounds than in the control group. Immunohistochemical analysis of CD31 protein-positive cells showed angiogenesis was also more significant in HFSC-treated wounds than in the control group. Hair follicle stem cells accelerate skin wound healing. Isolating HFSC from a small skin biopsy could repair less-extensive full-thickness skin wounds by autologous stem cells and overcome major challenges regarding the use of stem cells in clinical application, while avoiding immune rejection and ethical concerns.

  18. Consequences of age on ischemic wound healing in rats: altered antioxidant activity and delayed wound closure.

    PubMed

    Moor, Andrea N; Tummel, Evan; Prather, Jamie L; Jung, Michelle; Lopez, Jonathan J; Connors, Sarah; Gould, Lisa J

    2014-04-01

    Advertisements targeted at the elderly population suggest that antioxidant therapy will reduce free radicals and promote wound healing, yet few scientific studies substantiate these claims. To better understand the potential utility of supplemental antioxidant therapy for wound healing, we tested the hypothesis that age and tissue ischemia alter the balance of endogenous antioxidant enzymes. Using a bipedicled skin flap model, ischemic and non-ischemic wounds were created on young and aged rats. Wound closure and the balance of the critical antioxidants superoxide dismutase and glutathione in the wound bed were determined. Ischemia delayed wound closure significantly more in aged rats. Lower superoxide dismutase 2 and glutathione in non-ischemic wounds of aged rats indicate a basal deficit due to age alone. Ischemic wounds from aged rats had lower superoxide dismutase 2 protein and activity initially, coupled with decreased ratios of reduced/oxidized glutathione and lower glutathione peroxidase activity. De novo glutathione synthesis, to restore redox balance in aged ischemic wounds, was initiated as evidenced by increased glutamate cysteine ligase. Results demonstrate deficiencies in two antioxidant pathways in aged rats that become exaggerated in ischemic tissue, culminating in profoundly impaired wound healing and prolonged inflammation.

  19. Comparing the Tolerability of a Novel Wound Closure Device Using a Porcine Wound Model

    PubMed Central

    Townsend, Katy L.; Akeroyd, Jen; Russell, Duncan S.; Kruzic, Jamie J.; Robertson, Bria L.; Lear, William

    2018-01-01

    Objective: To compare the tolerability and mechanical tensile strength of acute skin wounds closed with nylon suture plus a novel suture bridge device (SBD) with acute skin wounds closed with nylon suture in a porcine model. Approach: Four Yucatan pigs each received 12 4.5 cm full-thickness incisions that were closed with 1 of 4 options: Suture bridge with nylon, suture bridge with nylon and subdermal polyglactin, nylon simple interrupted, and nylon simple interrupted with subdermal polyglactin. Epithelial reaction, inflammation, and scarring were examined histologically at days 10 and 42. Wound strength was examined mechanically at days 10 and 42 on ex vivo wounds from euthanized pigs. Results: Histopathology in the suture entry/exit planes showed greater dermal inflammation with a simple interrupted nylon suture retained for 42 days compared with the SBD retained for 42 days (p < 0.03). While tensile wound strength in the device and suture groups were similar at day 10, wounds closed with the devices were nearly 8 times stronger at day 42 compared with day 10 (p < 0.001). Innovation: A novel SBD optimized for cutaneous wound closure that protects the skin surface from suture strands, forms a protective bridge over the healing wound edges, and knotlessly clamps sutures. Conclusion: This study suggests that the use of a SBD increases the tolerability of nylon sutures in porcine acute skin wound closures allowing for prolonged mechanical support of the wound. For slow healing wounds, this may prevent skin wound disruption, such as edge necrosis and dehiscence. PMID:29892494

  20. Primary closure versus non-closure of dog bite wounds. a randomised controlled trial.

    PubMed

    Paschos, Nikolaos K; Makris, Eleftherios A; Gantsos, Apostolos; Georgoulis, Anastasios D

    2014-01-01

    Dog bite wounds represent a major health problem. Despite their importance, their management and especially the role of primary closure remain controversial. In this randomised controlled trial, the outcome between primary suturing and non-closure was compared. 168 consecutive patients with dog bite injuries were included in this study. The wounds were allocated randomly in two treatment approaches: Group 1, consisting of eighty-two patients, had their wound sutured, whilst Group 2, consisting of eighty-six patients, did not have their wounds sutured. All wounds were cleansed using high-pressure irrigation and povidone iodine. All patients received the same type of antibiotic treatment. Our measured outcomes included presence of infection and cosmetic appearance. Cosmetic outcome was evaluated using the Vancouver Scar Scale (VSS). Wound and patient characteristics, such as time of management, wound location and size, and patient age, were recorded and analysed for their potential role in the resulting outcome. The overall infection rate was 8.3%. No difference in the infection rate between primary suturing and non-suturing group was detected in the present study. The cosmetic appearance of the sutured wounds was significantly better (mean score 1.74) compared to the wounds that were left open (mean score 3.05) (p=0.0001). The infection rate was comparable among all age groups. Wounds treated within 8h of injury demonstrated an infection rate of 4.5%, which is lower compared to the 22.2% rate observed in wounds treated later than 8h. The wounds located at the head and neck exhibited better results in both infection rate and cosmetic outcome. Additionally, wounds >3 cm negatively affected the cosmetic appearance of the outcome. Primary suturing of wounds caused by dog bites resulted in similar infection rate compared to non-suturing. However, primary suturing exhibited improved cosmetic appearance. Time of management appeared to be critical, as early treatment

  1. Mesenchymal stem cell-conditioned medium accelerates skin wound healing: An in vitro study of fibroblast and keratinocyte scratch assays

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Walter, M.N.M.; School of Life and Health Science, Aston University, Aston Triangle, Birmingham, B4 7EJ; Wright, K.T.

    2010-04-15

    We have used in vitro scratch assays to examine the relative contribution of dermal fibroblasts and keratinocytes in the wound repair process and to test the influence of mesenchymal stem cell (MSC) secreted factors on both skin cell types. Scratch assays were established using single cell and co-cultures of L929 fibroblasts and HaCaT keratinocytes, with wound closure monitored via time-lapse microscopy. Both in serum supplemented and serum free conditions, wound closure was faster in L929 fibroblast than HaCaT keratinocyte scratch assays, and in co-culture the L929 fibroblasts lead the way in closing the scratches. MSC-CM generated under serum free conditionsmore » significantly enhanced the wound closure rate of both skin cell types separately and in co-culture, whereas conditioned medium from L929 or HaCaT cultures had no significant effect. This enhancement of wound closure in the presence of MSC-CM was due to accelerated cell migration rather than increased cell proliferation. A number of wound healing mediators were identified in MSC-CM, including TGF-{beta}1, the chemokines IL-6, IL-8, MCP-1 and RANTES, and collagen type I, fibronectin, SPARC and IGFBP-7. This study suggests that the trophic activity of MSC may play a role in skin wound closure by affecting both dermal fibroblast and keratinocyte migration, along with a contribution to the formation of extracellular matrix.« less

  2. Mesenchymal stem cell-conditioned medium accelerates skin wound healing: an in vitro study of fibroblast and keratinocyte scratch assays.

    PubMed

    Walter, M N M; Wright, K T; Fuller, H R; MacNeil, S; Johnson, W E B

    2010-04-15

    We have used in vitro scratch assays to examine the relative contribution of dermal fibroblasts and keratinocytes in the wound repair process and to test the influence of mesenchymal stem cell (MSC) secreted factors on both skin cell types. Scratch assays were established using single cell and co-cultures of L929 fibroblasts and HaCaT keratinocytes, with wound closure monitored via time-lapse microscopy. Both in serum supplemented and serum free conditions, wound closure was faster in L929 fibroblast than HaCaT keratinocyte scratch assays, and in co-culture the L929 fibroblasts lead the way in closing the scratches. MSC-CM generated under serum free conditions significantly enhanced the wound closure rate of both skin cell types separately and in co-culture, whereas conditioned medium from L929 or HaCaT cultures had no significant effect. This enhancement of wound closure in the presence of MSC-CM was due to accelerated cell migration rather than increased cell proliferation. A number of wound healing mediators were identified in MSC-CM, including TGF-beta1, the chemokines IL-6, IL-8, MCP-1 and RANTES, and collagen type I, fibronectin, SPARC and IGFBP-7. This study suggests that the trophic activity of MSC may play a role in skin wound closure by affecting both dermal fibroblast and keratinocyte migration, along with a contribution to the formation of extracellular matrix. Copyright 2010 Elsevier Inc. All rights reserved.

  3. Aloe vera: an in vitro study of effects on corneal wound closure and collagenase activity.

    PubMed

    Curto, Elizabeth M; Labelle, Amber; Chandler, Heather L

    2014-11-01

    To evaluate the in vitro effects of an aloe vera solution on (i) the viability and wound healing response of corneal cells and (ii) the ability to alter collagenase and gelatinase activities. Primary cultures of corneal epithelial cells and fibroblasts were prepared from grossly normal enucleated canine globes and treated with an aloe solution (doses ranging from 0.0-2 mg/mL). Cellular viability was evaluated using a colorimetric assay. A corneal wound healing model was used to quantify cellular ingrowth across a defect made on the confluent surface. Anticollagenase and antigelatinase activities were evaluated by incubating a bacterial collagenase/gelatinase with aloe solution (doses ranging from 0.0-500 μg/mL) and comparing outcome measures to a general metalloproteinase inhibitor, 1, 10-phenanthroline, and canine serum (doses ranging from 0.0-100%). None of the concentrations of aloe solution tested significantly affected the viability of corneal epithelial cells or fibroblasts. Concentrations ≤175 μg/mL slightly accelerated corneal epithelial cell wound closure; this change was not significant. Concentrations ≥175 μg/mL significantly (P ≤ 0.001) slowed the rate of corneal fibroblast wound closure, while aloe concentrations <175 μg/mL did not significantly alter fibroblast wound closure. Aloe solution did not alter the ability for collagenase to degrade gelatin or collagen Type I but increased the ability for collagenase to degrade Type IV collagen. Although additional experiments are required, lower concentrations of aloe solution may be beneficial in healing of superficial corneal wounds to help decrease fibrosis and speed epithelialization. An increase in collagenase activity with aloe vera warrants further testing before considering in vivo studies. © 2014 American College of Veterinary Ophthalmologists.

  4. Evaluation of a novel technique for wound closure using a barbed suture.

    PubMed

    Murtha, Amy P; Kaplan, Andrew L; Paglia, Michael J; Mills, Benjie B; Feldstein, Michael L; Ruff, Gregory L

    2006-05-01

    Suture knots present several disadvantages in wound closure, because they are tedious to tie and place ischemic demands on tissue. Bulky knots may be a nidus for infection, and they may extrude through skin weeks after surgery. Needle manipulations during knot-tying predispose the surgeon to glove perforation. A barbed suture was developed that is self-anchoring, requiring no knots or slack management for wound closure. The elimination of knot tying may have advantages over conventional wound closure methods. This prospective, randomized, controlled trial was designed to show that the use of barbed suture in dermal closure of the Pfannenstiel incision during nonemergent cesarean delivery surgery produces scar cosmesis at 5 weeks that is no worse than that observed with conventional closure using 3-0 polydioxanone suture. Cosmesis was assessed by review of postoperative photographs by a blinded, independent plastic surgeon using the modified Hollander cosmesis score. Secondary endpoints included infection, dehiscence, pain, closure time, and other adverse events. The study enrolled 195 patients, of whom 188 were eligible for analysis. Cosmesis scores did not significantly differ between the barbed suture group and the control group. Rates of infection, dehiscence, and other adverse events did not significantly differ between the two groups. Closure time and pain scores were comparable between the groups. The barbed suture represents an innovative option for wound closure. With a cosmesis and safety profile that is similar to that of conventional suture technique, it avoids the drawbacks inherent to suture knots.

  5. Is there a relationship between wound infections and laceration closure times?

    PubMed Central

    2012-01-01

    Background Lacerations account for a large number of ED visits. Is there a “golden period” beyond which lacerations should not be repaired primarily? What type of relationship exists between time of repair and wound infection rates? Is it linear or exponential? Currently, the influence of laceration age on the risk of infection in simple lacerations repaired is not clearly defined. We conducted this study to determine the influence of time of primary wound closure on the infection rate. Methods This is a prospective observational study of patients who presented to the Emergency Department (ED) with a laceration requiring closure from April 2009 to November 2010. The wound closure time was defined as the time interval from when the patient reported laceration occurred until the time of the start of the wound repair procedure. Univariate analysis was performed to determine the factors predictive of infection. A non-parametric Wilcoxon rank-sum test was performed to compare the median differences of time of laceration repair. Chi-square (Fisher's exact) tests were performed to test for infection differences with regard to gender, race, location of laceration, mechanism of injury, co-morbidities, type of anesthesia and type of suture material used. Results Over the study period, 297 participants met the inclusion criteria and were followed. Of the included participants, 224 (75.4%) were male and 73 (24.6%) were female. Ten patients (3.4%) developed a wound infection. Of these infections, five occurred on hands, four on extremities (not hands) and one on the face. One of these patients was African American, seven were Hispanic and two were Caucasian (p = 0.0005). Median wound closure time in the infection group was 867 min and in the non-infection group 330 min (p = 0.03). Conclusions Without controlling various confounding factors, the median wound closure time for the lacerations in the wound infection group was statistically significantly longer than

  6. Sanativo Wound Healing Product Does Not Accelerate Reepithelialization in a Mouse Cutaneous Wound Healing Model.

    PubMed

    Marshall, Clement D; Hu, Michael S; Leavitt, Tripp; Barnes, Leandra A; Cheung, Alexander T M; Malhotra, Samir; Lorenz, H Peter; Delp, Scott L; Quake, Stephen R; Longaker, Michael T

    2017-02-01

    Sanativo is an over-the-counter Brazilian product derived from Amazon rainforest plant extract that is purported to improve the healing of skin wounds. Two experimental studies have shown accelerated closure of nonsplinted excisional wounds in rat models. However, these models allow for significant contraction of the wound and do not approximate healing in the tight skin of humans. Full-thickness excisional wounds were created on the dorsal skin of mice and were splinted with silicone rings, a model that forces the wound to heal by granulation and reepithelialization. Sanativo or a control solution was applied either daily or every other day to the wounds. Photographs were taken every other day, and the degree of reepithelialization of the wounds was determined. With both daily and every-other-day applications, Sanativo delayed reepithelialization of the wounds. Average time to complete healing was faster with control solution versus Sanativo in the daily application group (9.4 versus 15.2 days; p < 0.0001) and the every-other-day application group (11 versus 13 days; p = 0.017). The size of visible scar at the last time point of the study was not significantly different between the groups, and no differences were found on histologic examination. Sanativo wound healing compound delayed wound reepithelialization in a mouse splinted excisional wound model that approximates human wound healing. The size of visible scar after complete healing was not improved with the application of Sanativo. These results should cast doubt on claims that this product can improve wound healing in humans.

  7. Vacuum-assisted closure therapy increases local interleukin-8 and vascular endothelial growth factor levels in traumatic wounds.

    PubMed

    Labler, Ludwig; Rancan, Mario; Mica, Ladislav; Härter, Luc; Mihic-Probst, Daniela; Keel, Marius

    2009-03-01

    Clinical observations are suggesting accelerated granulation tissue formation in traumatic wounds treated with vacuum-assisted closure (VAC). Aim of this study was to determine the impact of VAC therapy versus alternative Epigard application on local inflammation and neovascularization in traumatic soft tissue wounds. Thirty-two patients with traumatic wounds requiring temporary coverage (VAC n = 16; Epigard n = 16) were included. At each change of dressing, samples of wound fluid and serum were collected (n = 80). The cytokines interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 were measured by ELISA. Wound biopsies were examined histologically for inflammatory cells and degree of neovascularization present. All cytokines were found to be elevated in wound fluids during both VAC and Epigard treatment, whereas serum concentrations were negligible or not detectable. In wound fluids, significantly higher IL-8 (p < 0.001) and VEGF (p < 0.05) levels were detected during VAC therapy. Furthermore, histologic examination revealed increased neovascularization (p < 0.05) illustrated by CD31 and von Willebrand factor immunohistochemistry in wound biopsies of VAC treatment. In addition, there was an accumulation of neutrophils as well as an augmented expression of VEGF (p < 0.005) in VAC wound biopsies. This study suggests that VAC therapy of traumatic wounds leads to increased local IL-8 and VEGF concentrations, which may trigger accumulation of neutrophils and angiogenesis and thus, accelerate neovascularization.

  8. Wound healing effects of noni (Morinda citrifolia L.) leaves: a mechanism involving its PDGF/A2A receptor ligand binding and promotion of wound closure.

    PubMed

    Palu, Afa; Su, Chen; Zhou, Bing-Nan; West, Brett; Jensen, Jarakae

    2010-10-01

    Morinda citrifolia L. (Rubiaceae) commonly known as noni, has been used in Polynesia by traditional healers for the treatment of cuts, bruises and wounds. Our objective was to investigate the wound-healing mechanisms of the noni leaf. The investigations of its wound-healing mechanisms were carried out using fresh noni leaf juice (NLJ), noni leaf ethanol extract (NLEE) and its methanol (MFEE) and hexane (HFEE) fractions on the PDGF and A(2A) receptors in vitro and topically in mice. Fresh noni leaf juice showed significant affinity to PDGF receptors, and displayed 166% binding inhibition of the ligand binding to its receptors, while at the same concentration, it only had 7% inhibition of the ligand binding to the A(2A) receptors. NLEE, HFEE and MFEE showed significant affinity to A(2A) receptors, concentration dependently, with IC(50) values of 34.1, 42.9 and 86.7 μg/mL, respectively. However, MFEE significantly increased wound closure and reduced the half closure time in mice with a CT(50) of 5.4 ± 0.2 days compared with control (p < 0.05). These results suggest that noni leaf significantly accelerated wound healing in mice via its ligand binding to the PDGF and A(2A) receptors as its probable mechanisms of wound-healing and also support its traditional usage for wound-healing in Polynesia. Copyright © 2010 John Wiley & Sons, Ltd.

  9. Potential Activity of 3-(2-Chlorophenyl)-1-phenyl-propenonein Accelerating Wound Healing in Rats

    PubMed Central

    Dhiyaaldeen, Summaya M.; Alshawsh, Mohammed A.; Salama, Suzy M.; Alwajeeh, Nahla S. I.

    2014-01-01

    Wound healing involves inflammation followed by granular tissue development and scar formation. In this study, synthetic chalcone 3-(2-Chlorophenyl)-1-phenyl-propenone (CPPP) was investigated for a potential role in enhancing wound healing and closure. Twenty-four male rats were divided randomly into 4 groups: carboxymethyl cellulose (CMC) (0.2 mL), Intrasite gel, and CPPP (25 or 50 mg/mL). Gross morphology, wounds treatment with the CPPP, and Intrasite gel accelerate the rate of wound healing compared to CMC group. Ten days after surgery, the animals were sacrificed. Histological assessment revealed that the wounds treated with CPPP showed that wound closure site contained little amount of scar and the granulation tissue contained more collagen and less inflammatory cells than wound treated with CMC. This finding was confirmed with Masson's trichrome staining. The antioxidant defence enzymes catalase (CAT) and superoxide dismutase (SOD) were significantly increased in the wound homogenates treated with CPPP (P < 0.05) compared to CMC treated group. However, in the CPPP treatment group, lipid peroxidation (MDA) was significantly decreased (P < 0.05), suggesting that the CPPP also has an important role in protection against lipid peroxidation-induced skin injury after ten days of treatment with CPPP, which is similar to the values of cytokines TGF-β and TNF-α in tissue homogenate. Finally the administration of CPPP at a dosage of 25 and 50 mg/kg was suitable for the stimulation of wound healing. PMID:24587992

  10. Pereskia aculeata Miller leaves accelerate excisional wound healing in mice.

    PubMed

    Pinto, Nícolas de Castro Campos; Cassini-Vieira, Puebla; Souza-Fagundes, Elaine Maria de; Barcelos, Lucíola Silva; Castañon, Maria Christina Marques Nogueira; Scio, Elita

    2016-12-24

    The leaves of Pereskia aculeata Miller (Cactaceae), known as Barbados gooseberry, are used as emollients and to treat skin wounds and inflammatory process in Brazilian traditional medicine. This study investigated the topical wound healing activity of gels containing the methanol extract (ME) and hexane fraction (HF) of the leaves of this plant in a model of excisional wound healing in mice. Mice were anesthetized and excisional skin wounds were performed using a circular metal punch of 5mm diameter. Next, the animals were treated with 30µL of topical gel formulations containing the gel base (vehicle), HF 5% or ME 5%. The treatments were applied immediately after the injury and every 48h during 14 days. To verify the wound closure kinetics, a digital caliper was used throughout this period. Laser Doppler perfusion image (LDPI) was applied to evaluate the blood flow rate at the injury site. Microscopic examination of the skin tissues was performed by histopathological analysis with hematoxylin and eosin and Gomori trichrome staining. Picrosirius-red staining was also used for morphometric analysis for collagen quantification. Both HF and ME markedly accelerated the closeness of the skin wounds; however the HF activity was more evident, as this fraction induced the increase of blood flow rate and collagen deposition when statistically compared to the vehicle. The mice skin treated with HF and ME also showed less fibroplasia, blood vessels and inflammatory cells on the last day of experiment, which indicated a more advanced wound healing process. As the wound healing process was considerably accelerated, especially by HF gel formulation, the results of this study not only contributed to better understand the ethnopharmacological application of P. acuelata leaves, but also encouraged further investigations on how to explore the potential uses of this plant in skin therapies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Traction-assisted Internal Negative Pressure Wound Therapy With Bridging Retention Sutures to Facilitate Staged Closure of High-risk Wounds Under Tension.

    PubMed

    DeFazio, Michael V; Economides, James M; Anghel, Ersilia L; Mathis, Ryan K; Barbour, John R; Attinger, Christopher E

    2017-10-01

    Loss of domain often complicates attempts at delayed wound closure in regions of high tension. Wound temporization with traction-assisted internal negative pressure wound therapy (NPWT), using bridging retention sutures, can minimize the effects of edema and elastic recoil that contribute to progressive tissue retraction over time. The investigators evaluated the safety and efficacy of this technique for complex wound closure. Between May 2015 and November 2015, 18 consecutive patients underwent staged reconstruction of complex and/or contaminated soft tissue defects utilizing either conventional NPWT or modified NPWT with instillation and continuous dermatotraction via bridging retention sutures. Instillation of antimicrobial solution was reserved for wounds containing infected/exposed hardware or prosthetic devices. Demographic data, wound characteristics, reconstructive outcomes, and complications were reviewed retrospectively. Eighteen wounds were treated with traction-assisted internal NPWT using the conventional (n = 11) or modified instillation (n = 7) technique. Defects involved the lower extremity (n = 14), trunk (n = 3), and proximal upper extremity (n = 1), with positive cultures identified in 12 wounds (67%). Therapy continued for 3 to 8 days (mean, 4.3 days), resulting in an average wound surface area reduction of 78% (149 cm² vs. 33 cm²) at definitive closure. Seventeen wounds (94%) were closed directly, whereas the remaining defect required coverage with a local muscle flap and skin graft. At final follow-up (mean, 12 months), 89% of wounds remained closed. In 2 patients with delayed, recurrent periprosthetic infection (mean, 7.5 weeks), serial debridement/hardware removal mandated free tissue transfer for composite defect reconstruction. Traction-assisted internal NPWT provides a safe and effective alternative to reduce wound burden and facilitate definitive closure in cases where delayed reconstruction of high-tension wounds is planned.

  12. Neurotrophin-3 accelerates wound healing in diabetic mice by promoting a paracrine response in mesenchymal stem cells.

    PubMed

    Shen, Lei; Zeng, Wen; Wu, Yang-Xiao; Hou, Chun-Li; Chen, Wen; Yang, Ming-Can; Li, Li; Zhang, Ya-Fang; Zhu, Chu-Hong

    2013-01-01

    Angiogenesis is a major obstacle for wound healing in patients with diabetic foot wounds. Mesenchymal stem cells (MSCs) have an important function in wound repair, and neurotrophin-3 (NT-3) can promote nerve regeneration and angiogenesis. We investigated the effect of NT-3 on accelerating wound healing in the diabetic foot by improving human bone marrow MSC (hMSC) activation. In vitro, NT-3 significantly promoted VEGF, NGF, and BDNF secretion in hMSCs. NT-3 improved activation of the hMSC conditioned medium, promoted human umbilical vein endothelial cell (HUVEC) proliferation and migration, and significantly improved the closure rate of HUVEC scratches. In addition, we produced nanofiber mesh biological tissue materials through the electrospinning technique using polylactic acid, mixed silk, and collagen. The hMSCs stimulated by NT-3 were implanted into the material. Compared with the control group, the NT-3-stimulated hMSCs in the biological tissue material significantly promoted angiogenesis in the feet of diabetic C57BL/6J mice and accelerated diabetic foot wound healing. These results suggest that NT-3 significantly promotes hMSC secretion of VEGF, NGF, and other vasoactive factors and that it accelerates wound healing by inducing angiogenesis through improved activation of vascular endothelial cells. The hMSCs stimulated by NT-3 can produce materials that accelerate wound healing in the diabetic foot and other ischemic ulcers.

  13. Silk fibroin produced by transgenic silkworms overexpressing the Arg-Gly-Asp motif accelerates cutaneous wound healing in mice.

    PubMed

    Baba, Atsunori; Matsushita, Shigeto; Kitayama, Kasumi; Asakura, Tetsuo; Sezutsu, Hideki; Tanimoto, Akihide; Kanekura, Takuro

    2018-03-04

    We investigated the effect of silk fibroin (SF) on wound healing in mice. SF or an amorphous SF film (ASFF) prepared from silk produced by the wild-type silkworm Bombyx mori (WT-SF, WT-ASFF) or by transgenic worms that overexpress the Arg-Gly-Asp (RGD) sequence (TG-SF, TG-ASFF) was placed on 5-mm diameter full-thickness skin wounds made by biopsy punch on the back of 8-12 week-old BALB/c mice. Each wound was covered with WT-ASFF and urethane film (UF), TG-ASFF plus UF, or UF alone (control). Wound closure, histological thickness, the area of granulation tissue, and neovascularization were analyzed 4, 8, and 12 days later. The effect of SF on cell migration and proliferation was examined in vitro by scratch- and MTT-assay using human dermal fibroblasts. Wound closure was prompted by TG-ASFF, granulation tissue was thicker and larger in ASFF-treated wounds than the control, and neovascularization was promoted significantly by WT-ASFF. Both assays showed that SF induced the migration and proliferation of human dermal fibroblasts. The effects of TG-ASFF and TG-SF on wound closure, granulation formation, and cell proliferation were more profound than that of WT-ASFF and WT-SF. We document that SF accelerates cutaneous wound healing, and this effect is enhanced with TG-SF. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc.

  14. Lactate stimulates angiogenesis and accelerates the healing of superficial and ischemic wounds in mice.

    PubMed

    Porporato, Paolo E; Payen, Valéry L; De Saedeleer, Christophe J; Préat, Véronique; Thissen, Jean-Paul; Feron, Olivier; Sonveaux, Pierre

    2012-12-01

    Wounds notoriously accumulate lactate as a consequence of both anaerobic and aerobic glycolysis following microcirculation disruption, immune activation, and increased cell proliferation. Several pieces of evidence suggest that lactate actively participates in the healing process through the activation of several molecular pathways that collectively promote angiogenesis. Lactate indeed stimulates endothelial cell migration and tube formation in vitro, as well as the recruitment of circulating vascular progenitor cells and vascular morphogenesis in vivo. In this study, we examined whether the pro-angiogenic potential of lactate may be exploited therapeutically to accelerate wound healing. We show that lactate delivered from a Matrigel matrix improves reperfusion and opposes muscular atrophy in ischemic hindlimb wounds in mice. Both responses involve lactate-induced reparative angiogenesis. Using microdialysis and enzymatic measurements, we found that, contrary to poly-L-lactide (PLA), a subcutaneous implant of poly-D,L-lactide-co-glycolide (PLGA) allows sustained local and systemic lactate release. PLGA promoted angiogenesis and accelerated the closure of excisional skin wounds in different mouse strains. This polymer is FDA-approved for other applications, emphasizing the possibility of exploiting PLGA therapeutically to improve wound healing.

  15. LXA{sub 4} actions direct fibroblast function and wound closure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Herrera, Bruno S.; Microbiology Branch, US Army Dental and Trauma Research Detachment, Institute of Surgical Research, JBSA Fort Sam Houston, TX; Kantarci, Alpdogan

    Timely resolution of inflammation is crucial for normal wound healing. Resolution of inflammation is an active biological process regulated by specialized lipid mediators including the lipoxins and resolvins. Failure of resolution activity has a major negative impact on wound healing in chronic inflammatory diseases that is manifest as excess fibrosis and scarring. Lipoxins, including Lipoxin A{sub 4} (LXA{sub 4}), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA{sub 4} on fibroblast function. Mouse fibroblasts (3T3 Mus musculus Swiss) were cultured for 72 h in the presence of TGF-β1, to induce fibroblast activation.more » The impact of exogenous TGF-β1 (1 ng/mL) on LXA{sub 4} receptor expression (ALX/FPR2) was determined by flow cytometry. Fibroblast proliferation was measured by bromodeoxyuridine (BrdU) labeling and migration in a “scratch” assay wound model. Expression of α-smooth muscle actin (α-SMA), and collagen types I and III were measured by Western blot. We observed that TGF-β1 up-regulates LXA{sub 4} receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. α-SMA levels and Collagen type I and III deposition were also enhanced. LXA{sub 4} slowed fibroblast migration and scratch wound closure at early time points (24 h), but wound closure was equal to TGF-β1 alone at 48 and 72 h. LXA{sub 4} tended to slow fibroblast proliferation at both concentrations, but had no impact on α-SMA or collagen production by TGF-β1 stimulated fibroblasts. The generalizability of the actions of resolution molecules was examined in experiments repeated with resolvin D2 (RvD2) as the agonist. The activity of RvD2 mimicked the actions of LXA{sub 4} in all assays, through an as yet unidentified receptor. The results suggest that mediators of resolution of inflammation enhance wound healing and limit fibrosis in part by modulating fibroblast function. - Highlights

  16. Evaluation of a new tension relief system for securing wound closure: A single-centre, Chinese cohort study

    PubMed Central

    Huahui, Zhang; Dan, Xue; Hongfei, Jiang; Hang, Hu; Chunmao, Han; Haitao, Ren; Jianxin, Yu; Zhiping, Tao

    2016-01-01

    BACKGROUND Wounds that have been closed under excessive tension, and skin defects that cannot be closed primarily, pose a daily challenge for the reconstructive surgeon. OBJECTIVE To evaluate a new tension relief system (TRS) device for skin stretching and secure wound closure. METHODS From September 2013 to March 2014, a consecutive series of 41 Chinese patients with 43 wounds were enrolled for application of 50 cycles of TRS therapy. TRS was used for two main clinical applications: closure of a variety of surgical/traumatic wounds; and securing wound closure after high-tension suture closure. Basic information and details regarding this therapy and its complications were recorded. Follow-up visits were conducted three to six months after wound closure. RESULTS Mean residual wound width decreased approximately 20% every two days during cycles of TRS therapy. Infection was the most common complication (five cases). Other complications included dehiscence (two cases) and pressure ulcer (one case). At the six-month follow-up visit, (21 wounds in 20 patients), both the extent of healing and the scar were acceptable. DISCUSSION There are no absolute contraindications to TRS therapy. The authors have formulated instructions for the prevention and treatment of the most common complications. CONCLUSIONS The results demonstrate that TRS therapy is a simple, effective method for primary closure of difficult wounds, and large skin and soft-tissue defects. Larger randomized studies are required to further evaluate of the effectiveness, indications, complications and cost effectiveness of this innovative TRS therapy. PMID:28439506

  17. UV fluorescence excitation imaging of healing of wounds in skin: Evaluation of wound closure in organ culture model.

    PubMed

    Wang, Ying; Gutierrez-Herrera, Enoch; Ortega-Martinez, Antonio; Anderson, Richard Rox; Franco, Walfre

    2016-09-01

    Molecules native to tissue that fluoresce upon light excitation can serve as reporters of cellular activity and protein structure. In skin, the fluorescence ascribed to tryptophan is a marker of cellular proliferation, whereas the fluorescence ascribed to cross-links of collagen is a structural marker. In this work, we introduce and demonstrate a simple but robust optical method to image the functional process of epithelialization and the exposed dermal collagen in wound healing of human skin in an organ culture model. Non-closing non-grafted, partial closing non-grafted, and grafted wounds were created in ex vivo human skin and kept in culture. A wide-field UV fluorescence excitation imaging system was used to visualize epithelialization of the exposed dermis and quantitate wound area, closure, and gap. Histology (H&E staining) was also used to evaluate epithelialization. The endogenous fluorescence excitation of cross-links of collagen at 335 nm clearly shows the dermis missing epithelium, while the endogenous fluorescence excitation of tryptophan at 295 nm shows keratinocytes in higher proliferating state. The size of the non-closing wound was 11.4 ± 1.8 mm and remained constant during the observation period, while the partial-close wound reached 65.5 ± 4.9% closure by day 16. Evaluations of wound gaps using fluorescence excitation images and histology images are in agreement. We have established a fluorescence imaging method for studying epithelialization processes, evaluating keratinocyte proliferation, and quantitating closure during wound healing of skin in an organ culture model: the dermal fluorescence of pepsin-digestible collagen cross-links can be used to quantitate wound size, closure extents, and gaps; and, the epidermal fluorescence ascribed to tryptophan can be used to monitor and quantitate functional states of epithelialization. UV fluorescence excitation imaging has the potential to become a valuable tool for research, diagnostic

  18. Modelling wound closure in an epithelial cell sheet using the cellular Potts model.

    PubMed

    Noppe, Adrian R; Roberts, Anthony P; Yap, Alpha S; Gomez, Guillermo A; Neufeld, Zoltan

    2015-10-01

    We use a two-dimensional cellular Potts model to represent the behavior of an epithelial cell layer and describe its dynamics in response to a microscopic wound. Using an energy function to describe properties of the cells, we found that the interaction between contractile tension along cell-cell junctions and cell-cell adhesion plays an important role not only in determining the dynamics and morphology of cells in the monolayer, but also in influencing whether or not a wound in the monolayer will close. Our results suggest that, depending on the balance between cell-cell adhesion and junctional tension, mechanics of the monolayer can either correspond to a hard or a soft regime that determines cell morphology and polygonal organization in the monolayer. Moreover, the presence of a wound in a hard regime, where junctional tension is significant, can lead to two results: (1) wound closure or (2) an initial increase and expansion of the wound area towards an equilibrium value. Theoretical approximations and simulations allowed us to determine the thresholds in the values of cell-cell adhesion and initial wound size that allow the system to lead to wound closure. Overall, our results suggest that around the site of injury, changes in the balance between contraction and adhesion determine whether or not non-monotonous wound closure occurs.

  19. Biodegradable and plasma-treated electrospun scaffolds coated with recombinant Olfactomedin-like 3 for accelerating wound healing and tissue regeneration.

    PubMed

    Dunn, Louise L; de Valence, Sarra; Tille, Jean-Christophe; Hammel, Philippe; Walpoth, Beat H; Stocker, Roland; Imhof, Beat A; Miljkovic-Licina, Marijana

    2016-11-01

    Three-dimensional biomimetic scaffolds resembling the native extracellular matrix (ECM) are widely used in tissue engineering, however they often lack optimal bioactive cues needed for acceleration of cell proliferation, neovascularization, and tissue regeneration. In this study, the use of the ECM-related protein Olfactomedin-like 3 (Olfml3) demonstrates the importance and feasibility of fabricating efficient bioactive scaffolds without in vitro cell seeding prior to in vivo implantation. First, in vivo proangiogenic properties of Olfml3 were shown in a murine wound healing model by accelerated wound closure and a 1.4-fold increase in wound vascularity. Second, subcutaneous implantation of tubular scaffolds coated with recombinant Olfml3 resulted in enhanced cell in-growth and neovascularization compared with control scaffolds. Together, our data indicates the potential of Olfml3 to accelerate neovascularization during tissue regeneration by promoting endothelial cell proliferation and migration. This study provides a promising concept for the reconstruction of damaged tissue using affordable and effective bioactive scaffolds. © 2016 by the Wound Healing Society.

  20. Burn Wound Healing and Tissue Engineering.

    PubMed

    Singer, Adam J; Boyce, Steven T

    In 2016 the American Burn Association held a State of the Science conference to help identify burn research priorities for the next decade. The current paper summarizes the work of the sub-committee on Burn Wound Healing and Tissue Engineering. We first present the priorities in wound healing research over the next 10 years. We then summarize the current state of the science related to burn wound healing and tissue engineering including determination of burn depth, limiting burn injury progression, eschar removal, management of microbial contamination and wound infection, measuring wound closure, accelerating wound healing and durable wound closure, and skin substitutes and tissue engineering. Finally, a summary of the round table discussion is presented.

  1. Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes.

    PubMed

    Das, Amitava; Ghatak, Subhadip; Sinha, Mithun; Chaffee, Scott; Ahmed, Noha S; Parinandi, Narasimham L; Wohleb, Eric S; Sheridan, John F; Sen, Chandan K; Roy, Sashwati

    2016-06-15

    Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a peripheral glycoprotein that acts as a bridging molecule between the macrophage and apoptotic cells, thus executing a pivotal role in the scavenging of apoptotic cells from affected tissue. We have previously reported that apoptotic cell clearance activity or efferocytosis is compromised in diabetic wound macrophages. In this work, we test the hypothesis that MFG-E8 helps resolve inflammation, supports angiogenesis, and accelerates wound closure. MFG-E8(-/-) mice displayed impaired efferocytosis associated with exaggerated inflammatory response, poor angiogenesis, and wound closure. Wound macrophage-derived MFG-E8 was recognized as a critical driver of wound angiogenesis. Transplantation of MFG-E8(-/-) bone marrow to MFG-E8(+/+) mice resulted in impaired wound closure and compromised wound vascularization. In contrast, MFG-E8(-/-) mice that received wild-type bone marrow showed improved wound closure and improved wound vascularization. Hyperglycemia and exposure to advanced glycated end products inactivated MFG-E8, recognizing a key mechanism that complicates diabetic wound healing. Diabetic db/db mice suffered from impaired efferocytosis accompanied with persistent inflammation and slow wound closure. Topical recombinant MFG-E8 induced resolution of wound inflammation, improvements in angiogenesis, and acceleration of closure, upholding the potential of MFG-E8-directed therapeutics in diabetic wound care. Copyright © 2016 by The American Association of Immunologists, Inc.

  2. Accelerated re-epithelialization of partial-thickness skin wounds by a topical betulin gel: Results of a randomized phase III clinical trials program.

    PubMed

    Barret, Juan P; Podmelle, Fred; Lipový, Břetislav; Rennekampff, Hans-Oliver; Schumann, Hauke; Schwieger-Briel, Agnes; Zahn, Tobias R; Metelmann, Hans-Robert

    2017-09-01

    The clinical significance of timely re-epithelialization is obvious in burn care, since delayed wound closure is enhancing the risk of wound site infection and extensive scarring. Topical treatments that accelerate wound healing are urgently needed to reduce these sequelae. Evidence from preliminary studies suggests that betulin can accelerate the healing of different types of wounds, including second degree burns and split-thickness skin graft wounds. The goal of this combined study program consisting of two randomized phase III clinical trials in parallel is to evaluate whether a topical betulin gel (TBG) is accelerating re-epithelialization of split-thickness skin graft (STSG) donor site wounds compared to standard of care. Two parallel blindly evaluated, randomised, controlled, multicentre phase III clinical trials were performed in adults undergoing STSG surgery (EudraCT nos. 2012-003390-26 and 2012-000777-23). Donor site wounds were split into two equal halves and randomized 1:1 to standard of care (a non-adhesive moist wound dressing) or standard of care plus TBG consisting of 10% birch bark extract and 90% sunflower oil (Episalvan, Birken AG, Niefern-Oeschelbronn, Germany). The primary efficacy assessment was the intra-individual difference in time to wound closure assessed from digital photographs by three blinded experts. A total of 219 patients were included and treated in the two trials. Wounds closed faster with TBG than without it (15.3 vs. 16.5 days; mean intra-individual difference=-1.1 days [95% CI, -1.5 to -0.7]; p<0.0001). This agreed with unblinded direct clinical assessment (difference=-2.1 days [95% CI, -2.7 to -1.5]; p<0.0001). Adverse events possibly related to treatment were mild or moderate and mostly at the application site. TBG accelerates re-epithelialization of partial thickness wounds compared to the current standard of care, providing a well-tolerated contribution to burn care in practice. Copyright © 2017 The Authors. Published by

  3. Experience With Wound VAC and Delayed Primary Closure of Contaminated Soft Tissue Injuries in Iraq

    DTIC Science & Technology

    2006-11-01

    wound was definitively closed by delayed primary closure, flap mobilization, or split-thickness skin grafting . The VAC system was also used...postoperatively for 3 to 5 days over skin grafts , then removed at the bedside to assess graft take. Granulation tissue was not a prerequisite for wound closure...hospital until the closed wounds were clean and dry with good skin graft incorporation. All patients were scheduled for follow-up in our outpatient

  4. Placenta Growth Factor in Diabetic Wound Healing

    PubMed Central

    Cianfarani, Francesca; Zambruno, Giovanna; Brogelli, Laura; Sera, Francesco; Lacal, Pedro Miguel; Pesce, Maurizio; Capogrossi, Maurizio C.; Failla, Cristina Maria; Napolitano, Monica; Odorisio, Teresa

    2006-01-01

    Reduced microcirculation and diminished expression of growth factors contribute to wound healing impairment in diabetes. Placenta growth factor (PlGF), an angiogenic mediator promoting pathophysiological neovascularization, is expressed during cutaneous wound healing and improves wound closure by enhancing angiogenesis. By using streptozotocin-induced diabetic mice, we here demonstrate that PlGF induction is strongly reduced in diabetic wounds. Diabetic transgenic mice overexpressing PlGF in the skin displayed accelerated wound closure compared with diabetic wild-type littermates. Moreover, diabetic wound treatment with an adenovirus vector expressing the human PlGF gene (AdCMV.PlGF) significantly accelerated the healing process compared with wounds treated with a control vector. The analysis of treated wounds showed that PlGF gene transfer improved granulation tissue formation, maturation, and vascularization, as well as monocytes/macrophages local recruitment. Platelet-derived growth factor, fibroblast growth factor-2, and vascular endothelial growth factor mRNA levels were increased in AdCMV.PlGF-treated wounds, possibly enhancing PlGF-mediated effects. Finally, PlGF treatment stimulated cultured dermal fibroblast migration, pointing to a direct role of PlGF in accelerating granulation tissue maturation. In conclusion, our data indicate that reduced PlGF expression contributes to impaired wound healing in diabetes and that PlGF gene transfer to diabetic wounds exerts therapeutic activity by promoting different aspects of the repair process. PMID:17003476

  5. Re-epithelialization of cutaneous wounds in adult zebrafish combines mechanisms of wound closure in embryonic and adult mammals.

    PubMed

    Richardson, Rebecca; Metzger, Manuel; Knyphausen, Philipp; Ramezani, Thomas; Slanchev, Krasimir; Kraus, Christopher; Schmelzer, Elmon; Hammerschmidt, Matthias

    2016-06-15

    Re-epithelialization of cutaneous wounds in adult mammals takes days to complete and relies on numerous signalling cues and multiple overlapping cellular processes that take place both within the epidermis and in other participating tissues. Re-epithelialization of partial- or full-thickness skin wounds of adult zebrafish, however, is extremely rapid and largely independent of the other processes of wound healing. Live imaging after treatment with transgene-encoded or chemical inhibitors reveals that re-epithelializing keratinocytes repopulate wounds by TGF-β- and integrin-dependent lamellipodial crawling at the leading edges of the epidermal tongue. In addition, re-epithelialization requires long-range epithelial rearrangements, involving radial intercalations, flattening and directed elongation of cells - processes that are dependent on Rho kinase, JNK and, to some extent, planar cell polarity within the epidermis. These rearrangements lead to a massive recruitment of keratinocytes from the adjacent epidermis and make re-epithelialization independent of keratinocyte proliferation and the mitogenic effect of FGF signalling, which are only required after wound closure, allowing the epidermis outside the wound to re-establish its normal thickness. Together, these results demonstrate that the adult zebrafish is a valuable in vivo model for studying and visualizing the processes involved in cutaneous wound closure, facilitating the dissection of direct from indirect and motogenic from mitogenic effects of genes and molecules affecting wound re-epithelialization. © 2016. Published by The Company of Biologists Ltd.

  6. Microwave Tissue Soldering for Immediate Wound Closure

    NASA Technical Reports Server (NTRS)

    Arndt, G. Dickey; Ngo, Phong H.; Phan, Chau T.; Byerly, Diane; Dusl, John; Sognier, Marguerite A.; Carl, James

    2011-01-01

    A novel approach for the immediate sealing of traumatic wounds is under development. A portable microwave generator and handheld antenna are used to seal wounds, binding the edges of the wound together using a biodegradable protein sealant or solder. This method could be used for repairing wounds in emergency settings by restoring the wound surface to its original strength within minutes. This technique could also be utilized for surgical purposes involving solid visceral organs (i.e., liver, spleen, and kidney) that currently do not respond well to ordinary surgical procedures. A miniaturized microwave generator and a handheld antenna are used to deliver microwave energy to the protein solder, which is applied to the wound. The antenna can be of several alternative designs optimized for placement either in contact with or in proximity to the protein solder covering the wound. In either case, optimization of the design includes the matching of impedances to maximize the energy delivered to the protein solder and wound at a chosen frequency. For certain applications, an antenna could be designed that would emit power only when it is in direct contact with the wound. The optimum frequency or frequencies for a specific application would depend on the required depth of penetration of the microwave energy. In fact, a computational simulation for each specific application could be performed, which would then match the characteristics of the antenna with the protein solder and tissue to best effect wound closure. An additional area of interest with potential benefit that remains to be validated is whether microwave energy can effectively kill bacteria in and around the wound. Thus, this may be an efficient method for simultaneously sterilizing and closing wounds.

  7. Distinct Temporal-Spatial Roles for Rho Kinase and Myosin Light Chain Kinase in Epithelial Purse-String Wound Closure

    PubMed Central

    RUSSO, JOHN M.; FLORIAN, PETER; SHEN, LE; GRAHAM, W. VALLEN; TRETIAKOVA, MARIA S.; GITTER, ALFRED H.; MRSNY, RANDALL J.; TURNER, JERROLD R.

    2005-01-01

    Background & Aims Small epithelial wounds heal by purse-string contraction of an actomyosin ring that is regulated by myosin light chain (MLC) kinase (MLCK) and rho kinase (ROCK). These studies aimed to define the roles of these kinases in purse-string wound closure. Methods Oligocellular and single-cell wounds were created in intestinal epithelial monolayers. Fluorescence imaging and electrophysiologic data were collected during wound closure. Human biopsies were studied immunohistochemically. Results Live-cell imaging of enhanced green fluorescent protein-β-actin defined rapid actin ring assembly within 2 minutes after wounding. This progressed to a circumferential ring within 8 minutes that subsequently contracted and closed the wound. We therefore divided this process into 2 phases: ring assembly and wound contraction. Activated rho and ROCK localized to the wound edge during ring assembly. Consistent with a primary role in the assembly phase, ROCK inhibition prevented actin ring assembly and wound closure. ROCK inhibition after ring assembly was complete had no effect. Recruitment and activation of MLCK occurred after ring assembly was complete and coincided with ring contraction. MLCK inhibition slowed and then stopped contraction but did not prevent ring assembly. MLCK inhibition also delayed barrier function recovery. Studies of human colonic biopsy specimens suggest that purse-string wound closure also occurs in vivo, because MLC phosphorylation was enhanced surrounding oligocellular wounds. Conclusions These results suggest complementary roles for these kinases in purse-string closure of experimental and in vivo oligocellular epithelial wounds; rho and ROCK are critical for actin ring assembly, while the activity of MLCK drives contraction. PMID:15825080

  8. Randomized controlled multicentre study comparing biological mesh closure of the pelvic floor with primary perineal wound closure after extralevator abdominoperineal resection for rectal cancer (BIOPEX-study)

    PubMed Central

    2014-01-01

    Background Primary perineal wound closure after conventional abdominoperineal resection (cAPR) for rectal cancer has been the standard of care for many years. Since the introduction of neo-adjuvant radiotherapy and the extralevator APR (eAPR), oncological outcome has been improved, but at the cost of increased rates of perineal wound healing problems and perineal hernia. This has progressively increased the use of biological meshes, although not supported by sufficient evidence. The aim of this study is to determine the effectiveness of pelvic floor reconstruction using a biological mesh after standardized eAPR with neo-adjuvant (chemo)radiotherapy compared to primary perineal wound closure. Methods/Design In this multicentre randomized controlled trial, patients with a clinical diagnosis of primary rectal cancer who are scheduled for eAPR after neo-adjuvant (chemo)radiotherapy will be considered eligible. Exclusion criteria are prior radiotherapy, sacral resection above S4/S5, allergy to pig products or polysorbate, collagen disorders, and severe systemic diseases affecting wound healing, except for diabetes. After informed consent, 104 patients will be randomized between standard care using primary wound closure of the perineum and the experimental arm consisting of suturing a biological mesh derived from porcine dermis in the pelvic floor defect, followed by perineal closure similar to the control arm. Patients will be followed for one year after the intervention and outcome assessors and patients will be blinded for the study treatment. The primary endpoint is the percentage of uncomplicated perineal wound healing, defined as a Southampton wound score of less than II on day 30. Secondary endpoints are hospital stay, incidence of perineal hernia, quality of life, and costs. Discussion The BIOPEX-study is the first randomized controlled multicentre study to determine the additive value of using a biological mesh for perineal wound closure after eAPR with neo

  9. A blinded, prospective, randomized controlled trial of topical negative pressure wound closure in India.

    PubMed

    Mody, Gita N; Nirmal, Ida Anita; Duraisamy, Sulochana; Perakath, Benjamin

    2008-12-01

    Wound closure using topical negative pressure (TNP) has been reported to be effective, but equipment costs can be prohibitive in resource-challenged countries. Because nonhealing wounds are exceedingly common in developing countries such as India, the ability to optimize wound care with limited resources is very important. To investigate the feasibility and efficacy of providing TNP in an Indian medical referral center, a randomized controlled trial comparing a locally constructed TNP device (treatment) to wet-to-dry gauze dressings (control) was conducted. Eligible study participants (N = 48) were recruited from the inpatient wards. Wound etiologies included diabetic foot ulcers (15), pressure ulcers (11), cellulitis/fasciitis (11), and "other" (11). Following enrollment, wound size was assessed using computer-aided measurements of digital photographs and block-randomized to the study arms using a concealed allocation table. Wounds in both treatment groups were débrided before dressing application and patients were followed until wound closure or being lost to follow-up for an average of 26.3 days (+/- 18.5) in the control and 33.1 days (+/- 37.3) in the treatment group. No statistically significant differences in time to closure between the two treatment groups were observed except in a subset analysis of pressure ulcers (mean 10 +/- 7.11 days for treatment and 27 +/- 10.6 days in control group, P = 0.05). Direct costs to close a pressure ulcer also were lower in the TNP than in the control group. A review of the literature suggests the outcomes obtained using a locally constructed TNP device are similar to those obtained using commercially available devices. As a result of this study, a dedicated tissue viability team has been established to identify wounds suitable for TNP, oversee treatment, monitor the need for surgical débridement, and employ wound healing principles and technology appropriately. These results suggest that inexpensive materials can be

  10. Controlled Delivery of a Focal Adhesion Kinase Inhibitor Results in Accelerated Wound Closure with Decreased Scar Formation.

    PubMed

    Ma, Kun; Kwon, Sun Hyung; Padmanabhan, Jagannath; Duscher, Dominik; Trotsyuk, Artem A; Dong, Yixiao; Inayathullah, Mohammed; Rajadas, Jayakumar; Gurtner, Geoffrey C

    2018-05-15

    Formation of scars following wounding or trauma represents a significant healthcare burden costing the economy billions of dollars every year. Activation of focal adhesion kinase (FAK) has been shown to play a pivotal role in transducing mechanical signals to elicit fibrotic responses and scar formation during wound repair. We have previously shown that inhibition of FAK using local injections of a small molecule FAK inhibitor (FAKI) can attenuate scar development in a hypertrophic scar model. Clinical translation of FAKI therapy has been challenging, however, due to the lack of an effective drug delivery system for extensive burn injuries, blast injuries, and large excisional injuries. To address this issue, we have developed a pullulan collagen-based hydrogel to deliver FAKI to excisional and burn wounds in mice. Specifically, two distinct drug-laden hydrogels were developed for rapid or sustained release of FAKI for treatment of burn wounds and excisional wounds, respectively. Controlled delivery of FAKI via pullulan collagen hydrogels accelerated wound healing, reduced collagen deposition and activation of scar forming myofibroblasts in both wound healing models. Our study highlights a biomaterial-based drug delivery approach for wound and scar management that has significant translational implications. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  11. The Cdk5 inhibitor olomoucine promotes corneal debridement wound closure in vivo

    PubMed Central

    Tripathi, Brajendra K.; Stepp, Mary A.; Gao, Chun Y.

    2008-01-01

    Purpose To investigate the effect of the Cdk5 inhibitor olomoucine on corneal debridement wound healing in vivo. Methods Corneal debridement wounds of 1.5 mm were made on the ocular surface of CD-1 mice. A 20 μl drop of 15 µM olomoucine in 1% DMSO was applied to the wound area immediately after wounding and again after 6 h. Control mice received identical applications of 1% DMSO. Mice were euthanized after 18 h, two weeks, and three weeks for evaluation of wound healing and restratification. Corneas were stained with Richardson’s dye, photographed, and processed for histology and immunofluorescence as whole mounts or paraffin sections. The remaining wound area at 18 h was measured by image analysis. Scratch wounded cultures of human corneal-limbal epithelial cells (HCLE) were used to examine the effect of olomoucine on matrix metalloproteinase (MMP) expression in vitro. MMP-2 and MMP-9 were detected by immunofluorescence and immunoblotting. Results Olomoucine treatment significantly enhanced corneal wound closure without increasing inflammation or infiltration of polymorphonuclear leukocytes 18 h after wounding (p<0.05). The increased localization of MMP-9 within epithelial cells at the wound edge was further enhanced by olomoucine while the expression of MMP-2 was reduced. Olomoucine treatment of scratch wounded HCLE cells produced similar changes in MMP-9 and MMP-2 expression. The examination of treated corneas two and three weeks after wounding showed normal epithelial restratification with no evidence of inflammation or stromal disorganization. Conclusions Topical application of olomoucine in 1% DMSO significantly enhances closure of small epithelial debridement wounds without increasing inflammation or impairing reepithelialization. PMID:18385789

  12. Planned secondary wound closure at the circular stapler insertion site after laparoscopic gastric bypass reduces postoperative morbidity, costs, and hospital stay.

    PubMed

    Vetter, Diana; Raptis, Dimitri Aristotle; Giama, Mira; Hosa, Hanna; Muller, Markus K; Nocito, Antonio; Schiesser, Marc; Moos, Rudolf; Bueter, Marco

    2017-12-01

    The aims of the present study were to assess whether planned secondary wound closure at the insertion site of the circular stapler reduces wound infection rate and postoperative morbidity after laparoscopic Roux-en-Y gastric bypass (RYGB) and to identify independent predictive factors increasing the risk for wound infections after RYGB. This paper is a retrospective single-center analysis of a prospectively collected database of 1400 patients undergoing RYGB surgery in circular technique between June 2000 and June 2016. Planned secondary wound closure at the circular stapler introduction site was performed at postoperative day 3 in 291 (20.8%) consecutive patients and compared to a historical control of 1109 (79.2%) consecutive patients with primary wound closure. Independent predictive factors for wound infection were assessed by multivariable analysis. Secondary wound closure significantly decreased wound infection rate from 9.3% (103/1109) to 1% (3/291) (p < 0.001) leading to a shorter hospital stay (mean 9 (SD8) vs. 7 days (SD2), p < 0.001), lower costs (p = 0.039), and reduced postoperative morbidity (mean 90-day Comprehensive Complication Index (CCI) 7.4 (SD14.0) vs. 5.1 (SD11.1) p = 0.008) when compared to primary wound closure. Primary wound closure, dyslipidemia, and preoperative gastritis were independent predictive risk factors for developing wound infections both in the univariate (p < 0.001; p = 0.048; p = 0.003) and multivariable analysis (p < 0.001; p = 0.040; p = 0.012). Further, on multivariable analysis, the female gender was a predictive factor (p = 0.034) for wound infection development. Secondary wound closure at the circular stapler introduction site in laparoscopic RYGB significantly reduces the overall wound infection rate as well as postoperative morbidity, costs, and hospital stay when compared to primary wound closure.

  13. Wound Closure in the Lamellipodia of Single Cells: Mediation by Actin Polymerization in the Absence of an Actomyosin Purse String

    PubMed Central

    Henson, John H.; Nazarian, Ronniel; Schulberg, Katrina L.; Trabosh, Valerie A.; Kolnik, Sarah E.; Burns, Andrew R.; McPartland, Kenneth J.

    2002-01-01

    The actomyosin purse string is an evolutionarily conserved contractile structure that is involved in cytokinesis, morphogenesis, and wound healing. Recent studies suggested that an actomyosin purse string is crucial for the closure of wounds in single cells. In the present study, morphological and pharmacological methods were used to investigate the role of this structure in the closure of wounds in the peripheral cytoplasm of sea urchin coelomocytes. These discoidal shaped cells underwent a dramatic form of actin-based centripetal/retrograde flow and occasionally opened and closed spontaneous wounds in their lamellipodia. Fluorescent phalloidin staining indicated that a well defined fringe of actin filaments assembles from the margin of these holes, and drug studies with cytochalasin D and latrunculin A indicated that actin polymerization is required for wound closure. Additional evidence that actin polymerization is involved in wound closure was provided by the localization of components of the Arp2/3 complex to the wound margin. Significantly, myosin II immunolocalization demonstrated that it is not associated with wound margins despite being present in the perinuclear region. Pharmacological evidence for the lack of myosin II involvement in wound closure comes from experiments in which a microneedle was used to produce wounds in cells in which actomyosin contraction was inhibited by treatment with kinase inhibitors. Wounds produced in kinase inhibitor-treated cells closed in a manner similar to that seen with control cells. Taken together, our results suggest that an actomyosin purse string mechanism is not responsible for the closure of lamellar wounds in coelomocytes. We hypothesize that the wounds heal by means of a combination of the force produced by actin polymerization alone and centripetal flow. Interestingly, these cells did assemble an actomyosin structure around the margin of phagosome-like membrane invaginations, indicating that myosin is not simply

  14. Wound closure in the lamellipodia of single cells: mediation by actin polymerization in the absence of an actomyosin purse string.

    PubMed

    Henson, John H; Nazarian, Ronniel; Schulberg, Katrina L; Trabosh, Valerie A; Kolnik, Sarah E; Burns, Andrew R; McPartland, Kenneth J

    2002-03-01

    The actomyosin purse string is an evolutionarily conserved contractile structure that is involved in cytokinesis, morphogenesis, and wound healing. Recent studies suggested that an actomyosin purse string is crucial for the closure of wounds in single cells. In the present study, morphological and pharmacological methods were used to investigate the role of this structure in the closure of wounds in the peripheral cytoplasm of sea urchin coelomocytes. These discoidal shaped cells underwent a dramatic form of actin-based centripetal/retrograde flow and occasionally opened and closed spontaneous wounds in their lamellipodia. Fluorescent phalloidin staining indicated that a well defined fringe of actin filaments assembles from the margin of these holes, and drug studies with cytochalasin D and latrunculin A indicated that actin polymerization is required for wound closure. Additional evidence that actin polymerization is involved in wound closure was provided by the localization of components of the Arp2/3 complex to the wound margin. Significantly, myosin II immunolocalization demonstrated that it is not associated with wound margins despite being present in the perinuclear region. Pharmacological evidence for the lack of myosin II involvement in wound closure comes from experiments in which a microneedle was used to produce wounds in cells in which actomyosin contraction was inhibited by treatment with kinase inhibitors. Wounds produced in kinase inhibitor-treated cells closed in a manner similar to that seen with control cells. Taken together, our results suggest that an actomyosin purse string mechanism is not responsible for the closure of lamellar wounds in coelomocytes. We hypothesize that the wounds heal by means of a combination of the force produced by actin polymerization alone and centripetal flow. Interestingly, these cells did assemble an actomyosin structure around the margin of phagosome-like membrane invaginations, indicating that myosin is not simply

  15. Comparison of rate of surgical wound infection, length of hospital stay and patient convenience in complicated appendicitis between primary closure and delayed primary closure.

    PubMed

    Khan, Khizar Ishtiaque; Mahmood, Shahid; Akmal, Muhammad; Waqas, Ahmed

    2012-06-01

    To compare the difference in the rate of surgical wound infection, patient's convenience and length of hospital stay between Primary Closure and Delayed Primary Closure in cases of complicated appendicitis in adults. This randomised control trial was conducted at the Combined Military Hospital, Kharian and Malir from June 5, 2006, to September 10, 2009. Patients > or = 15 years of both gender who underwent appendectomy through grid iron or Lanz incision and having complicated appendicitis were included. The 100 patients who were included in the study out of the initial size of 393, were randomised into two equal groups of 50 each (Group A: Primary Closure; Group B: Delayed Primary Closure) using a computer-generated table. All the surgeries were done by the same surgeon and the operative steps and antibiotic coverage were standardised. The rate of surgical wound infection, patient's convenience (on visual analogue scale in mm) and the length of hospital stay were recorded. Data was analysed using SPSS version 11, and p value was calculated. Demographic data, comorbids and medication of both the groups was comparable. There was no significant difference in rate of surgical wound infection (p > 0.05). The difference in patient's convenience and length of hospital stay were significant (p < 0.05), showing superiority of Primary Closure over Delayed Primary Closure with no added morbidity/mortality. Primary Closure in complicated appendicitis not only reduces the cost of treatment, but is also more convenient and satisfying for the patients, with no added risk of surgical wound infection.

  16. Barbed suture material technique for wound closure and concomitant tube placement in uniportal VATS for pneumothorax

    PubMed Central

    2017-01-01

    Background Uniportal video-assisted thoracoscopic surgery (VATS) is an alternative modality for treatment of primary spontaneous pneumothorax (PSP) with its less invasiveness and acceptable surgical outcomes. However, a few reports have been introduced for wound management to achieve better cosmetic wound healing and for placement of the chest tube in uniportal VATS. Thus, we aimed to evaluate the feasibility of our novel method for wound closure and concomitant tube placement using continuous barbed suture material in uniportal VATS for PSP. Methods Between July 2012 and December 2015, consecutive 31 patients (22 males) underwent uniportal VATS to treat PSP. Bilateral approaches were performed in four patients, thus total 35 cases were enrolled. We divided them into two groups with one group of 17 (48.5%) cases (group A), using barbed absorbable wound closure device for knotless continuous wound closure and subsequent chest tube anchoring, and the other group of 18 (51.4%) cases (group B), using conventional suture anchoring after skin closure using absorbable suture device. Postoperative surgical outcomes were compared to assess the feasibility of this technique. Results Demographic data demonstrate no significant difference in both groups. There was no significant difference in length of hospital stay (3.7±1.2 vs. 4.1±1.2 days, P=0.267) and in median chest tube indwelling time (2.4±0.9 vs. 3.1±1.2 days, P=0.066), respectively. Operation time in group A was shorter than in group B but there was no significant difference (41.7±11.8 vs. 45.6±16.0 minutes, P=0.415). There was neither conversion to two or three port VATS in all cases. In group A, all chest tubes were removed with concomitant sealing the tube removal site by pulling the thread. Residual knots do not exist that stitch out procedure is not required. There was no wound complication in both groups during the median follow-up period of 18 months. Conclusions Knotless, barbed suture material technique

  17. Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs

    PubMed Central

    Bhatia, Ayesha; O’Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T.; Li, Wei

    2016-01-01

    Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5–treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing. PMID:27382602

  18. Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs.

    PubMed

    Bhatia, Ayesha; O'Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T; Li, Wei

    2016-01-01

    Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5-treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing.

  19. Vacuum-assisted wound closure and mesh-mediated fascial traction for open abdomen therapy - a systematic review.

    PubMed

    Acosta, Stefan; Björck, Martin; Petersson, Ulf

    2017-01-01

    The aim of this paper was to review the literature on vacuum-assisted wound closure and mesh-mediated fascial traction (VAWCM) in open abdomen therapy. It was designed as systematic review of observational studies. A Pub Med, EMBASE and Cochrane search from 2007/01-2016/07 was performed combining the Medical Subject Headings "vacuum", "mesh-mediated fascial traction", "temporary abdominal closure", "delayed abdominal closure", "open abdomen", "abdominal compartment syndrome", "negative pressure wound therapy" or "vacuum assisted wound closure". Eleven original studies were found including patients numbering from 7 to 111. Six studies were prospective and five were retrospective. Nine studies were on mixed surgical (n = 9), vascular (n = 6) and trauma (n = 6) patients, while two were exclusively on vascular patients. The primary fascial closure rate per protocol varied from 80-100%. The time to closure of the open abdomen varied between 9-32 days. The entero-atmospheric fistula rate varied from 0-10.0%. The in-hospital survival rate varied from 57-100%. In the largest prospective study, the incisional hernia rate among survivors at 63 months of median follow-up was 54% (27/50), and 16 (33%) repairs out of 48 incisional hernias were performed throughout the study period. The study patients reported lower short form health survey (SF-36) scores than the mean reference population, mainly dependent on the prevalence of major co-morbidities. There was no difference in SF-36 scores or a modified ventral hernia pain questionnaire (VHPQ) at 5 years of follow up between those with versus those without incisional hernias. A high primary fascial closure rate can be achieved with the vacuum-assisted wound closure and meshmediated fascial traction technique in elderly, mainly non-trauma patients, in need of prolonged open abdomen therapy.

  20. Acceleration Of Wound Healing Ny Photodynamic Therapy

    DOEpatents

    Hasan, Tayyaba; Hamblin, Michael R.; Trauner, Kenneth

    2000-08-22

    Disclosed is a method for accelerating wound healing in a mammal. The method includes identifying an unhealed wound site or partially-healed wound site in a mammal; administering a photosensitizer to the mammal; waiting for a time period wherein the photosensitizer reaches an effective tissue concentration at the wound site; and photoactivating the photosensitizer at the wound site. The dose of photodynamic therapy is selected to stimulate the production of one or more growth factor by cells at the wound site, without causing tissue destruction.

  1. Complications and risk factors of castration with primary wound closure: Retrospective study in 159 horses.

    PubMed

    Robert, Mickaël P; Chapuis, Ronan J J; de Fourmestraux, Claire; Geffroy, Olivier J

    2017-05-01

    Castration with primary wound closure reportedly has lower complication rates and shorter recovery periods compared to castration with second intention healing. However, little is known about risk factors associated with complications using primary wound closure. Medical records of 159 horses castrated and having primary wound closure were reviewed. Main short-term complications were: scrotal hematoma in 12 horses (7.6%), signs of colic in 6 horses (3.8%), fever in 4 horses (2.5%), and peri-incisional edema in 3 horses (1.9%). As for long-term complications, 24 out of 105 (23%) horses sustained some form of edema. One horse was euthanized because of a suspected inguinal abscess. Among tested parameters, horses aged 3 to 6 years old and French trotters appeared to be more at risk of developing complications. Intraoperative ligation of the cremaster muscle and use of electrocautery prevented complications. Overall, client satisfaction was excellent (98%).

  2. Endothelium-specific GTP cyclohydrolase I overexpression accelerates refractory wound healing by suppressing oxidative stress in diabetes

    PubMed Central

    Tie, Lu; Li, Xue-Jun; Wang, Xian; Channon, Keith M.; Chen, Alex F.

    2009-01-01

    Refractory wound is a severe complication that leads to limb amputation in diabetes. Endothelial nitric oxide synthase (eNOS) plays a key role in normal wound repair but is uncoupled in streptozotocin (STZ)-induced type 1 diabetes because of reduced cofactor tetrahydrobiopterin (BH4). We tested the hypothesis that overexpression of GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme for de novo BH4 synthesis, retards NOS uncoupling and accelerates wound healing in STZ mice. Blood glucose levels were significantly increased in both male endothelium-specific GTPCH I transgenic mice (Tg-GCH; via a tie-2 promoter) and wild-type (WT) littermates 5 days after STZ regimen. A full-thickness excisional wound was created on mouse dorsal skin by a 4-mm punch biopsy. Wound closure was delayed in STZ mice, which was rescued in STZ Tg-GCH mice. Cutaneous BH4 level was significantly reduced in STZ mice vs. WT mice, which was maintained in STZ Tg-GCH mice. In STZ mice, constitutive NOS (cNOS) activity and nitrite levels were decreased compared with WT mice, paralleled by increased superoxide anion (O2−) level and inducible NOS (iNOS) activity. In STZ Tg-GCH mice, nitrite level and cNOS activity were potentiated and O2− level and iNOS activity were suppressed compared with STZ mice. Thus endothelium-specific BH4 overexpression accelerates wound healing in type 1 diabetic mice by enhancing cNOS activity and suppressing oxidative stress. PMID:19336662

  3. Effect of Adhesive Strips and Dermal Sutures vs Dermal Sutures Only on Wound Closure

    PubMed Central

    Custis, Trenton; Armstrong, April W.; King, Thomas H.; Sharon, Victoria R.; Eisen, Daniel B.

    2016-01-01

    IMPORTANCE Although applying adhesive strips to a wound closure has been shown to have outcomes equivalent to those with cuticular suturing, it is unknown whether adhesive strips provide additional benefit compared with dermal suturing alone. OBJECTIVE To determine whether the addition of adhesive strips to a wound closed with buried interrupted subcuticular sutures improves outcomes following wound closure. DESIGN, SETTING, AND PARTICIPANTS A prospective, randomized split-wound intervention was conducted between November 14, 2013, and May 16, 2014, in patients who underwent cutaneous surgical procedures at the University of California, Davis, outpatient dermatology clinic. Fifty-seven patients 18 years or older with postoperative defects of at least 3 cm, resulting from either Mohs micrographic surgical procedures or surgical excision, were screened for participation. Nine patients were excluded and 48 were enrolled. INTERVENTIONS Half of each wound was randomized to receive buried interrupted subcuticular sutures and overlying adhesive strips and the other half received buried interrupted subcuticular sutures only. MAIN OUTCOMES AND MEASURES At 3 months’ follow-up, each patient and 2 blinded observers evaluated the wound using the Patient Observer Scar Assessment Scale. RESULTS The total mean (SD) Patient Observer Scar Assessment Scale score for observers for the side that received a combination of adhesive strips and buried interrupted subcuticular suturing (12.3 [4.8]) and the side that received sutures only (12.9 [6.3]) did not differ significantly at 3 months (P = .32). There was no significant difference in the total patient assessment scale score between the combination closure (14.0 [7.6]) and sutures only (14.7 [7.6]) sides at 3 months (P = .39). There was also no significant difference between the 2 closure methods in terms of mean (SD) scar width (both methods: 1.1 [0.8] mm, P = .89) at follow-up. CONCLUSIONS AND RELEVANCE Combination closure with

  4. Dendritic cells modulate burn wound healing by enhancing early proliferation.

    PubMed

    Vinish, Monika; Cui, Weihua; Stafford, Eboni; Bae, Leon; Hawkins, Hal; Cox, Robert; Toliver-Kinsky, Tracy

    2016-01-01

    Adequate wound healing is vital for burn patients to reduce the risk of infections and prolonged hospitalization. Dendritic cells (DCs) are antigen presenting cells that release cytokines and are central for the activation of innate and acquired immune responses. Studies have showed their presence in human burn wounds; however, their role in burn wound healing remains to be determined. This study investigated the role of DCs in modulating healing responses within the burn wound. A murine model of full-thickness contact burns was used to study wound healing in the absence of DCs (CD11c promoter-driven diphtheria toxin receptor transgenic mice) and in a DC-rich environment (using fms-like tyrosine kinase-3 ligand, FL- a DC growth factor). Wound closure was significantly delayed in DC-deficient mice and was associated with significant suppression of early cellular proliferation, granulation tissue formation, wound levels of TGFβ1 and formation of CD31+ vessels in healing wounds. In contrast, DC enhancement significantly accelerated early wound closure, associated with increased and accelerated cellular proliferation, granulation tissue formation, and increased TGFβ1 levels and CD31+ vessels in healing wounds. We conclude that DCs play an important role in the acceleration of early wound healing events, likely by secreting factors that trigger the proliferation of cells that mediate wound healing. Therefore, pharmacological enhancement of DCs may provide a therapeutic intervention to facilitate healing of burn wounds. © 2016 by the Wound Healing Society.

  5. Periodic direct current does not promote wound closure in an in vitro dynamic model of cell migration.

    PubMed

    Godbout, Charles; Frenette, Jérôme

    2006-01-01

    A prevailing paradigm is that electrical fields can promote cell migration and tissue healing. To further validate this paradigm, we tested the hypothesis that periodic direct current (DC) can enhance wound closure using an in vitro dynamic model of cell migration. Layers of primary fibroblasts were wounded and treated with DC under various voltages. Repair area, cell velocity, and directionality as well as lamellipodium area were evaluated at different times. Direct current had no beneficial effect on cell migration. Moreover, prolonged stimulation under the highest voltage led to significant reduction in wound closure and cell velocity. The reduction of membrane protusions in stimulated cells may be associated with the deleterious effect of DC. Contrary to the authors' expectations, they found that periodic DC did not promote wound closure, a finding that emphasizes the need to clarify the complex effects of electrical fields on migrating cells.

  6. Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate Healing of Large Skin Wounds

    PubMed Central

    Skardal, Aleksander; Mack, David; Kapetanovic, Edi; Atala, Anthony; Jackson, John D.; Yoo, James

    2012-01-01

    Stem cells obtained from amniotic fluid show high proliferative capacity in culture and multilineage differentiation potential. Because of the lack of significant immunogenicity and the ability of the amniotic fluid-derived stem (AFS) cells to modulate the inflammatory response, we investigated whether they could augment wound healing in a mouse model of skin regeneration. We used bioprinting technology to treat full-thickness skin wounds in nu/nu mice. AFS cells and bone marrow-derived mesenchymal stem cells (MSCs) were resuspended in fibrin-collagen gel and “printed” over the wound site. At days 0, 7, and 14, AFS cell- and MSC-driven wound closure and re-epithelialization were significantly greater than closure and re-epithelialization in wounds treated by fibrin-collagen gel only. Histological examination showed increased microvessel density and capillary diameters in the AFS cell-treated wounds compared with the MSC-treated wounds, whereas the skin treated only with gel showed the lowest amount of microvessels. However, tracking of fluorescently labeled AFS cells and MSCs revealed that the cells remained transiently and did not permanently integrate in the tissue. These observations suggest that the increased wound closure rates and angiogenesis may be due to delivery of secreted trophic factors, rather than direct cell-cell interactions. Accordingly, we performed proteomic analysis, which showed that AFS cells secreted a number of growth factors at concentrations higher than those of MSCs. In parallel, we showed that AFS cell-conditioned media induced endothelial cell migration in vitro. Taken together, our results indicate that bioprinting AFS cells could be an effective treatment for large-scale wounds and burns. PMID:23197691

  7. Negative pressure wound therapy combined with acoustic pressure wound therapy for infected post surgery wounds: a case series.

    PubMed

    Howell-Taylor, Melania; Hall, Macy G; Brownlee Iii, William J; Taylor, Mary

    2008-09-01

    Acute infection of surgical incision sites often requires specialized wound care in preparation for surgical closure. Optimal therapy for preparing such wounds for a secondary closure procedure remains uncertain. The authors report wound outcomes after administering acoustic pressure wound therapy in conjunction with negative pressure wound therapy with reticulated open-cell foam dressing changes to assist with bacteria removal from open, infected surgical-incision sites in preparation for secondary surgical closure in three patients. Before incorporating acoustic pressure wound therapy at the authors' facility, the average negative pressure wound therapy with reticulated open-cell foam dressing course prior to secondary surgical closure was 30 days; with its addition, two of three patients underwent successful surgical closure with no postoperative complications after 21 and 14 days, respectively; one patient succumbed to nonwound-related complications before wound closure. Larger, prospective studies are needed to evaluate combining negative pressure wound therapy with reticulated open-cell foam dressing and acoustic pressure wound therapy for infected, acute post surgery wounds.

  8. Microwave Tissue Soldering for Immediate Wound Closure

    NASA Technical Reports Server (NTRS)

    Arndt, G. Dickey; Ngo, Phong H.; Plan, Chau T.; Byerly, Diane; Dusl, John; Sognier, Marguerite A.

    2011-01-01

    A novel approach for the immediate sealing of traumatic wounds is under development. A portable microwave generator and handheld antenna are used to seal wounds, binding the edges of the wound together using a biodegradable protein sealant or solder. This method could be used for repairing wounds in emergency settings, by restoring the wound surface to its original strength within minutes. This technique could also be utilized for surgical purposes involving solid visceral organs (i.e., liver, spleen, and kidney) that currently do not respond well to ordinary surgical procedures. A miniaturized microwave generator and a handheld antenna are used to deliver microwave energy to the protein solder, which is applied to the wound. The antenna can be of several alternative designs optimized for placement either in contact with or proximity to the protein solder covering the wound. In either case, optimization of the design includes the matching of impedances to maximize the energy delivered to the protein solder and wound at a chosen frequency. For certain applications, an antenna could be designed that would emit power only when it is in direct contact with the wound. The optimum frequency or frequencies for a specific application would depend on the required depth of penetration of the microwave energy. In fact, a computational simulation for each specific application could be performed, which would then match the characteristics of the antenna with the protein solder and tissue to best effect wound closure. An additional area of interest with potential benefit that remains to be validated is whether microwave energy can effectively kill bacteria in and around the wound. Thus, this may be an efficient method for simultaneously sterilizing and closing wounds. Using microwave energy to seal wounds has a number of advantages over lasers, which are currently in experimental use in some hospitals. Laser tissue welding is unsuitable for emergency use because its large, bulky

  9. Tensile strength of surgical knots in abdominal wound closure.

    PubMed

    Fong, Eva D M; Bartlett, Adam S R; Malak, Sharif; Anderson, Iain A

    2008-03-01

    Abdominal wound dehiscence is a surgical catastrophe that can be attributed to patients or technical factors. The technical properties of the monofilament sutures and knots that are commonly used in abdominal closure are poorly understood. The aim of this study was to compare the tensile strength of monofilament sutures tied with conventional knots. To do this, the knot-holding capacity of four types of knots (square, surgeons', Aberdeen and loop) were tested using three types of gauge 1 monofilament suture, namely nylon, polyglyconate and polydioxanone, using a tensiometer. We found that the knot-holding capacity of the loop knot was between twofold and threefold greater than all the other knots examined. In comparing suture types, polyglyconate had the highest knot-holding capacity for all the knots that were examined and there was no difference in the tensile strength of nylon and polyglyconate tied in a square, surgeons' or Aberdeen knot (P < 0.05). In conclusion, our findings suggest that closure of an abdominal wound would be best commenced with a loop knot, using gauge 1 polyglyconate and finished with either an Aberdeen square or surgeons' knot would be appropriate.

  10. A simple technique of laparoscopic port closure allowing wound extension.

    PubMed

    Christey, G R; Poole, G

    2002-04-01

    Reliable and safe access to the abdominal cavity and efficient removal of the resected gallbladder are essential to laparoscopic cholecystectomy. The unpredictable size of the cholecystectomy specimen can sometimes lead to frustration at the time of removal. A simple technique has been developed that allows for tissue extraction and easy fascial closure regardless of the size of the specimen. This is achieved by using a four bite "U-shaped" purse string at the time of Hasson insertion, with cephalad advancement of the proximal two bites. This allows for variable wound extension and secure closure, without the need for additional sutures.

  11. Closure of large wounds using rubber bands in rabbits.

    PubMed

    Magalhães, Maria Angélica Baron; Petroianu, Andy; Martins, Silmar Grey de Oliveira; Resende, Vivian; Alberti, Luiz Ronaldo; Barbosa, Alfredo José Afonso; Vasconcellos, Leonardo de Souza; Tavares Junior, Wilson Campos

    2015-01-01

    to verify the effectiveness of the rubber elastic band in the treatment of large wounds of the body wall of rabbits by means of traction of its edges. we studied 30 New Zealand rabbits, divided into three groups (n=10): Group 1- healing by secondary intention; Group 2- removal and eutopic repositioning of skin as full thickness skin graft; Group 3- Approximation of wound edges with elastic rubber band. In all animals, we removed a segment of the back skin and subcutaneous tissue down to the fascia, in accordance with an acrylic mold of 8 cm long by 12 cm wide. All animals were observed for 21 days. two animals of groups 1 and 2 had wound abscess. In Group 2, there was partial or total graft loss in 90% of animals. The complete closure of the wounds was observed in four animals of Group 1, six of Group 2 and eight of Group 3. There was no difference between the scar resistance values of groups 2 and 3, which were higher than those in Group 1. The scars of the three groups were characterized by the presence of mature connective tissue mixed with blood vessels and inflammatory infiltration, predominantly polymorphonuclear. the tensile strength of the wound edges with rubber elastic band is as efficient as the skin graft to treat rabbits' large body wounds.

  12. Ghrelin accelerates wound healing in combined radiation and wound injury in mice.

    PubMed

    Liu, Cong; Hao, Yuhui; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Li, Rong

    2017-02-01

    Impaired wound healing caused by radiation happens frequently in clinical practice, and the exact mechanisms remain partly unclear. Various countermeasures have been taken to tackle with this issue. Ghrelin was considered as a potent endogenous growth hormone-releasing peptide, and its role in enhancing wound repair and regeneration was firstly investigated in whole-body irradiated (γ-ray) mice in this study. Collagen deposition and neovascularization were mostly discussed. The results demonstrated that ghrelin administration promoted cutaneous wound healing in irradiated mice, followed with reduced average wound closure time, increased spleen index (SI) and improved haematopoiesis. After isolation and analysis of granulation tissues in combined radiation and wound injury (CRWI) mice treated with and without ghrelin, a phenomenon of increased DNA, hexosamine, nitrate and nitrite synthesis, elevated collagen content and enhanced neovascularization was observed after ghrelin treatment. Western blotting indicated that ghrelin also increased the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β), both responsible for wound healing. However, previous administration of growth hormone secretagogue receptor 1a (GHS-R1a) blocker blunted these therapeutic effects of ghrelin on CRWI mice. Our results identify ghrelin as a novel peptide that could be used for radiation-induced impaired wound healing. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. [Comparative description and retrospective analisis of modern methods of surgical wounds closure for intraoperative prophylaxis of development of pathologic cutaneous cicatrices].

    PubMed

    Stavyts'kyĭ, S O; Avetikov, D S; Lokes, K P; Rozkolupa, O O; Boĭko, I V

    2014-05-01

    The experience of application of various methods of closure was presented for the head and neck cutaneous wound surfaces after elective operative interventions. The variant of the postoperative results estimation and optimization of the wounds healing by primary closure was proposed.

  14. Acceleration of skin wound healing with tragacanth (Astragalus) preparation: an experimental pilot study in rats.

    PubMed

    Fayazzadeh, Ehsan; Rahimpour, Sina; Ahmadi, Seyed Mohsen; Farzampour, Shahrokh; Sotoudeh Anvari, Maryam; Boroumand, Mohammad Ali; Ahmadi, Seyed Hossein

    2014-01-01

    Gum tragacanth is a natural complex mixture of polysaccharides and alkaline minerals extracted from species of Astragalus plant, which is found widely in arid regions of the Middle East. In a pilot experimental study we examined the effects of its topical application on wound healing in ten albino adult male rats. Two similar parasagittal elliptical full-thickness wounds (control vs. test samples) were created on the dorsum of each animal. Test group samples were fully covered by a thin layer of gum tragacanth daily. The extent of wound healing was evaluated by planimetric analysis on multiple occasions during the 10-day study period. On the 7th day of the study, the percent of wound closure was significantly higher in gum tragacanth-treated specimens compared to the control samples (87%±2% vs. 70%±4%, P<0.001). The majority of wounds in the test group were completely closed by the 10th day of the study. The difference in wound healing index measured by histological examination on day 10 of the study was also statistically meaningful between the two groups (0.624±0.097 vs. 0.255±0.063, P<0.05). The results of this study clearly showed the useful effects of topical application of gum tragacanth in acceleration of skin wound contraction and healing. More studies are encouraged to identify the implicating agents and precisely understand the mechanism by which they exert their wound healing effects.

  15. Negative pressure wound therapy-assisted dermatotraction for the closure of large open wounds in a patient with non-clostridial gas gangrene.

    PubMed

    Ishida, Kenichiro; Noborio, Mitsuhiro; Nishimura, Tetsuro; Ieki, Yohei; Shimahara, Yumiko; Sogabe, Taku; Ehara, Naoki; Saoyama, Yuki; Sadamitsu, Daikai

    2016-04-01

    A 53-year-old woman developed septic shock associated with non-clostridial gas gangrene. She presented to the emergency department with two large open wounds on both thighs and in her sacral region. Non-enhanced computed tomography showed air density in contact with the right iliopsoas, which extended to the posterior compartment of the thigh. We made repeated efforts at surgical debridement of the wound with resection of necrotic tissues. Using negative pressure wound therapy-assisted dermatotraction, the pus pockets and the wound dehiscence decreased in size. Using this method we were successful in achieving delayed closure without skin grafts. Negative pressure wound therapy can be an effective treatment for large and infected open contoured wounds. Negative pressure wound therapy-assisted dermatotraction might be beneficial for poorly healing, large, open wounds in patients in poor condition and with insufficient reserve to tolerate reconstructive surgery.

  16. Negative pressure wound therapy‐assisted dermatotraction for the closure of large open wounds in a patient with non‐clostridial gas gangrene

    PubMed Central

    Noborio, Mitsuhiro; Nishimura, Tetsuro; Ieki, Yohei; Shimahara, Yumiko; Sogabe, Taku; Ehara, Naoki; Saoyama, Yuki; Sadamitsu, Daikai

    2015-01-01

    Case A 53‐year‐old woman developed septic shock associated with non‐clostridial gas gangrene. She presented to the emergency department with two large open wounds on both thighs and in her sacral region. Non‐enhanced computed tomography showed air density in contact with the right iliopsoas, which extended to the posterior compartment of the thigh. We made repeated efforts at surgical debridement of the wound with resection of necrotic tissues. Outcome Using negative pressure wound therapy‐assisted dermatotraction, the pus pockets and the wound dehiscence decreased in size. Using this method we were successful in achieving delayed closure without skin grafts. Conclusion Negative pressure wound therapy can be an effective treatment for large and infected open contoured wounds. Negative pressure wound therapy‐assisted dermatotraction might be beneficial for poorly healing, large, open wounds in patients in poor condition and with insufficient reserve to tolerate reconstructive surgery. PMID:29123764

  17. Silicone absorption of elastomeric closures--an accelerated study.

    PubMed

    Degrazio, F L; Hlobik, T; Vaughan, S

    1998-01-01

    There is a trend in the parenteral industry to move from the use of elastomeric closures which are washed, siliconized, dried and sterilized in-house at the pharmaceutical manufacturers' site to pre-prepared closures purchased from the closure supplier. This preparation can consist of washing to reduce particle-load and bioburden, siliconization, placement in ready-to-sterilize bags and may eventually extend to sterilization by steam autoclave or gamma irradiation. Since silicone oil lubrication is critical to the processability/machinability of closures, research was designed to investigate this phenomenon in closures prepared using the Westar RS (Ready-to-Sterilize) process. This paper presents the data gathered in a study of the characteristic of silicone absorption into elastomeric closures under accelerated conditions. Variables such as silicone viscosity, rubber formulation, effect of sterilization and others are considered.

  18. Wound Closure and Outcome in Extensively Burned Patients Treated with Cultured Autologous Keratinocytes,

    DTIC Science & Technology

    1993-05-01

    long-term joint consequently has exerted no demonstrable effect on the contractures could be expected. Was any increase noted in this outcome of...ELECTE . , AD-A268 707 THE JOURNAL or TRAUMA so AU 3 019934 N Copyright 1993 by Wils & Printed in U.S.A. WOUND CLOSLRE AND OUTCOME IN EXTENSIVELY...Ultimate patient outcome remains dependent upon ocytes has prompted many investigators to assess the early, timely closure of the burn wound, typically

  19. Multistep Approach for Improved Aesthetic and Functional Outcomes for Lower Extremity Wound Closure After Mohs Micrographic Surgery.

    PubMed

    Kiwanuka, Elizabeth; Cruz, Antonio P

    2017-05-01

    Lower extremity wounds present a major clinical challenge. This paper introduces a new multistep approach for improved aesthetic and functional outcome for lower extremity wound closure after Mohs micrographic surgery. In this prospective case series, 12 consecutive patients undergoing Mohs micrographic surgery for cutaneous malignancies of the lower extremities underwent closure assisted by elastic bandages, proper positioning with 45° flexion of the knee, buried vertical mattress sutures, and careful eversion, using a premium angled stapler. Assessment of cosmetic outcome was performed by 2 blinded observers, using the Hollander Wound Evaluation Scale. The mean age was 73 ± 9 years with most patients having at least one comorbidity. Six patients (50%) underwent resection of a basal cell carcinoma and 5 patients (42%) underwent resection of a squamous cell carcinoma and 1 patient (8%) underwent resection of a keratoacanthomatous carcinoma. There were no wound complications, and at the 3- to 6-month follow-up, 11 of the 12 wounds (92%) had an optimal Hollander Wound Evaluation Scale score of 6. This new approach to lower extremity wounds provides excellent cosmetic outcome with no reported complications.

  20. The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization: In vitro and in vivo study.

    PubMed

    Kruse, Carla R; Singh, Mansher; Targosinski, Stefan; Sinha, Indranil; Sørensen, Jens A; Eriksson, Elof; Nuutila, Kristo

    2017-04-01

    Wound microenvironment plays a major role in the process of wound healing. It contains various external and internal factors that participate in wound pathophysiology. The pH is an important factor that influences wound healing by changing throughout the healing process. Several previous studies have investigated the role of pH in relation to pathogens but studies concentrating on the effects of pH on wound healing itself are inconclusive. The purpose of this study was to comprehensively and in a controlled fashion investigate the effect of pH on wound healing by studying its effect on human primary keratinocyte and fibroblast function in vitro and on wound healing in vivo. In vitro, primary human keratinocytes and fibroblasts were cultured in different levels of pH (5.5-12.5) and the effect on cell viability, proliferation, and migration was studied. A rat full-thickness wound model was used to investigate the effect of pH (5.5-9.5) on wound healing in vivo. The effect of pH on inflammation was monitored by measuring IL-1 α concentrations from wounds and cell cultures exposed to different pH environments. Our results showed that both skin cell types tolerated wide range of pH very well. They further demonstrated that both acidic and alkaline environments decelerated cell migration in comparison to neutral environments and interestingly alkaline conditions significantly enhanced cell proliferation. Results from the in vivo experiments indicated that a prolonged, strongly acidic wound environment prevents both wound closure and reepithelialization while a prolonged alkaline environment did not have any negative impact on wound closure or reepithelialization. Separately, both in vitro and in vivo studies showed that prolonged acidic conditions significantly increased the expression of IL-1 α in fibroblast cultures and in wound fluid, whereas prolonged alkaline conditions did not result in elevated amounts of IL-1 α. © 2017 by the Wound Healing Society.

  1. Topical Naltrexone Is a Safe and Effective Alternative to Standard Treatment of Diabetic Wounds.

    PubMed

    McLaughlin, Patricia J; Cain, Jarrett D; Titunick, Michelle B; Sassani, Joseph W; Zagon, Ian S

    2017-09-01

    Objective: Diabetes affects more than 29 million individuals in the United States, resulting in healthcare costs approaching $245 billion. Approximately 15% of these individuals will develop a chronic, non-healing foot ulcer (diabetic foot ulcer [DFU]) that, if untreated, may lead to amputation. The current treatments for DFU are expensive, have significant side-effects, and often result in non-compliance. A new topical treatment is described that accelerates cutaneous wound repair and is disease modifying by targeting underlying aberrant diabetic pathways. Approach: The efficacy of naltrexone (NTX), an opioid receptor antagonist, and Regranex ® was compared in preclinical studies using type 1 diabetic rats. Dorsal cutaneous wounds were treated topically with 0.03% NTX, Regranex, or moisturizing cream alone. Wound closure, DNA synthesis, and cytokine production were monitored. Results: Wound closure rates with topical NTX in type 1 diabetic rats were comparable to Regranex. Topical NTX accelerated DNA synthesis, as measured by BrdU incorporation, increased mast cells, and enhanced expression of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), a marker for angiogenesis. Regranex had little effect on DNA synthesis, mast cells, and VEGF expression relative to vehicle-treated wounds, and it only temporarily increased PDGF expression. Fibroblast growth factor expression was not altered by either treatment. Innovation: Topical application of 0.03% NTX cream accelerates diabetic wound closure. Conclusion: Blockade of the opioid growth factor (OGF)-OGF receptor (OGFr) axis utilizing 0.03% NTX cream is comparable to standard care in preclinical studies, and it provides a safe, inexpensive, and effective alternative for treatment of diabetic wounds.

  2. The effect of tourniquet and knee position during wound closure after total knee arthroplasty on early recovery of range of motion: a prospective, randomized study.

    PubMed

    Şükür, Erhan; Öztürkmen, Yusuf; Akman, Yunus Emre; Senel, Ahmet; Azboy, İbrahim

    2016-12-01

    There is no consensus on the position of the knee joint while performing wound closure after total knee arthroplasty (TKA). Further, there are no studies focusing on the association between early functional outcomes and different wound closure strategies. Therefore, we investigated the effects of tourniquet and knee position during wound closure on early recovery of range of motion (ROM) after primary TKA. To our knowledge, this is the first study to evaluate the influence of both tourniquet and knee position during wound closure in primary TKA. One hundred-twenty eligible patients were consecutively enrolled in this study and randomly divided into four groups according to wound closure strategy. Wound closure was either performed with the knee in flexion at 90° or in full extension, with the combination of an inflated or deflated tourniquet. Visual analogue score (VAS), knee ROM, ROM recovery, knee society score (KSS), and wound complications were evaluated in the early postoperative period. After the first postoperative week, ROM recovery in the group with knee in extension and inflated tourniquet was significantly lesser than the two groups with deflated tourniquets. Between the first and fourth postoperative weeks, ROM recovery in the group with knee inflection and deflated tourniquet was significantly higher than the two groups with knee in extension. After the first postoperative week, the visual analog score (VAS) for pain in the group with knee inflection and deflated tourniquet was significantly lesser than the two groups with inflated tourniquets. The differences in the outcomes between the four groups were not significant after the fourth postoperative week. The incidence of wound complications and KSS were not significantly different between the four groups. Following TKA, wound closure with the knee in flexion and after deflating the tourniquet significantly decreased postoperative pain and promoted the recovery of ROM in the early postoperative

  3. Wound complications in rectal cancer patients undergoing primary closure of the perineal wound after abdominoperineal resection.

    PubMed

    El-Gazzaz, Galal; Kiran, Ravi Pokala; Lavery, Ian

    2009-12-01

    Perineal wound complications have a significant impact on postoperative morbidity after excision of the rectum and anus. The aim of this study is to evaluate factors affecting perineal wound complications after primary closure of the wound following abdominoperineal resection. Data were reviewed from all patients who underwent abdominoperineal resection for rectal carcinoma between 1982 and 2007. Data pertaining to demographics, tumor characteristics, and use of preoperative neoadjuvant therapy were retrieved. Complications studied included delayed wound healing, wound infection, dehiscence, abscess or sinus, reoperation, and perineal hernias. Patients who developed perineal wound complications (Group A) were compared with the remaining patients (Group B) to evaluate factors associated with the development of perineal wound complications. Six hundred ninety-six patients (59% male) met the inclusion criteria. The mean age was 63 years (standard deviation, 13), and the mean body mass index was 28.9 kg/m2 (standard deviation, 7.8). Two hundred seventy-three patients (39.2%) received neoadjuvant chemoradiation. The overall rate of wound complications was 16.2%, and reoperation was required in 5.2% of patients. Group A and Group B patients were similar with respect to age (P = 0.1), gender (P = 0.7), grade (P = 0.4), and stage of disease (P = 0.5). A greater proportion of Group A patients had associated comorbidity (P = 0.001), obesity (0.04), neoadjuvant chemoradiation (0.02), and intraoperative bleeding (0.04). In multivariate analysis, comorbidity was the only independent factor associated with the development of perineal complications (odds ratio, 1.8 (1.09-2.96)). Most patients have perineal wound healing without complications after abdominoperineal resection. In multivariate analysis, comorbidity was the only significant factor that predicted perineal wound complications.

  4. Macrophage Differentiation in Normal and Accelerated Wound Healing.

    PubMed

    Kotwal, Girish J; Chien, Sufan

    2017-01-01

    Chronic wounds pose considerable public health challenges and burden. Wound healing is known to require the participation of macrophages, but mechanisms remain unclear. The M1 phenotype macrophages have a known scavenger function, but they also play multiple roles in tissue repair and regeneration when they transition to an M2 phenotype. Macrophage precursors (mononuclear cells/monocytes) follow the influx of PMN neutrophils into a wound during the natural wound-healing process, to become the major cells in the wound. Natural wound-healing process is a four-phase progression consisting of hemostasis, inflammation, proliferation, and remodeling. A lag phase of 3-6 days precedes the remodeling phase, which is characterized by fibroblast activation and finally collagen production. This normal wound-healing process can be accelerated by the intracellular delivery of ATP to wound tissue. This novel ATP-mediated acceleration arises due to an alternative activation of the M1 to M2 transition (macrophage polarization), a central and critical feature of the wound-healing process. This response is also characterized by an early increased release of pro-inflammatory cytokines (TNF, IL-1 beta, IL-6), a chemokine (MCP-1), an activation of purinergic receptors (a family of plasma membrane receptors found in almost all mammalian cells), and an increased production of platelets and platelet microparticles. These factors trigger a massive influx of macrophages, as well as in situ proliferation of the resident macrophages and increased synthesis of VEGFs. These responses are followed, in turn, by rapid neovascularization and collagen production by the macrophages, resulting in wound covering with granulation tissue within 24 h.

  5. The Hanikoda Method: 3-layered Negative Pressure Wound Therapy in Wound Bed Preparation.

    PubMed

    Chik, Ian; Kelly, Enda G; Jarmin, Razman; Imran, Farrah-Hani

    2016-10-01

    Negative pressure wound therapy is a widely used method of wound dressing with various commercially available brands. The authors created the Hanikoda Method (HM) for effective wound bed preparation or definite wound closure. In this case series, the authors discuss 8 different wound cases that presented to their Plastics Unit from January 2014 to June 2015. Patients with traumatic or infected wounds were selected for treatment with the HM. Selected patients underwent multiple cycles of this method until their wounds were ready for definite wound closure or the wounds had closed by secondary closure. The purpose of any wound dressing is to encourage epithelization while ensuring no factors impede wound healing. An additional benefit is to reduce wound bed size so that it may close by secondary intention or require less skin graft coverage. Each layer of the dressing is described, along with its function in wound bed preparation or in closure. The HM facilitates reduction of wound size, wound bed preparation, and overall management.

  6. Pursestring closure of the stoma site leads to fewer wound infections: results from a multicenter randomized controlled trial.

    PubMed

    Lee, Janet T; Marquez, Thao T; Clerc, Daniel; Gie, Olivier; Demartines, Nicolas; Madoff, Robert D; Rothenberger, David A; Christoforidis, Dimitrios

    2014-11-01

    Surgical site infection after stoma reversal is common. The optimal skin closure technique after stoma reversal has been widely debated in the literature. We hypothesized that pursestring near-complete closure of the stoma site would lead to fewer surgical site infections compared with conventional primary closure. This study was a parallel prospective multicenter randomized controlled trial. This study was conducted at 2 university medical centers. Patients (N = 122) presenting for elective colostomy or ileostomy reversal were selected. Pursestring versus conventional primary closure of stoma sites were compared. Stoma site surgical site infection within 30 days of surgery, overall surgical site infection, delayed healing (open wound for >30 days), time to wound epithelialization, and patient satisfaction were the primary outcomes measured. The pursestring group had a significantly lower stoma site infection rate (2% vs 15%, p = 0.01). There was no difference in delayed healing or patient satisfaction between groups. Time to epithelialization was measured in only 51 patients but was significantly longer in the pursestring group (34.6 ± 20 days vs 24.1 ± 17 days, p = 0.02). This study was limited by the variability in procedures and surgeons, the limited follow-up after 30 days, and the inability to perform blinding. Pursestring closure after stoma reversal has a lower risk of stoma site surgical site infection than conventional primary closure, although wounds may take longer to heal with the use of this approach. NCT01713452 (www.clinicaltrials.gov).

  7. Use of the"bogota bag"for closure of open abdominal wound after exploratory laparotomy - our experience at Mayo Hospital Lahore.

    PubMed

    Muhammad, Yar; Gondal, Khalid Masood; Khan, Umair Ahmed

    2016-08-01

    To assess the efficacy of Bogota bag for closure of open abdominal wounds after laparotomy where the primary closure cannot be achieved and other closure techniques are not available. The descriptive study was conducted at Mayo Hospital, Lahore, Pakistan, from September 2011 to February2015, and comprised patients who underwent laparotomy and peritoneal cavities and who could not be closed primarily because of various reasons like traumatic loss and oedematous gut. They were managed with Bogota bag for abdominal closure. SPSS 18 was used for statistical analysis. Of the 55 patients, 37(67.27%) were male and 18(32.73%) were female. There was traumatic loss in 34(61.8%), oedematous gut and omentum in 15(27.27%) and gangrenous abdominal wall in 6(10.9%) patients. Bogota bag was applied in all (100%) of them. In 19(34.55%) patients, delayed primary closure was possible, so the Bogota was used temporarily. In 36(65.45%) cases managed with Bogota bag, healing occurred by granulation tissue or skin grafting/flaps were applied and these patients developed hernia. Five (9.09%) patients developed small bowel fistula which was managed conservatively. No patient developed complication due to exposure or abdominal compartment. There were 7(12.8%) postoperative deaths due to the disease process and were unrelated to the closure technique. Bogota bag was an effective means of closure of open abdominal wound and prevented the complications due to open abdominal wounds or closure under tension.

  8. Enhanced healing of full-thickness burn wounds using di-rhamnolipid

    PubMed Central

    Stipcevic, Tamara; Piljac, Ante; Piljac, Goran

    2006-01-01

    The aim of this study was to investigate the properties of di-rhamnolipid [α-L-rhamnopyranosyl-(1–2)-α-L-rhamnopyranosyl-3-hydroxydecanoyl-3-hydroxydecanoic acid, also referred to as di-rhamnolipid BAC-3] relating to the process of cutaneous wound healing. Di-rhamnolipid was prepared in a eucerin ointment and applied topically on full-thickness burn wounds in normal Sprague–Dawley rats covering 5% of the total body surface area. The rate of wound closure was measured over the period of 45 days. The collagen content was evaluated microscopically, by performing densitometric analysis on Verhoeff’s stained histopathological slides of wound biopsies taken at the end of 45th day of di-rhamnolipid treatment. Di-rhamnolipid toxicity was assessed with the subcutaneous multi-dose study in Swiss–Webster mice. The treatment of full-thickness-burn wounds with topical 0.1% di-rhamnolipid accelerated the closure of wounds on day 21 of the treatment by 32% compared to the control ( p < 0.05). On day 35, the wounds closed in all animals-treated with 0.1% di-rhamnolipid ointment while some rats in the control group had open wounds on days 35 and even 45. Histologic comparisons have shown that di-rhamnolipid significantly decreased collagen content in burn wounds (47.5%, p < 0.05) as compared to the vehicle-treated (control) wounds. Di-rhamnolipid was well-tolerated. The results of this study raise the possibility of potential efficacy of di-rhamnolipid in accelerating normal wound healing and perhaps in overcoming defects associated with healing failure in chronic wounds. PMID:16380213

  9. ROCK Inhibition Promotes Attachment, Proliferation, and Wound Closure in Human Embryonic Stem Cell–Derived Retinal Pigmented Epithelium

    PubMed Central

    Croze, Roxanne H.; Thi, William J.; Clegg, Dennis O.

    2016-01-01

    Purpose Nonexudative (dry) age-related macular degeneration (AMD), a leading cause of blindness in the elderly, is associated with the loss of retinal pigmented epithelium (RPE) cells and the development of geographic atrophy, which are areas devoid of RPE cells and photoreceptors. One possible treatment option would be to stimulate RPE attachment and proliferation to replace dying/dysfunctional RPE and bring about wound repair. Clinical trials are underway testing injections of RPE cells derived from pluripotent stem cells to determine their safety and efficacy in treating AMD. However, the factors regulating RPE responses to AMD-associated lesions are not well understood. Here, we use cell culture to investigate the role of RhoA coiled coil kinases (ROCKs) in human embryonic stem cell–derived RPE (hESC-RPE) attachment, proliferation, and wound closure. Methods H9 hESC were spontaneously differentiated into RPE cells. hESC-RPE cells were treated with a pan ROCK1/2 or a ROCK2 only inhibitor; attachment, and proliferation and cell size within an in vitro scratch assay were examined. Results Pharmacological inhibition of ROCKs promoted hESC-RPE attachment and proliferation, and increased the rate of closure of in vitro wounds. ROCK inhibition decreased phosphorylation of cofilin and myosin light chain, suggesting that regulation of the cytoskeleton underlies the mechanism of action of ROCK inhibition. Conclusions ROCK inhibition promotes attachment, proliferation, and wound closure in H9 hESC-RPE cells. ROCK isoforms may have different roles in wound healing. Translational Relevance Modulation of the ROCK-cytoskeletal axis has potential in stimulating wound repair in transplanted RPE cells and attachment in cellular therapies. PMID:27917311

  10. Wound Complication Rates After Staples or Suture for Midline Vertical Skin Closure in Obese Women: A Randomized Controlled Trial.

    PubMed

    Kuroki, Lindsay M; Mullen, Mary M; Massad, L Stewart; Wu, Ningying; Liu, Jingxia; Mutch, David G; Powell, Matthew A; Hagemann, Andrea R; Thaker, Premal H; McCourt, Carolyn K; Novetsky, Akiva P

    2017-07-01

    To compare wound complication rates after skin closure with staples and subcuticular suture in obese gynecology patients undergoing laparotomy through a midline vertical incision. In this randomized controlled trial, women with body mass indexes (BMIs) of 30 or greater undergoing surgery by a gynecologic oncologist through a midline vertical incision were randomized to skin closure with staples or subcuticular 4-0 monofilament suture. The primary outcome was the rate of wound complication, defined as the presence of a wound breakdown, or infection, within 8 weeks postoperatively. Secondary outcomes included operative time, Stony Brook scar cosmetic score, and patient satisfaction. A sample size of 162 was planned to detect a 50% reduction in wound complications. At planned interim review (n=82), there was no significant difference in primary outcome. Between 2013 and 2016, 163 women were analyzed, including 84 who received staples and 79 suture. Women who received staples were older (mean age 59 compared with 57 years), had lower mean BMI (37.3 compared with 38.9), and fewer benign indications for surgery (22 compared with 27). There were no differences in wound complication rates between staple compared with suture skin closure (28 [33%] compared with 25 [32%], relative risk 1.05, 95% confidence interval [CI] 0.68-1.64). Women with staples reported worse median cosmetic scores (four of five compared with five of five, P<.001), darker scar color (37 [49%] compared with 13 [18%], relative risk 2.69, 95% CI 1.57-4.63), and more skin marks (30 [40%] compared with three [4%], relative risk 9.47, 95% CI 3.02-29.65) compared with women with suture closure. There was no group difference regarding satisfaction with their scar. Stepwise multivariate analysis revealed BMI (odds ratio [OR] 1.13, 95% CI 1.07-1.20), maximum postoperative glucose (OR 1.01, 95% CI 1.00-1.01), and cigarette smoking (OR 4.96, 95% CI 1.32-18.71) were correlates of wound complication. Closure of

  11. Metalloproteinase Expression is Associated with Traumatic Wound Failure

    DTIC Science & Technology

    2010-04-01

    Traumatic amputation- no.(%) 15 Size of wound (cm3 )* Associated vascular injury- no.(%) 7 Wound closure method no.(%) Suture 29 Skin graft 9 Number...definitive closure or coverage with skin graft . Im- paired wound healing included delayed wound closure or wound dehiscence after closure or coverage...closure time period of 10 d. Dehiscence was defined as spontaneous partial or com- plete wound disruption after primary closure or > 90% skin graft loss

  12. Effect of Adhesive Strips and Dermal Sutures vs Dermal Sutures Only on Wound Closure: A Randomized Clinical Trial.

    PubMed

    Custis, Trenton; Armstrong, April W; King, Thomas H; Sharon, Victoria R; Eisen, Daniel B

    2015-08-01

    Although applying adhesive strips to a wound closure has been shown to have outcomes equivalent to those with cuticular suturing, it is unknown whether adhesive strips provide additional benefit compared with dermal suturing alone. To determine whether the addition of adhesive strips to a wound closed with buried interrupted subcuticular sutures improves outcomes following wound closure. A prospective, randomized split-wound intervention was conducted between November 14, 2013, and May 16, 2014, in patients who underwent cutaneous surgical procedures at the University of California, Davis, outpatient dermatology clinic. Fifty-seven patients 18 years or older with postoperative defects of at least 3 cm, resulting from either Mohs micrographic surgical procedures or surgical excision, were screened for participation. Nine patients were excluded and 48 were enrolled. Half of each wound was randomized to receive buried interrupted subcuticular sutures and overlying adhesive strips and the other half received buried interrupted subcuticular sutures only. At 3 months' follow-up, each patient and 2 blinded observers evaluated the wound using the Patient Observer Scar Assessment Scale. The total mean (SD) Patient Observer Scar Assessment Scale score for observers for the side that received a combination of adhesive strips and buried interrupted subcuticular suturing (12.3 [4.8]) and the side that received sutures only (12.9 [6.3]) did not differ significantly at 3 months (P = .32). There was no significant difference in the total patient assessment scale score between the combination closure (14.0 [7.6]) and sutures only (14.7 [7.6]) sides at 3 months (P = .39). There was also no significant difference between the 2 closure methods in terms of mean (SD) scar width (both methods: 1.1 [0.8] mm, P = .89) at follow-up. Combination closure with adhesive strips and buried interrupted subcuticular suturing was not significantly associated with improved overall scar

  13. Biomimetic Delivery of Keratinocyte Growth Factor upon Cellular Demand for Accelerated Wound Healing in Vitro and in Vivo

    PubMed Central

    Geer, David J.; Swartz, Daniel D.; Andreadis, Stelios T.

    2005-01-01

    Exogenous keratinocyte growth factor (KGF) significantly enhances wound healing, but its use is hampered by a short biological half-life and lack of tissue selectivity. We used a biomimetic approach to achieve cell-controlled delivery of KGF by covalently attaching a fluorescent matrix-binding peptide that contained two domains: one recognized by factor XIII and the other by plasmin. Modified KGF was incorporated into the fibrin matrix at high concentration in a factor XIII-dependent manner. Cell-mediated activation of plasminogen to plasmin degraded the fibrin matrix and cleaved the peptides, releasing active KGF to the local microenvironment and enhancing epithelial cell proliferation and migration. To demonstrate in vivo effectiveness, we used a hybrid model of wound healing that involved transplanting human bioengineered skin onto athymic mice. At 6 weeks after grafting, the transplanted tissues underwent full thickness wounding and treatment with fibrin gels containing bound KGF. In contrast to topical KGF, fibrin-bound KGF persisted in the wounds for several days and was released gradually, resulting in significantly enhanced wound closure. A fibrinolytic inhibitor prevented this healing, indicating the requirement for cell-mediated fibrin degradation to release KGF. In conclusion, this biomimetic approach of localized, cell-controlled delivery of growth factors may accelerate healing of large full-thickness wounds and chronic wounds that are notoriously difficult to heal. PMID:16314471

  14. Cutaneous wound healing after treatment with plant-derived human recombinant collagen flowable gel.

    PubMed

    Shilo, Shani; Roth, Sigal; Amzel, Tal; Harel-Adar, Tamar; Tamir, Eran; Grynspan, Frida; Shoseyov, Oded

    2013-07-01

    Chronic wounds, particularly diabetic ulcers, represent a main public health concern with significant costs. Ulcers often harbor an additional obstacle in the form of tunneled or undermined wounds, requiring treatments that can reach the entire wound tunnel, because bioengineered grafts are typically available only in a sheet form. While collagen is considered a suitable biodegradable scaffold material, it is usually extracted from animal and human cadaveric sources, and accompanied by potential allergic and infectious risks. The purpose of this study was to test the performance of a flowable gel made of human recombinant type I collagen (rhCollagen) produced in transgenic tobacco plants, indicated for the treatment of acute, chronic, and tunneled wounds. The performance of the rhCollagen flowable gel was tested in an acute full-thickness cutaneous wound-healing rat model and compared to saline treatment and two commercial flowable gel control products made of bovine collagen and cadaver human skin collagen. When compared to the three control groups, the rhCollagen-based gel accelerated wound closure and triggered a significant jumpstart to the healing process, accompanied by enhanced re-epithelialization. In a cutaneous full-thickness wound pig model, the rhCollagen-based flowable gel induced accelerated wound healing compared to a commercial product made of bovine tendon collagen. By day 21 post-treatment, 95% wound closure was observed with the rhCollagen product compared to 68% closure in wounds treated with the reference product. Moreover, rhCollagen treatment induced an early angiogenic response and induced a significantly lower inflammatory response than in the control group. In summary, rhCollagen flowable gel proved to be efficacious in animal wound models and is expected to be capable of reducing the healing time of human wounds.

  15. Cutaneous Wound Healing After Treatment with Plant-Derived Human Recombinant Collagen Flowable Gel

    PubMed Central

    Roth, Sigal; Amzel, Tal; Harel-Adar, Tamar; Tamir, Eran; Grynspan, Frida; Shoseyov, Oded

    2013-01-01

    Chronic wounds, particularly diabetic ulcers, represent a main public health concern with significant costs. Ulcers often harbor an additional obstacle in the form of tunneled or undermined wounds, requiring treatments that can reach the entire wound tunnel, because bioengineered grafts are typically available only in a sheet form. While collagen is considered a suitable biodegradable scaffold material, it is usually extracted from animal and human cadaveric sources, and accompanied by potential allergic and infectious risks. The purpose of this study was to test the performance of a flowable gel made of human recombinant type I collagen (rhCollagen) produced in transgenic tobacco plants, indicated for the treatment of acute, chronic, and tunneled wounds. The performance of the rhCollagen flowable gel was tested in an acute full-thickness cutaneous wound-healing rat model and compared to saline treatment and two commercial flowable gel control products made of bovine collagen and cadaver human skin collagen. When compared to the three control groups, the rhCollagen-based gel accelerated wound closure and triggered a significant jumpstart to the healing process, accompanied by enhanced re-epithelialization. In a cutaneous full-thickness wound pig model, the rhCollagen-based flowable gel induced accelerated wound healing compared to a commercial product made of bovine tendon collagen. By day 21 post-treatment, 95% wound closure was observed with the rhCollagen product compared to 68% closure in wounds treated with the reference product. Moreover, rhCollagen treatment induced an early angiogenic response and induced a significantly lower inflammatory response than in the control group. In summary, rhCollagen flowable gel proved to be efficacious in animal wound models and is expected to be capable of reducing the healing time of human wounds. PMID:23259631

  16. Endonasal Suturing of Nasoseptal Flap to Nasopharyngeal Fascia Using the V-Loc™ Wound Closure Device: 2-Dimensional Operative Video.

    PubMed

    Zwagerman, Nathan T; Geltzeiler, Mathew N; Wang, Eric W; Fernandez-Miranda, Juan C; Snyderman, Carl H; Gardner, Paul A

    2018-05-30

    We present a case of cerebrospinal fluid (CSF) leak after endoscopic endonasal resection of a large clival chordoma in an obese patient. The leak was at the lower reconstruction at the craniocervical junction and had failed repositioning. Using the V-Loc™ wound closure device (Covidien, New Haven, Connecticut) to suture the nasoseptal flap to the nasopharyngeal fascia, a water-tight seal was created and, along with a lumbar drain, the patient healed successfully.CSF leak after an endoscopic endonasal approach (EEA) to intradural pathologies remains one of the more common complications.1-4 Various closure techniques have been developed5-8 with success in mitigating this risk, but all have their limitations and rely on multiple layers including vascularized flaps like the nasoseptal flap.9-11 Endonasal suturing of graft materials offers the advantage of creating a water-tight seal. We present the use of the V-Loc™ wound closure device (Covidien) to successfully seal a postoperative CSF leak. The absorbable V-Loc™ wound closure device does not require the surgeon to tie knots, which is the most challenging step in a deep, 2-dimensional corridor. The suture is barbed and is anchored by threading the needle through a prefabricated loop at the end of the suture which locks in place. Each throw of the suture through tissue maintains the suture line as the barbs catch the tissue and prevent retraction. After successful closure, the needle can simply be cut off.The V-Loc™ wound closure device (Covidien) is a safe and effective adjunct to reconstruction after endoscopic endonasal skull base surgery as it provides an option for graft/flap suturing.A written release from the patient whose name or likeness is submitted as part of this Work is on file.

  17. [Evaluation of the external tissue extender (Ete) in secondary wound closure].

    PubMed

    Zutt, Markus; Beckmann, Iris; Kretschmer, Lutz

    2003-09-01

    For surgical closure of large skin defects, elaborate reconstructive plastic surgery or other methods such as internal subcutaneous balloon tissue expanders are required in order to avoid tension on the closure margins. Here we point to the benefits and disadvantages of an improved and simple method of secondary wound closure by secondary sutures. We employed a system called External Tissue Extender (ETE), which consists of silicone strings and plastic stoppers pulling the corresponding surgical sites together and evenly distributing the tension. Possible indications in dermatologic surgery and our experiences with this technique are outlined. Implantation and handling of the ETE are very easy and fast. The functional results are good and the cosmetic outcome satisfactory. More invasive surgical procedures can be avoided by using this method. A major disadvantage is the possibility of developing necrosis under the plastic stoppers. According to our experience, the ETE is a useful alternative indicated in certain dermatosurgical situations.

  18. [Application of modified adjustable skin stretching and secure wound-closure system in repairing of skin and soft tissue defect].

    PubMed

    Dong, Qiqiang; Gu, Guojun; Wang, Lijun; Fu, Keda; Xie, Shuqiang; Zhang, Songjian; Zhang, Huafeng; Wu, Zhaosen

    2017-12-01

    To investigate the application of modified adjustable skin stretching and secure wound-closure system in repairing of skin and soft tissue defect. Between March 2016 and April 2017, 21 cases of skin and soft tissue defects were repaired with the modified adjustable skin stretching and secure wound-closure system (the size of regulating pressure and the times of adjustment were determined according to the color, temperature, capillary response, and swelling degree of the skin edge). There were 11 males and 10 females, with an average age of 49.2 years (range, 21-67 years). Among them, 1 case was the residual wound after amputation of leg; 18 cases were the wounds after traumatic injury operation, including 4 cases in the lower leg, 3 cases in the knee joint, 7 cases in the upper limb, and 4 cases in the foot; and 2 cases were diabetic feet. The skin defect area ranged from 4.0 cm×2.5 cm to 21.0 cm×10.0 cm. Skin defect wounds closed directly in one stage in 4 cases; 12 cases were closed after continuously stretching for 5-14 days (mean, 10 days); 5 cases were reduced to less than one-half area, and the wound healed after the second skin grafting or flap repairing. All the 21 patients were followed up 3-12 months (mean, 5.2 months). The wound was linear healing with small scar, and no invasive margin, poor blood flow, necrosis, and poor sensory function happened. The modified adjustable skin stretching and secure wound-closure system can reduce the skin and soft tissue defects or close the wound directly, and even replace the skin graft and skin flap repairing. It was a good method for the treatment of skin and soft tissue defect.

  19. Papineau debridement, Ilizarov bone transport, and negative-pressure wound closure for septic bone defects of the tibia.

    PubMed

    Karargyris, Orestis; Polyzois, Vasilios D; Karabinas, Panayiotis; Mavrogenis, Andreas F; Pneumaticos, Spyros G

    2014-08-01

    Ilizarov pioneered bone transport using a circular external fixator. Papineau described a staged technique for the treatment for infected pseudarthrosis of the long bones. This article presents a single-stage Papineau technique and Ilizarov bone transport, and postoperative negative-pressure wound dressing changes for septic bone defects of the tibia. We studied the files of seven patients (mean age, 32 years) with septic bone defects of the tibia treated with a Papineau technique and Ilizarov bone transport in a single stage, followed by postoperative negative-pressure wound dressing changes. All patients had septic pseudarthrosis and skin necrosis of the tibia. The technique included a single-stage extensive surgical debridement of necrotic bone, open bone grafting with cancellous bone autograft and bone transport, and postoperative negative-pressure wound dressing changes for wound closure. The mean time from the initial injury was 6 months (range, 4-8 months). The mean follow-up was 14 months (range, 10-17 months). All patients experienced successful wound healing at a mean of 29 days. Six patients experienced successful bone regeneration and union at the docking side at a mean of 6 months. One patient experienced delayed union at the docking site, which was treated with autologous cancellous bone grafting. Two patients experienced pin track infection, which was successfully treated with antibiotics and pin site dressing changes. All patients were able to return to their work and previous levels of activity, except one patient who had a stiff ankle joint and had to change his job. No patient experienced recurrence of infection, or fracture of the regenerated or transported bone segment until the period of this study. The combined Papineau and Ilizarov bone transport technique with negative-pressure wound closure provides for successful eradication of the infection, reconstruction of the bone defect, and soft-tissue closure. A single-stage surgical treatment is

  20. Topical application of quercetin improves wound healing in pressure ulcer lesions.

    PubMed

    Yin, Guimei; Wang, Zhijing; Wang, Zhaoxia; Wang, Xirui

    2018-05-07

    The ischemia-reperfusion (I/R) induced skin lesion has been identified as primary cause of pressure ulcers. To date, attempts to prevent pressure ulcers have not produced a significant improvement. Quercetin, one of the most widely distributed flavonoids in fruits and vegetables, exhibits its antioxidant and anti-inflammatory properties against many diseases, including ischemic heart disease, atherosclerosis, and renal injury. In vitro wound scratch assay was first used to assess the function of quercetin in wounding cell model. Next, animal pressure ulcers model was established with two cycles of I/R. The impact of quercetin in the wound recovery, immune cell infiltration and pro-inflammatory cytokines production was investigated in this model. Mechanistic regulation of quercetin at the wound site was also studied. Quercetin accelerated wound closure in cell scratch assay. Dose response study suggested 1 μM quercetin for in vivo study. In I/R injury model, quercetin treatment significantly accelerated wound closure, reduced immune cell infiltration and pro-inflammatory cytokines production. Signaling study showed quercetin treatment inhibited MAPK but not NFĸB activation. Quercetin treatment improved the wound healing process in I/R lesions by suppressing MAPK pathway. Our results supported that quercetin could be a potential therapeutic agent for pressure ulcers. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. Thyrotropin-releasing hormone and its analogs accelerate wound healing.

    PubMed

    Nie, Chunlei; Yang, Daping; Liu, Nan; Dong, Deli; Xu, Jin; Zhang, Jiewu

    2014-06-15

    Thyrotropin-releasing hormone (TRH) is a classical hormone that controls thyroid hormone production in the anterior pituitary gland. However, recent evidence suggested that TRH is expressed in nonhypothalamic tissues such as epidermal keratinocytes and dermal fibroblasts, but its function is not clear. This study aimed to investigate the effects of TRH and its analogs on wound healing and explore the underlying mechanisms. A stented excisional wound model was established, and the wound healing among vehicle control, TRH, and TRH analog taltirelin treatment groups was evaluated by macroscopic and histologic analyses. Primary fibroblasts were isolated from rat dermis and treated with vehicle control, TRH or taltirelin, cell migration, and proliferation were examined by scratch migration assay, MTT, and 5-ethynyl-2'- deoxyuridine (EdU) assay. The expression of α-Smooth muscle actin in fibroblasts was detected by Western blot and immunocytochemical analysis. TRH or taltirelin-treated wounds exhibited accelerated wound healing with enhanced granulation tissue formation and increased re-epithelialization and tissue formation. Furthermore, TRH or taltirelin promoted the migration and proliferation of fibroblasts and induced the expression of α-Smooth muscle actin in fibroblasts. TRH is important in upregulating the phenotypes of dermal fibroblasts and plays a role in accelerating wound healing. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells

    PubMed Central

    Milan, P. Brouki; Lotfibakhshaiesh, N.; Joghataie, M.T.; Ai, J.; Pazouki, A.; Kaplan, D.L.; kargozar, S.; Amini, N.; Hamblin, M.R.; Mozafari, M.; Samadikuchaksaraei, A.

    2016-01-01

    There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7 days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation. Statement of Significance The aim of the present study was to design a novel tissue-engineered system to promote angiogenesis, re-epithelization and granulation of skin tissue using human umbilical cord perivascular

  3. Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells.

    PubMed

    Milan, P Brouki; Lotfibakhshaiesh, N; Joghataie, M T; Ai, J; Pazouki, A; Kaplan, D L; Kargozar, S; Amini, N; Hamblin, M R; Mozafari, M; Samadikuchaksaraei, A

    2016-11-01

    There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation. The aim of the present study was to design a novel tissue-engineered system to promote angiogenesis, re-epithelization and granulation of skin tissue using human umbilical cord perivascular stem cells and

  4. Hyperforin/HP-β-Cyclodextrin Enhances Mechanosensitive Ca2+ Signaling in HaCaT Keratinocytes and in Atopic Skin Ex Vivo Which Accelerates Wound Healing.

    PubMed

    Takada, Hiroya; Yonekawa, Jun; Matsumoto, Masami; Furuya, Kishio; Sokabe, Masahiro

    2017-01-01

    Cutaneous wound healing is accelerated by mechanical stretching, and treatment with hyperforin, a major component of a traditional herbal medicine and a known TRPC6 activator, further enhances the acceleration. We recently revealed that this was due to the enhancement of ATP-Ca 2+ signaling in keratinocytes by hyperforin treatment. However, the low aqueous solubility and easy photodegradation impede the topical application of hyperforin for therapeutic purposes. We designed a compound hydroxypropyl- β -cyclodextrin- (HP- β -CD-) tetracapped hyperforin, which had increased aqueous solubility and improved photoprotection. We assessed the physiological effects of hyperforin/HP- β -CD on wound healing in HaCaT keratinocytes using live imaging to observe the ATP release and the intracellular Ca 2+ increase. In response to stretching (20%), ATP was released only from the foremost cells at the wound edge; it then diffused to the cells behind the wound edge and activated the P2Y receptors, which caused propagating Ca 2+ waves via TRPC6. This process might facilitate wound closure, because the Ca 2+ response and wound healing were inhibited in parallel by various inhibitors of ATP-Ca 2+ signaling. We also applied hyperforin/HP- β -CD on an ex vivo skin model of atopic dermatitis and found that hyperforin/HP- β -CD treatment for 24 h improved the stretch-induced Ca 2+ responses and oscillations which failed in atopic skin.

  5. Abietic acid isolated from pine resin (Resina Pini) enhances angiogenesis in HUVECs and accelerates cutaneous wound healing in mice.

    PubMed

    Park, Jun Yeon; Lee, Yun Kyung; Lee, Dong-Soo; Yoo, Jeong-Eun; Shin, Myoung-Sook; Yamabe, Noriko; Kim, Su-Nam; Lee, Seulah; Kim, Ki Hyun; Lee, Hae-Jeung; Roh, Seok Sun; Kang, Ki Sung

    2017-05-05

    Resin known as Resina Pini is listed in the Korean and Japanese pharmacopoeias and has been used for treating skin wounds and inflammation. Resin is composed of more than 50% abietic acid and 10% neutral substances. In the present study, the wound-healing effects of abietic acid and the possible underlying mechanism of action were investigated in various in vitro and in vivo models. The effects of abietic acid on tube formation and migration were measured in human umbilical vein vascular endothelial cells (HUVECs). Protein expression of mitogen-activated protein kinase (MAPK) activation was evaluated via Western blotting analysis. The wound-healing effects of abietic acid were assessed using a mouse model of cutaneous wounds. The results showed that abietic acid enhanced cell migration and tube formation in HUVECs. Abietic acid induced significant angiogenic potential, which is associated with upregulation of extracellular signal-regulated kinase (ERK) and p38 expression. Additionally, 0.8μM abietic acid-treated groups showed accelerated wound closure compared to the controls in a mouse model of cutaneous wounds. The current data indicate that abietic acid treatment elevated cell migration and tube formation in HUVECs by the activation of ERK and p38 MAPKs. We suggest that abietic acid can be developed as a wound-healing agent. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. An aligned porous electrospun fibrous membrane with controlled drug delivery - An efficient strategy to accelerate diabetic wound healing with improved angiogenesis.

    PubMed

    Ren, Xiaozhi; Han, Yiming; Wang, Jie; Jiang, Yuqi; Yi, Zhengfang; Xu, He; Ke, Qinfei

    2018-04-01

    A chronic wound in diabetic patients is usually characterized by poor angiogenesis and delayed wound closure. The exploration of efficient strategy to significantly improve angiogenesis in the diabetic wound bed and thereby accelerate wound healing is still a significant challenge. Herein, we reported a kind of aligned porous poly (l-lactic acid) (PlLA) electrospun fibrous membranes containing dimethyloxalylglycine (DMOG)-loaded mesoporous silica nanoparticles (DS) for diabetic wound healing. The PlLA electrospun fibers aligned in a single direction and there were ellipse-shaped nano-pores in situ generated onto the surface of fibers, while the DS were well distributed in the fibers and the DMOG as well as Si ion could be controlled released from the nanopores on the fibers. The in vitro results revealed that the aligned porous composite membranes (DS-PL) could stimulate the proliferation, migration and angiogenesis-related gene expression of human umbilical vein endothelial cells (HUVECs) compared with the pure PlLA membranes. The in vivo study further demonstrated that the prepared DS-PL membranes significantly improved neo-vascularization, re-epithelialization and collagen formation as well as inhibited inflammatory reaction in the diabetic wound bed, which eventually stimulated the healing of the diabetic wound. Collectively, these results suggest that the combination of hierarchical structures (nanopores on the aligned fibers) with the controllable released DMOG drugs as well as Si ions from the membranes, which could create a synergetic effect on the rapid stimulation of angiogenesis in the diabetic wound bed, is a potential novel therapeutic strategy for highly efficient diabetic wound healing. A chronic wound in diabetic patients is usually characterized by the poor angiogenesis and the delayed wound closure. The main innovation of this study is to design a new kind of skin tissue engineered scaffold, aligned porous poly (l-lactic acid) (PlLA) electrospun

  7. Polysaccharides-Rich Extract of Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst Accelerates Wound Healing in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Cheng, Poh-Guat; Sabaratnam, Vikineswary; Kuppusamy, Umah Rani

    2013-01-01

    Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats. PMID:24348715

  8. Peroxide-based oxygen generating topical wound dressing for enhancing healing of dermal wounds.

    PubMed

    Chandra, Prafulla K; Ross, Christina L; Smith, Leona C; Jeong, Seon S; Kim, Jaehyun; Yoo, James J; Harrison, Benjamin S

    2015-01-01

    Oxygen generating biomaterials represent a new trend in regenerative medicine that aims to generate and supply oxygen at the site of requirement, to support tissue healing and regeneration. To enhance the healing of dermal wounds, we have developed a highly portable, in situ oxygen generating wound dressings that uses sodium percarbonate (SPO) and calcium peroxide (CPO) as chemical oxygen sources. The dressing continuously generated oxygen for more than 3 days, after which it was replaced. In the in vivo testing on porcine full-thickness porcine wound model, the SPO/CPO dressing showed enhanced wound healing during the 8 week study period. Quantitative measurements of wound healing related parameters, such as wound closure, reepithelialization, epidermal thickness and collagen content of dermis showed that supplying oxygen topically using the SPO/CPO dressing significantly accelerated the wound healing. An increase in neovascularization, as determined using Von Willebrand factor (vWF) and CD31 staining, was also observed in the presence of SPO/CPO dressing. This novel design for a wound dressing that contains oxygen generating biomaterials (SPO/CPO) for supplying topical oxygen, may find utility in treating various types of acute to chronic wounds. © 2015 by the Wound Healing Society.

  9. A clinical review of infected wound treatment with Vacuum Assisted Closure (V.A.C.) therapy: experience and case series.

    PubMed

    Gabriel, Allen; Shores, Jaimie; Bernstein, Brent; de Leon, Jean; Kamepalli, Ravi; Wolvos, Tom; Baharestani, Mona M; Gupta, Subhas

    2009-10-01

    Over the last decade Vacuum Assisted Closure((R)) (KCI Licensing, Inc., San Antonio, TX) has been established as an effective wound care modality for managing complex acute and chronic wounds. The therapy has been widely adopted by many institutions to treat a variety of wound types. Increasingly, the therapy is being used to manage infected and critically colonized, difficult-to-treat wounds. This growing interest coupled with practitioner uncertainty in using the therapy in the presence of infection prompted the convening of an interprofessional expert advisory panel to determine appropriate use of the different modalities of negative pressure wound therapy (NPWT) as delivered by V.A.C.((R)) Therapy and V.A.C. Instill((R)) with either GranuFoam() or GranuFoam Silver() Dressings. The panel reviewed infected wound treatment methods within the context of evidence-based medicine coupled with experiential insight using V.A.C.((R)) Therapy Systems to manage a variety of infected wounds. The primary objectives of the panel were 1) to exchange state-of-practice evidence, 2) to review and evaluate the strength of existing data, and 3) to develop practice recommendations based on published evidence and clinical experience regarding use of the V.A.C.((R)) Therapy Systems in infected wounds. These recommendations are meant to identify which infected wounds will benefit from the most appropriate V.A.C.((R)) Therapy System modality and provide an infected wound treatment algorithm that may lead to a better understanding of optimal treatment strategies.

  10. Saliva and wound healing.

    PubMed

    Brand, Henk S; Ligtenberg, Antoon J M; Veerman, Enno C I

    2014-01-01

    Oral wounds heal faster and with less scar formation than skin wounds. One of the key factors involved is saliva, which promotes wound healing in several ways. Saliva creates a humid environment, thus improving the survival and functioning of inflammatory cells that are crucial for wound healing. In addition, saliva contains several proteins which play a role in the different stages of wound healing. Saliva contains substantial amounts of tissue factor, which dramatically accelerates blood clotting. Subsequently, epidermal growth factor in saliva promotes the proliferation of epithelial cells. Secretory leucocyte protease inhibitor inhibits the tissue-degrading activity of enzymes like elastase and trypsin. Absence of this protease inhibitor delays oral wound healing. Salivary histatins in vitro promote wound closure by enhancing cell spreading and cell migration, but do not stimulate cell proliferation. A synthetic cyclic variant of histatin exhibits a 1,000-fold higher activity than linear histatin, which makes this cyclic variant a promising agent for the development of a new wound healing medication. Conclusively, recognition of the many roles salivary proteins play in wound healing makes saliva a promising source for the development of new drugs involved in tissue regeneration.

  11. Hyperforin/HP-β-Cyclodextrin Enhances Mechanosensitive Ca2+ Signaling in HaCaT Keratinocytes and in Atopic Skin Ex Vivo Which Accelerates Wound Healing

    PubMed Central

    Takada, Hiroya; Yonekawa, Jun; Matsumoto, Masami; Sokabe, Masahiro

    2017-01-01

    Cutaneous wound healing is accelerated by mechanical stretching, and treatment with hyperforin, a major component of a traditional herbal medicine and a known TRPC6 activator, further enhances the acceleration. We recently revealed that this was due to the enhancement of ATP-Ca2+ signaling in keratinocytes by hyperforin treatment. However, the low aqueous solubility and easy photodegradation impede the topical application of hyperforin for therapeutic purposes. We designed a compound hydroxypropyl-β-cyclodextrin- (HP-β-CD-) tetracapped hyperforin, which had increased aqueous solubility and improved photoprotection. We assessed the physiological effects of hyperforin/HP-β-CD on wound healing in HaCaT keratinocytes using live imaging to observe the ATP release and the intracellular Ca2+ increase. In response to stretching (20%), ATP was released only from the foremost cells at the wound edge; it then diffused to the cells behind the wound edge and activated the P2Y receptors, which caused propagating Ca2+ waves via TRPC6. This process might facilitate wound closure, because the Ca2+ response and wound healing were inhibited in parallel by various inhibitors of ATP-Ca2+ signaling. We also applied hyperforin/HP-β-CD on an ex vivo skin model of atopic dermatitis and found that hyperforin/HP-β-CD treatment for 24 h improved the stretch-induced Ca2+ responses and oscillations which failed in atopic skin. PMID:28210627

  12. C. elegans epidermal wounding induces a mitochondrial ROS burst that promotes wound repair

    PubMed Central

    Xu, Suhong; Chisholm, Andrew D.

    2014-01-01

    SUMMARY Reactive oxygen species (ROS) such as hydrogen peroxide are generated at wound sites and act as long-range signals in wound healing. The roles of other ROS in wound repair are little explored. Here we reveal a cytoprotective role for mitochondrial ROS (mtROS) in C. elegans skin wound healing. We show that skin wounding causes local production of mtROS superoxide at the wound site. Inhibition of mtROS levels by mitochondrial superoxide-specific antioxidants blocks actin-based wound closure, whereas elevation of mtROS promotes wound closure and enhances survival of mutant animals defective in wound healing. mtROS act downstream of wound-triggered Ca2+ influx. We find that the Mitochondrial Calcium Uniporter MCU-1 is essential for rapid mitochondrial Ca2+ uptake and mtROS production after wounding. mtROS can promote wound closure by local inhibition of Rho GTPase activity via a redox-sensitive motif. These findings delineate a pathway acting via mtROS that promotes cytoskeletal responses in wound healing. PMID:25313960

  13. Acceleration of diabetic wound healing using a novel protease–anti-protease combination therapy

    PubMed Central

    Gao, Ming; Nguyen, Trung T.; Suckow, Mark A.; Wolter, William R.; Gooyit, Major; Mobashery, Shahriar; Chang, Mayland

    2015-01-01

    Nonhealing chronic wounds are major complications of diabetes resulting in >70,000 annual lower-limb amputations in the United States alone. The reasons the diabetic wound is recalcitrant to healing are not fully understood, and there are limited therapeutic agents that could accelerate or facilitate its repair. We previously identified two active forms of matrix metalloproteinases (MMPs), MMP-8 and MMP-9, in the wounds of db/db mice. We argued that the former might play a role in the body’s response to wound healing and that the latter is the pathological consequence of the disease with detrimental effects. Here we demonstrate that the use of compound ND-336, a novel highly selective inhibitor of gelatinases (MMP-2 and MMP-9) and MMP-14, accelerates diabetic wound healing by lowering inflammation and by enhancing angiogenesis and re-epithelialization of the wound, thereby reversing the pathological condition. The detrimental role of MMP-9 in the pathology of diabetic wounds was confirmed further by the study of diabetic MMP-9–knockout mice, which exhibited wounds more prone to healing. Furthermore, topical administration of active recombinant MMP-8 also accelerated diabetic wound healing as a consequence of complete re-epithelialization, diminished inflammation, and enhanced angiogenesis. The combined topical application of ND-336 (a small molecule) and the active recombinant MMP-8 (an enzyme) enhanced healing even more, in a strategy that holds considerable promise in healing of diabetic wounds. PMID:26598687

  14. Acceleration of diabetic wound healing using a novel protease-anti-protease combination therapy.

    PubMed

    Gao, Ming; Nguyen, Trung T; Suckow, Mark A; Wolter, William R; Gooyit, Major; Mobashery, Shahriar; Chang, Mayland

    2015-12-08

    Nonhealing chronic wounds are major complications of diabetes resulting in >70,000 annual lower-limb amputations in the United States alone. The reasons the diabetic wound is recalcitrant to healing are not fully understood, and there are limited therapeutic agents that could accelerate or facilitate its repair. We previously identified two active forms of matrix metalloproteinases (MMPs), MMP-8 and MMP-9, in the wounds of db/db mice. We argued that the former might play a role in the body's response to wound healing and that the latter is the pathological consequence of the disease with detrimental effects. Here we demonstrate that the use of compound ND-336, a novel highly selective inhibitor of gelatinases (MMP-2 and MMP-9) and MMP-14, accelerates diabetic wound healing by lowering inflammation and by enhancing angiogenesis and re-epithelialization of the wound, thereby reversing the pathological condition. The detrimental role of MMP-9 in the pathology of diabetic wounds was confirmed further by the study of diabetic MMP-9-knockout mice, which exhibited wounds more prone to healing. Furthermore, topical administration of active recombinant MMP-8 also accelerated diabetic wound healing as a consequence of complete re-epithelialization, diminished inflammation, and enhanced angiogenesis. The combined topical application of ND-336 (a small molecule) and the active recombinant MMP-8 (an enzyme) enhanced healing even more, in a strategy that holds considerable promise in healing of diabetic wounds.

  15. Acceleration of diabetic wound healing with adipose-derived stem cells, endothelial-differentiated stem cells, and topical conditioned medium therapy in a swine model.

    PubMed

    Irons, Robin F; Cahill, Kevin W; Rattigan, Deviney A; Marcotte, Joseph H; Fromer, Marc W; Chang, Shaohua; Zhang, Ping; Behling, Eric M; Behling, Kathryn C; Caputo, Francis J

    2018-05-09

    The purpose of our study was to investigate the effect of adipose-derived stem cells (ASCs), endothelial-differentiated ASCs (EC/ASCs), and various conditioned media (CM) on wound healing in a diabetic swine model. We hypothesized that ASC-based therapies would accelerate wound healing. Diabetes was induced in four Yorkshire swine through intravenous injection of streptozotocin. ASCs were harvested from flank fat and cultured in either M199 or EGM-2 medium. A duplicate series of seven full-thickness dorsal wounds were surgically created on each swine. The wounds in the cellular treatment group underwent injection of low-dose or high-dose ASCs or EC/ASCs on day 0, with a repeat injection of one half of the initial dose on day 15. Wounds assigned to the topical CM therapy were covered with 2 mL of either serum-free M199 primed by ASCs or human umbilical vein endothelial cells every 3 days. Wounds were assessed at day 0, 10, 15, 20, and 28. The swine were sacrificed on day 28. ImageJ software was used to evaluate the percentage of wound healing. The wounded skin underwent histologic, reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay examinations to evaluate markers of angiogenesis and inflammation. We found an increase in the percentage of wound closure rates in cell-based treatments and topical therapies at various points compared with the untreated control wounds (P < .05). The results from the histologic, messenger RNA, and protein analyses suggested the treated wounds displayed increased angiogenesis and a diminished inflammatory response. Cellular therapy with ASCs, EC/ASCs, and topical CM accelerated diabetic wound healing in the swine model. Enhanced angiogenesis and immunomodulation might be key contributors to this process. The purpose of the present study was to translate the known beneficial effects of adipose-derived stem cells and associated conditioned medium therapy on diabetic wound healing to a large animal

  16. Accelerated Burn Wound Closure in Mice with a New Formula Based on Traditional Medicine

    PubMed Central

    Mehrabani, Mehrnaz; Seyyedkazemi, Seyyed Mohsen; Nematollahi, Mohammad Hadi; Jafari, Elham; Mehrabani, Mitra; Mehdipour, Mohammad; Sheikhshoaee, Zahra; Mandegary, Ali

    2016-01-01

    Background A combination of the oils of sesame, hemp, wild pistachio, and walnut has been used for treatment of skin disorders, including wound burns, in some parts of Kerman, Iran. Evaluation of this remedy in the form of a pharmaceutical formulation in animal models can pave the way for its future application in wound burn healing in humans. Objectives This experimental study investigated the healing potential of a new formula (NF) based on folk medicine from Iran for the treatment of third degree burns in mice. The formula was a combination of the oils of four plants: sesame (Sesamum indicum L.), wild pistachio (Pistacia atlantica Desf.), hemp (Cannabis sativa L.), and walnut (Juglans regia L.) Methods Twenty-four mice were selected based on simple random sampling. Twenty-five percent of the total body surface area was burned by exposure to boiling water, according to the Walker-Mason method. NF and silver sulfadiazine (the positive control) were applied topically twice a day for 21 days. The burned area in the negative control group was left untreated. Epithelialization time and the percent of wound contraction were measured during the treatment period. The process of wound repairing was evaluated using histological (H and E and trichrome staining) and immunohistological (anti-pancytokeratin) methods. Results When compared to the controls, NF significantly improved wound contraction after day 10. Epithelialization time in the NF group was significantly faster than in the other groups (20 vs. 25.5 days) (P < 0.001). Histopathological and immunohistochemical findings confirmed the efficacy of the NF. Conclusions A new therapeutic remedy was introduced for the treatment of burn wounds. Further clinical and molecular studies are suggested to determine the exact mechanism(s) involved in the burn wound healing effect of NF. PMID:28191338

  17. Titanium wound chambers for wound healing research.

    PubMed

    Nuutila, Kristo; Singh, Mansher; Kruse, Carla; Philip, Justin; Caterson, Edward J; Eriksson, Elof

    2016-11-01

    Standardized and reproducible animal models are crucial in medical research. Rodents are commonly used in wound healing studies since, they are easily available, affordable and simple to handle and house. However, the most significant limitation of rodent models is that the wounds heal by contraction while in humans the primary mechanisms of healing are reepithelialization and granulation tissue formation. The robust contraction results in faster wound closure that complicates the reproducibility of rodent studies in clinical trials. We have developed a titanium wound chamber for rodent wound healing research. The chamber is engineered from two pieces of titanium and is placed transcutaneously on the dorsum of a rodent. The chamber inhibits wound contraction and provides a means for controlled monitoring and sampling of the wound environment in vivo with minimal foreign body reaction. This technical report introduces two modalities utilizing the titanium chambers in rats: (1) Wound in a skin island model and, (2) Wound without skin model. Here, we demonstrate in rats how the "wound in a skin island model" slows down wound contraction and how the "wound without skin" model completely prevents the closure. The titanium wound chamber provides a reproducible standardized models for wound healing research in rodents. © 2016 by the Wound Healing Society.

  18. Curcumin accelerates cutaneous wound healing via multiple biological actions: The involvement of TNF-α, MMP-9, α-SMA, and collagen.

    PubMed

    Yen, Yu-Hsiu; Pu, Chi-Ming; Liu, Chen-Wei; Chen, Ya-Chun; Chen, Yu-Chen; Liang, Chan-Jung; Hsieh, Jung-Hsien; Huang, Hui-Fu; Chen, Yuh-Lien

    2018-04-16

    Curcumin, a constituent of the turmeric plant, has antitumor, anti-inflammatory, and antioxidative effects, but its effects on wound healing are unclear. We created back wounds in 72 mice and treated them with or without topical curcumin (0.2 mg/mL) in Pluronic F127 gel (20%) daily for 3, 5, 7, 9, and 12 days. Healing in wounds was evaluated from gross appearance, microscopically by haematoxylin and eosin staining, by immunohistochemistry for tumour necrosis factor alpha and alpha smooth muscle actin, and by polymerase chain reaction amplification of mRNA expression levels. Treatment caused fast wound closure with well-formed granulation tissue dominated by collagen deposition and regenerating epithelium. Curcumin increased the levels of tumour necrosis factor alpha mRNA and protein in the early phase of healing, which then decreased significantly. However, these levels remained high in controls. Levels of collagen were significantly higher in curcumin-treated wounds. Immunohistochemical staining for alpha smooth muscle actin was increased in curcumin-treated mice on days 7 and 12. Curcumin treatment significantly suppressed matrix metallopeptidase-9 and stimulated alpha smooth muscle levels in tumour necrosis factor alpha-treated fibroblasts via nuclear factor kappa B signalling. Thus, topical curcumin accelerated wound healing in mice by regulating the levels of various cytokines. © 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  19. Sutureless closure of scleral wounds in animal models by the use of laser welded biocompatible patches

    NASA Astrophysics Data System (ADS)

    Rossi, Francesca; Matteini, Paolo; Menabuoni, Luca; Lenzetti, Ivo; Pini, Roberto

    2011-03-01

    The common procedures used to seal the scleral or conjunctival injuries are based on the traditional suturing techniques, that may induce foreign body reaction during the follow up, with subsequent inflammation and distress for the patient. In this work we present an experimental study on the laser welding of biocompatible patches onto ocular tissues, for the closure of surgical or trauma wounds. The study was performed ex vivo in animal models (porcine eyes). A penetrating perforation of the ocular tissue was performed with a surgical knife. The wound walls were approximated, and a biocompatible patch was put onto the outer surface of the tissue, in order to completely cover the wound as a plaster. The patches were prepared with a biocompatible and biodegradable polymer, showing high mechanical strength, good elasticity, high permeability for vapour and gases and rather low biodegradation. During preparation, Indocyanine Green (ICG) was included in the biopolymeric matrix, so that the films presented high absorption at 810 nm. Effective adhesion of the membranes to the ocular tissues was obtained by using diode laser light emitted from an 810 nm diode laser and delivered by means of a 300 μm core diameter optical fiber, to produce spots of local film/tissue adhesion, due to the photothermal effect at the interface. The result is an immediate closure of the wound, thus reducing post-operative complications due to inflammation.

  20. [Vertical rectus abdominis myocutaneous flap for the closure of perineal wound after abdominoperineal resection of the rectum].

    PubMed

    Orhalmi, J; Vreský, B; Holéczy, P; Jackanin, S; Biath, P

    2009-06-01

    A major source of morbidity after abdominoperineal resection (APR) after neoadjuvant external beam pelvic radiation are perineal wound complications. Wound complications are common for 25-66% of patients overall. There are many of procedures provided to reconstruct the perineal defect after APR e.g. primary closure, secondary closure, superior gluteal artery flap and vertical rectus abdominus myocutaneous (VRAM) flap. Our purpose was to describe the effect of VRAM flap on reconstruction of perineal wound. VRAM flaps are ideally suited to bring nonirradiated tissue into defect associated with radical surgical extirpation procedures and irradiated fields. This flap, distally based in the deep inferior epigastric vessels, provides several distinct advantages. It is well perfused by the robust dominant pedicle and the deep inferior epigastric artery and vein. In addition, this flap provides adequate muscle bulk to obliterate pelvic dead space. The skin island can be used for resurfacing the perineal region, including the vaginal wall, and provides versatility for all patterns of resection. VRAM flap provides very good aesthetic and functional results, is technically relatively simple and radically decreases wound complications rate. The additional possibility is pull-through the flap transpelvically intraabdominally instead of pull-through via subcutaneous channel, especially with females.

  1. Acellular dermal matrix scaffolds coated with connective tissue growth factor accelerate diabetic wound healing by increasing fibronectin through PKC signalling pathway.

    PubMed

    Yan, Wenxia; Liu, Hanping; Deng, Xiaoyuan; Jin, Ying; Wang, Ning; Chu, Jing

    2018-03-01

    The regional injection of connective tissue growth factor (CTGF) for diabetic wound healing requires multiple components and results in a substantial loss of its biological activity. Acellular dermal matrix (ADM) scaffolds are optimal candidates for delivering these factors to local ischaemic environments. In this study, we explored whether CTGF loaded on ADM scaffolds can enhance fibronectin (FN) expression to accelerate diabetic wound healing via the protein kinase C (PKC) signalling pathway. The performance of CTGF and CTGF + PKC inhibitor, which were loaded on ADM scaffolds to treat dorsal skin wounds in streptozotocin-induced diabetic mice, was evaluated with naked ADM as a control. Wound closure showed that ADM scaffolds loaded with CTGF induced greater diabetic wound healing in the early stage of the wound in diabetic mice. Moreover, ADM scaffolds loaded with CTGF obviously increased the expression of FN both at the mRNA and protein levels, whereas the expression of FN was significantly reduced in the inhibitor group. Furthermore, the ADM + CTGF group, which produce FN, obviously promoted alpha-smooth muscle actin and transforming growth factor-beta expression and enhanced neovasculature and collagen synthesis at the wound sites. ADM scaffolds loaded with CTGF + PKC inhibitor delayed diabetic wound healing, indicating that FN expression was mediated by the PKC signalling pathway. Our findings offer new perspectives for the treatment of diabetic wound healing and suggest a rationale for the clinical evaluation of CTGF use in diabetic wound healing. Copyright © 2017 John Wiley & Sons, Ltd.

  2. “Sugar-coating wound repair: A review of FGF-10 and dermatan sulfate in wound healing and their potential application in burn wounds”

    PubMed Central

    Plichta, Jennifer K.; Radek, Katherine A.

    2011-01-01

    Thousands of patients suffer from burn injuries each year, yet few therapies have been developed to accelerate the wound healing process. Most fibroblast growth factors (FGFs) have been extensively evaluated, but only a few have been found to participate in wound healing. In particular, FGF-10 is robustly increased in the wound microenvironment following injury and has demonstrated some ability to promote wound healing in vitro and in vivo. Glycosaminoglycans (GAGs) are linear carbohydrates that participate in wound repair by influencing cytokine/growth factor localization and interaction with cognate receptors. Dermatan sulfate (DS) is the most abundant GAG in human wound fluid and has been postulated to be directly involved in the healing process. Recently, the combination of FGF-10 and DS demonstrated the potential to accelerate wound healing via increased keratinocyte proliferation and migration. Based on these preliminary studies, DS may serve as a cofactor for FGF-10, and together, they are likely to expedite the healing process by stimulating keratinocyte activity. As a specific subtype of wounds, the overall healing process of burn injuries does not significantly differ from other types of wounds, where optimal repair results in matrix regeneration and complete re-epithelialization. At present, standard burn treatment primarily involves topical application of anti-microbial agents, while no routine therapies target acceleration of re-epithelialization, the key to wound closure. Thus, this novel therapeutic combination could be used in conjunction with some of the current therapies, but it would have the unique ability to initiate wound healing by stimulating keratinocyte epithelialization. PMID:22561305

  3. PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing.

    PubMed

    Chereddy, Kiran Kumar; Her, Charles-Henry; Comune, Michela; Moia, Claudia; Lopes, Alessandra; Porporato, Paolo E; Vanacker, Julie; Lam, Martin C; Steinstraesser, Lars; Sonveaux, Pierre; Zhu, Huijun; Ferreira, Lino S; Vandermeulen, Gaëlle; Préat, Véronique

    2014-11-28

    Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing and angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained release of both LL37 and lactate. In full thickness excisional wounds, the treatment with PLGA-LL37 NP significantly accelerated wound healing compared to PLGA or LL37 administration alone. PLGA-LL37 NP-treated wounds displayed advanced granulation tissue formation by significant higher collagen deposition, re-epithelialized and neovascularized composition. PLGA-LL37 NP improved angiogenesis, significantly up-regulated IL-6 and VEGFa expression, and modulated the inflammatory wound response. In vitro, PLGA-LL37 NP induced enhanced cell migration but had no effect on the metabolism and proliferation of keratinocytes. It displayed antimicrobial activity on Escherichia coli. In conclusion, we developed a biodegradable drug delivery system that accelerated healing processes due to the combined effects of lactate and LL37 released from the nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Vertical Profunda Artery Perforator Flap for Plantar Foot Wound Closure: A New Application.

    PubMed

    Alfonso, Allyson R; Mayo, James L; Sharma, Vishal K; Allen, Robert J; Chiu, Ernest S

    2018-02-01

    Plantar foot reconstruction requires special consideration of both form and function. There are several fasciocutaneous flap options, each with indications and reservations. This case presents a new application of the vertical profunda artery perforator flap for definitive closure of a neuropathic foot ulcer in a young woman with spina bifida. The postoperative course was uneventful, and the flap survived completely. The surgical and donor sites were without wound recurrence at 5-month follow-up. Understanding the variability of foot flap options is important because of unique cases such as the one presented where the wound was caused by specific and less commonly observed foot anatomy. The specific choice to use the vertical profunda artery perforator flap for this patient and her neuropathic wound type was made based on its excellent flexibility, durability, and donor site appeal. The vertical profunda artery perforator flap has adequate surface area and bulk and a favorable pedicle length and caliber, can be thinned, and leaves a donor scar in a less conspicuous area than other popular free flaps for lower-extremity reconstruction. For these reasons, it should be considered a first-line therapy for free flap coverage of selected foot wounds.

  5. Broad-Spectrum Inhibition of the CC-Chemokine Class Improves Wound Healing and Wound Angiogenesis.

    PubMed

    Ridiandries, Anisyah; Bursill, Christina; Tan, Joanne

    2017-01-13

    Angiogenesis is involved in the inflammation and proliferation stages of wound healing, to bring inflammatory cells to the wound and provide a microvascular network to maintain new tissue formation. An excess of inflammation, however, leads to prolonged wound healing and scar formation, often resulting in unfavourable outcomes such as amputation. CC-chemokines play key roles in the promotion of inflammation and inflammatory-driven angiogenesis. Therefore, inhibition of the CC-chemokine class may improve wound healing. We aimed to determine if the broad-spectrum CC-chemokine inhibitor "35K" could accelerate wound healing in vivo in mice. In a murine wound healing model, 35K protein or phosphate buffered saline (PBS, control) were added topically daily to wounds. Cohorts of mice were assessed in the early stages (four days post-wounding) and in the later stages of wound repair (10 and 21 days post-wounding). Topical application of the 35K protein inhibited CC-chemokine expression (CCL5, CCL2) in wounds and caused enhanced blood flow recovery and wound closure in early-mid stage wounds. In addition, 35K promoted neovascularisation in the early stages of wound repair. Furthermore, 35K treated wounds had significantly lower expression of the p65 subunit of NF-κB, a key inflammatory transcription factor, and augmented wound expression of the pro-angiogenic and pro-repair cytokine TGF-β. These findings show that broad-spectrum CC-chemokine inhibition may be beneficial for the promotion of wound healing.

  6. Potential of oncostatin M to accelerate diabetic wound healing.

    PubMed

    Shin, Soo Hye; Han, Seung-Kyu; Jeong, Seong-Ho; Kim, Woo-Kyung

    2014-08-01

    Oncostatin M (OSM) is a multifunctional cytokine found in a variety of pathologic conditions, which leads to excessive collagen deposition. Current studies demonstrate that OSM is also a mitogen for fibroblasts and has an anti-inflammatory action. It was therefore hypothesised that OSM may play an important role in healing of chronic wounds that usually involve decreased fibroblast function and persist in the inflammatory stage for a long time. In a previous in vitro study, the authors showed that OSM increased wound healing activities of diabetic dermal fibroblasts. However, wound healing in vivo is a complex process involving multiple factors. Thus, the purpose of this study was to evaluate the effect of OSM on diabetic wound healing in vivo. Five diabetic mice were used in this study. Four full-thickness round wounds were created on the back of each mouse (total 20 wounds). OSM was applied on the two left-side wounds (n = 10) and phosphate-buffered saline was applied on the two right-side wounds (n = 10). After 10 days, unhealed wound areas of the OSM and control groups were compared using the stereoimage optical topometer system. Also, epithelialisation, wound contraction and reduction in wound volume in each group were compared. The OSM-treated group showed superior results in all of the tested parameters. In particular, the unhealed wound area and the reduction in wound volume demonstrated statistically significant differences (P < 0·05). The results of this study indicate that topical application of OSM may have the potential to accelerate healing of diabetic wounds. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  7. Closure methods for laparotomy incisions for preventing incisional hernias and other wound complications.

    PubMed

    Patel, Sunil V; Paskar, David D; Nelson, Richard L; Vedula, Satyanarayana S; Steele, Scott R

    2017-11-03

    Surgeons who perform laparotomy have a number of decisions to make regarding abdominal closure. Material and size of potential suture types varies widely. In addition, surgeons can choose to close the incision in anatomic layers or mass ('en masse'), as well as using either a continuous or interrupted suturing technique, of which there are different styles of each. There is ongoing debate as to which suturing techniques and suture materials are best for achieving definitive wound closure while minimising the risk of short- and long-term complications. The objectives of this review were to identify the best available suture techniques and suture materials for closure of the fascia following laparotomy incisions, by assessing the following comparisons: absorbable versus non-absorbable sutures; mass versus layered closure; continuous versus interrupted closure techniques; monofilament versus multifilament sutures; and slow absorbable versus fast absorbable sutures. Our objective was not to determine the single best combination of suture material and techniques, but to compare the individual components of abdominal closure. On 8 February 2017 we searched CENTRAL, MEDLINE, Embase, two trials registries, and Science Citation Index. There were no limitations based on language or date of publication. We searched the reference lists of all included studies to identify trials that our searches may have missed. We included randomised controlled trials (RCTs) that compared suture materials or closure techniques, or both, for fascial closure of laparotomy incisions. We excluded trials that compared only types of skin closures, peritoneal closures or use of retention sutures. We abstracted data and assessed the risk of bias for each trial. We calculated a summary risk ratio (RR) for the outcomes assessed in the review, all of which were dichotomous. We used random-effects modelling, based on the heterogeneity seen throughout the studies and analyses. We completed subgroup

  8. Low-level stretching accelerates cell migration into a gap.

    PubMed

    Toume, Samer; Gefen, Amit; Weihs, Daphne

    2017-08-01

    We observed that radially stretching cell monolayers at a low level (3%) increases the rate at which they migrate to close a gap formed by in vitro injury. Wound healing has been shown to accelerate in vivo when deformations are topically applied, for example, by negative pressure wound therapy. However, the direct effect of deformations on cell migration during gap closure is still unknown. Thus, we have evaluated the effect of radially applied, sustained (static) tensile strain on the kinematics of en mass cell migration. Monolayers of murine fibroblasts were cultured on stretchable, linear-elastic substrates that were subjected to different tensile strains, using a custom-designed three-dimensionally printed stretching apparatus. Immediately following stretching, the monolayer was 'wounded' at its centre, and cell migration during gap closure was monitored and quantitatively evaluated. We observed a significant increase in normalised migration rates and a reduction of gap closure time with 3% stretching, relative to unstretched controls or 6% stretch. Interestingly, the initial gap area was linearly correlated with the maximum migration rate, especially when stretching was applied. Therefore, small deformations applied to cell monolayers during gap closure enhance en mass cell migration associated with wound healing and can be used to fine-tune treatment protocols. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  9. Gelam (Melaleuca spp.) Honey-Based Hydrogel as Burn Wound Dressing

    PubMed Central

    Mohd Zohdi, Rozaini; Abu Bakar Zakaria, Zuki; Yusof, Norimah; Mohamed Mustapha, Noordin; Abdullah, Muhammad Nazrul Hakim

    2012-01-01

    A novel cross-linked honey hydrogel dressing was developed by incorporating Malaysian honey into hydrogel dressing formulation, cross-linked and sterilized using electron beam irradiation (25 kGy). In this study, the physical properties of the prepared honey hydrogel and its wound healing efficacy on deep partial thickness burn wounds in rats were assessed. Skin samples were taken at 7, 14, 21, and 28 days after burn for histopathological and molecular evaluations. Application of honey hydrogel dressings significantly enhanced (P < 0.05) wound closure and accelerated the rate of re-epithelialization as compared to control hydrogel and OpSite film dressing. A significant decrease in inflammatory response was observed in honey hydrogel treated wounds as early as 7 days after burn (P < 0.05). Semiquantitative analysis using RT-PCR revealed that treatment with honey hydrogel significantly (P < 0.05) suppressed the expression of proinflammatory cytokines (IL-1α, IL-1β, and IL-6). The present study substantiates the potential efficacy of honey hydrogel dressings in accelerating burn wound healing. PMID:21941590

  10. Evaluation of Antimicrobial and Healing Activities of Frog Skin on Guinea Pigs Wounds

    PubMed Central

    Rezazade Bazaz, Mahere; Mashreghi, Mohammad; Mahdavi Shahri, Nasser; Mashreghi, Mansour; Asoodeh, Ahmad; Behnam Rassouli, Morteza

    2015-01-01

    Background: Frog skin secretions have potentials against a wide spectrum of bacteria. Also, frog skin compositions have healing properties. Objectives: The aim of this study was to investigate the antibacterial potentials along with healing properties of frog skin Rana ridibunda, a species which thoroughly lives in Iran marshes, as a biological dressing on wounds. Materials and Methods: In this study, excisional wounds, dressed with frog skin, were compared between experimental and control groups of guinea pigs. In the experimental groups, wounds were dressed with the dermal (FS) and epidermal (RFS) sides of fresh frog R. ridibunda skin, while only usual cotton gauze covered the wounds of the control group. Furthermore, microbial samples were taken on different days (0, 3, 5, and 7 days post injury) to count the number of the colony-forming units. Additionally, the microbial penetration test was performed on frog skin and then the progression of wound closure was evaluated. Results: In the microbial studies, the bacterial load considerably declined in the wounds treated with FS and RFS compared with the control wounds. On day 7 post injury, the numbers of the colony-forming units for the FS, RFS, and control groups were 6.75, 105, and 375, respectively. In the penetration test, fresh frog skin showed to be a bacterial resistant dressing. The results revealed that the rate of wound closure in the experimental groups significantly was accelerated in comparison with that in the control group. Conclusions: Our results demonstrated the antimicrobial properties of frog skin as a wound dressing, which has antimicrobial effects per se. This biological dressing shows promise as an effective biological wound dressing insofar as not only is it capable of resisting microbes and accelerating wound healing but also it is cost-effective and easy to use. PMID:26468364

  11. A Cooperative Copper Metal-Organic Framework-Hydrogel System Improves Wound Healing in Diabetes.

    PubMed

    Xiao, Jisheng; Chen, Siyu; Yi, Ji; Zhang, Hao; Ameer, Guillermo A

    2017-01-05

    Chronic non-healing wounds remain a major clinical challenge that would benefit from the development of advanced, regenerative dressings that promote wound closure within a clinically relevant time frame. The use of copper ions has shown promise in wound healing applications possibly by promoting angiogenesis. However, reported treatments that use copper ions require multiple applications of copper salts or oxides to the wound bed, exposing the patient to potentially toxic levels of copper ions and resulting in variable outcomes. Herein we set out to assess whether copper metal organic framework nanoparticles (HKUST-1 NPs) embedded within an antioxidant thermoresponsive citrate-based hydrogel would decrease copper ion toxicity and accelerate wound healing in diabetic mice. HKUST-1 and poly-(polyethyleneglycol citrate-co- N -isopropylacrylamide) (PPCN) were synthesized and characterized. HKUST-1 NP stability in a protein solution with and without embedding them in PPCN hydrogel was determined. Copper ion release, cytotoxicity, apoptosis, and in vitro migration processes were measured. Wound closure rates and wound blood perfusion were assessed in vivo using the splinted excisional dermal wound diabetic mouse model. HKUST-1 NP disintegrated in protein solution while HKUST-1 NPs embedded in PPCN (H-HKUST-1) were protected from degradation and copper ions were slowly released. Cytotoxicity and apoptosis due to copper ion release were significantly reduced while dermal cell migration in vitro and wound closure rates in vivo were significantly enhanced. In vivo , H-HKUST-1 induced angiogenesis, collagen deposition, and re-epithelialization during wound healing in diabetic mice. These results suggest that a cooperatively stabilized, copper ion-releasing H-HKUST-1 hydrogel is a promising innovative dressing for the treatment of chronic wounds.

  12. Prospective, randomized, controlled trial comparing a tissue adhesive (Dermabond™) with adhesive strips (Steri-Strips™) for the closure of laparoscopic trocar wounds in children.

    PubMed

    Romero, P; Frongia, G; Wingerter, S; Holland-Cunz, S

    2011-05-01

    4 methods are used in pediatric laparoscopic surgery to close trocar wounds. While tissue adhesives or adhesive strips have been shown to produce fewer wound complications and a better cosmetic result compared to trans- or only subcutaneous sutures, the choice of technique is still often based on the surgeon's personal experience. Thus, the objective of this trial was to assess the impact of tissue adhesives (Dermabond™) compared to adhesive strips (Steri-Strip™) on potential complications of wound healing, wound pain, cosmetic outcome, and patient satisfaction after laparoscopic appendectomy in children. 49 patients undergoing laparoscopic appendectomy were enrolled in this prospective randomized trial. In every patient, two 5-mm and one 10-mm port-site incision was closed either with Dermabond™ or Steri-Strip™ after placing subcuticular absorbable sutures (4-0 Vicryl™). Postoperative complications, pain, and patient satisfaction with scars were evaluated at follow-up on day 10 and day 90 after the operation using a questionnaire and a visual analogue scale (VAS). Photographs of scars taken on day 90 were evaluated on a VAS by 2 pediatric surgeons blinded to the closure method used. According to the surgeons' evaluation of the cosmetic outcome, a significant difference between the 2 groups with regard to the cosmetic score was found on day 90 of follow-up, favoring Steri-Strip™ wound closure (p < 0.05). On day 10 and 90 there were no statistical differences between the 2 methods as regards the result of patient evaluations (p > 0.05). Only one wound infection (4%) was observed in the Steri-Strip™ group (n = 25) on day 10. At follow-up on day 90 two patients (9.1%) in the Dermabond™ group and one (4.8%) in the Steri-strip™ group complained of wound pain (p = 0.52). Both tissue adhesives and adhesive strips are excellent "no needle" alternatives for the closure of laparoscopic port-site incisions in children. As regards cosmetic outcome, Steri

  13. Topical effects of frog "Rana ridibunda" skin secretions on wound healing and reduction of wound microbial load.

    PubMed

    Mashreghi, Mohammad; Rezazade Bazaz, Mahere; Mahdavi Shahri, Nasser; Asoodeh, Ahmad; Mashreghi, Mansour; Behnam Rassouli, Morteza; Golmohammadzadeh, Shiva

    2013-02-13

    Study of the interrelationships between human and the animals in their environment has always been a subject of interest and caused discoveries of the animal applications in medicine. From the latest century, these remedies called back in traditional medicine of Vietnam and South America and frog skin was used as a biological dressing and had good effects in healing wounds. Also, frog skin secretions have wound healing properties and reduce inflammation. In this study we applied these secretions in the form of ointment to investigate their healing activities. Skin secretions were extracted from Rana ridibunda to evaluate their effects on wound healing in mice. Secretion used as raw extract (RE) and ultrafiltrated extract, using a membrane with cutoff 10kDa as under 10kDa (U10E), was administrated as ointment every 48h on wound site. Control group was left without any treatment and also there was other group treated with ointment (O group) alone. On 2, 4 and 6 days post injury, animals were euthanized and images were taken for wound closure evaluation. Then wound locations were removed for histological assays. Also wound microbial load was examined. Observational parameters including wound closure and wound microbiology in experimental groups compared with the control and O groups have been studied. The results showed U10E group has better effects than RE, O and control groups. Histological parameters, including numbers of inflammatory and fibroblast cells and amount of collagen fibers, neovascularization, as well, represented greater degree of wound healing in U10E group compared with RE, O, and control groups. Our results showed that frog skin secretions were significantly effective in promoting wound healing process. The U10E extract from the frog R. ridibunda possesses a potent accelerating wound healing effect that promises good potential for clinical application in wound care. Further studies will be required to characterize special molecules encompassing

  14. Platelet-Rich Fibrin Accelerates Skin Wound Healing in Diabetic Mice.

    PubMed

    Ding, Yinjia; Cui, Lei; Zhao, Qiming; Zhang, Weiqiang; Sun, Huafeng; Zheng, Lijun

    2017-09-01

    Diabetic foot ulcers (DFUs) are associated with an increased risk of secondary infection and amputation. Platelet-rich fibrin (PRF), a platelet and leukocyte concentrate containing several cytokines and growth factors, is known to promote wound healing. However, the effect of PRF on diabetic wound healing has not been adequately investigated. The aim of the study was to investigate the effect of PRF on skin wound healing in a diabetic mouse model. Platelet-rich fibrin was prepared from whole blood of 8 healthy volunteers. Two symmetrical skin wounds per mouse were created on the back of 16 diabetic nude mice. One of the 2 wounds in each mouse was treated with routine dressings (control), whereas the other wound was treated with PRF in addition to routine dressings (test), each for a period of 14 days. Skin wound healing rate was calculated.Use of PRF was associated with significantly improved skin wound healing in diabetic mice. On hematoxylin and eosin and CD31 staining, a significant increase in the number of capillaries and CD31-positive cells was observed, suggesting that PRF may have promoted blood vessel formation in the skin wound. In this study, PRF seemed to accelerate skin wound healing in diabetic mouse models, probably via increased blood vessel formation.

  15. Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia

    PubMed Central

    Smout, Michael J.; Sotillo, Javier; Laha, Thewarach; Papatpremsiri, Atiroch; Rinaldi, Gabriel; Pimenta, Rafael N.; Chan, Lai Yue; Johnson, Michael S.; Turnbull, Lynne; Whitchurch, Cynthia B.; Giacomin, Paul R.; Moran, Corey S.; Golledge, Jonathan; Daly, Norelle; Sripa, Banchob; Mulvenna, Jason P.

    2015-01-01

    Abstract Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated with wound healing and cancer pathways. Given the notable but seemingly paradoxical properties of liver fluke granulin in promoting not only wound healing but also a carcinogenic microenvironment, Ov-GRN-1 likely holds marked potential as a therapeutic wound-healing agent and as a vaccine against an infection-induced cancer of major public health significance in the developing world. PMID:26485648

  16. Significantly Accelerated Wound Healing of Full-Thickness Skin Using a Novel Composite Gel of Porcine Acellular Dermal Matrix and Human Peripheral Blood Cells.

    PubMed

    Kuna, Vijay K; Padma, Arvind M; Håkansson, Joakim; Nygren, Jan; Sjöback, Robert; Petronis, Sarunas; Sumitran-Holgersson, Suchitra

    2017-02-16

    Here we report the fabrication of a novel composite gel from decellularized gal-gal-knockout porcine skin and human peripheral blood mononuclear cells (hPBMCs) for full-thickness skin wound healing. Decellularized skin extracellular matrix (ECM) powder was prepared via chemical treatment, freeze drying, and homogenization. The powder was mixed with culture medium containing hyaluronic acid to generate a pig skin gel (PSG). The effect of the gel in regeneration of full-thickness wounds was studied in nude mice. We found significantly accelerated wound closure already on day 15 in animals treated with PSG only or PSG + hPBMCs compared to untreated and hyaluronic acid-treated controls (p < 0.05). Addition of the hPBMCs to the gel resulted in marked increase of host blood vessels as well as the presence of human blood vessels. At day 25, histologically, the wounds in animals treated with PSG only or PSG + hPBMCs were completely closed compared to those of controls. Thus, the gel facilitated generation of new skin with well-arranged epidermal cells and restored bilayer structure of the epidermis and dermis. These results suggest that porcine skin ECM gel together with human cells may be a novel and promising biomaterial for medical applications especially for patients with acute and chronic skin wounds.

  17. IL-17A promotes neutrophilic inflammation and disturbs acute wound healing in skin.

    PubMed

    Takagi, Naoyuki; Kawakami, Kazuyoshi; Kanno, Emi; Tanno, Hiromasa; Takeda, Atsushi; Ishii, Keiko; Imai, Yoshimichi; Iwakura, Yoichiro; Tachi, Masahiro

    2017-02-01

    In the wound healing process, neutrophils are the first inflammatory cells to move to the wound tissues. They sterilize wounds by killing microbes, and they stimulate other immune cells to protect the host from infection. In contrast, neutrophil-derived proteases cause damage to host tissues, so neutrophils play dual opposite roles in wound healing. Interleukin-17A (IL-17A) is a proinflammatory cytokine that promotes the recruitment of these cells. The role of this cytokine in the wound healing process is not fully clarified. In the present study, therefore, we examined how defect in IL-17A production affected the wound healing in skin. IL-17A-knockout (KO) mice showed promoted wound closure, myofibroblast differentiation and collagen deposition and decreased the neutrophil accumulation compared with wild-type (WT) mice. In contrast, the administration of recombinant IL-17A led to delayed wound closure, low collagen deposition and accelerated neutrophilic accumulation. In addition, the treatment of IL-17A-administered mice with a neutrophil elastase inhibitor improved the wound repair to the same level as that of WT mice. These results indicated that IL-17A hampered the wound healing process and suggested that neutrophilic inflammation caused by IL-17A may be associated with impaired wound healing in skin. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Mesenchymal stem cells-derived MFG-E8 accelerates diabetic cutaneous wound healing.

    PubMed

    Uchiyama, Akihiko; Motegi, Sei-Ichiro; Sekiguchi, Akiko; Fujiwara, Chisako; Perera, Buddhini; Ogino, Sachiko; Yokoyama, Yoko; Ishikawa, Osamu

    2017-06-01

    Diabetic wounds are intractable due to complex factors, such as the inhibition of angiogenesis, dysfunction of phagocytosis by macrophages and abnormal inflammatory responses. It is recognized that mesenchymal stem cells (MSCs) promote wound healing in diabetic mice. We previously demonstrated that MSCs produce large amounts of MFG-E8. The objective was to ascertain the role of MSCs-derived MFG-E8 in murine diabetic wounds. MFG-E8 WT/KO MSCs or rMFG-E8 were subcutaneously injected around the wound in diabetic db/db mice, and wound areas were analyzed. Quantification of angiogenesis, infiltrating inflammatory cells, apoptotic cells at the wound area was performed by immunofluorescence staining and real-time PCR. Phagocytosis assay was performed using peritoneal macrophages from WT or db/db mice. MFG-E8 expression in granulation tissue in diabetic mice was significantly reduced compared with that in non-diabetic mice. We next examined the effect of subcutaneous injection of MFG-E8 WT/KO MSCs around the wound. Diabetic wound healing was significantly accelerated by the injection of MSCs. Diabetic wound healing in MFG-E8 KO MSCs-injected wounds was significantly delayed compared to that in WT MSCs-injected wounds. The numbers of CD31 + EC and NG2 + pericytes, as well as M2 macrophages in wounds in KO MSCs-injected mice were significantly decreased. MFG-E8 WT MSCs treatment suppressed the number of apoptotic cells and TNF-α + cells in wounds. In an in vitro assay, MFG-E8 WT MSCs-conditioned medium enhanced phagocytosis of apoptotic cells by peritoneal macrophages from diabetic mice. MSCs-derived MFG-E8 might accelerate diabetic wound healing by promoting angiogenesis, the clearance of apoptotic cells, and the infiltration of M2 macrophages, and by suppressing inflammatory cytokines in wound area. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  19. Effect of astaxanthin on cutaneous wound healing.

    PubMed

    Meephansan, Jitlada; Rungjang, Atiya; Yingmema, Werayut; Deenonpoe, Raksawan; Ponnikorn, Saranyoo

    2017-01-01

    Wound healing consists of a complex series of convoluted processes which involve renewal of the skin after injury. ROS are involved in all phases of wound healing. A balance between oxidative and antioxidative forces is necessary for a favorable healing outcome. Astaxanthin, a member of the xanthophyll group, is considered a powerful antioxidant. In this study, we investigated the effect of topical astaxanthin on cutaneous wound healing. Full-thickness dermal wounds were created in 36 healthy female mice, which were divided into a control group and a group receiving 78.9 µM topical astaxanthin treatment twice daily for 15 days. Astaxanthin-treated wounds showed noticeable contraction by day 3 of treatment and complete wound closure by day 9, whereas the wounds of control mice revealed only partial epithelialization and still carried scabs. Wound healing biological markers including Col1A1 and bFGF were significantly increased in the astaxanthin-treated group since day 1. Interestingly, the oxidative stress marker iNOS showed a significantly lower expression in the study. The results indicate that astaxanthin is an effective compound for accelerating wound healing.

  20. Effect of astaxanthin on cutaneous wound healing

    PubMed Central

    Meephansan, Jitlada; Rungjang, Atiya; Yingmema, Werayut; Deenonpoe, Raksawan; Ponnikorn, Saranyoo

    2017-01-01

    Wound healing consists of a complex series of convoluted processes which involve renewal of the skin after injury. ROS are involved in all phases of wound healing. A balance between oxidative and antioxidative forces is necessary for a favorable healing outcome. Astaxanthin, a member of the xanthophyll group, is considered a powerful antioxidant. In this study, we investigated the effect of topical astaxanthin on cutaneous wound healing. Full-thickness dermal wounds were created in 36 healthy female mice, which were divided into a control group and a group receiving 78.9 µM topical astaxanthin treatment twice daily for 15 days. Astaxanthin-treated wounds showed noticeable contraction by day 3 of treatment and complete wound closure by day 9, whereas the wounds of control mice revealed only partial epithelialization and still carried scabs. Wound healing biological markers including Col1A1 and bFGF were significantly increased in the astaxanthin-treated group since day 1. Interestingly, the oxidative stress marker iNOS showed a significantly lower expression in the study. The results indicate that astaxanthin is an effective compound for accelerating wound healing. PMID:28761364

  1. Silver oxysalts promote cutaneous wound healing independent of infection.

    PubMed

    Thomason, Helen A; Lovett, Jodie M; Spina, Carla J; Stephenson, Christian; McBain, Andrew J; Hardman, Matthew J

    2018-03-12

    Chronic wounds often exist in a heightened state of inflammation whereby excessive inflammatory cells release high levels of proteases and reactive oxygen species (ROS). While low levels of ROS play a fundamental role in the regulation of normal wound healing, their levels need to be tightly regulated to prevent a hostile wound environment resulting from excessive levels of ROS. Infection amplifies the inflammatory response, augmenting levels of ROS which creates additional tissue damage that supports microbial growth. Antimicrobial dressings are used to combat infection; however, the effects of these dressing on the wound environment and healing independent of infection are rarely assessed. Cytotoxic or adverse effects on healing may exacerbate the hostile wound environment and prolong healing. Here we assessed the effect on healing independent of infection of silver oxysalts which produce higher oxidative states of silver (Ag 2+ /Ag 3+ ). Silver oxysalts had no adverse effect on fibroblast scratch wound closure whilst significantly promoting closure of keratinocyte scratch wounds (34% increase compared with control). Furthermore, dressings containing silver oxysalts accelerated healing of full-thickness incisional wounds in wild-type mice, reducing wound area, promoting reepithelialization, and dampening inflammation. We explored the mechanisms by which silver oxysalts promote healing and found that unlike other silver dressings tested, silver oxysalt dressings catalyze the breakdown of hydrogen peroxide to water and oxygen. In addition, we found that silver oxysalts directly released oxygen when exposed to water. Collectively, these data provide the first indication that silver oxysalts promote healing independent of infection and may regulate oxidative stress within a wound through catalysis of hydrogen peroxide. © 2018 by the Wound Healing Society.

  2. Wound management.

    PubMed

    Moreira, Maria E; Markovchick, Vincent J

    2007-08-01

    Wound management makes up an important part of the emergency physician's practice. Understanding the physiology of wound healing and the patient and wound factors affecting this process is essential for the proper treatment of wounds. There are many options available for wound closure. Each modality has its benefits and its drawbacks, and some are appropriate only for certain types of wounds. The goal is to achieve the best functional and cosmetically appealing scar while avoiding complications.

  3. Use of negative pressure wound therapy in the treatment of neonatal and pediatric wounds: a retrospective examination of clinical outcomes.

    PubMed

    Baharestani, Mona Mylene

    2007-06-01

    The clinical effectiveness of negative pressure wound therapy for the management of acute and chronic wounds is well documented in the adult population but information regarding its use in the pediatric population is limited. A retrospective, descriptive study was conducted to examine the clinical outcomes of using negative pressure wound therapy in the treatment of pediatric wounds. The medical records of 24 consecutive pediatric patients receiving negative pressure wound therapy were reviewed. Demographic data, wound etiology, time to closure, closure method, duration of negative pressure wound therapy, complications, dressing change frequency, dressing type used, and pressure settings were analyzed. All categorical variables in the dataset were summarized using frequency (count and percentages) and all continuous variables were summarized using median (minimum, maximum). The 24 pediatric patients (mean age 8.5 years [range 14 days to 18 years old]) had 24 wounds - 12 (50%) were infected at baseline. Sixteen patients had hypoalbuminemia and six had exposed hardware and bone in their wounds. Twenty-two wounds reached full closure in a median time of 10 days (range 2 to 45) following negative pressure wound therapy and flap closure (11), split-thickness skin graft (three), secondary (four), and primary (four) closure. Pressures used in this population ranged from 50 to 125 mm Hg and most wounds were covered with reticulated polyurethane foam. One patient developed a fistula during the course of negative pressure wound therapy. When coupled with appropriate systemic antibiotics, surgical debridement, and medical and nutritional optimization, in this population negative pressure wound therapy resulted in rapid granulation tissue and 92% successful wound closure. Future neonatal and pediatric negative pressure wound therapy usage registries and prospective studies are needed to provide a strong evidence base from which treatment decisions can be made in the management

  4. Accelerated healing of full-thickness wounds by genipin-crosslinked silk sericin/PVA scaffolds.

    PubMed

    Aramwit, Pornanong; Siritienthong, Tippawan; Srichana, Teerapol; Ratanavaraporn, Juthamas

    2013-01-01

    Silk sericin has recently been studied for its advantageous biological properties, including its ability to promote wound healing. This study developed a delivery system to accelerate the healing of full-thickness wounds. Three-dimensional scaffolds were fabricated from poly(vinyl alcohol) (PVA), glycerin (as a plasticizer) and genipin (as a crosslinking agent), with or without sericin. The physical and biological properties of the genipin-crosslinked sericin/PVA scaffolds were investigated and compared with those of scaffolds without sericin. The genipin-crosslinked sericin/PVA scaffolds exhibited a higher compressive modulus and greater swelling in water than the scaffolds without sericin. Sericin also exhibited controlled release from the scaffolds. The genipin-crosslinked sericin/PVA scaffolds promoted the attachment and proliferation of L929 mouse fibroblasts. After application to full-thickness rat wounds, the wounds treated with genipin-crosslinked sericin/PVA scaffolds showed a significantly greater reduction in wound size, collagen formation and epithelialization compared with the control scaffolds without sericin but lower numbers of macrophages and multinucleated giant cells. These results indicate that the delivery of sericin from the novel genipin-crosslinked scaffolds efficiently healed the wound. Therefore, these genipin-crosslinked sericin/PVA scaffolds represent a promising candidate for the accelerated healing of full-thickness wounds. Copyright © 2013 S. Karger AG, Basel.

  5. The Immediate and Delayed Post-Debridement Effects on Tissue Bacterial Wound Counts of Hypochlorous Acid Versus Saline Irrigation in Chronic Wounds.

    PubMed

    Hiebert, John M; Robson, Martin C

    2016-01-01

    Introduction: Wound debridement is considered essential in chronic wound management. Hypochlorous acid has been shown to be an effective agent in reducing wound bacterial counts in open wounds. Ultrasound-enabled wound debridement is an effective and efficient method of debridement. This study compared ultrasound irrigation with hypochlorous acid versus saline irrigation for wound debridement on pre- and postoperative wounds and determined regrowth of bacteria over 1 week period of time. Finally, the outcome of definitive wound closure of the clinically clean-appearing wounds was recorded. Methods: Seventeen consenting adult patients with chronic open wounds were randomly selected for study. The patients were randomly divided into the hypochlorous acid irrigation or saline irrigation group. All patients provided pre- and postoperative tissue samples for qualitative and quantitative bacteriology. For the time (7 days) between the debridement procedure and the definitive closure procedure, the wounds were dressed with a silver-impregnated dressing and a hydroconductive dressing. Results : Both types of irrigation in the ultrasonic system initially lowered the bacterial counts by 4 to 6 logs. However, by the time of definitive closure, the saline-irrigated wounds had bacterial counts back up to 10 5 whereas the hypochlorous acid-irrigated wounds remained at 10 2 or fewer. More than 80% of patients in the saline group had postoperative closure failure compared with 25% of patients in the hypochlorous acid group. Conclusions: Hypochlorous acid irrigation with ultrasound debridement reduced bacterial growth in chronic open wounds more efficiently than saline alone. Postoperative wound closure outcomes suggest a remarkable reduction in wound complications after wound debridement using hypochlorous acid irrigation with ultrasound versus saline alone.

  6. A comparison of 2-octyl cyanoacrylate with nylon for wound closure of knee arthroscopy portals.

    PubMed

    Imbuldeniya, A M; Rashid, A; Murphy, J P

    2014-09-01

    To compare the cosmetic results, complications and patient satisfaction of 2-octyl cyanoacrylate (Dermabond, Ethicon Inc. Somerville, NJ, USA), a liquid bonding agent, with 3-0 nylon sutures (Ethilon, Ethicon Inc) skin closure in two groups of patients undergoing elective knee arthroscopy at 6 weeks. The retrospective clinical audit recruited patients undergoing knee surgery for the first time between October 2010 and August 2011. The patients were either treated with the liquid bonding agent or nylon sutures. The patients in the bonding agent group were allowed to shower as normal on postoperative day one, while patients in the suture group kept their wounds dry for 2 weeks. Between the two groups (40 patients per group) there was no difference in the cosmetic outcome (p=0.285), patient satisfaction (p=0.29), pain scores (p=0.44) or wound complication rate (p<0.05). Patient satisfaction was high in both groups. Furthermore, 83.75% of all patients indicated they would prefer the liquid bonding closure over nylon sutures if undergoing the same procedure in the future as they could shower the next day and avoid suture removal. 2-octyl cyanoacrylate is safe to use in the short term in knee arthroscopy providing comparable results to nylon suture closure. Allowing patients to shower the next day appears to cause no adverse effects. The authors would like to state that they do not have any economic or social interest in any of the products used or mentioned. No grant or finance was received for this study, nor any input from other sources.

  7. Wound healing potential of Spirulina platensis extracts on human dermal fibroblast cells

    PubMed Central

    Syarina, Pauzi Nur Aimi; Karthivashan, Govindarajan; Abas, Faridah; Arulselvan, Palanisamy; Fakurazi, Sharida

    2015-01-01

    Blue-green alga (Spirulina platensis) is a well renowned nutri-supplement due to its high nutritional and medicinal properties. The aim of this study was to examine the wound healing efficiency of Spirulina platensis at various solvent extracts using in vitro scratch assay on human dermal fibroblast cells (HDF). Various gradient solvent extracts (50 μg/ml of methanolic, ethanolic and aqueous extracts) from Spirulina platensis were treated on HDF cells to acquire its wound healing properties through scratch assay and in this investigation we have used allantoin, as a positive control to compare efficacy among the phytoextracts. Interestingly, aqueous extract were found to stimulate proliferation and migration of HDF cells at given concentrations and enhanced closure rate of wound area within 24 hours after treatment. Methanolic and ethanolic extracts have shown proliferative effect, however these extracts did not aid in the migration and closure of wound area when compared to aqueous extract. Based on phytochemical profile of the plant extracts analyzed by LC-MS/MS, it was shown that compounds supposedly involved in accelerating wound healing are cinnamic acid, narigenin, kaempferol, temsirolimus, phosphatidylserine isomeric derivatives and sulphoquinovosyl diacylglycerol. Our findings concluded that blue-green algae may pose potential biomedical application to treat various chronic wounds especially in diabetes mellitus patients. PMID:27004048

  8. Filamin A Mediates Wound Closure by Promoting Elastic Deformation and Maintenance of Tension in the Collagen Matrix

    PubMed Central

    Mohammadi, Hamid; Pinto, Vanessa I.; Wang, Yongqiang; Hinz, Boris; Janmey, Paul A.; McCulloch, Christopher A.

    2016-01-01

    Cell-mediated remodeling and wound closure are critical for efficient wound healing, but the contribution of actin-binding proteins to contraction of the extracellular matrix is not defined. We examined the role of filamin A (FLNa), an actin filament cross-linking protein, in wound contraction and maintenance of matrix tension. Conditional deletion of FLNa in fibroblasts in mice was associated with ~ 4 day delay of full-thickness skin wound contraction compared with wild-type (WT) mice. We modeled the healing wound matrix using cultured fibroblasts plated on grid-supported collagen gels that create lateral boundaries, which are analogues to wound margins. In contrast to WT cells, FLNa knockdown (KD) cells could not completely maintain tension when matrix compaction was resisted by boundaries, which manifested as relaxed matrix tension. Similarly, WT cells on cross-linked collagen, which requires higher levels of sustained tension, exhibited approximately fivefold larger deformation fields and approximately twofold greater fiber alignment compared with FLNa KD cells. Maintenance of boundary-resisted tension markedly influenced the elongation of cell extensions: in WT cells, the number (~50%) and length (~300%) of cell extensions were greater than FLNa KD cells. We conclude that FLNa is required for wound contraction, in part by enabling elastic deformation and maintenance of tension in the matrix. PMID:26134946

  9. Modified off-midline closure of pilonidal sinus disease.

    PubMed

    Saber, Aly

    2014-05-01

    Numerous surgical procedures have been described for pilonidal sinus disease, but treatment failure and disease recurrence are frequent. Conventional off-midline flap closures have relatively favorable surgical outcomes, but relatively unfavorable cosmetic outcomes. The author reported outcomes of a new simplified off-midline technique for closure of the defect after complete excision of the sinus tracts. Two hundred patients of both sexes were enrolled for modified D-shaped excisions were used to include all sinuses and their ramifications, with a simplified procedure to close the defect. The overall wound infection rate was 12%, (12.2% for males and 11.1% for females). Wound disruption was necessitating laying the whole wound open and management as open technique. The overall wound disruption rate was 6%, (6.1% for males and 5.5% for females) and the overall recurrence rate was 7%. Our simplified off-midline closure without flap appeared to be comparable to conventional off-midline closure with flap, in terms of wound infection, wound dehiscence, and recurrence. Advantages of the simplified procedure include potentially reduced surgery complexity, reduced surgery time, and improved cosmetic outcome.

  10. Three point-advancement closure for skin defects.

    PubMed

    Tamir, G; Birkby, C S; Berg, D

    1999-10-01

    Circular skin defects are common following Mohs' surgery. Traditional closure (primary, flap, or graft) may involve extensive surgery. Multidirectional advancement closures such as the purse-string closure have been advocated as another useful tool in such cases. To describe a variation on purse-string closure that, in certain cases, is an excellent alternative to other reconstructions, and will provide good cosmetic and functional outcome. A three-point anchoring suture is placed after undermining to advance the surrounding tissue toward the centre, creating a "Mercedes Benz" or tripod closure following removal of "dog-ears." Circular wounds in designated areas can be more easily closed, creating well-tolerated, favourable scars. Large wounds may be closed with the advantage of avoidance of larger flaps, of decreased wound healing compared to second intention, and of minimizing removal of healthy tissue. An initial trial of closure with this method does not limit subsequent use of other repairs should it be less than satisfactory.

  11. Aloesin from Aloe vera accelerates skin wound healing by modulating MAPK/Rho and Smad signaling pathways in vitro and in vivo.

    PubMed

    Wahedi, Hussain Mustatab; Jeong, Minsun; Chae, Jae Kyoung; Do, Seon Gil; Yoon, Hyeokjun; Kim, Sun Yeou

    2017-05-15

    Cutaneous wound healing is a complex process involving various regulatory factors at the molecular level. Aloe vera is widely used for cell rejuvenation, wound healing, and skin moisturizing. This study aimed to investigate the effects of aloesin from Aloe vera on cutaneous wound healing and mechanisms involved therein. This study consisted of both in vitro and in vivo experiments involving skin cell lines and mouse model to demonstrate the wound healing effects of aloesin by taking into account several parameters ranging from cultured cell migration to wound healing in mice. The activities of Smad signaling molecules (Smad2 and Smad3), MAPKs (ERK and JNK), and migration-related proteins (Cdc42, Rac1, and α-Pak) were assessed after aloesin treatment in cultured cells (1, 5 and 10µM) and mouse skin (0.1% and 0.5%). We also monitored macrophage recruitment, secretion of cytokines and growth factors, tissue development, and angiogenesis after aloesin treatment using IHC analysis and ELISAs. Aloesin increased cell migration via phosphorylation of Cdc42 and Rac1. Aloesin positively regulated the release of cytokines and growth factors (IL-1β, IL-6, TGF-β1 and TNF-α) from macrophages (RAW264.7) and enhanced angiogenesis in endothelial cells (HUVECs). Aloesin treatment accelerated wound closure rates in hairless mice by inducing angiogenesis, collagen deposition and granulation tissue formation. More importantly, aloesin treatment resulted in the activation of Smad and MAPK signaling proteins that are key players in cell migration, angiogenesis and tissue development. Aloesin ameliorates each phase of the wound healing process including inflammation, proliferation and remodeling through MAPK/Rho and Smad signaling pathways. These findings indicate that aloesin has the therapeutic potential for treating cutaneous wounds. Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. Novel Locally Active Estrogens Accelerate Cutaneous Wound Healing-Part 2.

    PubMed

    Brufani, Mario; Rizzi, Nicoletta; Meda, Clara; Filocamo, Luigi; Ceccacci, Francesca; D'Aiuto, Virginia; Bartoli, Gabriele; Bella, Angela La; Migneco, Luisa M; Bettolo, Rinaldo Marini; Leonelli, Francesca; Ciana, Paolo; Maggi, Adriana

    2017-05-31

    Estrogen deprivation is associated with delayed healing, while estrogen replacement therapy (ERT) accelerates acute wound healing and protects against development of chronic wounds. However, current estrogenic molecules have undesired systemic effects, thus the aim of our studies is to generate new molecules for topic administration that are devoid of systemic effects. Following a preliminary study, the new 17β-estradiol derivatives 1 were synthesized. The estrogenic activity of these novel compounds was evaluated in vitro using the cell line ERE-Luc B17 stably transfected with an ERE-Luc reporter. Among the 17β-estradiol derivatives synthesized, compounds 1e and 1f showed the highest transactivation potency and were therefore selected for the study of their systemic estrogenic activity. The study of these compounds in the ERE-Luc mouse model demonstrated that both compounds lack systemic effects when administered in the wound area. Furthermore, wound-healing experiments showed that 1e displays a significant regenerative and anti-inflammatory activity. It is therefore confirmed that this class of compounds are suitable for topical administration and have a clear beneficial effect on wound healing.

  13. Early Induction of NRF2 Antioxidant Pathway by RHBDF2 Mediates Rapid Cutaneous Wound Healing

    PubMed Central

    Hosur, Vishnu; Burzenski, Lisa M.; Stearns, Timothy M.; Farley, Michelle L.; Sundberg, John P.; Wiles, Michael V.; Shultz, Leonard D.

    2017-01-01

    Rhomboid family protein RHBDF2, an upstream regulator of the epidermal growth factor (EGF) receptor signaling, has been implicated in cutaneous wound healing. However, the underlying molecular mechanisms are still emerging. In humans, a gain-of-function mutation in the RHBDF2 gene accelerates cutaneous wound healing in an EGFR-dependent manner. Likewise, a gain-of-function mutation in the mouse Rhbdf2 gene (Rhbdf2cub/cub) shows a regenerative phenotype (rapid ear-hole closure) resulting from constitutive activation of the EGFR pathway. Because the RHBDF2-regulated EGFR pathway is relevant to cutaneous wound healing in humans, we used Rhbdf2cub/cub mice to investigate the biological networks and pathways leading to accelerated ear-hole closure, with the goal of identifying therapeutic targets potentially effective in promoting wound healing in humans. Comparative transcriptome analysis of ear pinna tissue from Rhbdf2cub/cub and Rhbdf2+/+ mice at 0h, 15 min, 2h, and 24h post-wounding revealed an early induction of the nuclear factor E2-related factor 2 (NRF2)-mediated anti-oxidative pathway (0h and 15 min), followed by the integrin-receptor aggregation pathway (2h) as early-stage events immediately and shortly after wounding in Rhbdf2cub/cub mice. Additionally, we observed genes enriched for the Fc fragment of the IgG receptor IIIa (FCGR3A)-mediated phagocytosis pathway 24h post-wounding. Although cutaneous wound repair in healthy individuals is generally non-problematic, it can be severely impaired due to aging, diabetes, and chronic inflammation. This study suggests that activation of the NRF2-antioxidant pathway by rhomboid protein RHBDF2 might be beneficial in treating chronic non-healing wounds. PMID:28268192

  14. Early induction of NRF2 antioxidant pathway by RHBDF2 mediates rapid cutaneous wound healing.

    PubMed

    Hosur, Vishnu; Burzenski, Lisa M; Stearns, Timothy M; Farley, Michelle L; Sundberg, John P; Wiles, Michael V; Shultz, Leonard D

    2017-04-01

    Rhomboid family protein RHBDF2, an upstream regulator of the epidermal growth factor (EGF) receptor signaling, has been implicated in cutaneous wound healing. However, the underlying molecular mechanisms are still emerging. In humans, a gain-of-function mutation in the RHBDF2 gene accelerates cutaneous wound healing in an EGFR-dependent manner. Likewise, a gain-of-function mutation in the mouse Rhbdf2 gene (Rhbdf2 cub/cub ) shows a regenerative phenotype (rapid ear-hole closure) resulting from constitutive activation of the EGFR pathway. Because the RHBDF2-regulated EGFR pathway is relevant to cutaneous wound healing in humans, we used Rhbdf2 cub/cub mice to investigate the biological networks and pathways leading to accelerated ear-hole closure, with the goal of identifying therapeutic targets potentially effective in promoting wound healing in humans. Comparative transcriptome analysis of ear pinna tissue from Rhbdf2 cub/cub and Rhbdf2 +/+ mice at 0h, 15min, 2h, and 24h post-wounding revealed an early induction of the nuclear factor E2-related factor 2 (NRF2)-mediated anti-oxidative pathway (0h and 15min), followed by the integrin-receptor aggregation pathway (2h) as early-stage events immediately and shortly after wounding in Rhbdf2 cub/cub mice. Additionally, we observed genes enriched for the Fc fragment of the IgG receptor IIIa (FCGR3A)-mediated phagocytosis pathway 24h post-wounding. Although cutaneous wound repair in healthy individuals is generally non-problematic, it can be severely impaired due to aging, diabetes, and chronic inflammation. This study suggests that activation of the NRF2-antioxidant pathway by rhomboid protein RHBDF2 might be beneficial in treating chronic non-healing wounds. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Optimizing the patient for surgical treatment of the wound.

    PubMed

    Myers, Wesley T; Leong, Mimi; Phillips, Linda G

    2007-10-01

    Plastic surgeons are consulted often to close wounds that fail or are difficult to heal. Optimizing the patient's medical condition before surgical closure of a wound can mean the difference between a successful outcome and an undesirable one. It is imperative that plastic surgeons have an extensive knowledge of the modifiable risk factors affecting the wound-healing process and their subsequent complications. This knowledge allows the surgeon to tailor the treatment options and intervene when appropriate to optimize outcomes for successful surgical closure of a wound. Whether the impairments to wound healing and closure are local or systemic, they must be addressed appropriately.

  16. Enhancement of wound closure by modifying dual release patterns of stromal-derived cell factor-1 and a macrophage recruitment agent from gelatin hydrogels.

    PubMed

    Kim, Yang-Hee; Tabata, Yasuhiko

    2017-11-01

    The objective of the present study is to evaluate the effects of the release patterns of stromal derived factor (SDF)-1 and sphingosine-1 phosphate agonist (SEW2871), used as MSC and macrophage recruitment agents, on the wound closure of diabetic mouse skin defects. To achieve different release patterns, hydrogels were prepared using two types of gelatin with isoelectric points (IEP) of 5 and 9, into which SDF-1 and SEW2871 were then incorporated in various combinations. When the hydrogels incorporating SDF-1 and SEW2871 were applied into wound defects of diabetic mice, the number of MSCs and macrophages recruited to the defects and the levels of pro- and anti- inflammatory cytokines were found to be dependent on the release profiles of SDF-1 and SEW2871. Of particular interest was the case of a rapid release of SDF-1 combined with a controlled release of SEW2871. This resulted in a higher number of M2 macrophages and gene expression levels of anti-inflammatory cytokines 3 days after implantation and faster wound closure than when pairing the controlled release of SDF-1 with a rapid release of SEW2871. Therefore, the present study demonstrates that different release patterns of SDF-1 and SEW2871 can enhance the in vivo recruitment of MSCs and macrophages, and can promote skin wound closure through the modulation of inflammation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. GM-CSF ameliorates microvascular barrier integrity via pericyte-derived Ang-1 in wound healing.

    PubMed

    Yan, Min; Hu, Yange; Yao, Min; Bao, Shisan; Fang, Yong

    2017-11-01

    Skin wound healing involves complex coordinated interactions of cells, tissues, and mediators. Maintaining microvascular barrier integrity is one of the key events for endothelial homeostasis during wound healing. Vasodilation is observed after vasoconstriction, which causes blood vessels to become porous, facilitates leukocyte infiltration and aids angiogenesis at the wound-area, postinjury. Eventually, vessel integrity has to be reestablished for vascular maturation. Numerous studies have found that granulocyte macrophage colony-stimulating factor (GM-CSF) accelerates wound healing by inducing recruitment of repair cells into the injury area and releases of cytokines. However, whether GM-CSF is involving in the maintaining of microvascular barrier integrity and the underlying mechanism remain still unclear. Aim of this study was to investigate the effects of GM-CSF on modulation of microvascular permeability in wound healing and underlying mechanisms. Wound closure and microvascular leakage was investigated using a full-thickness skin wound mouse model after GM-CSF intervention. The endothelial permeability was measured by Evans blue assay in vivo and in vitro endothelium/pericyte co-culture system using a FITC-Dextran permeability assay. To identify the source of angiopoietin-1 (Ang-1), double staining is used in vivo and ELISA and qPCR are used in vitro. To determine the specific effect of Ang-1 on GM-CSF maintaining microvascular stabilization, Ang-1 siRNA was applied to inhibit Ang-1 production in vivo and in vitro. Wound closure was significantly accelerated and microvascular leakage was ameliorated after GM-CSF treatment in mouse wound sites. GM-CSF decreased endothelial permeability through tightening endothelial junctions and increased Ang-1 protein level that was derived by perictye. Furthermore, applications of siRNAAng-1 inhibited GM-CSF mediated protection of microvascular barrier integrity both in vivo and in vitro. Our data indicate that GM

  18. Acceleration of Wound Healing by α-gal Nanoparticles Interacting with the Natural Anti-Gal Antibody

    PubMed Central

    Galili, Uri

    2015-01-01

    Application of α-gal nanoparticles to wounds and burns induces accelerated healing by harnessing the natural anti-Gal antibody which constitutes ~1% of human immunoglobulins. α-gal nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R), the carbohydrate ligand of anti-Gal. Studied α-gal nanoparticles were comprised of glycolipids with α-gal epitopes, phospholipids, and cholesterol. Binding of anti-Gal to α-gal nanoparticles in wounds activates the complement cascade, resulting in formation of chemotactic complement cleavage peptides that induce rapid recruitment of many macrophages. The Fc/Fcγ receptors interaction between anti-Gal coating α-gal nanoparticles and the recruited macrophages activates macrophages to produce cytokines/growth factors that promote wound healing and recruit stem cells. Studies of wound healing by α-gal nanoparticles were feasible in α1,3galactosyltransferase knockout mice and pigs. In contrast to other nonprimate mammals, these mice and pigs lack the α-gal epitope, and thus they are not immunotolerant to it and produce anti-Gal. Treatment of skin wounds and burns with α-gal nanoparticles resulted in 40–60% decrease in healing time in comparison with control wounds treated with saline. This accelerated healing is associated with increased recruitment of macrophages and extensive angiogenesis in wounds, faster regrowth of epidermis, and regeneration of the dermis. The accelerated healing further decreases and may completely eliminate fibrosis and scar formation in wounds. Since healing of internal injuries is mediated by mechanisms similar to those in external wound healing, it is suggested that α-gal nanoparticles treatment may also improve regeneration and restoration of biological function following internal injuries such as surgical incisions, myocardial ischemia following infarction, and nerve injuries. PMID:25922849

  19. In vivo imaging of epithelial wound healing in the cnidarian Clytia hemisphaerica demonstrates early evolution of purse string and cell crawling closure mechanisms.

    PubMed

    Kamran, Zach; Zellner, Katie; Kyriazes, Harry; Kraus, Christine M; Reynier, Jean-Baptiste; Malamy, Jocelyn E

    2017-12-19

    All animals have mechanisms for healing damage to the epithelial sheets that cover the body and line internal cavities. Epithelial wounds heal either by cells crawling over the wound gap, by contraction of a super-cellular actin cable ("purse string") that surrounds the wound, or some combination of the two mechanisms. Both cell crawling and purse string closure of epithelial wounds are widely observed across vertebrates and invertebrates, suggesting early evolution of these mechanisms. Cnidarians evolved ~600 million years ago and are considered a sister group to the Bilateria. They have been much studied for their tremendous regenerative potential, but epithelial wound healing has not been characterized in detail. Conserved elements of wound healing in bilaterians and cnidarians would suggest an evolutionary origin in a common ancestor. Here we test this idea by characterizing epithelial wound healing in live medusae of Clytia hemisphaerica. We identified cell crawling and purse string-mediated mechanisms of healing in Clytia epithelium that appear highly analogous of those seen in higher animals, suggesting that these mechanisms may have emerged in a common ancestor. Interestingly, we found that epithelial wound healing in Clytia is 75 to >600 times faster than in cultured cells or embryos of other animals previously studied, suggesting that Clytia may provide valuable clues about optimized healing efficiency. Finally, in Clytia, we show that damage to the basement membrane in a wound gap causes a rapid shift between the cell crawling and purse string mechanisms for wound closure. This is consistent with work in other systems showing that cells marginal to a wound choose between a super-cellular actin cable or lamellipodia formation to close wounds, and suggests a mechanism underlying this decision. 1. Cell crawling and purse string mechanisms of epithelial wound healing likely evolved before the divergence of Cnidaria from the bilaterian lineage ~ 600mya 2. In

  20. Neutral endopeptidase inhibition in diabetic wound repair.

    PubMed

    Spenny, Michelle L; Muangman, Pornprom; Sullivan, Stephen R; Bunnett, Nigel W; Ansel, John C; Olerud, John E; Gibran, Nicole S

    2002-01-01

    In response to cutaneous injury, sensory nerves release substance P, a proinflammatory neuropeptide. Substance P stimulates mitogenesis and migration of keratinocytes, fibroblasts, and endothelial cells. Neutral endopeptidase (NEP), a cell surface metallopeptidase, degrades substance P. Chronic nonhealing wounds and skin from patients with diabetes mellitus show increased NEP localization and activity. We hypothesized that increased NEP may retard wound healing and that NEP inhibition would improve closure kinetics in an excisional murine wound model. NEP enzyme activity was measured in skin samples from mutant diabetic mice (db/db) and nondiabetic (db/-) littermates by degradation of glutaryl-ala-ala-phe-4-methoxy-2-naphthylamine. Full-thickness 6-mm dorsal excisional wounds treated with normal saline or the NEP inhibitor thiorphan (10 microM or 25 microM) for 7 days were followed until closure. Histological examination and NEP activity were evaluated in a subset of wounds. NEP activity in unwounded db/db skin (20.6 pmol MNA/hr/ microg) significantly exceeded activity in db/-skin (7.9 pmol MNA/hr/ microg; p = 0.02). In db/db mice, 25 microM thiorphan shortened time to closure (18.0 days; p < 0.05) compared to normal saline (23.5 days). NEP inhibition did not alter closure kinetics in db/-mice. While the inflammatory response appeared enhanced in early wounds treated with thiorphan, blinded histological scoring of healed wounds using a semiquantitative scale showed no difference in inflammation. Unwounded skin from diabetic mice shows increased NEP activity and NEP inhibition improved wound closure kinetics without affecting contraction, suggesting that its principal effect was to augment epithelialization.

  1. Modified Off-Midline Closure of Pilonidal Sinus Disease

    PubMed Central

    Saber, Aly

    2014-01-01

    Background: Numerous surgical procedures have been described for pilonidal sinus disease, but treatment failure and disease recurrence are frequent. Conventional off-midline flap closures have relatively favorable surgical outcomes, but relatively unfavorable cosmetic outcomes. Aim: The author reported outcomes of a new simplified off-midline technique for closure of the defect after complete excision of the sinus tracts. Patients and Methods: Two hundred patients of both sexes were enrolled for modified D-shaped excisions were used to include all sinuses and their ramifications, with a simplified procedure to close the defect. Results: The overall wound infection rate was 12%, (12.2% for males and 11.1% for females). Wound disruption was necessitating laying the whole wound open and management as open technique. The overall wound disruption rate was 6%, (6.1% for males and 5.5% for females) and the overall recurrence rate was 7%. Conclusion: Our simplified off-midline closure without flap appeared to be comparable to conventional off-midline closure with flap, in terms of wound infection, wound dehiscence, and recurrence. Advantages of the simplified procedure include potentially reduced surgery complexity, reduced surgery time, and improved cosmetic outcome. PMID:24926445

  2. Evaluation of gelatin-hyaluronic acid composite hydrogels for accelerating wound healing.

    PubMed

    Wu, Song; Deng, Liang; Hsia, Hanson; Xu, Kai; He, Yu; Huang, Qiangru; Peng, Yi; Zhou, Zhihua; Peng, Cheng

    2017-05-01

    Excellent wound dressings maintain a warm and moist environment, thus accelerating wound healing. In this study, we cross-linked gelatin and hyaluronic acid with ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in different ratios (gelatin/hyaluronic acid = 8:2, gelatin/hyaluronic acid = 5:5, gelatin/hyaluronic acid = 2:8), and explored the effects and mechanisms of gelatinhyaluronic acid hydrogels on wound healing. This was done by examining dressing properties, such as fluid uptake ability, water vapor transmission rate, and the rate of water evaporation. We further verified biological function by using in vitro and in vivo wound models. The hydrogels display appropriate fluid uptake ability and good water vapor transmission rate and rate of water evaporation all of which can provide an adequate moisture environment for wound healing. Cell cytotoxicity and proliferation tests show that the hydrogels have no cytotoxicity, furthermore, gelatin/hyaluronic acid = 8:2 hydrogels have the potential to promote cell proliferation. Animal wound models demonstrate that the hydrogels can effectively promote wound healing in vivo, in particular, the gelatin/hyaluronic acid = 8:2 group which promoted the most rapid healing. Accordingly, gelatin-hyaluronic acid dressings, especially the gelatin/hyaluronic acid = 8:2 hydrogels, have a promising outlook for clinical applications in wound healing.

  3. Rapid Healing of Cutaneous Leishmaniasis by High-Frequency Electrocauterization and Hydrogel Wound Care with or without DAC N-055: A Randomized Controlled Phase IIa Trial in Kabul

    PubMed Central

    Steiner, Reto; Wentker, Pia; Mahfuz, Farouq; Stahl, Hans-Christian; Amin, Faquir Mohammad; Bogdan, Christian; Stahl, Kurt-Wilhelm

    2014-01-01

    Background Anthroponotic cutaneous leishmaniasis (CL) due to Leishmania (L.) tropica infection is a chronic, frequently disfiguring skin disease with limited therapeutic options. In endemic countries healing of ulcerative lesions is often delayed by bacterial and/or fungal infections. Here, we studied a novel therapeutic concept to prevent superinfections, accelerate wound closure, and improve the cosmetic outcome of ACL. Methodology/Principal Findings From 2004 to 2008 we performed a two-armed, randomized, double-blinded, phase IIa trial in Kabul, Afghanistan, with patients suffering from L. tropica CL. The skin lesions were treated with bipolar high-frequency electrocauterization (EC) followed by daily moist-wound-treatment (MWT) with polyacrylate hydrogel with (group I) or without (group II) pharmaceutical sodium chlorite (DAC N-055). Patients below age 5, with facial lesions, pregnancy, or serious comorbidities were excluded. The primary, photodocumented outcome was the time needed for complete lesion epithelialization. Biopsies for parasitological and (immuno)histopathological analyses were taken prior to EC (1st), after wound closure (2nd) and after 6 months (3rd). The mean duration for complete wound closure was short and indifferent in group I (59 patients, 43.1 d) and II (54 patients, 42 d; p = 0.83). In patients with Leishmania-positive 2nd biopsies DAC N-055 caused a more rapid wound epithelialization (37.2 d vs. 58.3 d; p = 0.08). Superinfections occurred in both groups at the same rate (8.8%). Except for one patient, reulcerations (10.2% in group I, 18.5% in group II; p = 0.158) were confined to cases with persistent high parasite loads after healing. In vitro, DAC N-055 showed a leishmanicidal effect on pro- and amastigotes. Conclusions/Significance Compared to previous results with intralesional antimony injections, the EC plus MWT protocol led to more rapid wound closure. The tentatively lower rate of relapses and the acceleration of

  4. A prospective study of two methods of closing surgical scalp wounds.

    PubMed

    Adeolu, A A; Olabanji, J K; Komolafe, E O; Ademuyiwa, A O; Awe, A O; Oladele, A O

    2012-02-01

    Scalp wounds are commonly closed in two layers, although single layer closure is feasible. This study prospectively compared the two methods of closing scalp wounds. Patients with non-traumatic scalp wounds were allocated to either the single layer closure group or the multilayer closure group. We obtained relevant data from the patients. The primary outcome measures were wound edge related complications, rate of suturing and cost of sutures used for suturing. Thirty-one wounds were in the single layer closure group and 30 were in the multilayer closure group. Age range was 1-80 years. The most common indication for making a scalp incision was subdural hematoma, representing 27.8% of all the indications. The most common surgery was burr hole drainage of subdural hematoma. Polyglactin acid suture was used for the inner layer and polyamide -00- for the final layer in the multilayer closure group. Only the latter suture was used for the single layer closure method. Total cost of suturing per wound in the single layer closure group was N= 100 (0.70USD) and N= 800 (5.30USD) in the multilayer group. The mean rate of closure was 0.39 ± 1.89 mm/sec for single layer closure and 0.23 ± 0.89 mm/sec in multilayer closure. The difference was statistically significant. Wound edge related complication rate was 19.35% in the single layer closure group and 16.67% in the multilayer closure method group. The difference was not statistically significant (z: 0.00, p value: 1.000; Pearson chi-squared (DF = 1)= 0.0075, p = 0.0785). The study shows that closing the scalp in one layer is much faster and more cost effective compared to the multilayer closure method. We did not observe significant difference in the complication rates in the two methods of closure. Long-term outcome, especially cosmetic outcome, remains to be determined in this preliminary study.

  5. A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice

    PubMed Central

    Chan, Sic L.; Arumugam, Thiruma V.; Baharani, Akanksha; Tang, Sung-Chun; Yu, Qian-Sheng; Holloway, Harold W.; Wheeler, Ross; Poosala, Suresh; Greig, Nigel H.; Mattson, Mark P.

    2010-01-01

    Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA) modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily) to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions. PMID:20386608

  6. An In Vivo Screen of Secreted Proteins Identifies Adiponectin as a Regulator of Murine Cutaneous Wound Healing

    PubMed Central

    Salathia, Neeraj S; Shi, Jian; Zhang, Jay; Glynne, Richard J

    2013-01-01

    Skin wounds comprise a serious medical issue for which few pharmacological interventions are available. Moreover, the inflammatory, angiogenic, and proliferative facets of a typical response to a wound each have broader relevance in other pathological conditions. Here we describe a genomics-driven approach to identify secreted proteins that modulate wound healing in a mouse ear punch model. We show that adiponectin, when injected into the wound edge, accelerates wound healing. Notably, adiponectin injection causes upregulation of keratin gene transcripts within hours of treatment, and subsequently promotes collagen organization, formation of pilosebaceous units, and proliferation of cells in the basal epithelial cell layer and pilosebaceous units of healing tissue. The globular domain of adiponectin is sufficient to mediate accelerated dorsal skin wound closure, and the effects are lost in mice that are homozygous null for the adiponectin receptor 1 gene. These findings extend recent observations of a protective role of adiponectin in other tissue injury settings, suggest modulation of AdipoR1 for the clinical management of wounds, and demonstrate a new approach to the identification of regulators of a wound healing response. PMID:23096717

  7. Impact of Mucorales and Other Invasive Molds on Clinical Outcomes of Polymicrobial Traumatic Wound Infections

    PubMed Central

    Shaikh, Faraz; Weintrob, Amy C.; Rodriguez, Carlos J.; Murray, Clinton K.; Lloyd, Bradley A.; Ganesan, Anuradha; Aggarwal, Deepak; Carson, M. Leigh; Tribble, David R.

    2015-01-01

    Combat trauma wounds with invasive fungal infections (IFIs) are often polymicrobial with fungal and bacterial growth, but the impact of the wound microbiology on clinical outcomes is uncertain. Our objectives were to compare the microbiological features between IFI and non-IFI wounds and evaluate whether clinical outcomes differed among IFI wounds based upon mold type. Data from U.S. military personnel injured in Afghanistan with IFI wounds were examined. Controls were matched by the pattern/severity of injury, including blood transfusion requirements. Wound closure timing was compared between IFI and non-IFI control wounds (with/without bacterial infections). IFI wound closure was also assessed according to mold species isolation. Eighty-two IFI wounds and 136 non-IFI wounds (63 with skin and soft tissue infections [SSTIs] and 73 without) were examined. The time to wound closure was longer for the IFI wounds (median, 16 days) than for the non-IFI controls with/without SSTIs (medians, 12 and 9 days, respectively; P < 0.001). The growth of multidrug-resistant Gram-negative rods was reported among 35% and 41% of the IFI and non-IFI wounds with SSTIs, respectively. Among the IFI wounds, times to wound closure were significantly longer for wounds with Mucorales growth than for wounds with non-Mucorales growth (median, 17 days versus 13 days; P < 0.01). When wounds with Mucorales and Aspergillus spp. growth were compared, there was no significant difference in wound closure timing. Trauma wounds with SSTIs were often polymicrobial, yet the presence of invasive molds (predominant types: order Mucorales, Aspergillus spp., and Fusarium spp.) significantly prolonged the time to wound closure. Overall, the times to wound closure were longest for the IFI wounds with Mucorales growth. PMID:25972413

  8. Impact of Mucorales and Other Invasive Molds on Clinical Outcomes of Polymicrobial Traumatic Wound Infections.

    PubMed

    Warkentien, Tyler E; Shaikh, Faraz; Weintrob, Amy C; Rodriguez, Carlos J; Murray, Clinton K; Lloyd, Bradley A; Ganesan, Anuradha; Aggarwal, Deepak; Carson, M Leigh; Tribble, David R

    2015-07-01

    Combat trauma wounds with invasive fungal infections (IFIs) are often polymicrobial with fungal and bacterial growth, but the impact of the wound microbiology on clinical outcomes is uncertain. Our objectives were to compare the microbiological features between IFI and non-IFI wounds and evaluate whether clinical outcomes differed among IFI wounds based upon mold type. Data from U.S. military personnel injured in Afghanistan with IFI wounds were examined. Controls were matched by the pattern/severity of injury, including blood transfusion requirements. Wound closure timing was compared between IFI and non-IFI control wounds (with/without bacterial infections). IFI wound closure was also assessed according to mold species isolation. Eighty-two IFI wounds and 136 non-IFI wounds (63 with skin and soft tissue infections [SSTIs] and 73 without) were examined. The time to wound closure was longer for the IFI wounds (median, 16 days) than for the non-IFI controls with/without SSTIs (medians, 12 and 9 days, respectively; P < 0.001). The growth of multidrug-resistant Gram-negative rods was reported among 35% and 41% of the IFI and non-IFI wounds with SSTIs, respectively. Among the IFI wounds, times to wound closure were significantly longer for wounds with Mucorales growth than for wounds with non-Mucorales growth (median, 17 days versus 13 days; P < 0.01). When wounds with Mucorales and Aspergillus spp. growth were compared, there was no significant difference in wound closure timing. Trauma wounds with SSTIs were often polymicrobial, yet the presence of invasive molds (predominant types: order Mucorales, Aspergillus spp., and Fusarium spp.) significantly prolonged the time to wound closure. Overall, the times to wound closure were longest for the IFI wounds with Mucorales growth. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Early versus delayed dressing removal after primary closure of clean and clean-contaminated surgical wounds.

    PubMed

    Toon, Clare D; Lusuku, Charnelle; Ramamoorthy, Rajarajan; Davidson, Brian R; Gurusamy, Kurinchi Selvan

    2015-09-03

    Most surgical procedures involve a cut in the skin that allows the surgeon to gain access to the deeper tissues or organs. Most surgical wounds are closed fully at the end of the procedure (primary closure). The surgeon covers the closed surgical wound with either a dressing or adhesive tape. The dressing can act as a physical barrier to protect the wound until the continuity of the skin is restored (within about 48 hours) and to absorb exudate from the wound, keeping it dry and clean, and preventing bacterial contamination from the external environment. Some studies have found that the moist environment created by some dressings accelerates wound healing, although others believe that the moist environment can be a disadvantage, as excessive exudate can cause maceration (softening and deterioration) of the wound and the surrounding healthy tissue. The utility of dressing surgical wounds beyond 48 hours of surgery is, therefore, controversial. To evaluate the benefits and risks of removing a dressing covering a closed surgical incision site within 48 hours permanently (early dressing removal) or beyond 48 hours of surgery permanently with interim dressing changes allowed (delayed dressing removal), on surgical site infection. In March 2015 we searched the following electronic databases: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We also searched the references of included trials to identify further potentially-relevant trials. Two review authors independently identified studies for inclusion. We included all randomised clinical trials (RCTs) conducted with people of any age and sex, undergoing a surgical procedure, who had their wound closed and a dressing applied. We included only trials that compared

  10. Early versus delayed dressing removal after primary closure of clean and clean-contaminated surgical wounds.

    PubMed

    Toon, Clare D; Ramamoorthy, Rajarajan; Davidson, Brian R; Gurusamy, Kurinchi Selvan

    2013-09-05

    Most surgical procedures involve a cut in the skin that allows the surgeon to gain access to the deeper tissues or organs. Most surgical wounds are closed fully at the end of the procedure (primary closure). The surgeon covers the closed surgical wound with either a dressing or adhesive tape. The dressing can act as a physical barrier to protect the wound until the continuity of the skin is restored (within about 48 hours) and to absorb exudate from the wound, keeping it dry and clean, and preventing bacterial contamination from the external environment. Some studies have found that the moist environment created by some dressings accelerates wound healing, although others believe that the moist environment can be a disadvantage, as excessive exudate can cause maceration (softening and deterioration) of the wound and the surrounding healthy tissue. The utility of dressing surgical wounds beyond 48 hours of surgery is, therefore, controversial. To evaluate the benefits and risks of removing a dressing covering a closed surgical incision site within 48 hours permanently (early dressing removal) or beyond 48 hours of surgery permanently with interim dressing changes allowed (delayed dressing removal), on surgical site infection. In July 2013 we searched the following electronic databases: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We also searched the references of included trials to identify further potentially-relevant trials. Two review authors independently identified studies for inclusion. We included all randomised clinical trials (RCTs) conducted with people of any age and sex, undergoing a surgical procedure, who had their wound closed and a dressing applied. We included only trials that compared

  11. Is adhesive paper-tape closure of video assisted thoracoscopic port-sites safe?

    PubMed

    Luckraz, Heyman; Rammohan, Kandadai S; Phillips, Mabel; O'Keefe, Peter A

    2007-07-01

    Video assisted thoracoscopic surgery (VATS) is used in lung surgery for diagnostic, staging, curative and palliative purposes. The port-sites are usually sutured with dissolvable sutures. The use of adhesive paper-tape for port-site closure was assessed by a prospective randomised double-blind control trial comparing sutured to adhesive paper-tape closure. The following outcomes were assessed: incidence of clinically significant pneumothorax, wound healing using the ASEPSIS score, patient's comfort (pain score using a visual analog score), the time difference between the two techniques of wound closure and cost savings. Thirty patients were recruited in each group. No clinically significant pneumothoraces occurred in either group. There were no significant differences between the two groups in terms of immediate post-operative pain scores, wound cosmesis and wound complications. It was quicker to close the wound with adhesive paper-tape with a mean time of closure per unit length of wound of 9.3 and 2.2s/mm for the groups, respectively. The cost for wound closure (per patient) was $0.8 for the adhesive paper-tape group and $4.00 for the sutures.

  12. Negative Pressure Wound Therapy in the Management of Combat Wounds: A Critical Review

    PubMed Central

    Maurya, Sanjay; Bhandari, Prem Singh

    2016-01-01

    Significance: Wounds sustained in a combat trauma often result in a composite tissue loss. Combat injuries, due to high energy transfer to tissues, lead to trauma at multiple anatomical sites. An early wound cover is associated with lower rate of infections and a faster wound healing. The concept of negative pressure wound therapy (NPWT) in the management of combat-related wounds has evolved from the civilian trauma and the wounds from nontraumatic etiologies. Recent Advances: Encouraged by the results of NPWT in noncombat-related wounds, the military surgeons during Operation Iraqi Freedom and Operation Enduring Freedom used this novel method in a large percentage of combat wounds, with gratifying results. The mechanism of NPWT in wound healing is multifactorial and often complex reconstructive procedure can be avoided in a combat trauma setting. Critical Issues: Wounds sustained in military trauma are heavily contaminated with dirt, patient clothing, and frequently associated with extensive soft tissue loss and osseous destruction. Delay in evacuation during an ongoing conflict carries the risk of systemic infection. Early debridement is indicated followed by delayed closure of wounds. NPWT helps to provide temporary wound cover during the interim period of debridement and wound closure. Future Directions: Future area of research in combat wounds is related to abdominal trauma with loss of abdominal wall. The concept of negative pressure incisional management system in patients with a high risk of wound breakdown following surgery is under review, and may be of relevance in combat wounds. PMID:27679749

  13. Negative Pressure Wound Therapy in the Management of Combat Wounds: A Critical Review.

    PubMed

    Maurya, Sanjay; Bhandari, Prem Singh

    2016-09-01

    Significance: Wounds sustained in a combat trauma often result in a composite tissue loss. Combat injuries, due to high energy transfer to tissues, lead to trauma at multiple anatomical sites. An early wound cover is associated with lower rate of infections and a faster wound healing. The concept of negative pressure wound therapy (NPWT) in the management of combat-related wounds has evolved from the civilian trauma and the wounds from nontraumatic etiologies. Recent Advances: Encouraged by the results of NPWT in noncombat-related wounds, the military surgeons during Operation Iraqi Freedom and Operation Enduring Freedom used this novel method in a large percentage of combat wounds, with gratifying results. The mechanism of NPWT in wound healing is multifactorial and often complex reconstructive procedure can be avoided in a combat trauma setting. Critical Issues: Wounds sustained in military trauma are heavily contaminated with dirt, patient clothing, and frequently associated with extensive soft tissue loss and osseous destruction. Delay in evacuation during an ongoing conflict carries the risk of systemic infection. Early debridement is indicated followed by delayed closure of wounds. NPWT helps to provide temporary wound cover during the interim period of debridement and wound closure. Future Directions: Future area of research in combat wounds is related to abdominal trauma with loss of abdominal wall. The concept of negative pressure incisional management system in patients with a high risk of wound breakdown following surgery is under review, and may be of relevance in combat wounds.

  14. EASApprox® skin-stretching system: A secure and effective method to achieve wound closure.

    PubMed

    Song, Mingzhi; Zhang, Zhen; Liu, Tao; Liu, Song; Li, Gang; Liu, Zhaochang; Huang, Jingyang; Chen, Song; Li, Linan; Guo, Li; Qiu, Yang; Wan, Jiajia; Liu, Yuejian; Wu, Tao; Wang, Xiaoyong; Lu, Ming; Wang, Shouyu

    2017-07-01

    Large skin defects are commonly observed in the clinic and have attracted much attention recently. Therefore, finding an effective solution for large skin defects is a global problem. The objective of the present study was to assess the effectiveness of the EASApprox ® skin-stretching system for closing large skin defects. Skin defects (5×5 cm) were created on the forearms of 9 Bama miniature pigs, which were randomly divided into the following three groups: Direct suture, the new EASApprox ® skin-stretching device and Kirschner wires. Microcirculation was assessed before surgery and after wound closure. Following the different treatments, the defects were sutured, and wound healing was assessed based on a clinical score. Furthermore, microscopic and ultramicroscopic structures were evaluated, including collagen, elastic fibers and the microvessel density. Significant differences in the clinical score and microvessel density were observed among the groups. Additionally, the mean length obtained for elastic fibers was larger than that obtained for the other two groups. Finally, the new EASApprox ® skin-stretching device resulted in successful wound management and with only minor side effects on skin histology and microcirculation. Therefore, this method has the potential to be used for healing large skin defects.

  15. Flax Fiber Hydrophobic Extract Inhibits Human Skin Cells Inflammation and Causes Remodeling of Extracellular Matrix and Wound Closure Activation

    PubMed Central

    Styrczewska, Monika; Kostyn, Anna; Kulma, Anna; Majkowska-Skrobek, Grazyna; Augustyniak, Daria; Prescha, Anna; Czuj, Tadeusz; Szopa, Jan

    2015-01-01

    Inflammation is the basis of many diseases, with chronic wounds amongst them, limiting cell proliferation and tissue regeneration. Our previous preclinical study of flax fiber applied as a wound dressing and analysis of its components impact on the fibroblast transcriptome suggested flax fiber hydrophobic extract use as an anti-inflammatory and wound healing preparation. The extract contains cannabidiol (CBD), phytosterols, and unsaturated fatty acids, showing great promise in wound healing. In in vitro proliferation and wound closure tests the extract activated cell migration and proliferation. The activity of matrix metalloproteinases in skin cells was increased, suggesting activation of extracellular components remodeling. The expression of cytokines was diminished by the extract in a cannabidiol-dependent manner, but β-sitosterol can act synergistically with CBD in inflammation inhibition. Extracellular matrix related genes were also analyzed, considering their importance in further stages of wound healing. The extract activated skin cell matrix remodeling, but the changes were only partially cannabidiol- and β-sitosterol-dependent. The possible role of fatty acids also present in the extract is suggested. The study shows the hydrophobic flax fiber components as wound healing activators, with anti-inflammatory cannabidiol acting in synergy with sterols, and migration and proliferation promoting agents, some of which still require experimental identification. PMID:26347154

  16. Differential effects of Losartan and Atorvastatin in partial and full thickness burn wounds

    PubMed Central

    Akershoek, Johanneke J.; Brouwer, Katrien M.; Vlig, Marcel; Boekema, Bouke K. H. L.; Beelen, Rob H. J.; Middelkoop, Esther

    2017-01-01

    Healing of burn wounds is often associated with scar formation due to excessive inflammation and delayed wound closure. To date, no effective treatment is available to prevent the fibrotic process. The Renin Angiotensin System (RAS) was shown to be involved in fibrosis in various organs. Statins (e.g. Atorvastatin), Angiotensin receptor antagonists (e.g. Losartan) and the combination of these drugs are able to reduce the local RAS activation, and reduced fibrosis in other organs. We investigated whether inhibition of the RAS could improve healing of burn wounds by treatment with Atorvastatin, Losartan or the combination of both drugs. Therefore, full and partial thickness burn wounds were inflicted on both flanks of Yorkshire pigs. Oral administration of Atorvastatin, Losartan or the combination was started at post-burn day 1 and continued for 28 days. Full thickness wounds were excised and transplanted with an autologous meshed split-thickness skin graft at post-burn day 14. Partial thickness wounds received conservative treatment. Atorvastatin treatment resulted in enhanced graft take and wound closure of the full thickness wounds, faster resolution of neutrophils compared to all treatments and reduced alpha-smooth muscle actin positive cells compared to control treatment. Treatment with Losartan and to a lesser extent the combination therapy resulted in diminished graft take, increased wound contraction and poorer scar outcome. In contrast, Losartan treatment in partial thickness wounds decreased the alpha-smooth muscle actin+ fibroblasts and contraction. In conclusion, we showed differential effects of Losartan and Atorvastatin in full and partial thickness wounds. The extensive graft loss seen in Losartan treated wounds is most likely responsible for the poor clinical outcome of these full thickness burn wounds. Therefore, Losartan treatment should not be started before transplantation in order to prevent graft loss. Atorvastatin seems to accelerate the

  17. Differential effects of Losartan and Atorvastatin in partial and full thickness burn wounds.

    PubMed

    Akershoek, Johanneke J; Brouwer, Katrien M; Vlig, Marcel; Boekema, Bouke K H L; Beelen, Rob H J; Middelkoop, Esther; Ulrich, Magda M W

    2017-01-01

    Healing of burn wounds is often associated with scar formation due to excessive inflammation and delayed wound closure. To date, no effective treatment is available to prevent the fibrotic process. The Renin Angiotensin System (RAS) was shown to be involved in fibrosis in various organs. Statins (e.g. Atorvastatin), Angiotensin receptor antagonists (e.g. Losartan) and the combination of these drugs are able to reduce the local RAS activation, and reduced fibrosis in other organs. We investigated whether inhibition of the RAS could improve healing of burn wounds by treatment with Atorvastatin, Losartan or the combination of both drugs. Therefore, full and partial thickness burn wounds were inflicted on both flanks of Yorkshire pigs. Oral administration of Atorvastatin, Losartan or the combination was started at post-burn day 1 and continued for 28 days. Full thickness wounds were excised and transplanted with an autologous meshed split-thickness skin graft at post-burn day 14. Partial thickness wounds received conservative treatment. Atorvastatin treatment resulted in enhanced graft take and wound closure of the full thickness wounds, faster resolution of neutrophils compared to all treatments and reduced alpha-smooth muscle actin positive cells compared to control treatment. Treatment with Losartan and to a lesser extent the combination therapy resulted in diminished graft take, increased wound contraction and poorer scar outcome. In contrast, Losartan treatment in partial thickness wounds decreased the alpha-smooth muscle actin+ fibroblasts and contraction. In conclusion, we showed differential effects of Losartan and Atorvastatin in full and partial thickness wounds. The extensive graft loss seen in Losartan treated wounds is most likely responsible for the poor clinical outcome of these full thickness burn wounds. Therefore, Losartan treatment should not be started before transplantation in order to prevent graft loss. Atorvastatin seems to accelerate the

  18. Assessment of platelet-derived growth factor using A splinted full thickness dermal wound model in bearded dragons (Pogona vitticeps).

    PubMed

    Keller, Krista A; Paul-Murphy, Joanne; Weber, E P Scott; Kass, Philip H; Guzman, Sanchez-Migallon David; Park, Shin Ae; Raghunathan, Vijay Krishna; Gustavsen, Kate A; Murphy, Christopher J

    2014-12-01

    Wounds in reptiles are a common reason for presentation to a veterinarian. At this time there is limited information on effective topical medications to aid in wound closure. The objectives of this study were to translate the splinted, full-thickness dermal wound model, validated in mice, to the bearded dragon (Pogona vitticeps) and to determine the effect of topical becaplermin (BP), a platelet-derived growth factor (0.01%), on the rate of wound closure. Ten bearded dragons were anesthetized and two full-thickness cutaneous wounds were made on the dorsum of each lizard. Encircling splints were applied surrounding each wound and subsequently covered by a semi-occlusive dressing. Five lizards had one wound treated with BP and the adjacent wound treated with a vehicle control. Five additional lizards had one wound treated with saline and the second wound treated with a vehicle control. Wounds were imaged daily, and the wound area was measured using digital image analysis. The change in percentage wound closure over 17 days and the time to 50% wound closure was compared among the four treatment groups. There was no significant difference in wound closure rates between BP-treated and saline-treated wounds or in the time to 50% wound closure between any treatments. Vehicle-treated wounds adjacent to saline-treated wounds closed significantly slower than did BP (P < 0.010), saline (P < 0.001), and vehicle-treated wounds adjacent to BP-treated wounds (P < 0.013). Our preliminary study indicates that the splinted wound model, with modifications, may be used to determine wound closure rates in bearded dragons. When compared with saline, BP did not have a significant effect on wound closure rates, while the vehicle alone delayed wound closure. Histologic analysis of experimentally created wounds throughout the wound healing process is needed to further evaluate the effects of these treatments on reptile dermal wound healing.

  19. Honey: an immunomodulator in wound healing.

    PubMed

    Majtan, Juraj

    2014-01-01

    Honey is a popular natural product that is used in the treatment of burns and a broad spectrum of injuries, in particular chronic wounds. The antibacterial potential of honey has been considered the exclusive criterion for its wound healing properties. The antibacterial activity of honey has recently been fully characterized in medical-grade honeys. Recently, the multifunctional immunomodulatory properties of honey have attracted much attention. The aim of this review is to provide closer insight into the potential immunomodulatory effects of honey in wound healing. Honey and its components are able to either stimulate or inhibit the release of certain cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6) from human monocytes and macrophages, depending on wound condition. Similarly, honey seems to either reduce or activate the production of reactive oxygen species from neutrophils, also depending on the wound microenvironment. The honey-induced activation of both types of immune cells could promote debridement of a wound and speed up the repair process. Similarly, human keratinocytes, fibroblasts, and endothelial cell responses (e.g., cell migration and proliferation, collagen matrix production, chemotaxis) are positively affected in the presence of honey; thus, honey may accelerate reepithelization and wound closure. The immunomodulatory activity of honey is highly complex because of the involvement of multiple quantitatively variable compounds among honeys of different origins. The identification of these individual compounds and their contributions to wound healing is crucial for a better understanding of the mechanisms behind honey-mediated healing of chronic wounds. © 2014 by the Wound Healing Society.

  20. Topical erythropoietin promotes wound repair in diabetic rats.

    PubMed

    Hamed, Saher; Ullmann, Yehuda; Masoud, Muhannad; Hellou, Elias; Khamaysi, Ziad; Teot, Luc

    2010-01-01

    Wound healing in diabetic patients is slower than in healthy individuals. Erythropoietin (EPO) has non-hemopoietic targets in the skin, and systemically administered EPO promotes wound healing in experimental animals. This study investigated the effect of topical EPO treatment on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 38 rats, of which 30 had diabetes. The wounds were then treated topically with a cream that contained either vehicle, 600 IU ml(-1) EPO (low dose), or 3,000 IU ml(-1) (high dose) EPO. We assessed the rate of wound closure during the 12-day treatment period, and microvascular density (MVD), vascular endothelial growth factor (VEGF), and hydroxyproline (HP) contents, and the extent of apoptosis in wound tissues at the end of the 12-day treatment period. Topical EPO treatment significantly reduced the time to final wound closure. This increased rate of closure of the two EPO-treated wounds in diabetic rats was associated with increased MVD, VEGF, and HP contents, and a reduced extent of apoptosis. In light of our finding that topical EPO treatment promotes skin wound repair in diabetic rats, we propose that topical EPO treatment is a therapeutically beneficial method of treating chronic diabetic wounds.

  1. Greater Success of Primary Fascial Closure of the Open Abdomen: A Retrospective Study Analyzing Applied Surgical Techniques, Success of Fascial Closure, and Variables Affecting the Results.

    PubMed

    Kääriäinen, M; Kuuskeri, M; Helminen, M; Kuokkanen, H

    2017-06-01

    The open abdomen technique is a standard procedure in the treatment of intra-abdominal catastrophe. Achieving primary abdominal closure within the initial hospitalization is a main objective. This study aimed to analyze the success of closure rate and the effect of negative pressure wound therapy, mesh-mediated medial traction, and component separation on the results. We present the treatment algorithm used in our institution in open abdomen situations based on these findings. Open abdomen patients (n = 61) treated in Tampere University Hospital from May 2005 until October 2013 were included in the study. Patient characteristics, treatment prior to closure, closure technique, and results were retrospectively collected and analyzed. The first group included patients in whom direct or bridged fascial closure was achieved, and the second group included those in whom only the skin was closed or a free skin graft was used. Background variables and variables related to surgery were compared between groups. Most of the open abdomen patients (72.1%) underwent fascial defect repair during the primary hospitalization, and 70.5% of them underwent direct fascial closure. Negative pressure wound therapy was used as a temporary closure method for 86.9% of the patients. Negative pressure wound therapy combined with mesh-mediated medial traction resulted in the shortest open abdomen time (p = 0.039) and the highest fascial repair rate (p = 0.000) compared to negative pressure wound therapy only or no negative pressure wound therapy. The component separation technique was used for 11 patients; direct fascial closure was achieved in 5 and fascial repair by bridging the defect with mesh was achieved in 6. A total of 8 of 37 (21.6%) patients with mesh repair had a mesh infection. The negative pressure wound therapy combined with mesh-mediated medial traction promotes definitive fascial closure with a high closure rate and a shortened open abdomen time. The component

  2. Gender Affects Skin Wound Healing in Plasminogen Deficient Mice

    PubMed Central

    Rønø, Birgitte; Engelholm, Lars Henning; Lund, Leif Røge; Hald, Andreas

    2013-01-01

    The fibrinolytic activity of plasmin plays a fundamental role in resolution of blood clots and clearance of extravascular deposited fibrin in damaged tissues. These vital functions of plasmin are exploited by malignant cells to accelerate tumor growth and facilitate metastases. Mice lacking functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds revealed larger amounts of fibrotic scars in the provisional matrix of plasmin deficient male mice compared to female mice. These fibrotic scars correlated to an obstruction of cell infiltration of the granulation tissue, which is a prerequisite for wound healing. In conclusion, the presented data show that the gender dependent effect of plasmin deficiency is tissue specific and may be secondary to already established differences between genders, such as skin thickness and

  3. Abdominal wall integrity after open abdomen: long-term results of vacuum-assisted wound closure and mesh-mediated fascial traction (VAWCM).

    PubMed

    Willms, A; Schaaf, S; Schwab, R; Richardsen, I; Bieler, D; Wagner, B; Güsgen, C

    2016-12-01

    The open abdomen has become a standard technique in the management of critically ill patients undergoing surgery for severe intra-abdominal conditions. Negative pressure and mesh-mediated fascial traction are commonly used and achieve low fistula rates and high fascial closure rates. In this study, long-term results of a standardised treatment approach are presented. Fifty-five patients who underwent OA management for different indications at our institution from 2006 to 2013 were enrolled. All patients were treated under a standardised algorithm that uses a combination of vacuum-assisted wound closure and mesh-mediated fascial traction. Structured follow-up assessments were offered to patients and included a medical history, a clinical examination and abdominal ultrasonography. The data obtained were statistically analysed. The fascial closure rate was 74 % in an intention-to-treat analysis and 89 % in a per-protocol analysis. The fistula rate was 1.8 %. Thirty-four patients attended follow-up. The median follow-up was 46 months (range 12-88 months). Incisional hernias developed in 35 %. Patients with hernias needed more operative procedures (10.3 vs 3.4, p = 0.03) than patients without hernia formation. A Patient Observer Scar Assessment Scale (POSAS) of 31.1 was calculated. Patients with symptomatic hernias (NAS of 2-10) had a significantly lower mean POSAS score (p = 0.04). Vacuum-assisted wound closure and mesh-mediated fascial traction (VAWCM) seem to result in low complication rates and high fascial closure rates. Abdominal wall reconstruction, which is a challenging and complex procedure and causes considerable patient discomfort, can thus be avoided in the majority of cases. Available results are based on studies involving only a small number of cases. Multi-centre studies and registry-based data are therefore needed to validate these findings.

  4. Early controlled release of peroxisome proliferator-activated receptor β/δ agonist GW501516 improves diabetic wound healing through redox modulation of wound microenvironment.

    PubMed

    Wang, Xiaoling; Sng, Ming Keat; Foo, Selin; Chong, Han Chung; Lee, Wei Li; Tang, Mark Boon Yang; Ng, Kee Woei; Luo, Baiwen; Choong, Cleo; Wong, Marcus Thien Chong; Tong, Benny Meng Kiat; Chiba, Shunsuke; Loo, Say Chye Joachim; Zhu, Pengcheng; Tan, Nguan Soon

    2015-01-10

    Diabetic wounds are imbued with an early excessive and protracted reactive oxygen species production. Despite the studies supporting PPARβ/δ as a valuable pharmacologic wound-healing target, the therapeutic potential of PPARβ/δ agonist GW501516 (GW) as a wound healing drug was never investigated. Using topical application of polymer-encapsulated GW, we revealed that different drug release profiles can significantly influence the therapeutic efficacy of GW and consequently diabetic wound closure. We showed that double-layer encapsulated GW microparticles (PLLA:PLGA:GW) provided an earlier and sustained dose of GW to the wound and reduced the oxidative wound microenvironment to accelerate healing, in contrast to single-layered PLLA:GW microparticles. The underlying mechanism involved an early GW-mediated activation of PPARβ/δ that stimulated GPx1 and catalase expression in fibroblasts. GPx1 and catalase scavenged excessive H2O2 accumulation in diabetic wound beds, prevented H2O2-induced ECM modification and facilitated keratinocyte migration. The microparticles with early and sustained rate of GW release had better therapeutic wound healing activity. The present study underscores the importance of drug release kinetics on the therapeutic efficacy of the drug and warrants investigations to better appreciate the full potential of controlled drug release. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Tissue adhesives for closure of surgical incisions.

    PubMed

    Coulthard, P; Worthington, H; Esposito, M; Elst, M; Waes, O J F

    2004-01-01

    Sutures, staples and adhesive tapes are the traditional methods of wound closure, whilst tissue adhesives have entered clinical practice more recently. Closure of wounds with sutures enables meticulous closure, but sutures may induce tissue reactivity and they usually require removal. Tissue adhesives offer the advantages there are no sutures to remove later for the patient and no risk of needlestick injury to the surgeon. Tissue adhesives have been used primarily in emergency rooms but this review looks at the use of tissue adhesives in the operating room where surgeons are increasingly using these for the closure of surgical skin incisions. To determine the relative effects of various tissue adhesives and conventional skin closure techniques on the healing of surgical wounds. The Cochrane Wounds Group Specialised Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched. Bibliographies of review articles were checked for studies outside the handsearched journals and wound care product manufacturers were contacted. Randomised controlled clinical trials only. Screening of eligible studies and data extraction was conducted independently and in triplicate whilst assessment of the methodological quality of the trials was conducted independently and in duplicate. Results were expressed as random effect models using weighted mean differences for continuous outcomes and relative risk with 95% confidence intervals for dichotomous outcomes. Heterogeneity was investigated including both clinical and methodological factors. Eight RCTs were included (630 patients). No statistically significant differences were found between various tissue adhesives and sutures (8 trials) for dehiscence, infection, satisfaction with cosmetic appearance when assessed by patients' or surgeons' general satisfaction. Nor were differences found between a tissue adhesive and tapes (2 trials) for infection, patients' assessment of cosmetic

  6. Stimulation of skin and wound fibroblast migration by mesenchymal stem cells derived from normal donors and chronic wound patients.

    PubMed

    Rodriguez-Menocal, Luis; Salgado, Marcela; Ford, Dwayne; Van Badiavas, Evangelos

    2012-03-01

    Chronic wounds continue to be a major cause of morbidity for patients and an economic burden on the health care system. Novel therapeutic approaches to improved wound healing will need, however, to address cellular changes induced by a number of systemic comorbidities seen in chronic wound patients, such as diabetes, chronic renal failure, and arterial or venous insufficiency. These effects likely include impaired inflammatory cell migration, reduced growth factor production, and poor tissue remodeling. The multifunctional properties of bone marrow-derived mesenchymal stem cells (MSCs), including their ability to differentiate into various cell types and capacity to secrete factors important in accelerating healing of cutaneous wounds, have made MSCs a promising agent for tissue repair and regeneration. In this study we have used an in vitro scratch assay procedure incorporating labeled MSCs and fibroblasts derived from normal donors and chronic wound patients in order to characterize the induction of mobilization when these cells are mixed. A modified Boyden chamber assay was also used to examine the effect of soluble factors on fibroblast migration. These studies suggest that MSCs play a role in skin wound closure by affecting dermal fibroblast migration in a dose-dependent manner. Deficiencies were noted, however, in chronic wound patient fibroblasts and MSCs as compared with those derived from normal donors. These findings provide a foundation to develop therapies targeted specifically to the use of bone marrow-derived MSCs in wound healing and may provide insight into why some wounds do not heal.

  7. Arginase inhibition promotes wound healing in mice.

    PubMed

    Kavalukas, Sandra L; Uzgare, Aarti R; Bivalacqua, Trinity J; Barbul, Adrian

    2012-02-01

    Arginase plays important regulatory roles in polyamine, ornithine, and nitric oxide syntheses. However, its role in the healing process has not been delineated. In this study, we used a highly potent and specific inhibitor of arginase, namely 2(S)-amino-6-boronohexanoic acid NH4 (ABH) to evaluate the role of arginase function in wound healing. ABH or saline was applied topically to full thickness, dorsal, excisional wounds in C57BL/6 mice every 8 hours for 14 days post surgery and the rate of wound closure was estimated planimetrically. Wound tissue was harvested from mice sacrificed on postoperative days 3 and 7 and examined histologically. The extent of epithelial, connective, and granulation tissue present within the wound area was estimated histomorphometrically. The effect of ABH on wound arginase activity, production of nitric oxide metabolites (NO(x)), and presence of smooth muscle actin positive cells (myofibroblasts) was evaluated. While arginase activity was inhibited in vivo, the rate of wound closure significantly increased 7 days post-surgery, (21 ± 4%: P < .01; Student t test) in ABH treated animals. This was accompanied by an early increase in wound granulation tissue and accumulation of NO(x) followed by enhanced re-epithelialization and localization of myofibroblasts beneath the wound epithelium. Arginase inhibition improves excisional wound healing and may be used to develop therapeutics for early wound closure. Copyright © 2012 Mosby, Inc. All rights reserved.

  8. Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing

    PubMed Central

    Spitler, Ryan; Ho, Hsiang; Norpetlian, Frederique; Kong, Xiangduo; Jiang, Jingjing; Yokomori, Kyoko; Andersen, Bogi; Boss, Gerry R.; Berns, Michael W.

    2015-01-01

    Abstract. Low level light therapy (LLLT) has numerous therapeutic benefits, including improving wound healing, but the precise mechanisms involved are not well established; in particular, the underlying role of cytochrome C oxidase (C-ox) as the primary photoacceptor and the associated biochemical mechanisms still require further investigation. We previously showed the nitric oxide (NO) donating drug nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT-enhanced wound healing proceeded through an electron transport chain-C-ox-dependent mechanism with a reduction of reactive oxygen species and increased adenosine triphosphate production. C-ox was validated as the primary photoacceptor by three observations: increased oxygen consumption, reduced wound healing in the presence of sodium azide, and disassociation of cyanide, a known C-ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound healing through two independent mechanisms, the electron transport chain-C-ox pathway and cGMP signaling, respectively, with both resulting in ERK1/2 activation. PMID:25562608

  9. Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing

    NASA Astrophysics Data System (ADS)

    Spitler, Ryan; Ho, Hsiang; Norpetlian, Frederique; Kong, Xiangduo; Jiang, Jingjing; Yokomori, Kyoko; Andersen, Bogi; Boss, Gerry R.; Berns, Michael W.

    2015-05-01

    Low level light therapy (LLLT) has numerous therapeutic benefits, including improving wound healing, but the precise mechanisms involved are not well established; in particular, the underlying role of cytochrome C oxidase (C-ox) as the primary photoacceptor and the associated biochemical mechanisms still require further investigation. We previously showed the nitric oxide (NO) donating drug nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT-enhanced wound healing proceeded through an electron transport chain-C-ox-dependent mechanism with a reduction of reactive oxygen species and increased adenosine triphosphate production. C-ox was validated as the primary photoacceptor by three observations: increased oxygen consumption, reduced wound healing in the presence of sodium azide, and disassociation of cyanide, a known C-ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound healing through two independent mechanisms, the electron transport chain-C-ox pathway and cGMP signaling, respectively, with both resulting in ERK1/2 activation.

  10. Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing.

    PubMed

    Spitler, Ryan; Ho, Hsiang; Norpetlian, Frederique; Kong, Xiangduo; Jiang, Jingjing; Yokomori, Kyoko; Andersen, Bogi; Boss, Gerry R; Berns, Michael W

    2015-05-01

    Low level light therapy (LLLT) has numerous therapeutic benefits, including improving wound healing, but the precise mechanisms involved are not well established; in particular, the underlying role of cytochrome C oxidase (C-ox) as the primary photoacceptor and the associated biochemical mechanisms still require further investigation. We previously showed the nitric oxide (NO) donating drug nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT-enhanced wound healing proceeded through an electron transport chain-C-ox-dependent mechanism with a reduction of reactive oxygen species and increased adenosine triphosphate production. C-ox was validated as the primary photoacceptor by three observations: increased oxygen consumption, reduced wound healing in the presence of sodium azide, and disassociation of cyanide, a known C-ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound healing through two independent mechanisms, the electron transport chain-C-ox pathway and cGMP signaling, respectively, with both resulting in ERK1/2 activation.

  11. Combined effect of substance P and curcumin on cutaneous wound healing in diabetic rats.

    PubMed

    Kant, Vinay; Kumar, Dinesh; Prasad, Raju; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surender K

    2017-05-15

    Our earlier studies demonstrated that topically applied substance P (SP) or curcumin on excision skin wound accelerated the wound healing in streptozotocin-induced diabetic rats. In the present study, we aimed to evaluate the wound healing potential of combination of SP and curcumin in diabetic rats. Open cutaneous excision wound was created on the back of each of the 60 diabetic rats. Wound-inflicted rats were equally divided into three groups namely, control, gel treated, and SP + curcumin treated. Normal saline, pluronic gel, and SP (0.5 × 10 -6 M) + curcumin (0.15%) were topically applied once daily for 19 d to these control, gel-treated, and SP + curcumin groups, respectively. SP + curcumin combination significantly accelerated wound closure and decreased messenger RNA expressions of tumor necrosis factor-alpha, interleukin-1beta, and matrix metalloproteinase-9, whereas the combination markedly increased the expressions of interleukin-10, vascular endothelial growth factor, transforming growth factor-beta1, hypoxia-inducible factor 1-alpha, stromal cell-derived factors-1alpha, heme oxygenase-1 and endothelial nitric oxide synthase, and activities of superoxide dismutase, catalase, and glutathione peroxidase in granulation-healing tissue, compared with control and gel-treated groups. In combination group, granulation tissue was better, as was evidenced by improved fibroblast proliferation, collagen deposition, microvessel density, growth-associated protein 43-positive nerve fibers, and thick regenerated epithelial layer. The combination of SP and curcumin accelerated wound healing in diabetic rats and both the drugs were compatible at the doses used in this study. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Comparison of Negative Pressure Wound Therapy and Silver-Coated Foam Dressings in Open Wound Treatment in Dogs: A Prospective Controlled Clinical Trial.

    PubMed

    Nolff, Mirja C; Albert, Rebecca; Reese, Sven; Meyer-Lindenberg, Andrea

    2018-06-11

     To evaluate negative pressure wound therapy (NPWT) for treatment of complicated wounds in dogs.  Prospective randomized clinical study MATERIALS AND METHODS:  Dogs ( n  = 26) undergoing open-wound treatment were randomly assigned to one of two groups: Group A ( n  = 13) NPWT; Group B ( n  = 13) silver-coated foam dressing. Pairs of patients were matched based on wound conformation, localization, and underlying cause and compared in terms of duration of previous treatment, development of wound size (wound planimetry), time to closure, bacterial bio-burden and complications. Wound dressing changes were performed every 3 days during the first 9 days of therapy for both groups. Statistical analysis was performed.  Pre-treatment signalment and bacterial status were comparable between groups. Total time to closure was significantly ( p  = 0.018) shorter in Group A (14.2 days) compared with Group B (28.6 days), and wound planimetry on days 3, 6 and 9 showed significant greater reduction in total wound area for Group A at all-time points ( p  < 0.05). Furthermore, wounds in Group A showed less progression of local infection than did wounds in Group B ( p  = 0.01).  NPWT-treated wounds showed faster closure, improved macro-deformation and less local signs of infection. Schattauer GmbH Stuttgart.

  13. The accelerating effect of chitosan-silica hybrid dressing materials on the early phase of wound healing.

    PubMed

    Park, Ji-Ung; Jung, Hyun-Do; Song, Eun-Ho; Choi, Tae-Hyun; Kim, Hyoun-Ee; Song, Juha; Kim, Sukwha

    2017-10-01

    Commercialized dressing materials with or without silver have played a passive role in early-phase wound healing, protecting the skin defects from infections, absorbing exudate, and preventing dehydration. Chitosan (CTS)-based sponges have been developed in pure or hybrid forms for accelerating wound healing, but their wound-healing capabilities have not been extensively compared with widely used commercial dressing materials, providing limited information in a practical aspect. In this study, we have developed CTS-silica (CTS-Si) hybrid sponges with water absorption, flexibility, and mechanical behavior similar to those of CTS sponges. In vitro and in vivo tests were performed to compare the CTS-Si sponges with three commercial dressing materials [gauze, polyurethane (PU), and silver-containing hydrofiber (HF-Ag)] in addition to CTS sponges. Both in vitro and in vivo tests showed that CTS-Si sponges promoted fibroblast proliferation, leading to accelerated collagen synthesis, whereas the CTS sponges did not exhibit significant differences in fibroblast proliferation and collagen synthesis from gauze, PU, and HF-Ag sponges. In case of CTS-Si, the inflammatory cells were actively recruited to the wound by the influence of the released silicon ions from CTS-Si sponges, which, in return, led to an enhanced secretion of growth factors, particularly TGF-β during the early stage. The higher level of TGF-β likely improved the proliferation of fibroblasts, and as a result, collagen synthesis by fibroblasts became remarkably productive, thereby increasing collagen density at the wound site. Therefore, the CTS-Si hybrid sponges have considerable potential as a wound-dressing material for accelerating wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1828-1839, 2017. © 2016 Wiley Periodicals, Inc.

  14. [Effect of taspine hydrochloride on skin wound healing in rats and its mechanism].

    PubMed

    Dong, Ya-Lin; He, Lang-Chong; Wang, Huai-Hui; You, Hai-Sheng; Wu, Jiao-Feng

    2005-09-01

    To study the effect of taspine hydrochloride (TA/HCl) on skin wound healing in rats and its mechanism. Bilateral round wounds were made on the backs of SD rats. The effect of TA/HCl on the skin wound was evaluated through determining closure time and contracting ability of the skin wound, observing histopathological characteristics and measuring contents of hydroxyproline (Hyp) and protein in the wound tissue. The closure time of the skin wounds was significantly shorter in the TA/HCl-treated groups than that in the model group. The percentages of wound contraction were higher in the TA/HCl-treated groups than that in the dimethyl sulfoxide (DMSO) control group of the same group (P<0.05 or P<0.01) on the 3rd to 14th days after wounding. The content of the protein in the wound tissue in the TA/HCl-treated group (2 mg/ml) was higher than that in the model group (P<0.05) on the 3rd to 7th days after wounding, and it arrived at the peak on the 7th day and gradually decreased to the normal level in skin tissue on the 14th to 21st days after wounding. The contents of Hyp in the wound tissues in the TA/HCl-treated groups were higher than that in the model group (P<0.05 or P<0.015) on the 3rd to 21st days after wounding, and they arrived at the peak on the 14th day and at the normal level in skin tissue on the 21st day. Histopathological test results showed that TA/HCl could promote the formation of newly born capillaries in the early period of the wound healing. TA/HCl has the ability of promoting skin wound healing in rats, and it can also accelerate the growth of newly born capillaries and raise the production of protein and collagen in wound tissue.

  15. Oral Administration of Linoleic Acid Induces New Vessel Formation and Improves Skin Wound Healing in Diabetic Rats.

    PubMed

    Rodrigues, Hosana G; Vinolo, Marco A R; Sato, Fabio T; Magdalon, Juliana; Kuhl, Carolina M C; Yamagata, Ana S; Pessoa, Ana Flávia M; Malheiros, Gabriella; Dos Santos, Marinilce F; Lima, Camila; Farsky, Sandra H; Camara, Niels O S; Williner, Maria R; Bernal, Claudio A; Calder, Philip C; Curi, Rui

    2016-01-01

    Impaired wound healing has been widely reported in diabetes. Linoleic acid (LA) accelerates the skin wound healing process in non-diabetic rats. However, LA has not been tested in diabetic animals. We investigated whether oral administration of pure LA improves wound healing in streptozotocin-induced diabetic rats. Dorsal wounds were induced in streptozotocin-induced type-1 diabetic rats treated or not with LA (0.22 g/kg b.w.) for 10 days. Wound closure was daily assessed for two weeks. Wound tissues were collected at specific time-points and used to measure fatty acid composition, and contents of cytokines, growth factors and eicosanoids. Histological and qPCR analyses were employed to examine the dynamics of cell migration during the healing process. LA reduced the wound area 14 days after wound induction. LA also increased the concentrations of cytokine-induced neutrophil chemotaxis (CINC-2αβ), tumor necrosis factor-α (TNF-α) and leukotriene B4 (LTB4), and reduced the expression of macrophage chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). These results together with the histological analysis, which showed accumulation of leukocytes in the wound early in the healing process, indicate that LA brought forward the inflammatory phase and improved wound healing in diabetic rats. Angiogenesis was induced by LA through elevation in tissue content of key mediators of this process: vascular-endothelial growth factor (VEGF) and angiopoietin-2 (ANGPT-2). Oral administration of LA hastened wound closure in diabetic rats by improving the inflammatory phase and angiogenesis.

  16. ReSure Sealant for Pars Plana Vitrectomy Wound Closure.

    PubMed

    Ho, Vincent Y; Shah, Gaurav K; Liu, Enchun M

    2015-01-01

    ReSure Sealant (Ocular Therapeutix, Bedford, MA) is an ocular sealant that demonstrated both safety and effectiveness in a prospective, randomized clinical trial for sealing clear corneal incisions following cataract surgery and intraocular lens placement in adults.1 PATIENTS AND METHODS: This is the first literature report of ReSure Sealant used for the closure of 23-gauge (G) pars plana vitrectomy (PPV) sclerotomies. A 70-year-old pseudophakic female with a history of epiretinal membrane and branch retinal vein occlusion of the right eye underwent 23-G PPV, membrane peel, and air-fluid exchange and was found to have leaking subconjunctival air at the end of the case. A linear conjunctival incision was performed to access the sclerotomy site. The incisions were then carefully dried before the sealant was applied to seal both the sclera and conjunctiva. After polymerization, the sealant formed a polyethylene glycol (PEG) hydrogel that was 89% water and 9.44% PEG. PEG is a synthetic material that is non-toxic and inert and, thus, suitable for use in medical products. ReSure Sealant may be a safe, quick method to close sclerotomy wounds in select cases. [ Copyright 2015, SLACK Incorporated.

  17. Review on experiment-based two- and three-dimensional models for wound healing

    PubMed Central

    Gefen, Amit

    2016-01-01

    Traumatic and chronic wounds are a considerable medical challenge that affects many populations and their treatment is a monetary and time-consuming burden in an ageing society to the medical systems. Because wounds are very common and their treatment is so costly, approaches to reveal the responses of a specific wound type to different medical procedures and treatments could accelerate healing and reduce patient suffering. The effects of treatments can be forecast using mathematical modelling that has the predictive power to quantify the effects of induced changes to the wound-healing process. Wound healing involves a diverse and complex combination of biophysical and biomechanical processes. We review a wide variety of contemporary approaches of mathematical modelling of gap closure and wound-healing-related processes, such as angiogenesis. We provide examples of the understanding and insights that may be garnered using those models, and how those relate to experimental evidence. Mathematical modelling-based simulations can provide an important visualization tool that can be used for illustrational purposes for physicians, patients and researchers. PMID:27708762

  18. Epidermal stem cells (ESCs) accelerate diabetic wound healing via the Notch signalling pathway.

    PubMed

    Yang, Rong-Hua; Qi, Shao-Hai; Shu, Bin; Ruan, Shu-Bin; Lin, Ze-Peng; Lin, Yan; Shen, Rui; Zhang, Feng-Gang; Chen, Xiao-Dong; Xie, Ju-Lin

    2016-08-01

    Chronic, non-healing wounds are a major complication of diabetes. Recently, various cell therapies have been reported for promotion of diabetic wound healing. Epidermal stem cells (ESCs) are considered a powerful tool for tissue therapy. However, the effect and the mechanism of the therapeutic properties of ESCs in the diabetic wound healing are unclear. Herein, to determine the ability of ESCs to diabetic wound healing, a dorsal skin defect in a streptozotocin (STZ)-induced diabetes mellitus (DM) mouse model was used. ESCs were isolated from mouse skin. We found that both the mRNA and protein levels of a Notch ligand Jagged1 (Jag1), Notch1 and Notch target gene Hairy Enhancer of Split-1 (Hes1) were significantly increased at the wound margins. In addition, we observed that Jag1 was high expressed in ESCs. Overexpression of Jag1 promotes ESCs migration, whereas knockdown Jag1 resulted in a significant reduction in ESCs migration in vitro Importantly, Jag1 overexpression improves diabetic wound healing in vivo These results provide evidence that ESCs accelerate diabetic wound healing via the Notch signalling pathway, and provide a promising potential for activation of the Notch pathway for the treatment of diabetic wound. © 2016 The Author(s).

  19. Use of negative pressure wound therapy in the management of infected abdominal wounds containing mesh: an analysis of outcomes.

    PubMed

    Baharestani, Mona Mylene; Gabriel, Allen

    2011-04-01

    The purpose of this study was to examine the clinical outcomes of negative pressure wound therapy (NPWT) using reticulated open-cell foam (ROCF) in the adjunctive management of abdominal wounds with exposed and known infected synthetic mesh. A non randomised, retrospective review of medical records for 21 consecutive patients with infected abdominal wounds treated with NPWT was conducted. All abdominal wounds contained exposed synthetic mesh [composite, polypropylene (PP), or knitted polyglactin 910 (PG) mesh]. Demographic and bacteriological data, wound history, pre-NPWT and comparative post-NPWT, operative procedures and complications, hospital length of stay (LOS) and wound healing outcomes were all analysed. Primary endpoints measured were (1) hospital LOS prior to initiation of NPWT, (2) total time on NPWT, (3) hospital LOS from NPWT initiation to discharge and (4) wound closure status at discharge. A total of 21 patients with abdominal wounds with exposed, infected mesh were treated with NPWT. Aetiology of the wounds was ventral hernia repair (n = 11) and acute abdominal wall defect (n = 10). Prior to NPWT initiation, the mean hospital LOS for the composite, PP and PG meshes were 76 days (range: 21-171 days), 51 days (range: 32-62 days) and 19 days (range: 12-39 days), respectively. The mean hospital LOS following initiation of NPWT for wounds with exposed composite, PP and PG mesh were 28, 31 and 32 days, respectively. Eighteen of the 21 wounds (86%) reached full closure after a mean time of 26 days of NPWT and a mean hospital LOS of 30 days postinitiation of NPWT. Three wounds, all with composite mesh left in situ, did not reach full closure, although all exhibited decreased wound dimensions, granulating beds and decreased surface area exposure of mesh. During NPWT/ROCF, one hypoalbuminemic patient with exposed PP mesh developed an enterocutaneous fistula over a prior enterotomy site. This patient subsequently underwent total mesh extraction, takedown of

  20. Antioxidant and hemolytic activities, and effects in rat cutaneous wound healing of a novel polysaccharide from fenugreek (Trigonella foenum-graecum) seeds.

    PubMed

    Ktari, Naourez; Trabelsi, Imen; Bardaa, Sana; Triki, Mehdi; Bkhairia, Intidhar; Ben Slama-Ben Salem, Rabab; Nasri, Moncef; Ben Salah, Riadh

    2017-02-01

    The aim of this work was to evaluate the antioxidant and hemolytic activities as well as the in vivo wound healing performance of a novel polysaccharide (FWEP) extracted from fenugreek (Trigonella foenum-graecum) seeds. The antioxidant activity was evaluated in vivo and in vitro using various assays. Results showed that FWEP exhibited strong antioxidant activities but no hemolytic activity was observed towards bovine erythrocytes. The application of FWEP hydrogel on the wound site in a rat model enhanced significantly wound healing activity and accelerated the wound closure after 14days of wound induction. Histological examination also demonstrated fully re-epithelialized wound with a complete epidermal regeneration. Altogether, these evidences demonstrated that FWEP had strong wound healing potential presumably achieved through its antioxidant activities. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Ephrin-B2 is differentially expressed in the intestinal epithelium in Crohn’s disease and contributes to accelerated epithelial wound healing in vitro

    PubMed Central

    Hafner, Christian; Meyer, Stefanie; Langmann, Thomas; Schmitz, Gerd; Bataille, Frauke; Hagen, Ilja; Becker, Bernd; Roesch, Alexander; Rogler, Gerhard; Landthaler, Michael; Vogt, Thomas

    2005-01-01

    AIM: Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meaning of this system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA expression in the intestinal epithelium of healthy controls and patients with inflammatory bowel disease (IBD). METHODS: mRNA expression profiles of all Eph/ephrin family members in normal small intestine and colon were established by real-time RT-PCR. In addition, differential expression in IBD was investigated by cDNA array technology, and validated by both real-time RT-PCR and immunohistochemistry. Potential effects of enhanced EphB/ephrin-B signaling were analyzed in an in vitro IEC-6 cell scratch wound model. RESULTS: Human adult intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. Beside the known prominent co-expression of EphA2 and ephrinA1, we found abundantly co-expressed EphB2 and ephrin-B1/2. Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both perilesional and lesional intestinal epithelial cells of IBD patients, suggesting a role in epithelial homeostasis. Stimulation of ephrin-B signaling in ephrin-B1/2 expressing rat IEC-6-cells with recombinant EphB1-Fc resulted in a significant dose-dependent acceleration of wound closure. Furthermore, fluorescence microscopy showed that EphB1-Fc induced coordinated migration of wound edge cells is associated with enhanced formation of lamellipodial protrusions into the wound, increased actin stress fiber assembly and production of laminin at the wound edge. CONCLUSION: EphB/ephrin-B signaling might represent a novel protective mechanism that promotes intestinal epithelial wound healing, with potential impact on epithelial restitution in IBD. PMID:15996027

  2. Early intervention of negative pressure wound therapy using Vacuum-Assisted Closure in trauma patients: impact on hospital length of stay and cost.

    PubMed

    Kaplan, Mark; Daly, Darron; Stemkowski, Stephen

    2009-03-01

    The cost of treating complex traumatic wounds is substantial because of trauma severity, potential for infection, and delayed closure. Negative pressure wound therapy using reticulated open cell foam (NPWT/ROCF) as delivered by Vacuum-Assisted Closure* (KCI Licensing, Inc, San Antonio, Texas) is an established, viable option for treating traumatic wounds. The authors used retrospective data to study the clinical and cost-effective benefits of using NPWT/ROCF early on day 1 or day 2 of treatment for traumatic wounds as compared with using it late (on day 3 or later). Hospital data records from trauma wound patients treated with NPWT/ROCF were retrospectively analyzed. Data were subdivided into 2 groups based on start of treatment. The group of patients treated on day 1 or 2 of their hospital stay was referred to as the early group, and that composed of patients treated on day 3 or later as the late group. Clinical and cost-effective metrics were compared between the 2 groups. For the early group, 518 patient records were included; 1000 records were reviewed for the late group. Early-group patients had fewer hospital inpatient days (10.6 vs 20.6 days; P < .0001), fewer treatment days (5.1 vs 6.0 days; P = .0498), shorter intensive care unit (ICU) stays (5.3 vs 12.4 days; P < .0001), and higher ICU admission rates (51.5 vs 44.5%; P = .0091) than the late group. Compared with late-group patients, early-group patients had lower total and variable costs per patient discharge ($43,956 vs $32,175; P < .0001 and $22,891 vs $15,805; P < .0001, respectively). Acute-care trauma wound patients receiving early NPWT/ROCF demonstrated significant reductions in length of stay, treatment days, and ICU stay, which resulted in significant reduced patient treatment costs. These results indicate that early intervention with NPWT/ROCF has potential clinical and cost-effective benefits for the treatment of traumatic wounds.

  3. Elastic rubber strips to heal large wounds of the body wall.

    PubMed

    Petroianu, Andy

    2013-12-01

    Closure of large wounds is a difficult surgical challenge. This article reports on the effective closure of large surgical wounds using elastic rubber strips. One to 3 circular elastic rubber strips were sutured by applying moderate tension to the opposite edges of 30 large wounds in 28 patients. The strips were sutured in a successive "X" fashion by crossing one over the other. These rubber strips were replaced when they ruptured or after their tension had reduced because of the closure of the wounds. Complete closure of the wounds was achieved with no further need for any surgical procedure or device. One patient with laparostomy and colostomy presented with difficulty on adapting the colostomic bag, and the rubber strips were removed. The rubber strip had little effect on a large wound of the skull. In the late postoperative follow-up, 3 of the 15 closed laparostomies developed incisional hernias, and all these patients were subjected to hernioplasties with good results. The use of circular elastic rubber strips maintained at moderate tension is a simple, effective, and inexpensive surgical option for healing large wounds. It is readily available at any hospital and requires no extensive surgical experience.

  4. Enhanced wound healing of tissue-engineered human corneas through altered phosphorylation of the CREB and AKT signal transduction pathways.

    PubMed

    Couture, Camille; Desjardins, Pascale; Zaniolo, Karine; Germain, Lucie; Guérin, Sylvain L

    2018-06-01

    The cornea is a transparent organ, highly specialized and unique that is continually subjected to abrasive forces and occasional mechanical or chemical trauma because of its anatomical localization. Upon injury, the extracellular matrix (ECM) rapidly changes to promote wound healing through integrin-dependent activation of specific signal transduction mediators whose contribution is to favor faster closure of the wound by altering the adhesive and migratory properties of the cells surrounding the damaged area. In this study, we exploited the human tissue-engineered cornea (hTECs) as a model to study the signal transduction pathways that participate to corneal wound healing. By exploiting both gene profiling and activated kinases arrays, we could demonstrate the occurrence of important alterations in the level of expression and activation of a few mediators from the PI3K/Akt and CREB pathways in response to the ECM remodeling taking place during wound healing of damaged hTECs. Pharmacological inhibition of CREB with C646 considerably accelerated wound closure compared to controls. This process was considerably accelerated further when both C646 and SC79, an Akt agonist, were added together to wounded hTECs. Therefore, our study demonstrate that proper corneal wound healing requires the activation of Akt together with the inhibition of CREB and that wound healing in vitro can be altered by the use of pharmacological inhibitors (such as C646) or agonists (such as SC79) of these mediators. Corneal wounds account for a large proportion of all visual disabilities in North America. To our knowledge, this is the first time that a tissue-engineered human cornea (hTEC) entirely produced using normal untransformed human cells is used as a biomaterial to study the signal transduction pathways that are critical to corneal wound healing. Through the use of this biomaterial, we demonstrated that human corneal epithelial cells engaged in wound healing reduce phosphorylation of the

  5. Stimulation of Skin and Wound Fibroblast Migration by Mesenchymal Stem Cells Derived from Normal Donors and Chronic Wound Patients

    PubMed Central

    Rodriguez-Menocal, Luis; Salgado, Marcela; Ford, Dwayne

    2012-01-01

    Chronic wounds continue to be a major cause of morbidity for patients and an economic burden on the health care system. Novel therapeutic approaches to improved wound healing will need, however, to address cellular changes induced by a number of systemic comorbidities seen in chronic wound patients, such as diabetes, chronic renal failure, and arterial or venous insufficiency. These effects likely include impaired inflammatory cell migration, reduced growth factor production, and poor tissue remodeling. The multifunctional properties of bone marrow-derived mesenchymal stem cells (MSCs), including their ability to differentiate into various cell types and capacity to secrete factors important in accelerating healing of cutaneous wounds, have made MSCs a promising agent for tissue repair and regeneration. In this study we have used an in vitro scratch assay procedure incorporating labeled MSCs and fibroblasts derived from normal donors and chronic wound patients in order to characterize the induction of mobilization when these cells are mixed. A modified Boyden chamber assay was also used to examine the effect of soluble factors on fibroblast migration. These studies suggest that MSCs play a role in skin wound closure by affecting dermal fibroblast migration in a dose-dependent manner. Deficiencies were noted, however, in chronic wound patient fibroblasts and MSCs as compared with those derived from normal donors. These findings provide a foundation to develop therapies targeted specifically to the use of bone marrow-derived MSCs in wound healing and may provide insight into why some wounds do not heal. PMID:23197781

  6. Downregulation of miRNAs during Delayed Wound Healing in Diabetes: Role of Dicer

    PubMed Central

    Bhattacharya, Sushant; Aggarwal, Rangoli; Singh, Vijay Pal; Ramachandran, Srinivasan; Datta, Malabika

    2015-01-01

    Delayed wound healing is a major complication associated with diabetes and is a result of a complex interplay among diverse deregulated cellular parameters. Although several genes and pathways have been identified to be mediating impaired wound closure, the role of microRNAs (miRNAs) in these events is not very well understood. Here, we identify an altered miRNA signature in the prolonged inflammatory phase in a wound during diabetes, with increased infiltration of inflammatory cells in the basal layer of the epidermis. Nineteen miRNAs were downregulated in diabetic rat wounds (as compared with normal rat wound, d 7 postwounding) together with inhibited levels of the central miRNA biosynthesis enzyme, Dicer, suggesting that in wounds of diabetic rats, the decreased levels of Dicer are presumably responsible for miRNA downregulation. Compared with unwounded skin, Dicer levels were significantly upregulated 12 d postwounding in normal rats, and this result was notably absent in diabetic rats that showed impaired wound closure. In a wound-healing specific quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) array, 10 genes were significantly altered in the diabetic rat wound and included growth factors and collagens. Network analyses demonstrated significant interactions and correlations between the miRNA predicted targets (regulators) and the 10 wound-healing specific genes, suggesting altered miRNAs might fine-tune the levels of these genes that determine wound closure. Dicer inhibition prevented HaCaT cell migration and affected wound closure. Altered levels of Dicer and miRNAs are critical during delayed wound closure and offer promising targets to address the issue of impaired wound healing. PMID:26602065

  7. Role of non-mulberry silk fibroin in deposition and regulation of extracellular matrix towards accelerated wound healing.

    PubMed

    Chouhan, Dimple; Chakraborty, Bijayshree; Nandi, Samit K; Mandal, Biman B

    2017-01-15

    Bombyx mori silk fibroin (BMSF) as biopolymer has been extensively explored in wound healing applications. However, limited study is available on the potential of silk fibroin (SF) from non-mulberry (Antheraea assama and Philosamia ricini) silk variety. Herein, we have developed non-mulberry SF (NMSF) based electrospun mats functionalized with epidermal growth factor (EGF) and ciprofloxacin HCl as potential wound dressing. The NMSF based mats exhibited essential properties of wound dressing like biocompatibility, high water retention capacity (440%), water vapor transmission rate (∼2330gm -2 day -1 ), high elasticity (∼2.6MPa), sustained drug release and antibacterial activity. Functionalized NMSF mats enhanced the proliferation of human dermal fibroblasts and HaCaT cells in vitro as compared to non-functionalized mats (p⩽0.01) showing effective delivery of EGF. Extensive in vivo wound healing assesment demonstrated accelerated wound healing, enhanced re-epithelialization, highly vascularized granulation tissue and higher wound maturity as compared to BMSF based mats. NMSF mats treated wounds showed regulated deposition of mature elastin, collagen and reticulin fibers in the extracellular matrix of skin. Presence of skin appendages and isotropic collagen fibers in the regenerated skin also demonstrated scar-less healing and aesthetic wound repair. A facile fabrication of a ready-to-use bioactive wound dressing capable of concomitantly accelerating the healing process as well as deposition of the extracellular matrix (ECM) to circumvent further scarring complicacies has become a focal point of research. In this backdrop, our present work is based on non-mulberry silk fibroin (NMSF) electrospun antibiotic loaded semi-occlusive mats, mimicking the ECM of skin in terms of morphology, topology, microporous structure and mechanical stiffness. Regulation of ECM deposition and isotropic orientation evinced the potential of the mat as an instructive platform for skin

  8. Atrial Natriuretic Peptide Accelerates Human Endothelial Progenitor Cell-Stimulated Cutaneous Wound Healing and Angiogenesis.

    PubMed

    Lee, Tae Wook; Kwon, Yang Woo; Park, Gyu Tae; Do, Eun Kyoung; Yoon, Jung Won; Kim, Seung-Chul; Ko, Hyun-Chang; Kim, Moon-Bum; Kim, Jae Ho

    2018-05-26

    Atrial natriuretic peptide (ANP) is a powerful vasodilating peptide secreted by cardiac muscle cells, and endothelial progenitor cells (EPCs) have been reported to stimulate cutaneous wound healing by mediating angiogenesis. To determine whether ANP can promote the EPC-mediated repair of injured tissues, we examined the effects of ANP on the angiogenic properties of EPCs and on cutaneous wound healing. In vitro, ANP treatment enhanced the migration, proliferation, and endothelial tube-forming abilities of EPCs. Furthermore, small interfering RNA-mediated silencing of natriuretic peptide receptor-1, which is a receptor for ANP, abrogated ANP-induced migration, tube formation, and proliferation of EPCs. In a murine cutaneous wound model, administration of either ANP or EPCs had no significant effect on cutaneous wound healing or angiogenesis in vivo, whereas the co-administration of ANP and EPCs synergistically potentiated wound healing and angiogenesis. In addition, ANP promoted the survival and incorporation of transplanted EPCs into newly formed blood vessels in wounds. These results suggest ANP accelerates EPC-mediated cutaneous wound healing by promoting the angiogenic properties and survival of transplanted EPCs. This article is protected by copyright. All rights reserved. © 2018 by the Wound Healing Society.

  9. Combination of ciclopirox olamine and sphingosine-1-phosphate as granulation enhancer in diabetic wounds.

    PubMed

    Lim, Natalie Sheng Jie; Sham, Adeline; Chee, Stella Min Ling; Chan, Casey; Raghunath, Michael

    2016-09-01

    Granulation tissue formation requires a robust angiogenic response. As granulation tissue develops, collagen fibers are deposited and compacted. Forces generated in the wake of this process drive wound contraction to reduce the wound area. In diabetics, both angiogenesis and wound contraction are diminished leading to impaired wound healing. To emulate this pathology and to address it pharmacologically, we developed a wound healing model in the diabetic Zucker fatty rat and tested a topical proangiogenic strategy combining antifungal agent ciclopirox olamine (CPX) and lysophospholipid sphingosine-1-phosphate (S1P) to promote diabetic wound closure. In vitro, we demonstrated that CPX + S1P up-regulates a crucial driver of angiogenesis, hypoxia-inducible factor-1, in endothelial cells. Injection of CPX + S1P into subcutaneously implanted sponges in experimental rats showed, in an additive manner, a fivefold increased endothelial infiltration and lectin-perfused vessel length. We developed a splinted diabetic rodent model to achieve low wound contraction rates that are characteristic for the healing mode of diabetic ulcers in humans. We discovered specific dorsal sites that allowed for incremental full-thickness excisional wound depths from 1 mm (superficial) to 3 mm (deep). This enabled us to bring down wound contraction from 51% in superficial wounds to 8% in deep wounds. While the effects of topical gel treatment of CPX + S1P were masked by the rodent-characteristic dominant contraction in superficial wounds, they became clearly evident in deep diabetic wounds. Here, a fivefold increase of functional large vessels resulted in accelerated granulation tissue formulation, accompanied by a 40% increase of compacted thick collagen fibers. This was associated with substantially reduced matrix metalloproteinase-3 and -13 expression. These findings translated into a fivefold increase in granulation-driven contraction, promoting diabetic wound closure. With CPX

  10. Drosophila as a model of wound healing and tissue regeneration in vertebrates.

    PubMed

    Belacortu, Yaiza; Paricio, Nuria

    2011-11-01

    Understanding the molecular basis of wound healing and regeneration in vertebrates is one of the main challenges in biology and medicine. This understanding will lead to medical advances allowing accelerated tissue repair after wounding, rebuilding new tissues/organs and restoring homeostasis. Drosophila has emerged as a valuable model for studying these processes because the genetic networks and cytoskeletal machinery involved in epithelial movements occurring during embryonic dorsal closure, larval imaginal disc fusion/regeneration, and epithelial repair are similar to those acting during wound healing and regeneration in vertebrates. Recent studies have also focused on the use of Drosophila adult stem cells to maintain tissue homeostasis. Here, we review how Drosophila has contributed to our understanding of these processes, primarily through live-imaging and genetic tools that are impractical in mammals. Furthermore, we highlight future research areas where this insect may provide novel insights and potential therapeutic strategies for wound healing and regeneration. Copyright © 2011 Wiley Periodicals, Inc.

  11. Wound healing applications of sericin/chitosan-capped silver nanoparticles incorporated hydrogel.

    PubMed

    Verma, Jyoti; Kanoujia, Jovita; Parashar, Poonam; Tripathi, Chandra Bhusan; Saraf, Shubhini A

    2017-02-01

    Microbial contamination in wounds leading to severe sepsis can be treated by silver-based antiseptics. However, frequent application of silver-based antiseptics, staining of skin, burning, and irritation at application site resulted to poor patient compliances. Thus, we formulated sericin- and chitosan-capped silver nanoparticle (S/C-SNP)-loaded hydrogel for accelerated wound healing and antimicrobial properties. The wound healing property of sericin, antibacterial nature of chitosan and silver, and mucoadhesive property of carbopol were utilized in development of novel wound dressing hydrogel to investigate the combined effect of these materials for effective treatment of wounds. The chemical reduction method was successfully employed for the synthesis of SNPs using sericin and chitosan as a capping/reducing agent. The SNPs were characterized by ultraviolet-spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The optimized SNPs were further used for preparation of carbopol hydrogel (0.5, 0.75, and 1.0 % w/v). The prepared hydrogels were characterized for pH, viscosity, and texture analysis. The antimicrobial activity and wound healing activity of the optimized hydrogel (S/C-SNPs G-1) demonstrated higher bactericidal activity and wound closure, as supported by results of histopathology. Hydrogel containing capped SNPs has application in wound healing treatment.

  12. Tissue loads applied by a novel medical device for closing large wounds.

    PubMed

    Katzengold, Rona; Topaz, Moris; Gefen, Amit

    2016-02-01

    Closure of large soft tissue defects following surgery or trauma as well as closure of large chronic wounds constitutes substantial but common reconstructive challenges. In such cases, an attempt to use conventional suturing will result in high-tension closure, therefore alternative external skin stretching systems were developed. These types of devices were meant to reduce local mechanical loads in the skin and the underlying tissues, taking advantage of the viscoelastic properties of the skin, especially mechanical creep, for primary wound closure. Studies have shown the clinical advantages of skin stretching systems, however, quantitative bioengineering models, demonstrating closure of large wounds, are lacking. Here we present finite element (FE) modeling of the TopClosure(®) tension relief system (TRS) and its biomechanical efficacy in three (real) wound cases, compared with the alternative of a conventional surgical suturing closure technique. Our simulations showed that peak effective stresses on the skin were at least an order of magnitude greater (and sometimes nearly 2 orders-of-magnitude greater) when tension sutures were used with respect to the corresponding TRS data. For the tension suture simulations, the tensile stress was in the range of 415-648 MPa and in the TRS simulations, it was 16-30 MPa. Based on the present computational FE modeling, the TRS reduces localized tissue deformations and stress concentrations in skin and underlying tissues while closing large wounds, compared to the deformations and stresses that are inflicted during the process of suturing. This substantial reduction of loads allows surgeons to better employ the viscoelastic properties of the skin for primary wound closure. Copyright © 2015 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  13. [Synthesis of large wounds of the body wall with rubber elastic band].

    PubMed

    Petroianu, Andy

    2011-01-01

    The large wounds of the body wall, due to traumas, removal of tumors or prolonged laparostomies are a difficult surgical challenge with complex treatment. This paper presents the efficacy of the closure of large surgical wounds using rubber elastic bands. One or two circular rubber elastic bands were sutured under mean tension at the opposite edges of 22 large wounds located in different body sites. These rubber strips were replaced when they were broken or re-fixed when they have lost their tension until the complete closure of the wounds. Complete closure was achieved without any other surgical procedure or device in 21 wounds and one wound reduced its dimensions. No major complication due to this treatment was verified. The synthesis of large wounds with rubber elastic bands kept under mean tension is a simple, efficacious and inexpensive surgical option that may be useful for treatment in several circumstances.

  14. The use of honey as a topical dressing to treat a large, devitalized wound in a stumptail macaque (Macaca arctoides).

    PubMed

    Staunton, Christine J; Halliday, Lisa C; Garcia, Kelly D

    2005-07-01

    There are many reasons wounds are managed as open wounds rather than by primary closure. Indications include gross contamination, infection, and skin loss leading to insufficient adjacent tissue for wound closure. The most common method of managing an open wound is with wet-to-dry dressings. Wet-to-dry dressings provide mechanical debridement and promote the movement of viscous exudates away from the wound. Wet-to-dry bandages ideally are changed every 12 to 24 h. For nonhuman primates, it is desirable to develop wound management techniques that limit animal handling for bandage changes and thus the frequency of sedation. Anecdotal reports on the use of honey to treat wounds date back to 2000 B.C. Recently, scientific inquiries have found merit to these reports. Honey accelerates healing because of its direct effects on tissue and antibacterial properties. In addition, dressings with honey can be changed relatively infrequently. Honey decreases inflammatory edema, hastens sloughing of devitalized tissue, attracts macrophages which cleanse the wound, provides a local cellular energy source, and protectively covers the wound. A high osmolarity, acidity, and hydrogen peroxide content confer honey with antibacterial properties. Here we describe the use of honey to manage a bite wound in a stumptail macaque (Macaca arctoides). The wound healed rapidly: after 2 weeks of treatment, there was markedly less exudate and no necrotic tissue. This report describes how honey may be helpful in the management of open wounds in nonhuman primates by minimizing the need for sedation for bandage changes.

  15. Intestinal adhesion to the abdominal wall after skin closure with octylcyanoacrylate.

    PubMed

    Chaya, Miguel; Reyes-Cuervo, Humberto; Cruz, Vivian; Barroso, Gerardo; Garcia-León, Fernando

    2004-08-01

    Octylcyanoacrylate tissue adhesive glue is a wound closure device recently approved by the U.S. Food and Drug Administration. Few complications have been reported regarding the liquid adhesive entering the wound. The following report involves a patient who developed intestinal occlusion secondary to octylcyanoacrylate used for skin closure in laparoscopic surgery.

  16. Low-Intensity Vibration Improves Angiogenesis and Wound Healing in Diabetic Mice

    PubMed Central

    Weinheimer-Haus, Eileen M.; Judex, Stefan; Ennis, William J.; Koh, Timothy J.

    2014-01-01

    Chronic wounds represent a significant health problem, especially in diabetic patients. In the current study, we investigated a novel therapeutic approach to wound healing – whole body low-intensity vibration (LIV). LIV is anabolic for bone, by stimulating the release of growth factors, and modulating stem cell proliferation and differentiation. We hypothesized that LIV improves the delayed wound healing in diabetic mice by promoting a pro-healing wound environment. Diabetic db/db mice received excisional cutaneous wounds and were subjected to LIV (0.4 g at 45 Hz) for 30 min/d or a non-vibrated sham treatment (controls). Wound tissue was collected at 7 and 15 d post-wounding and wound healing, angiogenesis, growth factor levels and wound cell phenotypes were assessed. LIV increased angiogenesis and granulation tissue formation at day 7, and accelerated wound closure and re-epithelialization over days 7 and 15. LIV also reduced neutrophil accumulation and increased macrophage accumulation. In addition, LIV increased expression of pro-healing growth factors and chemokines (insulin-like growth factor-1, vascular endothelial growth factor and monocyte chemotactic protein-1) in wounds. Despite no evidence of a change in the phenotype of CD11b+ macrophages in wounds, LIV resulted in trends towards a less inflammatory phenotype in the CD11b− cells. Our findings indicate that LIV may exert beneficial effects on wound healing by enhancing angiogenesis and granulation tissue formation, and these changes are associated with increases in pro-angiogenic growth factors. PMID:24618702

  17. Tissue adhesives for closure of surgical incisions.

    PubMed

    Dumville, Jo C; Coulthard, Paul; Worthington, Helen V; Riley, Philip; Patel, Neil; Darcey, James; Esposito, Marco; van der Elst, Maarten; van Waes, Oscar J F

    2014-11-28

    Sutures (stitches), staples and adhesive tapes have been used for many years as methods of wound closure, but tissue adhesives have entered clinical practice more recently. Closure of wounds with sutures enables the closure to be meticulous, but the sutures may show tissue reactivity and can require removal. Tissue adhesives offer the advantages of an absence of risk of needlestick injury and no requirement to remove sutures later. Initially, tissue adhesives were used primarily in emergency room settings, but this review looks at the use of tissue adhesives in the operating room/theatre where surgeons are using them increasingly for the closure of surgical skin incisions. To determine the effects of various tissue adhesives compared with conventional skin closure techniques for the closure of surgical wounds. In March 2014 for this second update we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We did not restrict the search and study selection with respect to language, date of publication or study setting. Only randomised controlled trials were eligible for inclusion. We conducted screening of eligible studies, data extraction and risk of bias assessment independently and in duplicate. We expressed results as random-effects models using mean difference for continuous outcomes and risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. We investigated heterogeneity, including both clinical and methodological factors. This second update of the review identified 19 additional eligible trials resulting in a total of 33 studies (2793 participants) that met the inclusion criteria. There was low quality evidence that sutures were significantly better than tissue adhesives for reducing the risk of wound breakdown (dehiscence; RR 3.35; 95% CI 1.53 to 7

  18. Port closure techniques.

    PubMed

    Shaher, Z

    2007-08-01

    Laparoscopic trocars do create wounds. This article aims to review and list different techniques used for closure of the fascia incision at trocar sites. A literature search was performed for articles dealing with closure techniques. The author searched this subject in English on Medline by combining the words "trocar" and "hernia," as well as "Deschamps" and "Reverdin." All articles reporting techniques with their references were reviewed. The articles described many techniques in addition to classical closure using curved needles, including Grice needle, Maciol needles, Endoclose device, Carter-Thomason device, Tahoe ligature device, Endo-Judge device, eXit puncture closure device, Lowsley retractor, spinal cord needles, dual hemostat, suture carrier, Riverdin and Deschamps needles, and Gore-Tex closure device. Three main groups of techniques were found with favor of extracorporeal manipulations under direct visualization. Old methods are sufficient and cost-effective.

  19. Leishmania proteophosphoglycans regurgitated from infected sand flies accelerate dermal wound repair and exacerbate leishmaniasis via insulin-like growth factor 1-dependent signalling

    PubMed Central

    Giraud, Emilie; Martin, Oihane; Dillon, Rod J.; Műller, Ingrid

    2018-01-01

    Leishmania parasites are transmitted to vertebrate hosts by female phlebotomine sand flies as they bloodfeed by lacerating the upper capillaries of the dermis with their barbed mouthparts. In the sand fly midgut secreted proteophosphoglycans from Leishmania form a biological plug known as the promastigote secretory gel (PSG), which blocks the gut and facilitates the regurgitation of infective parasites. The interaction between the wound created by the sand fly bite and PSG is not known. Here we nanoinjected a sand fly egested dose of PSG into BALB/c mouse skin that lead to the differential expression of 7,907 transcripts. These transcripts were transiently up-regulated during the first 6 hours post-wound and enriched for pathways involved in inflammation, cell proliferation, fibrosis, epithelial cell differentiation and wound remodelling. We found that PSG significantly accelerated wound healing in vitro and in mice; which was associated with an early up-regulation of transcripts involved in inflammation (IL-1β, IL-6, IL-10, TNFα) and inflammatory cell recruitment (CCL2, CCL3, CCL4, CXCL2), followed 6 days later by enhanced expression of transcripts associated with epithelial cell proliferation, fibroplasia and fibrosis (FGFR2, EGF, EGFR, IGF1). Dermal expression of IGF1 was enhanced following an infected sand fly bite and was acutely responsive to the deposition of PSG but not the inoculation of parasites or sand fly saliva. Antibody blockade of IGF1 ablated the gel’s ability to promote wound closure in mouse ears and significantly reduced the virulence of Leishmania mexicana infection delivered by an individual sand fly bite. Dermal macrophages recruited to air-pouches on the backs of mice revealed that IGF1 was pivotal to the PSG’s ability to promote macrophage alternative activation and Leishmania infection. Our data demonstrate that through the regurgitation of PSG Leishmania exploit the wound healing response of the host to the vector bite by promoting

  20. The role of allogenic keratin-derived dressing in wound healing in a mouse model.

    PubMed

    Konop, Marek; Sulejczak, Dorota; Czuwara, Joanna; Kosson, Piotr; Misicka, Aleksandra; Lipkowski, Andrzej W; Rudnicka, Lidia

    2017-01-01

    Keratin is an interesting protein needed for wound healing and tissue recovery. We have recently proposed a new, simple and inexpensive method to obtain fur and hair keratin-derived biomaterials suitable for medical application. The aim of the study was to evaluate the role of the fur keratin-derived protein (FKDP) dressing in the allogenic full-thickness surgical skin wound model. The data obtained using scanning electron microscopy showed that employed processed biomaterial had higher surface porosity compared with control raw material. From the MTS test, it was found keratin biomaterial is not only toxic to the NIH/3T3 cell line (p < 0.05), but also enhances cell proliferation compared with the control. In vivo studies have shown keratin dressings are tissue biocompatible, accelerate wound closure and epithelialization to the statistically significant differences on day 5 (p < 0.05) in comparison to control wounds. Histological examination revealed, that in FKDP-treated wounds the inflammatory response contained predominantly macrophages whilst their morphological untreated variants showed mixed cell infiltrates rich in neutrophils. Predominant macrophages based response creates more favorable environment for healing. In FKDP-dressed wounds the number of microhemorrhages was also significantly decreased (p < 0.05) as compared with undressed wounds. Applied keratin dressing favors reconstruction of a more regular skin structure and assures better cosmetic effect in terms of scar formation and appearance. In conclusion, fur keratin-derived protein dressings significantly accelerated wound healing in the mouse model. Further studies are needed to determine the molecular mechanisms involved in the multilayer wound healing process and to assess the possible use of these dressings for medical purposes. © 2016 by the Wound Healing Society.

  1. Topical fentanyl stimulates healing of ischemic wounds in diabetic rats

    PubMed Central

    FAROOQUI, Mariya; ERICSON, Marna E; GUPTA, Kalpna

    2016-01-01

    Background Topically applied opioids promote angiogenesis and healing of ischemic wounds in rats. We examined if topical fentanyl stimulates wound healing in diabetic rats by stimulating growth-promoting signaling, angiogenesis, lymphangiogenesis and nerve regeneration. Methods We used Zucker diabetic fatty rats that develop obesity and diabetes on a high fat diet due to a mutation in the Leptin receptor. Fentanyl blended with hydrocream was applied topically on ischemic wounds twice daily, and wound closure was analyzed regularly. Wound histology was analyzed by hematoxylin and eosin staining. Angiogenesis, lymphangiogenesis, nerve fibers and phospho-PDGFR-β were visualized by CD31-, lymphatic vessel endothelium-1, protein gene product 9.5- and anti-phospho PDGFR-β-immunoreactivity, respectively. Nitric oxide synthase (NOS) and PDGFR-β signaling were analyzed using Western immunoblotting. Results Fentanyl significantly promoted wound closure as compared to PBS. Histology scores were significantly higher in fentanyl-treated wounds, indicative of increased granulation tissue formation, reduced edema and inflammation, and increased matrix deposition. Fentanyl treatment resulted in increased wound angiogenesis, lymphatic vasculature, nerve fibers, nitric oxide, NOS and PDGFR-β signaling as compared to PBS. Phospho PDGFR-β co-localized with CD31 co-staining for vasculature. Conclusions Topically applied fentanyl promotes closure of ischemic wounds in diabetic rats. Increased angiogenesis, lymphangiogenesis, peripheral nerve regeneration, NO and PDGFR-β signaling are associated with fentanyl-induced tissue remodeling and wound healing. PMID:25266258

  2. Risk factors for wound disruption following cesarean delivery.

    PubMed

    Subramaniam, Akila; Jauk, Victoria C; Figueroa, Dana; Biggio, Joseph R; Owen, John; Tita, Alan T N

    2014-08-01

    Risk factors for post-cesarean wound infection, but not disruption, are well-described in the literature. The primary objective of this study was to identify risk factors for non-infectious post-cesarean wound disruption. Secondary analysis was conducted using data from a single-center randomized controlled trial of staple versus suture skin closure in women ≥24 weeks' gestation undergoing cesarean delivery. Wound disruption was defined as subcutaneous skin or fascial dehiscence excluding primary wound infections. Composite wound morbidity (disruption or infection) was examined as a secondary outcome. Patient demographics, medical co-morbidities, and intrapartum characteristics were evaluated as potential risk factors using multivariable logistic regression. Of the 398 randomized patients, 340, including 26 with disruptions (7.6%) met inclusion criteria and were analyzed. After multivariable adjustments, African-American race (aOR 3.9, 95% CI 1.1-13.8) and staple - as opposed to suture - wound closure (aOR 5.4, 95% CI 1.8-16.1) remained significant risk factors for disruption; non-significant increases were observed for body mass index ≥30 (aOR 2.1, 95% CI 0.6-7.5), but not for diabetes mellitus (aOR 0.9, 95% CI 0.3-2.9). RESULTS for composite wound morbidity were similar. Skin closure with staples, African-American race, and considering the relatively small sample size, potentially obesity are associated with increased risk of non-infectious post-cesarean wound disruption.

  3. Injectable hyperbranched poly(β-amino ester) hydrogels with on-demand degradation profiles to match wound healing processes.

    PubMed

    Xu, Qian; Guo, Linru; A, Sigen; Gao, Yongsheng; Zhou, Dezhong; Greiser, Udo; Creagh-Flynn, Jack; Zhang, Hong; Dong, Yixiao; Cutlar, Lara; Wang, Fagang; Liu, Wenguang; Wang, Wei; Wang, Wenxin

    2018-02-28

    Adjusting biomaterial degradation profiles to match tissue regeneration is a challenging issue. Herein, biodegradable hyperbranched poly(β-amino ester)s (HP-PBAEs) were designed and synthesized via "A2 + B4" Michael addition polymerization, and displayed fast gelation with thiolated hyaluronic acid (HA-SH) via a "click" thiol-ene reaction. HP-PBAE/HA-SH hydrogels showed tunable degradation profiles both in vitro and in vivo using diamines with different alkyl chain lengths and poly(ethylene glycol) diacrylates with varied PEG spacers. The hydrogels with optimized degradation profiles encapsulating ADSCs were used as injectable hydrogels to treat two different types of humanized excisional wounds - acute wounds with faster healing rates and diabetic wounds with slower healing and neo-tissue formation. The fast-degrading hydrogel showed accelerated wound closure in acute wounds, while the slow-degrading hydrogel showed better wound healing for diabetic wounds. The results demonstrate that the new HP-PBAE-based hydrogel in combination with ADSCs can be used as a well-controlled biodegradable skin substitute, which demonstrates a promising approach in the treatment of various types of skin wounds.

  4. Hierarchy of cellular decisions in collective behavior: Implications for wound healing.

    PubMed

    Wickert, Lisa E; Pomerenke, Shaun; Mitchell, Isaiah; Masters, Kristyn S; Kreeger, Pamela K

    2016-02-02

    Collective processes such as wound re-epithelialization result from the integration of individual cellular decisions. To determine which individual cell behaviors represent the most promising targets to engineer re-epithelialization, we examined collective and individual responses of HaCaT keratinocytes seeded upon polyacrylamide gels of three stiffnesses (1, 30, and 100 kPa) and treated with a range of epidermal growth factor (EGF) doses. Wound closure was found to increase with substrate stiffness, but was responsive to EGF treatment only above a stiffness threshold. Individual cell behaviors were used to create a partial least squares regression model to predict the hierarchy of factors driving wound closure. Unexpectedly, cell area and persistence were found to have the strongest correlation to the observed differences in wound closure. Meanwhile, the model predicted a relatively weak correlation between wound closure with proliferation, and the unexpectedly minor input from proliferation was successfully tested with inhibition by aphidicolin. Combined, these results suggest that the poor clinical results for growth factor-based therapies for chronic wounds may result from a disconnect between the individual cellular behaviors targeted in these approaches and the resulting collective response. Additionally, the stiffness-dependency of EGF sensitivity suggests that therapies matched to microenvironmental characteristics will be more efficacious.

  5. Multifunctional activities of KSLW synthetic antimicrobial decapeptide: Implications for wound healing

    NASA Astrophysics Data System (ADS)

    Williams, Richard Leroy

    Wound healing is a complex process leading to the maintenance of skin integrity. Stress is known to increase susceptibility to bacterial infection, alter proinflammatory cytokine expression, and delay wound closure. Recently, antimicrobial peptides have generated interest due to their prokaryotic selectivity, decreased microbial resistance and multifunctional roles in wound healing, including fibroblast stimulation, keratinocyte migration and leukocyte migration. The objective of this dissertation project was to evaluate the effect of a synthetic antimicrobial decapeptide (KSLW) on bacterial clearance inflammation, and wound closure during stress-impaired healing. SKH-1 mice were randomly assigned to either control or restraint-stressed (RST) groups. Punch biopsy wounds (3.5 mm in diameter) were created bilaterally on the dorsal skin. Wounds were injected with 50 microL of empty carriers or KSLW prepared in Pluronic-F68, phospholipid micelles, or saline. Bacterial assays of harvested wounds were conducted on BHI agar. Wound closure was determined by photoplanimetry. Cytokine and growth factor mRNA expression was assessed with real-time RT-PCR. Human neutrophil migration assays and checkerboard analyses were performed using Transweli plates, and counting on hemacytometer. Oxidative burst activity was measured by spectrophotometric analysis of 2,7-dichlorofluorescein oxidation. KSLW-treatment resulted in significant reductions in bacterial load among RST mice, with no difference from control after 24h. The effect was sustained 5 days post-wounding, in RST mice treated with KSLW-F68. Temporal analysis of gene induction revealed reversals of stress-induced altered expression of growth factors, proinflammatory cytokines, and chemokines essential for favorable wound healing, at various time points. KSLW-treatment in RST mice demonstrated faster wound closure throughout the stress period. KSLW, at micromolar concentrations, demonstrated a significant effect on neutrophil

  6. Baseline factors affecting closure of venous leg ulcers.

    PubMed

    Marston, William A; Ennis, William J; Lantis, John C; Kirsner, Robert S; Galiano, Robert D; Vanscheidt, Wolfgang; Eming, Sabine A; Malka, Marcin; Cargill, D Innes; Dickerson, Jaime E; Slade, Herbert B

    2017-11-01

    The objective of this study was to characterize factors associated with closure of venous leg ulcers (VLUs) in a pooled analysis of subjects from three randomized clinical trials. Closure of VLUs after treatment with HP802-247, an allogeneic living cell therapy consisting of growth-arrested human keratinocytes and fibroblasts, vs standard therapy with compression bandaging was evaluated in three phase 3 clinical trials of similar design. Two trials enrolled subjects with VLUs ranging from 2 cm 2 to 12 cm 2 in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm 2 and ≤36 cm 2 with a 16-week treatment period. The first trial went to completion but failed to demonstrate a benefit to therapy with HP802-247 compared with placebo, and because of this, the remaining trials were terminated before completion. On the basis of no differences in outcomes between groups, subjects from both HP802-247 and control groups were pooled across all three studies. Cox proportional hazards regression analysis was employed to evaluate factors associated with VLU closure. This analysis included data from 716 subjects with VLU. Factors evaluated for association with healing included age, gender, race, diabetes, glycated hemoglobin level, body mass index, treatment (HP802-247 vs compression alone), and ulcer characteristics including location and area and duration at baseline. In an initial model including all of these putative factors, the following were significant at the P < .10 level: diagnosis of diabetes mellitus, gender, wound location (ankle or leg), baseline wound area, and wound duration at baseline. In a final model including only these factors, all but diabetes mellitus were significant at the P < .05 level. Effect sizes were as follows (hazard ratio [95% confidence interval]): female gender (1.384 [1.134-1.690]), wound location on the leg (1.490 [1.187-1.871]), smaller wound area at baseline (0.907 [0.887-0.927]), and shorter

  7. Effects of topical application of silver sulfadiazine cream, triple antimicrobial ointment, or hyperosmolar nanoemulsion on wound healing, bacterial load, and exuberant granulation tissue formation in bandaged full-thickness equine skin wounds.

    PubMed

    Harmon, Caroline C Gillespie; Hawkins, Jan F; Li, Jianming; Connell, Sean; Miller, Margaret; Saenger, Megan; Freeman, Lynetta J

    2017-05-01

    OBJECTIVE To determine the effects of 3 topically applied treatments (1% silver sulfadiazine cream [SSC], triple antimicrobial ointment [TAO], and hyperosmolar nanoemulsion [HNE]) on microbial counts, exuberant granulation tissue (EGT) development, and reepithelialization of contaminated wounds at the distal aspect of the limbs of horses. ANIMALS 8 healthy adult horses. PROCEDURES A 2.5 × 2.5-cm, full-thickness, cutaneous wound was created at the dorsal aspect of each metacarpus and metatarsus (1 wound/limb/horse), covered with nonadhesive dressing, and bandaged. Wounds were inoculated with bacteria and fungi the next day. Each wound on a given horse was randomly assigned to 1 of 4 treatment groups (SSC, TAO, HNE, or no topical treatment [control]). Bandage changes, culture of wound samples, treatments, photography for wound measurements, and biopsy were performed at predetermined time points. Time (days) until wound closure, number of EGT excisions, microbial counts, and scores for selected histologic characteristics were compared among groups. RESULTS Median time to wound closure for all groups was 42 days. Time to wound closure and histologic characteristics of wound healing did not differ among groups. Least squares mean microbial counts were significantly higher for HNE-treated wounds on days 9 and 21, compared with SSC-treated and TAO-treated wounds, but not controls. Proportions of SSC-treated (7/8) or HNE-treated (5/8) wounds needing EGT excision were significantly greater than that of TAO-treated (1/8) wounds. The proportion of SSC-treated wounds with EGT excision was greater than that of controls (3/8). CONCLUSIONS AND CLINICAL RELEVANCE None of the treatments resulted in more rapid wound closure, compared with that for untreated control wounds under the study conditions. When treatment is warranted, TAO may help to limit EGT formation.

  8. Nonerythropoietic Tissue Protective Compounds Are Highly Effective Facilitators of Wound Healing

    PubMed Central

    Erbayraktar, Zübeyde; Erbayraktar, Serhat; Yilmaz, Osman; Cerami, Anthony; Coleman, Thomas; Brines, Michael

    2009-01-01

    Erythropoietin (EPO) is a type I cytokine that utilizes different receptor isoforms either to maintain hematopoiesis or protect against injuries that arise from widely diverse etiologies. EPO also facilitates healing by reducing inflammation and mobilizing endothelial progenitor cells to participate in restorative neoangiogenesis, but it is unclear which EPO receptor isoform is responsible for healing and whether this receptor use varies according to the type of wound. In the present studies carried out in the rat, we have utilized receptor-selective derivatives of EPO to determine which receptor type operates in (i) a nonischemic wound (skin punch biopsy), (ii) a permanently ischemic wound (raised musculocutaneous flap), (iii) an intermittent ischemic reperfusion wound (pressure or decubitus ulcer), or (iv) wounds complicated by infection (cecal ligation and perforation). Using these models, we demonstrate that nonerythropoietic tissue protective compounds administered immediately following injury limit wound size and accelerate eschar closure independent of wound type. Moreover, in a model of peritonitis-induced adhesions, daily administration of the nonerythropoietic derivative carbamyl-EPO (10 μg/kg-bw) was associated with significantly lower serum TNFα concentration, illness scores, increased survival, as well as decreased adhesion formation. These results confirm that wound healing is mediated by the tissue protective receptor isoform and argue that nonerythropoietic tissue protective molecules constitute promising new PMID:19593407

  9. External tissue expansion for difficult wounds using a simple cost effective technique.

    PubMed

    Nandhagopal, Vijayaraghavan; Chittoria, Ravi Kumar; Mohapatra, Devi Prasad; Thiruvoth, Friji Meethale; Sivakumar, Dinesh Kumar; Ashokan, Arjun

    2015-01-01

    To study and discuss role of external tissue expansion and wound closure (ETEWC) technique using hooks and rubber bands. The present study is a retrospective analysis of nine cases of wounds of different aetiology where ETEWC technique was applied using hooks and rubber bands. All the wounds in the study healed completely without split thickness skin graft (SSG) or flap. ETEWC technique using hooks and rubber bands is a cost-effective technique which can be used for wound closure without SSG or flap.

  10. Negative pressure wound treatment improves Acute Physiology and Chronic Health Evaluation II score in mediastinitis allowing a successful elective pectoralis muscle flap closure: six-year experience of a single protocol.

    PubMed

    Salica, Andrea; Weltert, Luca; Scaffa, Raffaele; Guerrieri Wolf, Lorenzo; Nardella, Saverio; Bellisario, Alessandro; De Paulis, Ruggero

    2014-11-01

    Optimal management of poststernotomy mediastinitis is controversial. Negative pressure wound treatment improves wound environment and sternal stability with low surgical invasiveness. Our protocol was based on negative pressure followed by delayed surgical closure. The aim of this study was to provide the results at early follow-up and to identify the risk factors for adverse outcome. In 5400 cardiac procedures, 44 consecutive patients with mediastinitis were enrolled in the study. Mediastinitis treatment was based on urgent debridement and negative pressure as the first-line approach. After wound sterilization, chest closure was achieved by elective pectoralis muscle advancement flap. Each patient's hospital data were collected prospectively. Variables included patient demographics and clinical and biological data. Acute Physiology and Chronic Health Evaluation (APACHE) II score was calculated at the time of diagnosis and 48 hours after debridement. Focus outcome measures were mediastinitis-related death and need for reintervention after pectoralis muscle closure. El Oakley type I and type IIIA mediastinitis were the most frequent types (63.6%). Methicillin-resistant Staphylococcus aureus was present in 25 patients (56.8%). Mean APACHE II score was 19.4±4 at the time of diagnosis, and 30 patients (68.2%) required intensive care unit transfer before surgical debridement. APACHE II score improved 48 hours after wound debridement and negative pressure application (mean value, 19.4±4 vs 7.2±2; P=.005) independently of any other variables included in the study. One patient in septic shock at the time of diagnosis died (2.2%). Negative pressure promotes a significant improvement in clinical status according to APACHE II score and allows a successful elective surgical closure. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  11. Modulation of cutaneous scavenger receptor B1 levels by exogenous stressors impairs "in vitro" wound closure.

    PubMed

    Muresan, Ximena Maria; Sticozzi, Claudia; Belmonte, Giuseppe; Savelli, Vinno; Evelson, Pablo; Valacchi, Giuseppe

    2018-06-01

    Scavenger receptor B1 (SR-B1) is a trans-membrane protein, involved in tissue reverse cholesterol transport. Several studies have demonstrated that SR-B1 is also implicated in other physiological processes, such as bacteria and apoptotic cells recognition and regulation of intracellular tocopherol and carotenoids levels. Among the tissues where it is localized, SR-B1 has been shown to be significantly expressed in human epidermis. Our group has demonstrated that SR-B1 levels are down-regulated in human cultured keratinocytes by environmental stressors, such as cigarette smoke, via cellular redox imbalance. Our present study aimed to investigate whether such down-regulation was confirmed in a 3D skin model and under other environmental challengers such as particulate matter and ozone. We also investigated the association between oxidation-induced SR-B1 modulation and impaired wound closure. The data obtained showed that not only cigarette, but also the other environmental stressors reduced SR-B1 expression in epidermal cutaneous tissues and that this effect might be involved in impaired wound healing. Published by Elsevier B.V.

  12. Vγ4 T Cells Inhibit the Pro-healing Functions of Dendritic Epidermal T Cells to Delay Skin Wound Closure Through IL-17A

    PubMed Central

    Li, Yashu; Wang, Yangping; Zhou, Lina; Liu, Meixi; Liang, Guangping; Yan, Rongshuai; Jiang, Yufeng; Hao, Jianlei; Zhang, Xiaorong; Hu, Xiaohong; Huang, Yong; Wang, Rupeng; Yin, Zhinan; Wu, Jun; Luo, Gaoxing; He, Weifeng

    2018-01-01

    Dendritic epidermal T cells (DETCs) and dermal Vγ4 T cells engage in wound re-epithelialization and skin inflammation. However, it remains unknown whether a functional link between Vγ4 T cell pro-inflammation and DETC pro-healing exists to affect the outcome of skin wound closure. Here, we revealed that Vγ4 T cell-derived IL-17A inhibited IGF-1 production by DETCs to delay skin wound healing. Epidermal IL-1β and IL-23 were required for Vγ4 T cells to suppress IGF-1 production by DETCs after skin injury. Moreover, we clarified that IL-1β rather than IL-23 played a more important role in inhibiting IGF-1 production by DETCs in an NF-κB-dependent manner. Together, these findings suggested a mechanistic link between Vγ4 T cell-derived IL-17A, epidermal IL-1β/IL-23, DETC-derived IGF-1, and wound-healing responses in the skin. PMID:29483920

  13. Skin closure using staples and nylon sutures: a comparison of results.

    PubMed

    Stockley, I; Elson, R A

    1987-03-01

    A disposable skin stapler (Elite: Auto Suture UK Ltd) and Nylon vertical mattress sutures have been used for skin closure. The complications related to each method were evaluated in 129 wounds. There was a higher incidence of inflammation, discomfort on removal and spreading of the healing scar associated with staples. The only advantage of staples was speed of wound closure.

  14. Combined ionizing radiation and thermal injury in the rat. Evaluation of early excision and closure of the burn wound

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hirsch, E.F.; Vezina, R.; Corbett, S.

    1990-01-01

    The present study was undertaken to establish an animal model of combined whole-body irradiation and thermal injury and to determine the effectiveness of early excision and closure of the burn wound in such a model. Whole-body irradiation over a range of doses resulted in a predictable mortality rate, with an LD50/30 of 783 rad with 95% confidence limits of 737 and 823 rad. A controlled 10% body surface area full-thickness thermal injury resulted in no deaths in 30 animals. When combined with a standard nonlethal 10% thermal injury, varying doses of whole-body irradiation resulted in widely differing LD50/30 values inmore » three separate cohorts of rats. Excision and closure of a 10% burn 24 hours after exposure to 200 rads did not improve survival.« less

  15. Epithelialization in Wound Healing: A Comprehensive Review

    PubMed Central

    Pastar, Irena; Stojadinovic, Olivera; Yin, Natalie C.; Ramirez, Horacio; Nusbaum, Aron G.; Sawaya, Andrew; Patel, Shailee B.; Khalid, Laiqua; Isseroff, Rivkah R.; Tomic-Canic, Marjana

    2014-01-01

    Significance: Keratinocytes, a major cellular component of the epidermis, are responsible for restoring the epidermis after injury through a process termed epithelialization. This review will focus on the pivotal role of keratinocytes in epithelialization, including cellular processes and mechanisms of their regulation during re-epithelialization, and their cross talk with other cell types participating in wound healing. Recent Advances: Discoveries in epidermal stem cells, keratinocyte immune function, and the role of the epidermis as an independent neuroendocrine organ will be reviewed. Novel mechanisms of gene expression regulation important for re-epithelialization, including microRNAs and histone modifications, will also be discussed. Critical Issues: Epithelialization is an essential component of wound healing used as a defining parameter of a successful wound closure. A wound cannot be considered healed in the absence of re-epithelialization. The epithelialization process is impaired in all types of chronic wounds. Future Directions: A comprehensive understanding of the epithelialization process will ultimately lead to the development of novel therapeutic approaches to promote wound closure. PMID:25032064

  16. Formononetin accelerates wound repair by the regulation of early growth response factor-1 transcription factor through the phosphorylation of the ERK and p38 MAPK pathways.

    PubMed

    Huh, Jeong-Eun; Nam, Dong-Woo; Baek, Young-Hyun; Kang, Jung Won; Park, Dong-Suk; Choi, Do-Young; Lee, Jae-Dong

    2011-01-01

    Formononetin, a phytoestrogen from the root of Astragalus membranaceus, is used as a blood enhancer and to improve blood microcirculation in complementary and alternative medicine. The present study investigated the influence of formononetin on the expression of early growth response factor-1 (Egr-1) and growth factors contributing to wound healing. Formononetin significantly increased growth factors such as transforming growth factor-beta 1 (TGF-β1), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) in human umbilical vein endothelial cells (HUVECs). Formononetin also increased the expression of Egr-1 transcription factor by 3.2- and 10.5-fold, compared with recombinant VEGF(125) in HUVECs. The formononetin-mediated 12%-43% increase induced endothelial cell proliferation and recovered the migration of wounded HUVECs. In an ex vivo angiogenesis assay, formononetin produced a larger capillary sprouting area than produced using recombinant VEGF(125). Cell proliferation and migration of HUVECs were also greater in the presence of formonectin than VEGF(125). Western blot analysis of scratch-wounded confluent HUVECs showed that formononetin induced the phosphorylation of extracellular signal-regulated kinase (ERK) and slightly inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The formononetin-mediated sustained activation of Egr-1 was suppressed by the ERK inhibitor PD98059 and the p38 inhibitor SB203580. PD98059 inhibited the formononetin-induced endothelial proliferation and repair in scratch-wounded HUVECs, SB203580 increased the cell proliferation and wound healing. Formononetin accelerate wound closure rate as early as day 3 after surgery and consistently observed until day 10 after in wound animal model. These data suggest that formononetin promotes endothelial repair and wound healing in a process involving the over-expression of Egr-1 transcription factor

  17. Proteomic Changes of Tissue-Tolerable Plasma Treated Airway Epithelial Cells and Their Relation to Wound Healing.

    PubMed

    Lendeckel, Derik; Eymann, Christine; Emicke, Philipp; Daeschlein, Georg; Darm, Katrin; O'Neil, Serena; Beule, Achim G; von Woedtke, Thomas; Völker, Uwe; Weltmann, Klaus-Dieter; Jünger, Michael; Hosemann, Werner; Scharf, Christian

    2015-01-01

    The worldwide increasing number of patients suffering from nonhealing wounds requires the development of new safe strategies for wound repair. Recent studies suggest the possibility of nonthermal (cold) plasma application for the acceleration of wound closure. An in vitro wound healing model with upper airway S9 epithelial cells was established to determine the macroscopically optimal dosage of tissue-tolerable plasma (TTP) for wound regeneration, while a 2D-difference gel electrophoresis (2D-DIGE) approach was used to quantify the proteomic changes in a hypothesis-free manner and to evaluate the balance of beneficial and adverse effects due to TTP application. Plasma doses from 30 s up to 360 s were tested in relation to wound closure after 24 h, 48 h, 72 h, 96 h, and 120 h, in which lower doses (30, 60, and 120 s) resulted in dose-dependent improved wound healing rate compared to untreated cells. Thereby, the 120 s dose caused significantly the best wound healing properties after 96 and 120 h. The proteome analysis combined with IPA revealed that a lot of affected stress adaptation responses are linked to oxidative stress response emphasizing oxidative stress as a possible key event in the regeneration process of epithelial cells as well as in the adaptation to plasma exposure. Further cellular and molecular functions like proliferation and apoptosis were significantly up- or downregulated by all TTP treatments but mostly by the 120 s dose. For the first time, we were able to show plasma effects on cellular adaptation of upper airway epithelial S9 cells improving wound healing. This is of particular interest for plasma application, for example, in the surgery field of otorhinolaryngology or internal medicine.

  18. Proteomic Changes of Tissue-Tolerable Plasma Treated Airway Epithelial Cells and Their Relation to Wound Healing

    PubMed Central

    Lendeckel, Derik; Eymann, Christine; Emicke, Philipp; Daeschlein, Georg; Darm, Katrin; O'Neil, Serena; Beule, Achim G.; von Woedtke, Thomas; Völker, Uwe; Weltmann, Klaus-Dieter; Jünger, Michael; Hosemann, Werner; Scharf, Christian

    2015-01-01

    Background. The worldwide increasing number of patients suffering from nonhealing wounds requires the development of new safe strategies for wound repair. Recent studies suggest the possibility of nonthermal (cold) plasma application for the acceleration of wound closure. Methods. An in vitro wound healing model with upper airway S9 epithelial cells was established to determine the macroscopically optimal dosage of tissue-tolerable plasma (TTP) for wound regeneration, while a 2D-difference gel electrophoresis (2D-DIGE) approach was used to quantify the proteomic changes in a hypothesis-free manner and to evaluate the balance of beneficial and adverse effects due to TTP application. Results. Plasma doses from 30 s up to 360 s were tested in relation to wound closure after 24 h, 48 h, 72 h, 96 h, and 120 h, in which lower doses (30, 60, and 120 s) resulted in dose-dependent improved wound healing rate compared to untreated cells. Thereby, the 120 s dose caused significantly the best wound healing properties after 96 and 120 h. The proteome analysis combined with IPA revealed that a lot of affected stress adaptation responses are linked to oxidative stress response emphasizing oxidative stress as a possible key event in the regeneration process of epithelial cells as well as in the adaptation to plasma exposure. Further cellular and molecular functions like proliferation and apoptosis were significantly up- or downregulated by all TTP treatments but mostly by the 120 s dose. Conclusions. For the first time, we were able to show plasma effects on cellular adaptation of upper airway epithelial S9 cells improving wound healing. This is of particular interest for plasma application, for example, in the surgery field of otorhinolaryngology or internal medicine. PMID:26539504

  19. Androstenediol reduces the anti-inflammatory effects of restraint stress during wound healing.

    PubMed

    Head, Cynthia C; Farrow, Michael J; Sheridan, John F; Padgett, David A

    2006-11-01

    Restraint stress (RST) delays wound closure and suppresses pro-inflammatory gene expression by a glucocorticoid-dependent mechanism. Because androstenediol (AED) ameliorates many of the anti-inflammatory influences of glucocorticoids (GC) in vitro, it was hypothesized that treatment of stressed animals with AED would ameliorate the suppressive influence of restraint and restore healing to control levels. To test this hypothesis, male CD1 mice were subjected to nightly cycles of RST beginning 3 days prior to placement of two 3.5 mm full-thickness cutaneous wounds. To assess the influence of AED treatment on wound repair, mice were injected subcutaneously with 2.0 mg of AED or an equivalent volume of delivery vehicle (VEH) prior to wounding. The rate of wound closure was assessed daily by photoplanimetry. In addition, at 3, 6, 12, and 24 h post wounding, IL-1beta, MCP-1, and PDGF RNAs were quantified in wounds as a measure of inflammatory gene expression. The data showed that RST significantly delayed closure as compared to controls. In parallel, RST significantly decreased IL-1beta and PDGF gene expression as early as 12 h after wounding. In contrast, treatment with AED prevented the stress-induced delay in healing. Whereas wounds on VEH/RST mice did not achieve 50% closure until day 7, wounds on AED-treated animals, whether subjected to RST or not, had closed by 50% within 3 days of wounding. In addition, AED treatment prevented the stress-induced suppression of IL-1beta and PDGF gene expression 24 h after injury. Therefore, AED may provide a pharmacologic approach to ameliorate the anti-inflammatory effects of behavioral stress and in doing so, may improve tissue repair.

  20. Efficient Homodifunctional Bimolecular Ring-Closure Method for Cyclic Polymers by Combining RAFT and Self-Accelerating Click Reaction.

    PubMed

    Qu, Lin; Sun, Peng; Wu, Ying; Zhang, Ke; Liu, Zhengping

    2017-08-01

    An efficient metal-free homodifunctional bimolecular ring-closure method is developed for the formation of cyclic polymers by combining reversible addition-fragmentation chain transfer (RAFT) polymerization and self-accelerating click reaction. In this approach, α,ω-homodifunctional linear polymers with azide terminals are prepared by RAFT polymerization and postmodification of polymer chain end groups. By virtue of sym-dibenzo-1,5-cyclooctadiene-3,7-diyne (DBA) as small linkers, well-defined cyclic polymers are then prepared using the self-accelerating double strain-promoted azide-alkyne click (DSPAAC) reaction to ring-close the azide end-functionalized homodifunctional linear polymer precursors. Due to the self-accelerating property of DSPAAC ring-closing reaction, this novel method eliminates the requirement of equimolar amounts of telechelic polymers and small linkers in traditional bimolecular ring-closure methods. It facilitates this method to efficiently and conveniently produce varied pure cyclic polymers by employing an excess molar amount of DBA small linkers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Priming with a combination of proangiogenic growth factors improves wound healing in normoglycemic mice

    PubMed Central

    Ackermann, Maximilian; Wolloscheck, Tanja; Wellmann, Axel; Li, Vincent W.; Li, William W.; Konerding, Moritz A.

    2012-01-01

    Growth factors and/or angiogenic factors are supposed to improve wound healing. The aim of our study was to evaluate the effects of subcutaneous pretreatment with combinatory proangiogenic factors on wound closure, mechanical properties, vessel density, and morphology. Twenty-eight Balb/c mice were divided equally into two groups. A mixture of VEGF (35.0 μg), bFGF (2.5 μg), and PDGF (3.5 μg) was administered 3, 5, and 7 days subcutaneously to 14 mice before full thickness skin punch biopsy wounding, whereas 14 control animals received three times 0.2 ml saline solution. Wound sizes were assessed daily and the repaired tissues were harvested 7 days after complete wound closure. Complete closure (≥95% healing of initial wound area) was reached in all proangiogenic pretreated animals on day 10, whereas controls needed 13 days for complete closure. Tensile strengths were nearly twofold higher than in the controls (p≤0.01). The punch biopsy material revealed 4.2 fold higher vessel densities in the proangiogenic pretreated group. On day 17, the vessel densities in the proangiogenic pretreated wounds were also 3.2 fold higher than in the untreated controls. No significant differences were seen in the collagen ratio. Pretreatment with proangiogenic factors revealed several significant effects on wound healing: faster time to closure, a higher vessel density, better functional outcome. These results suggest a beneficial effect of pretreatment with combinatory growth factors in mouse skin wounds without impaired wound healing. This might be exploited in further investigations in diabetic healing as a therapeutic approach for elective surgery. PMID:21373751

  2. Enhancement of cutaneous wound healing by Dsg2 augmentation of uPAR secretion.

    PubMed

    Cooper, Felicia; Overmiller, Andrew M; Loder, Anthony; Brennan-Crispi, Donna M; McGuinn, Kathleen P; Marous, Molly R; Freeman, Theresa A; Riobo-Del Galdo, Natalia A; Siracusa, Linda D; Wahl, James K; Mahoney, Mỹ G

    2018-05-09

    In addition to playing a role in adhesion, desmoglein 2 (Dsg2) is an important regulator of growth and survival signaling pathways, cell proliferation, migration and invasion, and oncogenesis. While low-level Dsg2 expression is observed in basal keratinocytes and is downregulated in non-healing venous ulcers, overexpression has been observed in both melanomas and non-melanoma malignancies. Here, we show that transgenic mice overexpressing Dsg2 in basal keratinocytes primed the activation of mitogenic pathways, but did not induce dramatic epidermal changes or susceptibility to chemical-induced tumor development. Interestingly, acceleration of full-thickness wound closure and increased wound-adjacent keratinocyte proliferation was observed in these mice. As epidermal cytokines and their receptors play critical roles in wound healing, Dsg2-induced secretome alterations were assessed with an antibody profiler array and revealed increased release and proteolytic processing of the urokinase-type plasminogen activator receptor (uPAR). Dsg2 induced uPAR expression in the skin of transgenic compared to wild-type mice. Wound healing further enhanced uPAR in both epidermis and dermis with concomitant increase in the pro-healing laminin-332, a major component of the basement membrane zone, in transgenic mice. This study demonstrates that Dsg2 induces epidermal activation of various signaling cascades and accelerates cutaneous wound healing, in part, through uPAR-related signaling cascades. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Macrophage Phenotypes Regulate Scar Formation and Chronic Wound Healing.

    PubMed

    Hesketh, Mark; Sahin, Katherine B; West, Zoe E; Murray, Rachael Z

    2017-07-17

    Macrophages and inflammation play a beneficial role during wound repair with macrophages regulating a wide range of processes, such as removal of dead cells, debris and pathogens, through to extracellular matrix deposition re-vascularisation and wound re-epithelialisation. To perform this range of functions, these cells develop distinct phenotypes over the course of wound healing. They can present with a pro-inflammatory M1 phenotype, more often found in the early stages of repair, through to anti-inflammatory M2 phenotypes that are pro-repair in the latter stages of wound healing. There is a continuum of phenotypes between these ranges with some cells sharing phenotypes of both M1 and M2 macrophages. One of the less pleasant consequences of quick closure, namely the replacement with scar tissue, is also regulated by macrophages, through their promotion of fibroblast proliferation, myofibroblast differentiation and collagen deposition. Alterations in macrophage number and phenotype disrupt this process and can dictate the level of scar formation. It is also clear that dysregulated inflammation and altered macrophage phenotypes are responsible for hindering closure of chronic wounds. The review will discuss our current knowledge of macrophage phenotype on the repair process and how alterations in the phenotypes might alter wound closure and the final repair quality.

  4. Impaired wound healing in mice deficient in a matricellular protein SPARC (osteonectin, BM-40)

    PubMed Central

    Basu, Amitabha; Kligman, Lorraine H; Samulewicz, Stefan J; Howe, Chin C

    2001-01-01

    Background SPARC is a matricellular protein involved in cell-matrix interactions. From expression patterns at the wound site and in vitro studies, SPARC has been implicated in the control of wound healing. Here we examined the function of SPARC in cutaneous wound healing using SPARC-null mice and dermal fibroblasts derived from them. Results In large (25 mm) wounds, SPARC-null mice showed a significant delay in healing as compared to wild-type mice (31 days versus 24 days). Granulation tissue formation and extracellular matrix protein production were delayed in small 6 mm SPARC-null wounds initially but were resolved by day 6. In in vitro wound-healing assays, while wild-type primary dermal fibroblasts showed essentially complete wound closure at 11 hours, wound closure of SPARC-null cells was incomplete even at 31 hours. Addition of purified SPARC restored the normal time course of wound closure. Treatment of SPARC-null cells with mitomycin C to analyze cell migration without cell proliferation showed that wound repair remained incomplete after 31 hours. Cell proliferation as measured by 3H-thymidine incorporation and collagen gel contraction by SPARC-null cells were not compromised. Conclusions A significant delay in healing large excisional wounds and setback in granulation tissue formation and extracellular matrix protein production in small wounds establish that SPARC is required for granulation tissue formation during normal repair of skin wounds in mice. A defect in wound closure in vitro indicates that SPARC regulates cell migration. We conclude that SPARC plays a role in wound repair by promoting fibroblast migration and thus granulation tissue formation. PMID:11532190

  5. Contribution of Invariant Natural Killer T Cells to Skin Wound Healing.

    PubMed

    Tanno, Hiromasa; Kawakami, Kazuyoshi; Ritsu, Masae; Kanno, Emi; Suzuki, Aiko; Kamimatsuno, Rina; Takagi, Naoyuki; Miyasaka, Tomomitsu; Ishii, Keiko; Imai, Yoshimichi; Maruyama, Ryoko; Tachi, Masahiro

    2015-12-01

    In the present study, we determined the contribution of invariant natural killer T (iNKT) cells to the skin wound healing process. In iNKT cell-deficient (Jα18KO) mice lacking iNKT cells, wound closure was significantly delayed compared with wild-type mice. Collagen deposition, expression of α-smooth muscle actin and CD31, and wound breaking strength were significantly attenuated in Jα18KO mice. The adoptive transfer of liver mononuclear cells from wild-type but not from Jα18KO or interferon (IFN)-γ gene-disrupted (IFN-γKO) mice resulted in the reversal of this impaired wound healing in Jα18KO mice. IFN-γ expression was induced in the wounded tissues, which was significantly decreased at 6, 12, and 24 hours, but increased on day 3 after wounding in Jα18KO mice. The main source of the late-phase IFN-γ production in Jα18KO mice were neutrophils rather than NK cells and T cells. Administration of α-galactosylceramide, an activator of iNKT cells, resulted in the acceleration of wound healing on day 3 in wild-type mice. This effect was not observed in IFN-γKO mice. These results indicate that iNKT cells play important roles in wound healing. The iNKT cell-induced IFN-γ production may regulate the wound healing process in the early phase. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Negative Pressure Wound Therapy: Experience in 45 Dogs

    PubMed Central

    Pitt, Kathryn A.; Stanley, Bryden J.

    2016-01-01

    Objective To report experience with negative pressure wound therapy (NPWT) in 45 consecutive dogs admitted with extensive cutaneous wounds and to determine if NPWT is feasible in veterinary hospital practice. Study Design Prospective descriptive study Animals Dogs (n = 45) Methods Collected data were organized into 6 categories: patient data, wound data, NPWT data, adjunctive treatments, complications, and final outcome Results Wounds (53 in 45 dogs) were largely traumatic in origin, and distributed fairly evenly to the trunk, proximal and distal aspects of the limbs. Most wounds (34 dogs, 76%) had no granulation tissue and were treated a mean of 4.2 days after wounding, whereas 11 dogs had granulating wounds that were initially treated a mean of 87 days after wounding. Median NPWT use was 3 days with a mean hospitalization of 7.8 days. Most wounds (33; 62%) were closed surgically after NPWT and were healed by 14 days. The other 18 wounds healed (mean, 21 days) by second intention after hospital discharge. Overall, 96% of the wounds healed; 2 dogs died before definitive closure could be attempted. Conclusion NPWT is applicable to a wide variety of canine wounds is well tolerated, allows for several days between dressing changes, and can used to optimize the wound bed for surgical closure or second intention healing. PMID:24512302

  7. Synthesis of Novel Derivatives of Quinazoline Schiff base Compound Promotes Epithelial Wound Healing.

    PubMed

    Bagheri, Elham; Saremi, Kamelia; Hajiaghaalipour, Fatemeh; Faraj, Fadhil Lafta; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen; Khaing, Si Lay; Salehen, Nur'Ain

    2018-01-30

    Quinazoline is an aromatic bicyclic compound exhibiting several pharmaceutical and biological activities. This study was conducted to investigate the potential wound healing properties of synthetic quinazoline compound (SQC) on experimental rats. The toxicity of SQC was determined by MTT cell proliferation assay. The healing effect of SQC was assessed by in vitro wound healing scratch assay on the skin fibroblast cells (BJ-5ta) and in vivo wound healing experiment of low and high dose of SQC on adult Sprague-Dawley rats compared with negative (gum acacia) and positive control (Intrasite-gel). Hematoxylin and eosin (H&E), Masson's trichrome (MT) staining and immunohistochemistry analysis were performed to evaluate the histopathological alterations and proteins expression of Bax and Hsp70 on the wound tissue after 10 days. In addition, levels of antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase), and malondialdehyde (MDA) were measured in wound tissue homogenates. The SQC significantly enhanced BJ-5ta cell proliferation and accelerated the percentage of wound closure, with less scarring, increased fibroblast and collagen fibers and less inflammatory cells compared with the negative control. The compound also increases endogenous enzymes and decline lipid peroxidation in wound homogenate. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Endocytosis-dependent coordination of multiple actin regulators is required for wound healing

    PubMed Central

    Matsubayashi, Yutaka; Coulson-Gilmer, Camilla

    2015-01-01

    The ability to heal wounds efficiently is essential for life. After wounding of an epithelium, the cells bordering the wound form dynamic actin protrusions and/or a contractile actomyosin cable, and these actin structures drive wound closure. Despite their importance in wound healing, the molecular mechanisms that regulate the assembly of these actin structures at wound edges are not well understood. In this paper, using Drosophila melanogaster embryos, we demonstrate that Diaphanous, SCAR, and WASp play distinct but overlapping roles in regulating actin assembly during wound healing. Moreover, we show that endocytosis is essential for wound edge actin assembly and wound closure. We identify adherens junctions (AJs) as a key target of endocytosis during wound healing and propose that endocytic remodeling of AJs is required to form “signaling centers” along the wound edge that control actin assembly. We conclude that coordination of actin assembly, AJ remodeling, and membrane traffic is required for the construction of a motile leading edge during wound healing. PMID:26216900

  9. In vitro and In vivo characterization of quercetin loaded multiphase hydrogel for wound healing application.

    PubMed

    Jangde, Rajendra; Srivastava, Shikha; Singh, Manju R; Singh, Deependra

    2018-05-03

    The present work aim to prepare and evaluate multiphase hydrogel system incorporated with quercetin loaded liposomes (QLH), for wound healing. The quercetin loaded liposomal hydrogel were prepared by taking 15% carbopol and varying gelatin ratio. The clear and transparent hydrogel was obtained by taking ratio of gelatin to carbapol (6/4) compared to other ratios. The best prepared hydrogel were characterized for surface morphology, water vapor transmission rate (WVTR), swelling ratio, hemocompatibility, stability, in-vitro release and in-vivo studies. The evaluated results of (QLH) for surface morphology, WVTR, swelling ratio, hemocompatibility and in-vitro release were found to be significant compared to other prepared formulations. Consequently, on basis of optimized hydrogel was selected to study wound healing activity in albino rats. The results demonstrated accelerated wound-healing with significant decrease in wound closure time compared to conventional dosage form. The results of in-vitro and in-vivo promises reliable mode of treatment for connective tissue disorder as wound healing. Copyright © 2018. Published by Elsevier B.V.

  10. Wound-healing Activity of Zanthoxylum bungeanum Maxim Seed Oil on Experimentally Burned Rats

    PubMed Central

    Li, Xiao-Qiang; Kang, Rong; Huo, Jun-Cheng; Xie, Yan-Hua; Wang, Si-Wang; Cao, Wei

    2017-01-01

    Background: The seed oil of Zanthoxylum bungeanum Maxim (ZBSO) is considered to be rich source of fatty acids, mainly oleic and linoleic acids, and has been used for the treatment of burns in Chinese medicine. Objective: We evaluated the healing efficacy of ZBSO and explored its possible mechanism on scalded rats. Materials and Methods: Sprague-Dawley rat models with deep second-degree burns were set up, and ZBSO (500 and 1000 μl/wound) was topically applied twice daily for 7 days and then once daily until wound healing. The therapeutic effects of ZBSO were evaluated by observing wound closure time, decrustation time, wound-healing ratio, and pathological changes. Collagen type-III, matrix metalloproteinase-2 (MMP-2), MMP-9, phospho-nuclear factor-κB (p-NF-κB) p65, inhibitor of NF-κB subunit α p-IκBα, and inhibitor of NF-κB subunit α (IκBα) expression were determined using Western blotting. Results: The ZBSO-treated group showed a higher wound-healing ratio and shorter decrustation and wound closure times than the untreated group. The topical application of ZBSO increased collagen synthesis as evidenced by an increase in hydroxyproline level and upregulated expression of collagen type-III on days 7, 14, and 21 posttreatment. A reduction in MMP-2 and MMP-9 expressions also confirmed the collagen formation efficacy of ZBSO. Furthermore, there was a significant increase in superoxide dismutase levels and a decrease in malondialdehyde levels in ZBSO-treated wounds. ZBSO also decreased tumor necrosis factor alpha, interleukin-1 (IL-1) β, and IL-6 levels in serum, upregulated IκBα, and downregulated p-NF-κB p65 and p-IκBα expression in vivo, indicating the anti-inflammatory action of ZBSO. Conclusion: ZBSO has significant potential to treat burn wounds by accelerating collagen synthesis and the anti-inflammatory cascade of the healing process. SUMMARY The seed oil of Zanthoxylum bungeanum Maxim (ZBSO) is rich of fatty acidsThe healing efficacy of ZBSO on

  11. Androgen Deprivation Accelerates the Prostatic Urethra Wound Healing After Thulium Laser Resection of the Prostate by Promoting Re-Epithelialization and Regulating the Macrophage Polarization.

    PubMed

    Wang, Xing-Jie; Zhuo, Jian; Luo, Guang-Heng; Zhu, Yi-Ping; Yu, Dian-Jun; Zhao, Rui-Zhe; Jiang, Chen-Yi; Shi, Yun-Feng; Li, Hao; Chen, Lei; Hao, Kui-Yuan; Han, Xia; Zhao, Sheng; Bei, Xiao-Yu; Jing, Yi-Feng; Xia, Shu-Jie

    2017-05-01

    Complications after a thulium laser resection of the prostate (TmLRP) are related to re-epithelialization of the prostatic urethra. Since prostate growth and development are induced by androgen, the aim of this study was to determine the role and explore the mechanism of androgen in wound healing of the prostatic urethra. Beagles that received TmLRPs were randomly distributed into a castration group, a testosterone undecanoate (TU) group, and a control group. The prostate wound was assessed once a week using a cystoscope. Histological analysis was then carried out to study the re-epithelialization of the prostatic urethra in each group. The inflammatory response in the wound tissue and urine was also investigated. The healing of the prostatic urethra after a TmLRP was more rapid in the castration group and slower in the TU group than that in the control group. Castration accelerated re-epithelialization by promoting basal cell proliferation in the wound surface and beneath the wound and by accelerating the differentiation of basal cells into urothelial cells. Castration reduced the duration of the inflammatory phase and induced the conversion of M1 macrophages to M2 macrophages, thus accelerating the maturation of the wound. By contrast, androgen supplementation enhanced the inflammatory response and prolonged the inflammatory phase. Moreover, the anti-inflammatory phase was delayed and weakened. Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP. Prostate 77:708-717, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Ala42S100A8 Ameliorates Psychological-Stress Impaired Cutaneous Wound Healing

    PubMed Central

    Sroussi, Herve Y.; Williams, Richard L.; Zhang, Qing. L.; Villines, Dana.; Marucha, Phillip. T.

    2009-01-01

    Although wound healing is generally a successful, carefully orchestrated and evolutionary sound process, it can be disregulated by extrinsic factors such as psychological stress. In the SKH-1 restraint stress model of cutaneous wound healing, the rate of wound closure is approximately 30% slower in stressed mice. Delay in healing is associated with exaggerated acute inflammation and deficient bacterial clearance at the wound site. It has been suggested that wound hypoxia may contribute to the mechanisms of impaired cutaneous wound healing in the mouse SKH-1 model. Optimal healing of a cutaneous wound is a stepwise repair program. In its early phase, an inflammatory oxidative burst generated by neutrophils is observed. 40% of neutrophils cytosolic protein weight is comprised of two calcium binding proteins S100A8 and S100A9. Our previous work has shown that S100A8 act as an oxidation sensitive repellent of human neutrophils in-vitro. Ala42S100A8, a site-directed mutant protein is resistant to oxidative inhibition and inhibits neutrophil recruitment in-vivo. Accordingly, we tested the hypothesis that S100A8 may ameliorate wound healing in this model. We examined the effect of wild type and ala42S100A8 for their ability to ameliorate wound closure rates. The data indicated that a single local application of ala42S100A8 ameliorated the decreased rate of wound closure resulting from stress. This occurred without significantly affecting wound bacterial clearance. Wild type S100A8 only had a partial beneficial effect on the rate of wound closure. Those findings support further translational studies of S100 based intervention to ameliorate impaired wound healing. PMID:19336252

  13. Ala42S100A8 ameliorates psychological-stress impaired cutaneous wound healing.

    PubMed

    Sroussi, Herve Y; Williams, Richard L; Zhang, Qing L; Villines, Dana; Marucha, Phillip T

    2009-08-01

    Although wound healing is generally a successful, carefully orchestrated and evolutionary sound process, it can be disregulated by extrinsic factors such as psychological-stress. In the SKH-1 restraint stress model of cutaneous wound healing, the rate of wound closure is approximately 30% slower in stressed mice. Delay in healing is associated with exaggerated acute inflammation and deficient bacterial clearance at the wound site. It has been suggested that wound hypoxia may contribute to the mechanisms of impaired cutaneous wound healing in the mouse SKH-1 model. Optimal healing of a cutaneous wound is a stepwise repair program. In its early phase, an inflammatory oxidative burst generated by neutrophils is observed. About 40% of neutrophils cytosolic protein weight is comprised of two calcium binding proteins S100A8 and S100A9. Our previous work has shown that S100A8 act as an oxidation-sensitive repellent of human neutrophils in-vitro. Ala(42)S100A8, a site-directed mutant protein is resistant to oxidative inhibition and inhibits neutrophil recruitment in-vivo. Accordingly, we tested the hypothesis that S100A8 may ameliorate wound healing in this model. We examined the effect of wild-type and ala(42)S100A8 for their ability to ameliorate wound closure rates. The data indicated that a single local application of ala(42)S100A8 ameliorated the decreased rate of wound closure resulting from stress. This occurred without significantly affecting wound bacterial clearance. Wild-type S100A8 only had a partial beneficial effect on the rate of wound closure. Those findings support further translational studies of S100 based intervention to ameliorate impaired wound healing.

  14. Stromal cell-derived factor 1 (SDF-1) accelerated skin wound healing by promoting the migration and proliferation of epidermal stem cells.

    PubMed

    Guo, Rui; Chai, Linlin; Chen, Liang; Chen, Wenguang; Ge, Liangpeng; Li, Xiaoge; Li, Hongli; Li, Shirong; Cao, Chuan

    2015-06-01

    Epidermal stem cells could contribute to skin repair through the migration of cells from the neighboring uninjured epidermis, infundibulum, hair follicle, or sebaceous gland. However, little is known about the factors responsible for the complex biological processes in wound healing. Herein, we will show that the attracting chemokine, SDF-1/CXCR4, is a major regulator involved in the migration of epidermal stem cells during wound repair. We found that the SDF-1 levels were markedly increased at the wound margins following injury and CXCR4 expressed in epidermal stem cells and proliferating epithelial cells. Blocking the SDF-1/CXCR4 axis resulted in a significant reduction in epidermal stem cell migration toward SDF-1 in vitro and delayed wound healing in vivo, while an SDF-1 treatment enhanced epidermal stem cell migration and proliferation and accelerated wound healing. These results provide direct evidence that SDF-1 promotes epidermal stem cell migration, accelerates skin regeneration, and makes the development of new regenerative therapeutic strategies for wound healing possible.

  15. Effects of genistein on early-stage cutaneous wound healing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung

    2011-07-08

    Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected bymore » antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These

  16. Primary versus secondary closure of cutaneous abscesses in the emergency department: a randomized controlled trial.

    PubMed

    Singer, Adam J; Taira, Breena R; Chale, Stuart; Bhat, Rahul; Kennedy, David; Schmitz, Gillian

    2013-01-01

    Cutaneous abscesses have traditionally been treated with incision and drainage (I&D) and left to heal by secondary closure. The objective was to compare the healing rates of cutaneous abscesses following I&D after primary or secondary closure. This was a randomized, controlled, trial, balanced by center, with blocked randomization created by a random-number generator. One urban and one suburban academic emergency department (ED) participated. Subjects were randomized to primary or secondary wound closure following I&D of the abscess. Main outcome measures were the percentage of healed wounds (wound was completely closed by visual inspection; a 40% difference in wound healing was sought) and overall failure rate (need for additional intervention including suture removal, additional drainage, antibiotics, or admission within 7 days after drainage). Fifty-six adult patients with simple localized cutaneous abscesses were included; 29 were randomized to primary closure, and 27 were randomized to secondary closure. Healing rates at 7 days were similar between the primary and secondary closure groups (69.6%, 95% confidence interval [CI] = 49.1% to 84.4% vs. 59.3%, 95% CI = 40.7% to 75.5%; difference 10.3%, 95% CI = -15.8% to 34.1%). Overall failure rates at 7 days were also similar between the primary and secondary closure groups (30.4%, 95% CI = 15.6% to 50.9% vs. 28.6%, 95% CI = 15.2% to 47.1%; difference 1.8%, 95% CI = -24.2% to 28.8%). The rates of wound healing and treatment failure following I&D of simple abscesses in the ED are similar after primary or secondary closure. The authors did not detect a difference of at least 40% in healing rates between primary and secondary closure. © 2013 by the Society for Academic Emergency Medicine.

  17. Skin closure using staples and nylon sutures: a comparison of results.

    PubMed Central

    Stockley, I.; Elson, R. A.

    1987-01-01

    A disposable skin stapler (Elite: Auto Suture UK Ltd) and Nylon vertical mattress sutures have been used for skin closure. The complications related to each method were evaluated in 129 wounds. There was a higher incidence of inflammation, discomfort on removal and spreading of the healing scar associated with staples. The only advantage of staples was speed of wound closure. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:3566131

  18. Initial clinical assessment of a novel wound management system: a case series.

    PubMed

    Reyzelman, Alexander M; Vayser, Dean; Tam, S William; Dove, Cyaandi

    2011-06-01

    The importance of exudate management for maintaining local moisture balance and avoiding maceration in the chronic wound environment is well established. The authors performed the initial clinical testing of a novel wound management system, Sepaderm (Aalnex, Inc, Irvine, California), designed to vertically wick and sequester excess exudate away from wound/periwound tissues to promote a healthy wound environment. In this series of 14 patients with lower-extremity chronic venous leg and diabetic foot ulcers, the 3-component system was well tolerated and demonstrated the ability to prevent exudate leakage onto periwound tissue and reduce existing pain and itching. All ulcers lasting 1.2 to 360 months were previously treated with standard therapies, including human cell-derived skin substitutes in some of the patients. After treatment with the new system for 7 to 174 days, 8 patients had various degrees of wound closure, ranging from 44% to 100%. The 6 patients who failed to show wound closure were treated with the new system for an average of 5.7 days, but demonstrated other clinical benefits. Future studies in larger patient populations with quantitative wound closure assessments, as well as measurements of exudate, periwound maceration, and pain management, are needed.

  19. Use of 2-octyl cyanoacrylate for wound closure in a modified Roberts-Bistner procedure for eyelid agenesis in five cats (nine eyes).

    PubMed

    Reed, Zoe; Doering, Clinton J; Barrett, Paul M

    2018-01-15

    CASE DESCRIPTION 5 cats (9 eyes) were evaluated for surgical correction of bilateral eyelid agenesis. CLINICAL FINDINGS All eyes lacked > 25% of the temporal upper eyelid, and all cats had clinical signs attributable to chronic ocular exposure. Abnormalities were limited to the ocular surface in the 4 female cats, whereas the sole male cat had additional abnormalities consistent with anterior segment dysgenesis. TREATMENT AND OUTCOME A modified Roberts-Bistner procedure involving 2-octyl cyanoacrylate (2OCA) was performed on 9 eyes; 1 eye was enucleated. Surgical wounds in the initial 3 eyes were closed with 2OCA plus sutures, and flaps were lined with conjunctiva. The technique was optimized for remaining eyes by use of a single suture for flap apposition, no conjunctival lining of flaps, and 2OCA alone for wound closure. Median duration of surgery was 35 minutes/eye for the initial 3 eyes versus 16 minutes/eye for the subsequent 6 eyes treated with the optimized procedure. After surgery, all cats had complete palpebral reflexes and resolution of clinical signs of ocular irritation. Minor complications in the early postoperative period included eyelid swelling (n = 9), poor cosmesis (7), and persistent epiphora (3). By the second recheck examination, swelling had resolved and cosmesis was considered excellent. Two eyes with epiphora had been treated with the initial modified procedure and required cryoepilation for resolution of epiphora. CLINICAL RELEVANCE The modified Roberts-Bistner procedure for eyelid agenesis involving 2OCA for wound closure provided functional, cosmetic eyelids that improved comfort and provided protection of the ocular surface in affected cats.

  20. Embryonic wound healing by apical contraction and ingression in Xenopus laevis.

    PubMed

    Davidson, Lance A; Ezin, Akouavi M; Keller, Ray

    2002-11-01

    We have characterized excisional wounds in the animal cap of early embryos of the frog Xenopus laevis and found that these wounds close accompanied by three distinct processes: (1) the assembly of an actin purse-string in the epithelial cells at the wound margin, (2) contraction and ingression of exposed deep cells, and (3) protrusive activity of epithelial cells at the margin. Microsurgical manipulation allowing fine control over the area and depth of the wound combined with videomicroscopy and confocal analysis enabled us to describe the kinematics and challenge the mechanics of the closing wound. Full closure typically occurs only when the deep, mesenchymal cell-layer of the ectoderm is left intact; in contrast, when deep cells are removed along with the superficial, epithelial cell-layer of the ectoderm, wounds do not close. Actin localizes to the superficial epithelial cell-layer at the wound margin immediately after wounding and forms a contiguous "purse-string" in those cells within 15 min. However, manipulation and closure kinematics of shaped wounds and microsurgical cuts made through the purse-string rule out a major force-generating role for the purse-string. Further analysis of the cell behaviors within the wound show that deep, mesenchymal cells contract their apical surfaces and ingress from the exposed surface. High resolution time-lapse sequences of cells at the leading edge of the wound show that these cells undergo protrusive activity only during the final phases of wound closure as the ectoderm reseals. We propose that assembly of the actin purse-string works to organize and maintain the epithelial sheet at the wound margin, that contraction and ingression of deep cells pulls the wound margins together, and that protrusive activity of epithelial cells at the wound margin reseals the ectoderm and re-establishes tissue integrity during wound healing in the Xenopus embryonic ectoderm. Copyright 2002 Wiley-Liss, Inc.

  1. Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport

    PubMed Central

    Ozawa, Kentaro; Kondo, Toshikazu; Hori, Osamu; Kitao, Yasuko; Stern, David M.; Eisenmenger, Wolfgang; Ogawa, Satoshi; Ohshima, Tohru

    2001-01-01

    Expression of angiogenic factors such as VEGF under conditions of hypoxia or other kinds of cell stress contributes to neovascularization during wound healing. The inducible endoplasmic reticulum chaperone oxygen-regulated protein 150 (ORP150) is expressed in human wounds along with VEGF. Colocalization of these two molecules was observed in macrophages in the neovasculature, suggesting a role of ORP150 in the promotion of angiogenesis. Local administration of ORP150 sense adenovirus to wounds of diabetic mice, a treatment that efficiently targeted this gene product to the macrophages of wound beds, increased VEGF antigen in wounds and accelerated repair and neovascularization. In cultured human macrophages, inhibition of ORP150 expression caused retention of VEGF antigen within the endoplasmic reticulum (ER), while overexpression of ORP150 promoted the secretion of VEGF into hypoxic culture supernatants. Taken together, these data suggest an important role for ORP150 in the setting of impaired wound repair and identify a key, inducible chaperone-like molecule in the ER. This novel facet of the angiogenic response may be amenable to therapeutic manipulation. PMID:11435456

  2. Tissue adhesives for closure of surgical incisions.

    PubMed

    Coulthard, Paul; Esposito, Marco; Worthington, Helen V; van der Elst, Maarten; van Waes, Oscar J F; Darcey, James

    2010-05-12

    Sutures, staples and adhesive tapes are the traditional methods of wound closure, whilst tissue adhesives have entered clinical practice more recently. Closure of wounds with sutures enables meticulous closure, but they may show tissue reactivity and can require removal. Tissue adhesives offer the advantages of no risk of needlestick injury and no requirement to remove sutures later. Tissue adhesives have been used primarily in emergency rooms but this review looks at the use of tissue adhesives in the operating room where surgeons are increasingly using these for the closure of surgical skin incisions. To determine the relative effects of various tissue adhesives and conventional skin closure techniques on the healing of surgical wounds. For this update we searched the Cochrane Wounds Group Specialised Register (Searched 17/11/09); The Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library Issue 4 2009; Ovid MEDLINE - 1950 to November Week 1 2009; Ovid EMBASE - 1980 to 2009 Week 46; EBSCO CINAHL - 1982 to 17 November 20098. No date or language restrictions were applied. Only randomised controlled clinical trials were eligible for inclusion. Screening of eligible studies and data extraction were conducted independently and in triplicate whilst assessment of the methodological quality of the trials was conducted independently and in duplicate. Results were expressed as random effects models using mean difference for continuous outcomes and relative risks with 95% confidence intervals for dichotomous outcomes. Heterogeneity was investigated including both clinical and methodological factors. This update identified an additional six trials resulting in a total of fourteen RCTs (1152 patients) which met the inclusion criteria. Sutures were significantly better than tissue adhesives for minimising dehiscence (10 trials). Sutures were also found to be significantly faster to use. For all other analyses of infection, patient and operator

  3. Recruitment of mesenchymal stem cells and macrophages by dual release of stromal cell-derived factor-1 and a macrophage recruitment agent enhances wound closure.

    PubMed

    Kim, Yang-Hee; Tabata, Yasuhiko

    2016-04-01

    In this study, the wound closure of mouse skin defects was examined in terms of recruitment of mesenchymal stem cells (MSC) and macrophages. For the cells recruitment, stromal derived factor-1 (SDF-1) of a MSC recruitment agent and sphingosine-1 phosphate agonist (SEW2871) of a macrophages recruitment agent were incorporated into gelatin hydrogels, and then released in a controlled fashion. When applied to a skin wound defect of mice, gelatin hydrogels incorporating mixed 500 ng SDF-1 and 0.4, 0.8, or 1.6 mg SEW2871-micelles recruited a higher number of both MSC and macrophages than those incorporating SDF-1 or phosphate buffered saline. However, the number of M1 phenotype macrophages for the hydrogel incorporating mixed SDF-1 and SEW2871-micelles recruited was remarkably low to a significant extent compared with that for those hydrogel incorporating 0.4, 0.8, or 1.6 mg SEW2871-micelles. On the other hand, the number of M2 macrophages 3 days after the implantation of the hydrogels incorporating SDF-1 and 0.4 mg SEW2871-micelles significantly increased compared with that for other hydrogels. In vivo experiments revealed the hydrogels incorporating SDF-1 and 0.4 mg SEW2871-micelles promoted the wound closure of skin defect to a significant stronger extent than those incorporating SEW2871-micelles, SDF-1, and a mixture of SDF-1 and higher doses of SEW2871-micelles. It is concluded that the in vivo recruitment of MSC and macrophages to the defects may contribute to the tissue regeneration of skin wound. © 2016 Wiley Periodicals, Inc.

  4. Role of cathepsin S In periodontal wound healing-an in vitro study on human PDL cells.

    PubMed

    Memmert, Svenja; Nokhbehsaim, Marjan; Damanaki, Anna; Nogueira, Andressa V B; Papadopoulou, Alexandra K; Piperi, Christina; Basdra, Efthimia K; Rath-Deschner, Birgit; Götz, Werner; Cirelli, Joni A; Jäger, Andreas; Deschner, James

    2018-04-05

    Cathepsin S is a cysteine protease, which is expressed in human periodontal ligament (PDL) cells under inflammatory and infectious conditions. This in vitro study was established to investigate the effect of cathepsin S on PDL cell wound closure. An in vitro wound healing assay was used to monitor wound closure in wounded PDL cell monolayers for 72 h in the presence and absence of cathepsin S. In addition, the effects of cathepsin S on specific markers for apoptosis and proliferation were studied at transcriptional level. Changes in the proliferation rate due to cathepsin S stimulation were analyzed by an XTT assay, and the actions of cathepsin S on cell migration were investigated via live cell tracking. Additionally, PDL cell monolayers were treated with a toll-like receptor 2 agonist in the presence and absence of a cathepsin inhibitor to examine if periodontal bacteria can alter wound closure via cathepsins. Cathepsin S enhanced significantly the in vitro wound healing rate by inducing proliferation and by increasing the speed of cell migration, but had no effect on apoptosis. Moreover, the toll-like receptor 2 agonist enhanced significantly the wound closure and this stimulatory effect was dependent on cathepsins. Our findings provide original evidence that cathepsin S stimulates PDL cell proliferation and migration and, thereby, wound closure, suggesting that this cysteine protease might play a critical role in periodontal remodeling and healing. In addition, cathepsins might be exploited by periodontal bacteria to regulate critical PDL cell functions.

  5. Bioglass promotes wound healing by affecting gap junction connexin 43 mediated endothelial cell behavior.

    PubMed

    Li, Haiyan; He, Jin; Yu, Hongfei; Green, Colin R; Chang, Jiang

    2016-04-01

    It is well known that gap junctions play an important role in wound healing, and bioactive glass (BG) has been shown to help healing when applied as a wound dressing. However, the effects of BG on gap junctional communication between cells involved in wound healing is not well understood. We hypothesized that BG may be able to affect gap junction mediated cell behavior to enhance wound healing. Therefore, we set out to investigate the effects of BG on gap junction related behavior of endothelial cells in order to elucidate the mechanisms through which BG is operating. In in vitro studies, BG ion extracts prevented death of human umbilical vein endothelial cells (HUVEC) following hypoxia in a dose dependent manner, possibly through connexin hemichannel modulation. In addition, BG showed stimulatory effects on gap junction communication between HUVECs and upregulated connexin43 (Cx43) expression. Furthermore, BG prompted expression of vascular endothelial growth factor and basic fibroblast growth factor as well as their receptors, and vascular endothelial cadherin in HUVECs, all of which are beneficial for vascularization. In vivo wound healing results showed that the wound closure of full-thickness excisional wounds of rats was accelerated by BG with reduced inflammation during initial stages of healing and stimulated angiogenesis during the proliferation stage. Therefore, BG can stimulate wound healing through affecting gap junctions and gap junction related endothelial cell behaviors, including prevention of endothelial cell death following hypoxia, stimulation of gap junction communication and upregulation of critical vascular growth factors, which contributes to the enhancement of angiogenesis in the wound bed and finally to accelerate wound healing. Although many studies have reported that BG stimulates angiogenesis and wound healing, this work reveals the relationship between BG and gap junction connexin 43 mediated endothelial cell behavior and elucidates

  6. Low level diode laser accelerates wound healing.

    PubMed

    Dawood, Munqith S; Salman, Saif Dawood

    2013-05-01

    The effect of wound illumination time by pulsed diode laser on the wound healing process was studied in this paper. For this purpose, the original electronic drive circuit of a 650-nm wavelength CW diode laser was reconstructed to give pulsed output laser of 50 % duty cycle and 1 MHz pulse repetition frequency. Twenty male mice, 3 months old were used to follow up the laser photobiostimulation effect on the wound healing progress. They were subdivided into two groups and then the wounds were made on the bilateral back sides of each mouse. Two sessions of pulsed laser therapy were carried along 15 days. Each mice group wounds were illuminated by this pulsed laser for 12 or 18 min per session during these 12 days. The results of this study were compared with the results of our previous wound healing therapy study by using the same type of laser. The mice wounds in that study received only 5 min of illumination time therapy in the first and second days of healing process. In this study, we found that the wounds, which were illuminated for 12 min/session healed in about 3 days earlier than those which were illuminated for 18 min/session. Both of them were healed earlier in about 10-11 days than the control group did.

  7. Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing.

    PubMed

    Castilho, R M; Squarize, C H; Gutkind, J S

    2013-09-01

    The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K-PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Integration of silver nanoparticle-impregnated polyelectrolyte multilayers into murine splinted cutaneous wound beds

    PubMed Central

    Guthrie, Kathleen M.; Agarwal, Ankit; Teixeira, Leandro B. C.; Dubielzig, Richard R.; Abbott, Nicholas L.; Murphy, Christopher J.; Singh, Harpreet; McAnulty, Jonathan F.; Schurr, Michael J.

    2013-01-01

    Silver is a commonly used topical antimicrobial. However, technologies to immobilize silver at the wound surface are lacking, while currently available silver-containing wound dressings release excess silver that can be cytotoxic and impair wound healing. We have shown that precise concentrations of silver at lower levels can be immobilized into a wound bed using a polyelectrolyte multilayer (PEM) attachment technology. These silver nanoparticle-impregnated PEMs are non-cytotoxic yet bactericidal in vitro, but their effect on wound healing in vivo was previously unknown. Objective The purpose of this study was to determine the effect on wound healing of integrating silver nanoparticle/PEMs into the wound bed. Methods A full-thickness, splinted, excisional murine wound healing model was employed in both phenotypically normal mice and spontaneously diabetic mice (healing impaired model). Results Gross image measurements showed an initial small lag in healing in the silver-treated wounds in diabetic mice, but no difference in time to complete wound closure in either normal or diabetic mice. Histological analysis showed modest differences between silver-treated and control groups on day 9, but no difference between groups at the time of wound closure. Conclusions We conclude that silver nanoparticle/PEMs can be safely integrated into the wound beds of both normal and diabetic mice without delaying wound closure, and with transient histological effects. The results of this study suggest the feasibility of this technology for use as a platform to effect nanoscale wound engineering approaches to microbial prophylaxis or to augment wound healing. PMID:23511285

  9. [The modern approach to wound treatment].

    PubMed

    Komarcević, A

    2000-01-01

    Wound healing is a complex process involving interactions among a variety of different cell types. The normal wound repair process consists of three phases--inflammation, proliferation, and remodeling that occur in a predictable series of cellular and biochemical events. Wounds are classified according to various criteria: etiology, lasting, morphological characteristics, communications with solid or hollow organs, the degree of contamination. In the last few years many authors use the Color Code Concept, which classifies wounds as red, yellow and black wounds. This paper presents conventional methods of local wound treatment (mechanical cleansing, disinfection with antiseptic solutions, wound debridement--surgical, biological and autolytic; wound closure, topical antibiotic treatment, dressing), as well as general measures (sedation, antitetanous and antibiotic protection, preoperative evaluation and correction of malnutrition, vasoconstriction, hyperglycemia and steroid use, appropriate surgical technique, and postoperative prevention of vasoconstriction through pain relief, warming and adequate volume resuscitation). Growth factors play a role in cell division, migration, differentiation, protein expression, enzyme production and have a potential ability to heal wounds by stimulating angiogenesis and cellular proliferation, affecting the production and the degradation of the extracellular matrix, and by being chemotactic for inflammatory cells and fibroblasts. There are seven major families of growth factors: epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), interleukins (ILs), and colony-stimulating factor (CSF). Acute wounds contain many growth factors that play a crucial role in the initial phases of wound healing. The events of early wound healing reflect a finely balanced environment leading to uncomplicated and rapid wound

  10. Moderate treadmill running exercise prior to tendon injury enhances wound healing in aging rats

    PubMed Central

    Zhang, Jianying; Yuan, Ting; Wang, James H-C.

    2016-01-01

    The effect of exercise on wound healing in aging tendon was tested using a rat moderate treadmill running (MTR) model. The rats were divided into an MTR group that ran on a treadmill for 4 weeks and a control group that remained in cages. After MTR, a window defect was created in the patellar tendons of all rats and wound healing was analyzed. We found that MTR accelerated wound healing by promoting quicker closure of wounds, improving the organization of collagen fibers, and decreasing senescent cells in the wounded tendons when compared to the cage control. MTR also lowered vascularization, increased the numbers of tendon stem/progenitor cells (TSCs) and TSC proliferation than the control. Besides, MTR significantly increased the expression of stem cell markers, OCT-4 and Nanog, and tenocyte genes, Collagen I, Collagen III and tenomodulin, and down-regulated PPAR-γ, Collagen II and Runx-2 (non-tenocyte genes). These findings indicated that moderate exercise enhances healing of injuries in aging tendons through TSC based mechanisms, through which exercise regulates beneficial effects in tendons. This study reveals that appropriate exercise may be used in clinics to enhance tendon healing in aging patients. PMID:26885754

  11. Moderate treadmill running exercise prior to tendon injury enhances wound healing in aging rats.

    PubMed

    Zhang, Jianying; Yuan, Ting; Wang, James H-C

    2016-02-23

    The effect of exercise on wound healing in aging tendon was tested using a rat moderate treadmill running (MTR) model. The rats were divided into an MTR group that ran on a treadmill for 4 weeks and a control group that remained in cages. After MTR, a window defect was created in the patellar tendons of all rats and wound healing was analyzed. We found that MTR accelerated wound healing by promoting quicker closure of wounds, improving the organization of collagen fibers, and decreasing senescent cells in the wounded tendons when compared to the cage control. MTR also lowered vascularization, increased the numbers of tendon stem/progenitor cells (TSCs) and TSC proliferation than the control. Besides, MTR significantly increased the expression of stem cell markers, OCT-4 and Nanog, and tenocyte genes, Collagen I, Collagen III and tenomodulin, and down-regulated PPAR-γ, Collagen II and Runx-2 (non-tenocyte genes). These findings indicated that moderate exercise enhances healing of injuries in aging tendons through TSC based mechanisms, through which exercise regulates beneficial effects in tendons. This study reveals that appropriate exercise may be used in clinics to enhance tendon healing in aging patients.

  12. Topical oxygen as an adjunct to wound healing: a clinical case series.

    PubMed

    Kalliainen, Loree K.; Gordillo, Gayle M.; Schlanger, Richard; Sen, Chandan K.

    2003-01-01

    BACKGROUND: Disrupted vasculature and high energy-demand to support processing and regeneration of wounded tissue are typical characteristics of a wound site. Oxygen delivery is a critical element for the healing of wounds. Clinical experience with adjunctive hyperbaric oxygen therapy in the treatment of chronic wounds have shown that wound hyperoxia increases wound granulation tissue formation and accelerates wound contraction and secondary closure. Nevertheless, the physiologic basis for this modality remains largely unknown. Also, systemic hyperbaric oxygen therapy is associated with risks related to oxygen toxicity. Topical oxygen therapy represents a less explored modality in wound care. The advantages of topical oxygen therapy include low cost, lack of systemic oxygen toxicity, and the ability to receive treatment at home, making the benefits of oxygen therapy available to a much larger population of patients. MATERIALS AND METHODS: Over 9 months, seven surgeons treated 58 wounds in 32 patients with topical oxygen with follow-up ranging from 1 to 8 months. The data presented herein is a retrospective analysis of the results we have achieved using topical oxygen on complex wounds. RESULTS: Thirty-eight wounds in 15 patients healed while on topical oxygen. An additional five wounds in five patients had preoperative oxygen therapy; all wounds initially healed postoperatively. In two patients, wounds recurred post-healing. In ten wounds, topical oxygen had no effect; and two of those patients went on to require limb amputation. There were no complications attributable to topical oxygen. Three patients died during therapy and one died in the first postoperative month from underlying medical problems. Two patients were lost to follow-up. CONCLUSIONS: In this case series, topical oxygen had no detrimental effects on wounds and showed beneficial indications in promoting wound healing.

  13. The prevalence, management and outcome for acute wounds identified in a wound care survey within one English health care district.

    PubMed

    Vowden, Kathryn R; Vowden, Peter

    2009-02-01

    This paper reports the characteristics and local management of 826 acute wounds identified during an audit across all health care providers serving the population of Bradford, UK. Of the wounds encountered 303 were traumatic wounds and 237 primary closures with smaller numbers of other acute wound types. Of the 303 traumatic wounds 174 occurred in women (57.4%). Men predominated in the under 45s (65M:26F), this being largely accounted for by hand and finger trauma (n = 62) particularly in patients of working age (M32:F12). Women predominated in the over 65s (50M:130F), this being largely accounted for by lower limb traumatic wounds (M24:F91), the majority of these being in patients 65 and over (M14:F82). In this sub-group of 96 patients 25 had wounds of 6 weeks or longer duration, only 3 had undergone Doppler assessment and only 2 received compression bandaging. Typically these wounds were of recent origin and small in size (under 1 week and less than 5 cm2 in surface area) however exceptions occurred where 10 people had wounds over 25 cm2 in area while 3 wounds had been present for over 5 years. 101 (12.2%) of the encountered wounds were considered to be infected although the practice of wound swabbing in the presence of presumed infection seemed inadequate with 37.6% of all infected acute wounds not being swabbed while 97 non-infected wounds were swabbed. Where wounds were swabbed 4.5% were found to be MRSA positive. Across all acute wound types (with the sole exception of primary closures) antimicrobial wound dressings were the most prevalent form of dressing and covered 56 (55.4%) of all infected wounds.

  14. Effects of Hydrogen Peroxide on Wound Healing in Mice in Relation to Oxidative Damage

    PubMed Central

    Ho, Rongjian; Wasser, Martin; Du, Tiehua; Ng, Wee Thong; Halliwell, Barry

    2012-01-01

    It has been established that low concentrations of hydrogen peroxide (H2O2) are produced in wounds and is required for optimal healing. Yet at the same time, there is evidence that excessive oxidative damage is correlated with poor-healing wounds. In this paper, we seek to determine whether topical application of H2O2 can modulate wound healing and if its effects are related to oxidative damage. Using a C57BL/6 mice excision wound model, H2O2 was found to enhance angiogenesis and wound closure at 10 mM but retarded wound closure at 166 mM. The delay in closure was also associated with decreased connective tissue formation, increased MMP-8 and persistent neutrophil infiltration. Wounding was found to increase oxidative lipid damage, as measured by F2-isoprostanes, and nitrative protein damage, as measured by 3-nitrotyrosine. However H2O2 treatment did not significantly increase oxidative and nitrative damage even at concentrations that delay wound healing. Hence the detrimental effects of H2O2 may not involve oxidative damage to the target molecules studied. PMID:23152875

  15. Integrin-linked kinase (ILK) modulates wound healing through regulation of hepatocyte growth factor (HGF)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Serrano, Isabel; Diez-Marques, Maria L.; Rodriguez-Puyol, Manuel

    2012-11-15

    Integrin-linked kinase (ILK) is an intracellular effector of cell-matrix interactions and regulates many cellular processes, including growth, proliferation, survival, differentiation, migration, invasion and angiogenesis. The present work analyzes the role of ILK in wound healing in adult animals using a conditional knock-out of the ILK gene generated with the tamoxifen-inducible Cre-lox system (CRE-LOX mice). Results show that ILK deficiency leads to retarded wound closure in skin. Intracellular mechanisms involved in this process were analyzed in cultured mouse embryonic fibroblast (MEF) isolated from CRE-LOX mice and revealed that wounding promotes rapid activation of phosphatidylinositol 3-kinase (PI3K) and ILK. Knockdown of ILKmore » resulted in a retarded wound closure due to a decrease in cellular proliferation and loss of HGF protein expression during the healing process, in vitro and in vivo. Alterations in cell proliferation and wound closure in ILK-deficient MEF or mice could be rescued by exogenous administration of human HGF. These data demonstrate, for the first time, that the activation of PI3K and ILK after skin wounding are critical for HGF-dependent tissue repair and wound healing. -- Highlights: Black-Right-Pointing-Pointer ILK deletion results in decreased HGF expression and delayed scratch wound repair. Black-Right-Pointing-Pointer PI3K/ILK/AKT pathway signals through HGF to regulate wound healing. Black-Right-Pointing-Pointer An ILK-dependent increase in HGF expression is responsible for wound healing in vivo. Black-Right-Pointing-Pointer ILK-KO mice are used to confirm the requirement for ILK function in wound healing. Black-Right-Pointing-Pointer Human HGF treatment restores delayed wound closure in vitro and in vivo.« less

  16. [General principles of wound management in emergency departments].

    PubMed

    Zacher, M T; Högele, A M; Hanschen, M; von Matthey, F; Beer, A-K; Gebhardt, F; Biberthaler, P; Kanz, K-G

    2016-04-01

    Wound management is one of the major tasks in emergency departments. The surrounding intact skin but not the wound itself should be disinfected before starting definitive wound treatment. Hair should first be removed by clipping to 1-2 mm above the skin with scissors or clippers as shaving the area with a razor damages the hair follicles and increases the risk of wound infections. Administration of local anesthetics should be performed directly through the exposed edges of the wound. After wound examination, irrigation is performed with Ringer's solution, normal saline or distilled water. The next step is débridement of contaminated and devitalized tissue. There are several wound closure techniques available, including adhesive tapes, staples, tissue adhesives and numerous forms of sutures. Management of specific wounds requires particular strategies. A bleeding control problem frequently occurs with scalp lacerations. Superficial scalp lacerations can be closed by alternative wound closure methods, for example by twisting and fixing hair and the use of tissue adhesives, i.e. hair apposition technique (HAT). For strongly bleeding lacerations of the scalp, the epicranial aponeurosis should be incorporated into the hemostasis. Aftercare varies depending on both the characteristics of the wound and those of the patient and includes adequate analgesia as well as minimizing the risk of infection. Sufficient wound aftercare starts with the treating physician informing the patient about the course of events, potential complications and providing relevant instructions.

  17. Intestinal epithelial wound healing assay in an epithelial-mesenchymal co-culture system.

    PubMed

    Seltana, Amira; Basora, Nuria; Beaulieu, Jean-François

    2010-01-01

    Rapid and efficient healing of epithelial damage is critical to the functional integrity of the small intestine. Epithelial repair is a complex process that has largely been studied in cultured epithelium but to a much lesser extent in mucosa. We describe a novel method for the study of wound healing using a co-culture system that combined an intestinal epithelial Caco-2/15 cell monolayer cultured on top of human intestinal myofibroblasts, which together formed a basement membrane-like structure that contained many of the major components found at the epithelial-mesenchymal interface in the human intestine. To investigate the mechanism of restitution, small lesions were generated in epithelial cell monolayers on plastic or in co-cultures without disturbing the underlying mesenchymal layer. Monitoring of wound healing showed that repair was more efficient in Caco-2/15-myofibroblast co-cultures than in Caco-2/15 monolayers and involved the deposition of basement membrane components. Functional experiments showed that the addition of type I collagen or human fibronectin to the culture medium significantly accelerated wound closure on epithelial cell co-cultures. This system may provide a new tool to investigate the mechanisms that regulate wound healing in the intestinal epithelium.

  18. Anti-inflammatory and wound healing activities of calophyllolide isolated from Calophyllum inophyllum Linn.

    PubMed

    Nguyen, Van-Linh; Truong, Cong-Tri; Nguyen, Binh Cao Quan; Vo, Thanh-Niem Van; Dao, Trong-Thuc; Nguyen, Van-Dan; Trinh, Dieu-Thuong Thi; Huynh, Hieu Kim; Bui, Chi-Bao

    2017-01-01

    Due to the high-cost and limitations of current wound healing treatments, the search for alternative approaches or drugs, particularly from medicinal plants, is of key importance. In this study, we report anti-inflammatory and wound healing activities of the major calophyllolide (CP) compound isolated from Calophyllum inophyllum Linn. The results showed that CP had no effect on HaCaT cell viability over a range of concentrations. CP reduced fibrosis formation and effectively promoted wound closure in mouse model without causing body weight loss. The underlying molecular mechanisms of wound repair by CP was investigated. CP markedly reduced MPO activity, and increased M2 macrophage skewing, as shown by up-regulation of M2-related gene expression, which is beneficial to the wound healing process. CP treatment prevented a prolonged inflammatory process by down-regulation of the pro-inflammatory cytokines-IL-1β, IL-6, TNF-α, but up-regulation of the anti-inflammatory cytokine, IL-10. This study is the first to indicate a plausible role for CP in accelerating the process of wound healing through anti-inflammatory activity mechanisms, namely, by regulation of inflammatory cytokines, reduction in MPO, and switching of macrophages to an M2 phenotype. These findings may enable the utilization of CP as a potent therapeutic for cutaneous wound healing.

  19. Wound Healing Potential of Chlorogenic Acid and Myricetin-3-O-β-Rhamnoside Isolated from Parrotia persica.

    PubMed

    Moghadam, Sara E; Ebrahimi, Samad N; Salehi, Peyman; Moridi Farimani, Mahdi; Hamburger, Matthias; Jabbarzadeh, Ehsan

    2017-09-08

    Wound healing is a complex physiological process that is controlled by a well-orchestrated cascade of interdependent biochemical and cellular events, which has spurred the development of therapeutics that simultaneously target these active cellular constituents. We assessed the potential of Parrotia persica (Hamamelidaceae) in wound repair by analyzing the regenerative effects of its two main phenolic compounds, myricetin-3- O -β-rhamnoside and chlorogenic acid. To accomplish this, we performed phytochemical profiling and characterized the chemical structure of pure compounds isolated from P. persica , followed by an analysis of the biological effects of myricetin-3- O -β-rhamnoside and chlorogenic acid on three cell types, including keratinocytes, fibroblasts, and endothelial cells. Myricetin-3- O -β-rhamnoside and chlorogenic acid exhibited complementary pro-healing properties. The percentage of keratinocyte wound closure as measured by a scratch assay was four fold faster in the presence of 10 µg/mL chlorogenic acid, as compared to the negative control. On the other hand, myricetin-3- O -β-rhamnoside at 10 µg/mL was more effective in promoting fibroblast migration, demonstrating a two-fold higher rate of closure compared to the negative control group. Both compounds enhanced the capillary-like tube formation of endothelial cells in an in vitro angiogenesis assay. Our results altogether delineate the potential to synergistically accelerate the fibroblastic and remodelling phases of wound repair by administering appropriate amounts of myricetin-3- O -β-rhamnoside and chlorogenic acid.

  20. Wound Healing Potential of Chlorogenic Acid and Myricetin-3-O-β-Rhamnoside Isolated from Parrotia persica

    PubMed Central

    Moghadam, Sara E.; Ebrahimi, Samad N.; Salehi, Peyman; Farimani, Mahdi Moridi; Hamburger, Matthias; Jabbarzadeh, Ehsan

    2017-01-01

    Wound healing is a complex physiological process that is controlled by a well-orchestrated cascade of interdependent biochemical and cellular events, which has spurred the development of therapeutics that simultaneously target these active cellular constituents. We assessed the potential of Parrotia persica (Hamamelidaceae) in wound repair by analyzing the regenerative effects of its two main phenolic compounds, myricetin-3-O-β-rhamnoside and chlorogenic acid. To accomplish this, we performed phytochemical profiling and characterized the chemical structure of pure compounds isolated from P. persica, followed by an analysis of the biological effects of myricetin-3-O-β-rhamnoside and chlorogenic acid on three cell types, including keratinocytes, fibroblasts, and endothelial cells. Myricetin-3-O-β-rhamnoside and chlorogenic acid exhibited complementary pro-healing properties. The percentage of keratinocyte wound closure as measured by a scratch assay was four fold faster in the presence of 10 μg/mL chlorogenic acid, as compared to the negative control. On the other hand, myricetin-3-O-β-rhamnoside at 10 μg/mL was more effective in promoting fibroblast migration, demonstrating a two-fold higher rate of closure compared to the negative control group. Both compounds enhanced the capillary-like tube formation of endothelial cells in an in vitro angiogenesis assay. Our results altogether delineate the potential to synergistically accelerate the fibroblastic and remodelling phases of wound repair by administering appropriate amounts of myricetin-3-O-β-rhamnoside and chlorogenic acid. PMID:28885580

  1. Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice

    PubMed Central

    Shin, Jihyun; Yang, Soo Jin

    2016-01-01

    Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT). After two weeks of GT supplementation, excisional wounds were made by biopsy punches (4 mm). Diabetic mice showed increases in fasting blood glucose (FBG) level, hyper-inflammatory response, oxidative stress, and delayed wound closure rate compared to non-diabetic mice. However, GT supplementation reduced FBG level and accelerated wound closure rate by regulation of inflammatory response-related proteins such as nuclear factor kappa B, interleukin-1β, tumor necrosis factor-α, and c-reactive protein, and oxidative stress-related markers including nuclear factor (erythroid derived 2)-like 2, NAD(P)H dehydrogenase quinone1, heme oxygenase-1, manganese superoxide dismutase, catalase and glutathione peroxidase and apoptosis-related markers such as sirtuin-1, peroxisome proliferator-activated receptor gamma coactivator 1-α, and p53 in diabetic mice. Taken together, GT would be a potential therapeutic to prevent diabetes-induced delayed wound healing by regulation of inflammatory response, apoptosis, and oxidative stress. Impact statement Gamma tocopherol has shown ameliorative effect on diabetic wound healing by regulation of inflammation, oxidative stress, and apoptosis demonstrated by nuclear factor kappa B, nuclear factor (erythroid derived 2)-like 2, and sirtuin-1. PMID:28211759

  2. Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice.

    PubMed

    Shin, Jihyun; Yang, Soo Jin; Lim, Yunsook

    2017-03-01

    Delayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT). After two weeks of GT supplementation, excisional wounds were made by biopsy punches (4 mm). Diabetic mice showed increases in fasting blood glucose (FBG) level, hyper-inflammatory response, oxidative stress, and delayed wound closure rate compared to non-diabetic mice. However, GT supplementation reduced FBG level and accelerated wound closure rate by regulation of inflammatory response-related proteins such as nuclear factor kappa B, interleukin-1β, tumor necrosis factor-α, and c-reactive protein, and oxidative stress-related markers including nuclear factor (erythroid derived 2)-like 2, NAD(P)H dehydrogenase quinone1, heme oxygenase-1, manganese superoxide dismutase, catalase and glutathione peroxidase and apoptosis-related markers such as sirtuin-1, peroxisome proliferator-activated receptor gamma coactivator 1- α, and p53 in diabetic mice. Taken together, GT would be a potential therapeutic to prevent diabetes-induced delayed wound healing by regulation of inflammatory response, apoptosis, and oxidative stress. Impact statement Gamma tocopherol has shown ameliorative effect on diabetic wound healing by regulation of inflammation, oxidative stress, and apoptosis demonstrated by nuclear factor kappa B, nuclear factor (erythroid derived 2)-like 2, and sirtuin-1.

  3. A prospective randomized trial comparing subatmospheric wound therapy with a sealed gauze dressing and the standard vacuum-assisted closure device.

    PubMed

    Dorafshar, Amir H; Franczyk, Mieczyslawa; Gottlieb, Lawrence J; Wroblewski, Kristen E; Lohman, Robert F

    2012-07-01

    Two methods of subatmospheric pressure wound therapy--wall suction applied to a sealed gauze dressing (GSUC) and the vacuum-assisted closure device (VAC)--were compared in hospitalized patients at University of Chicago Medical Center. VAC therapy is widely used, but can be expensive and difficult to apply; it also fails in some patients. A randomized prospective study of 87 patients (N = 45 in the GSUC arm and N = 42 in the VAC arm) was undertaken between October 2006 and May 2008. The study comprised patients with acute wounds resulting from trauma, dehiscence, or surgery. Demographics and wound characteristics were similar in both groups. There were significant reductions in wound surface area and volume in each group. In the GSUC group, the reductions in wound surface area and volume were 4.5%/day and 8.4%/day, respectively (P < 0.001 for both), and in the VAC group, this was 4.9%/day and 9.8%/day, respectively (P < 0.001 for both). The reductions in wound surface area and volume were similar in both groups (P = 0.60 and 0.19, respectively, for the group-by-time interaction). The estimated difference (VAC - GSUC) was 0.4% (95% confidence interval: -1.0, 1.7) for wound surface area and 1.4% (95% confidence interval: -0.7, 3.5) for volume. The mean cost per day for GSUC therapy was $4.22 versus $96.51 for VAC therapy (P < 0.01) and the average time required for a GSUC dressing change was 19 minutes versus 31 minutes for a VAC dressing change (P < 0.01). The sum of pain intensity differences was 0.50 in the GSUC group compared with 1.73 for the VAC group (P = 0.02). GSUC is noninferior to VAC with respect to changes in wound volume and surface area in an acute care setting. In addition, GSUC dressings were easier to apply, less expensive, and less painful.

  4. Cell motility in models of wounded human skin is improved by Gap27 despite raised glucose, insulin and IGFBP-5

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wright, Catherine S.; Berends, Rebecca F.; Flint, David J.

    2013-02-15

    Reducing Cx43 expression stimulates skin wound healing. This is mimicked in models when Cx43 function is blocked by the connexin mimetic peptide Gap27. IGF-I also stimulates wound healing with IGFBP-5 attenuating its actions. Further, the IGF-I to IGFBP-5 ratio is altered in diabetic skin, where wound closure is impaired. We investigated whether Gap27 remains effective in augmenting scrape-wound closure in human skin wound models simulating diabetes-induced changes, using culture conditions with raised glucose, insulin and IGFBP-5. Gap27 increased scrape-wound closure in normal glucose and insulin (NGI) and to a lesser extent in high glucose and insulin (HGI). IGF-I enhanced scrape-woundmore » closure in keratinocytes whereas IGFBP-5 inhibited this response. Gap27 overcame the inhibitory effects of IGFBP-5 on IGF-I activity. Connexin-mediated communication (CMC) was reduced in HGI, despite raised Cx43, and Gap27 significantly decreased CMC in NGI and HGI. IGF-I and IGFBP-5 did not affect CMC. IGF-I increased keratinocyte proliferation in NGI, and Gap27 increased proliferation in NGI to a greater extent than in HGI. We conclude that IGF-I and Gap27 stimulate scrape-wound closure by independent mechanisms with Gap27 inhibiting Cx43 function. Gap27 can enhance wound closure in diabetic conditions, irrespective of the IGF-I:IGFBP-5 balance. - Highlights: ► Human organotypic and keratinocyte ‘diabetic’ skin models were used to demonstrate the ability of Gap27 to improve scrape-wound closure. ► Gap27 enhanced scrape-wound closure by reducing Cx43-mediated communication, whereas IGFBP-5 retarded cell migration. ► IGF-I and IGFBP-5 did not affect connexin-mediated pathways. ► Gap27 can override altered glucose, insulin, IGF-I, and IGFBP-5 in ‘diabetic’ skin models and thus has therapeutic potential.« less

  5. Fibronectin potentiates topical erythropoietin-induced wound repair in diabetic mice.

    PubMed

    Hamed, Saher; Ullmann, Yehuda; Egozi, Dana; Daod, Essam; Hellou, Elias; Ashkar, Manal; Gilhar, Amos; Teot, Luc

    2011-06-01

    Diabetes mellitus disrupts all phases of the wound repair cascade and leads to development of chronic wounds. We previously showed that topical erythropoietin (EPO) can promote wound repair in diabetic rats. Fibronectin (FN) has a critical role throughout the process of wound healing, yet it is deficient in wound tissues of diabetic patients. Therefore, we investigated the effect of topical treatment of both EPO and FN (EPO/FN) on wound repair in diabetic mice. Full-thickness excisional skin wounds in diabetic and nondiabetic mice were treated with a cream containing vehicle, EPO, FN, or EPO/FN. We assessed the rate of wound closure, angiogenesis, apoptosis, and expression of inflammatory cytokines, endothelial nitric oxide synthase (eNOS) and β1-integrin, in the wound tissues. We also investigated the effect of EPO, FN, and EPO/FN on human dermal microvascular endothelial cells and fibroblasts cultured on fibrin-coated plates, or in high glucose concentrations. EPO/FN treatment significantly increased the rate of wound closure and this effect was associated with increased angiogenesis, increased eNOS and β1-integrin expression, and reduced expression of inflammatory cytokines and apoptosis. Our findings show that EPO and FN have an additive effect on wound repair in diabetic mice.

  6. IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice.

    PubMed

    Kolumam, Ganesh; Wu, Xiumin; Lee, Wyne P; Hackney, Jason A; Zavala-Solorio, Jose; Gandham, Vineela; Danilenko, Dimitry M; Arora, Puneet; Wang, Xiaoting; Ouyang, Wenjun

    2017-01-01

    Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. Mechanistically, when compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU.

  7. IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice

    PubMed Central

    Kolumam, Ganesh; Wu, Xiumin; Lee, Wyne P.; Hackney, Jason A.; Zavala-Solorio, Jose; Gandham, Vineela; Danilenko, Dimitry M.; Arora, Puneet; Wang, Xiaoting; Ouyang, Wenjun

    2017-01-01

    Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. Mechanistically, when compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU. PMID:28125663

  8. Adipose-derived stem cells seeded in Pluronic F-127 hydrogel promotes diabetic wound healing.

    PubMed

    Kaisang, Lin; Siyu, Wang; Lijun, Fan; Daoyan, Pan; Xian, Cory J; Jie, Shen

    2017-09-01

    Chronic nonhealing wound is a multifactorial complication of diabetes that results specifically as a consequence of impaired angiogenesis and currently lacks in effective treatments. Although a stem cell-based therapy may provide a novel treatment to augment diabetic wound healing, inferior cell survival at the diabetic skin wound is one of the key causes that are responsible for the low efficacy of the stem cell therapy. In this work, we used an injectable, biocompatible, and thermosensitive hydrogel Pluronic F-127 to encapsulate allogeneic nondiabetic adipose-derived stem cells (ADSCs) and topically applied the cells to a full-thickness cutaneous wound in the streptozotocin-induced diabetic model in rats. The cells seeded in the hydrogel enhanced angiogenesis (CD31 marker) and promoted the cell proliferation (Ki67 marker) at the wound site and significantly accelerated wound closure, which was accompanied by facilitated regeneration of granulation tissue. Consistently, levels of the messenger RNA expression of key angiogenesis growth factor, vascular endothelial growth factor, and key wound healing growth factor, transforming growth factor beta 1, were also upregulated in the cell-treated wounds when compared with untreated wounds. The results indicated that the transplantation of allogeneic ADSCs via the hydrogel improves the efficiency of cell delivery and optimizes the performance of ADSCs for augmenting diabetic wound healing. In conclusion, this ADSC-based therapy may provide a novel therapeutic strategy for the treatment of nonhealing diabetic foot ulcers. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Silver nanoparticles enhance wound healing in zebrafish (Danio rerio).

    PubMed

    Seo, Seung Beom; Dananjaya, S H S; Nikapitiya, Chamilani; Park, Bae Keun; Gooneratne, Ravi; Kim, Tae-Yoon; Lee, Jehee; Kim, Cheol-Hee; De Zoysa, Mahanama

    2017-09-01

    Silver nanoparticles (AgNPs) were successfully synthesized by a chemical reduction method, physico-chemically characterized and their effect on wound-healing activity in zebrafish was investigated. The prepared AgNPs were circular-shaped, water soluble with average diameter and zeta potential of 72.66 nm and -0.45 mv, respectively. Following the creation of a laser skin wound on zebrafish, the effect of AgNPs on wound-healing activity was tested by two methods, direct skin application (2 μg/wound) and immersion in a solution of AgNPs and water (50 μg/L). The zebrafish were followed for 20 days post-wounding (dpw) by visual observation of wound size, calculating wound healing percentage (WHP), and histological examination. Visually, both direct skin application and immersion AgNPs treatments displayed clear and faster wound closure at 5, 10 and 20 dpw compared to the controls, which was confirmed by 5 dpw histology data. At 5 dpw, WHP was highest in the AgNPs immersion group (36.6%) > AgNPs direct application group (23.7%) > controls (18.2%), showing that WHP was most effective in fish immersed in AgNPs solution. In general, exposure to AgNPs induced gene expression of selected wound-healing-related genes, namely, transforming growth factor (TGF-β), matrix metalloproteinase (MMP) -9 and -13, pro-inflammatory cytokines (IL-1β and TNF-α) and antioxidant enzymes (superoxide dismutase and catalase), which observed differentiation at 12 and 24 h against the control; but the results were not consistently significant, and many either reached basal levels or were down regulated at 5 dpw in the wounded muscle. These results suggest that AgNPs are effective in acceleration of wound healing and altered the expression of some wound-healing-related genes. However, the detailed mechanism of enhanced wound healing remains to be investigated in fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Distinct Phospholipase C-β Isozymes Mediate Lysophosphatidic Acid Receptor 1 Effects on Intestinal Epithelial Homeostasis and Wound Closure

    PubMed Central

    Lee, Sei-Jung; Leoni, Giovanna; Neumann, Philipp-Alexander; Chun, Jerold; Nusrat, Asma

    2013-01-01

    Maintenance of the epithelial barrier in the intestinal tract is necessary to protect the host from the hostile luminal environment. Phospholipase C-β (PLC-β) has been implicated to control myriad signaling cascades. However, the biological effects of selective PLC-β isozymes are poorly understood. We describe novel findings that lysophosphatidic acid (LPA) regulates PLC-β1 and PLC-β2 via two distinct pathways to enhance intestinal epithelial cell (IEC) proliferation and migration that facilitate wound closure and recovery of the intestinal epithelial barrier. LPA acting on the LPA1 receptor promotes IEC migration by facilitating the interaction of Gαq with PLC-β2. LPA-induced cell proliferation is PLC-β1 dependent and involves translocation of Gαq to the nucleus, where it interacts with PLC-β1 to induce cell cycle progression. An in vivo study using LPA1-deficient mice (Lpar1−/−) shows a decreased number of proliferating IECs and migration along the crypt-luminal axis. Additionally, LPA enhances migration and proliferation of IECs in an LPA1-dependent manner, and Lpar1−/− mice display defective mucosal wound repair that requires cell proliferation and migration. These findings delineate novel LPA1-dependent lipid signaling that facilitates mucosal wound repair via spatial targeting of distinct PLC-βs within the cell. PMID:23478264

  11. Early Complications and Outcomes in Combat Injury Related Invasive Fungal Wound Infections: A Case-Control Analysis

    PubMed Central

    Lewandowski, Louis R.; Weintrob, Amy C.; Tribble, David R.; Rodriguez, Carlos J.; Petfield, Joseph; Lloyd, Bradley A.; Murray, Clinton K.; Stinner, Daniel; Aggarwal, Deepak; Shaikh, Faraz; Potter, Benjamin K.

    2015-01-01

    Objective Clinicians have anecdotally noted that combat-related invasive fungal wound infections (IFIs) lead to residual limb shortening, additional days and operative procedures prior to initial wound closure, and high early complication rates. We evaluated the validity of these observations and identified risk factors that may impact time to initial wound closure. Design Retrospective review and case-control analysis. Setting Military hospitals. Patients/Participants United States military personnel injured during combat operations (2009–2011). The IFI cases were identified based upon the presence of recurrent, necrotic extremity wounds with mold growth in culture and/or histopathologic fungal evidence. Non-IFI controls were matched on injury pattern and severity. In a supplemental matching analysis, non-IFI controls were also matched by blood volume transfused within 24 hours of injury. Intervention None. Main Outcome Measurements Amputation revision rate and loss of functional levels. Results Seventy-one IFI cases (112 fungal-infected extremity wounds) were identified and matched to 160 control patients (315 non-IFI extremity wounds). The IFI wounds resulted in significantly more changes in amputation level (p<0.001). Additionally, significantly (p<0.001) higher number of operative procedures and longer duration to initial wound closure was associated with IFI. A shorter duration to initial wound closure was significantly associated with wounds lacking IFIs (Hazard ratio: 1.53; 95% CI: 1.17, 2.01). The supplemental matching analysis found similar results. Conclusions Our analysis indicates that IFIs adversely impact wound healing and patient recovery, requiring more frequent proximal amputation revisions and leading to higher early complication rates. PMID:26360542

  12. Olive oil-induced reduction of oxidative damage and inflammation promotes wound healing of pressure ulcers in mice.

    PubMed

    Donato-Trancoso, Aline; Monte-Alto-Costa, Andréa; Romana-Souza, Bruna

    2016-07-01

    The overproduction of reactive oxygen species (ROS) and exacerbated inflammatory response are the main events that impair healing of pressure ulcers. Therefore, olive oil may be a good alternative to improve the healing of these chronic lesions due to its anti-inflammatory and antioxidant properties. This study investigated the effect of olive oil administration on wound healing of pressure ulcers in mice. Male Swiss mice were daily treated with olive oil or water until euthanasia. One day after the beginning of treatment, two cycles of ischemia-reperfusion by external application of two magnetic plates were performed in skin to induced pressure ulcer formation. The olive oil administration accelerated ROS and nitric oxide (NO) synthesis and reduced oxidative damage in proteins and lipids when compared to water group. The inflammatory cell infiltration, gene tumor necrosis factor-α (TNF-α) expression and protein neutrophil elastase expression were reduced by olive oil administration when compared to water group. The re-epithelialization and blood vessel number were higher in the olive oil group than in the water group. The olive oil administration accelerated protein expression of TNF-α, active transforming growth factor-β1 and vascular endothelial growth factor-A when compared to water group. The collagen deposition, myofibroblastic differentiation and wound contraction were accelerated by olive oil administration when compared to water group. Olive oil administration improves cutaneous wound healing of pressure ulcers in mice through the acceleration of the ROS and NO synthesis, which reduces oxidative damage and inflammation and promotes dermal reconstruction and wound closure. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  13. Heme Oxygenase-1 Promotes Delayed Wound Healing in Diabetic Rats

    PubMed Central

    Chen, Qing-Ying; Wang, Guo-Guang; Li, Wei; Jiang, Yu-Xin; Lu, Xiao-Hua; Zhou, Ping-Ping

    2016-01-01

    Diabetic ulcers are one of the most serious and costly chronic complications for diabetic patients. Hyperglycemia-induced oxidative stress may play an important role in diabetes and its complications. The aim of the study was to explore the effect of heme oxygenase-1 on wound closure in diabetic rats. Diabetic wound model was prepared by making an incision with full thickness in STZ-induced diabetic rats. Wounds from diabetic rats were treated with 10% hemin ointment for 21 days. Increase of HO-1 protein expression enhanced anti-inflammation and antioxidant in diabetic rats. Furthermore, HO-1 increased the levels of VEGF and ICAM-1 and expressions of CBS and CSE protein. In summary, HO-1 promoted the wound closure by augmenting anti-inflammation, antioxidant, and angiogenesis in diabetic rats. PMID:26798657

  14. Limited utility of preoperative studies in preparation for colostomy closure.

    PubMed

    Pokorny, R M; Heniford, T; Allen, J W; Tuckson, W B; Galandiuk, S

    1999-04-01

    Numerous diagnostic and therapeutic practices are used in an attempt to reduce the morbidity of colostomy closures. Our principal aim was to evaluate the role of preoperative studies, specifically barium enemas and endoscopic examinations, performed before colostomy closures. Additionally, we wished to identify other practices involved in the perioperative management of patients undergoing colostomy closure that influenced morbidity. The records of 100 consecutive patients who underwent elective colostomy closure at University of Louisville Hospital between January 1989 and July 1995 were reviewed. Wound infection was the most common complication (12%). Various bowel preparations were equivalent in efficacy and did not influence the complication rate. Intermittent wound irrigation with antibiotics for 3 days postoperatively, via subcutaneous drains, was associated with a low incidence of incision infection. Preoperative barium enema or sigmoidoscopy were often performed but rarely useful. Performing these examinations merely increased hospital cost without a corresponding decline in morbidity.

  15. The clinical evaluation of platelet-rich plasma on free gingival graft's donor site wound healing.

    PubMed

    Samani, Mahmoud Khosravi; Saberi, Bardia Vadiati; Ali Tabatabaei, S M; Moghadam, Mahdjoube Goldani

    2017-01-01

    It has been proved that platelet-rich plasma (PRP) can promote wound healing. In this way, PRP can be advantageous in periodontal plastic surgeries, free gingival graft (FGG) being one such surgery. In this randomized split-mouth controlled trial, 10 patients who needed bilateral FGG were selected, and two donor sites were randomly assigned to experience either natural healing or healing-assisted with PRP. The outcome was assessed based on the comparison of the extent of wound closure, Manchester scale, Landry healing scale, visual analog scale, and tissue thickness between the study groups at different time intervals. Repeated measurements of analysis of variance and paired t -test were used. Statistical significance was P ≤ 0.05. Significant differences between the study groups and also across different time intervals were seen in all parameters except for the changes in tissue thickness. PRP accelerates the healing process of wounds and reduces the healing time.

  16. Wounded cells drive rapid epidermal repair in the early Drosophila embryo

    PubMed Central

    Fernandez-Gonzalez, Rodrigo; Zallen, Jennifer A.

    2013-01-01

    Epithelial tissues are protective barriers that display a remarkable ability to repair wounds. Wound repair is often associated with an accumulation of actin and nonmuscle myosin II around the wound, forming a purse string. The role of actomyosin networks in generating mechanical force during wound repair is not well understood. Here we investigate the mechanisms of force generation during wound repair in the epidermis of early and late Drosophila embryos. We find that wound closure is faster in early embryos, where, in addition to a purse string around the wound, actomyosin networks at the medial cortex of the wounded cells contribute to rapid wound repair. Laser ablation demonstrates that both medial and purse-string actomyosin networks generate contractile force. Quantitative analysis of protein localization dynamics during wound closure indicates that the rapid contraction of medial actomyosin structures during wound repair in early embryos involves disassembly of the actomyosin network. By contrast, actomyosin purse strings in late embryos contract more slowly in a mechanism that involves network condensation. We propose that the combined action of two force-generating structures—a medial actomyosin network and an actomyosin purse string—contributes to the increased efficiency of wound repair in the early embryo. PMID:23985320

  17. Mitochondria-Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice

    PubMed Central

    Demyanenko, Ilya A.; Zakharova, Vlada V.; Ilyinskaya, Olga P.; Vasilieva, Tamara V.; Fedorov, Artem V.; Skulachev, Vladimir P.

    2017-01-01

    Oxidative stress is widely recognized as an important factor in the delayed wound healing in diabetes. However, the role of mitochondrial reactive oxygen species in this process is unknown. It was assumed that mitochondrial reactive oxygen species are involved in many wound-healing processes in both diabetic humans and animals. We have applied the mitochondria-targeted antioxidant 10-(6′-plastoquinonyl)decyltriphenylphosphonium (SkQ1) to explore the role of mitochondrial reactive oxygen species in the wound healing of genetically diabetic mice. Healing of full-thickness excisional dermal wounds in diabetic C57BL/KsJ-db−/db− mice was significantly enhanced after long-term (12 weeks) administration of SkQ1. SkQ1 accelerated wound closure and stimulated epithelization, granulation tissue formation, and vascularization. On the 7th day after wounding, SkQ1 treatment increased the number of α-smooth muscle actin-positive cells (myofibroblasts), reduced the number of neutrophils, and increased macrophage infiltration. SkQ1 lowered lipid peroxidation level but did not change the level of the circulatory IL-6 and TNF. SkQ1 pretreatment also stimulated cell migration in a scratch-wound assay in vitro under hyperglycemic condition. Thus, a mitochondria-targeted antioxidant normalized both inflammatory and regenerative phases of wound healing in diabetic mice. Our results pointed to nearly all the major steps of wound healing as the target of excessive mitochondrial reactive oxygen species production in type II diabetes. PMID:28761623

  18. Mitochondria-Targeted Antioxidant SkQ1 Improves Dermal Wound Healing in Genetically Diabetic Mice.

    PubMed

    Demyanenko, Ilya A; Zakharova, Vlada V; Ilyinskaya, Olga P; Vasilieva, Tamara V; Fedorov, Artem V; Manskikh, Vasily N; Zinovkin, Roman A; Pletjushkina, Olga Yu; Chernyak, Boris V; Skulachev, Vladimir P; Popova, Ekaterina N

    2017-01-01

    Oxidative stress is widely recognized as an important factor in the delayed wound healing in diabetes. However, the role of mitochondrial reactive oxygen species in this process is unknown. It was assumed that mitochondrial reactive oxygen species are involved in many wound-healing processes in both diabetic humans and animals. We have applied the mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) to explore the role of mitochondrial reactive oxygen species in the wound healing of genetically diabetic mice. Healing of full-thickness excisional dermal wounds in diabetic C57BL/KsJ-db - /db - mice was significantly enhanced after long-term (12 weeks) administration of SkQ1. SkQ1 accelerated wound closure and stimulated epithelization, granulation tissue formation, and vascularization. On the 7th day after wounding, SkQ1 treatment increased the number of α -smooth muscle actin-positive cells (myofibroblasts), reduced the number of neutrophils, and increased macrophage infiltration. SkQ1 lowered lipid peroxidation level but did not change the level of the circulatory IL-6 and TNF. SkQ1 pretreatment also stimulated cell migration in a scratch-wound assay in vitro under hyperglycemic condition. Thus, a mitochondria-targeted antioxidant normalized both inflammatory and regenerative phases of wound healing in diabetic mice. Our results pointed to nearly all the major steps of wound healing as the target of excessive mitochondrial reactive oxygen species production in type II diabetes.

  19. Chlorhexidine hexametaphosphate as a wound care material coating: antimicrobial efficacy, toxicity and effect on healing.

    PubMed

    Barbour, Michele E; Maddocks, Sarah E; Grady, Helena J; Roper, James A; Bass, Mark D; Collins, Andrew M; Dommett, Rachel M; Saunders, Margaret

    2016-08-01

    In this study, chlorhexidine hexametaphosphate (CHX-HMP) is investigated as a persistent antimicrobial coating for wound care materials. CHX-HMP was used as a wound care material coating and compared with chlorhexidine digluconate materials with respect to antimicrobial efficacy, toxicity and wound closure. Antimicrobial efficacy at day 1, 3 and 7 was observed with experimental and commercial materials. CHX-HMP coated materials had less toxic effect on human placental cells than commercial chlorhexidine dressings. CHX-HMP in pluronic gel did not delay healing but reduced wound colonization by E. faecalis. CHX-HMP could become a useful component of wound care materials with sustained antimicrobial efficacy, lower toxicity than chlorhexidine digluconate materials, and reduction in wound colonization without affecting closure.

  20. Effects of Remote Ischemic Preconditioning on Heme Oxygenase-1 Expression and Cutaneous Wound Repair

    PubMed Central

    Cremers, Niels A. J.; Wever, Kimberley E.; Wong, Ronald J.; van Rheden, René E. M.; Vermeij, Eline A.; van Dam, Gooitzen M.; Carels, Carine E.; Lundvig, Ditte M. S.; Wagener, Frank A. D. T. G.

    2017-01-01

    Skin wounds may lead to scar formation and impaired functionality. Remote ischemic preconditioning (RIPC) can induce the anti-inflammatory enzyme heme oxygenase-1 (HO-1) and protect against tissue injury. We aim to improve cutaneous wound repair by RIPC treatment via induction of HO-1. RIPC was applied to HO-1-luc transgenic mice and HO-1 promoter activity and mRNA expression in skin and several other organs were determined in real-time. In parallel, RIPC was applied directly or 24h prior to excisional wounding in mice to investigate the early and late protective effects of RIPC on cutaneous wound repair, respectively. HO-1 promoter activity was significantly induced on the dorsal side and locally in the kidneys following RIPC treatment. Next, we investigated the origin of this RIPC-induced HO-1 promoter activity and demonstrated increased mRNA in the ligated muscle, heart and kidneys, but not in the skin. RIPC did not change HO-1 mRNA and protein levels in the wound 7 days after cutaneous injury. Both early and late RIPC did not accelerate wound closure nor affect collagen deposition. RIPC induces HO-1 expression in several organs, but not the skin, and did not improve excisional wound repair, suggesting that the skin is insensitive to RIPC-mediated protection. PMID:28218659

  1. Wound-healing promoting effect of total tannins from Entada phaseoloides (L.) Merr. in rats.

    PubMed

    Su, Xiaowen; Liu, Xinguang; Wang, Shouyu; Li, Bin; Pan, Taowen; Liu, Dingrui; Wang, Fei; Diao, Yunpeng; Li, Kun

    2017-06-01

    The healing of wounds has always provided challenges for the medical community whether chronic or acute. Modern and traditional medicine has proved that herbal medicine shown superiority over chemical drugs. Herein, we report an Entada phaseoloides (L.) Merr. extract with a total tannin content of 76.18% showed wound-healing promoting effect in rat model. We found significantly accelerated wound closure already on day 7 in animals treated with total Entada phaseoloides (L.) Merr. tannins (TEPT) as compared to vaseline treated controls (p<0.05). At day 15, histologically, the wounds in animals treated with TEPT were completely closed as compared to controls. In vitro, TEPT promotes fibroblast proliferation and migration into wounds of NIH3T3 with concentration range of 9.38-37.50μg/ml. TEPT also had an inhibitory action against Staphylococcus aureus with MBC of 1.5mg/ml and the result was further proved by transmission electron microscope. Thus, TEPT could promote wound shrinkage, improve healing rate and promote healing of infectious wounds in rats. And this effect may due to antibacterial activities and NIH3T3 cell pro-proliferative effect of the tannins compounds, which indicating that TEPT can be used as efficient treatment in traumatic injury. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  2. Growth Factor-Reinforced ECM Fabricated from Chemically Hypoxic MSC Sheet with Improved In Vivo Wound Repair Activity.

    PubMed

    Du, Hui-Cong; Jiang, Lin; Geng, Wen-Xin; Li, Jing; Zhang, Rui; Dang, Jin-Ge; Shu, Mao-Guo; Li, Li-Wen

    2017-01-01

    MSC treatment can promote cutaneous wound repair through multiple mechanisms, and paracrine mediators secreted by MSC are responsible for most of its therapeutic benefits. Recently, MSC sheet composed of live MSCs and their secreted ECMs was reported to promote wound healing; however, whether its ECM alone could accelerate wound closure remained unknown. In this study, Nc-ECM and Cc-ECM were prepared from nonconditioned and CoCl 2 -conditioned MSC sheets, respectively, and their wound healing properties were evaluated in a mouse model of full-thickness skin defect. Our results showed that Nc-ECM can significantly promote wound repair through early adipocyte recruitment, rapid reepithelialization, enhanced granulation tissue growth, and augmented angiogenesis. Moreover, conditioning of MSC sheet with CoCl 2 dramatically enriched its ECM with collagen I, collagen III, TGF- β 1, VEGF, and bFGF via activation of HIF-1 α and hence remarkably improved its ECM's in vivo wound healing potency. All the Cc-ECM-treated wounds completely healed on day 7, while Nc-ECM-treated wounds healed about 85.0% ± 8.6%, and no-treatment wounds only healed 69.8% ± 9.6% ( p < 0.05). Therefore, we believe that such growth factor-reinforced ECM fabricated from chemically hypoxic MSC sheet has the potential for clinical translation and will lead to a MSC-derived, cost-effective, bankable biomaterial for wound management.

  3. Enhanced Healing of Diabetic Wounds by Subcutaneous Administration of Human Umbilical Cord Derived Stem Cells and Their Conditioned Media

    PubMed Central

    Shrestha, Chandrama; Zhao, Liling; Chen, Ke; He, Honghui; Mo, Zhaohui

    2013-01-01

    Objective. Mesenchymal stem cells (MSCs) isolated from the umbilical cord and their conditioned media (CM) can be easily obtained and refined compared with stem cells from other sources. Here, we explore the possibility of the benefits of these cells in healing diabetic wounds. Methodology and Results. Delayed wound healing animal models were established by making a standard wound on the dorsum of eighteen db/db mice, which were divided into three groups with six mice in each: groups I, II, and III received PBS, UC-MSC, and CM, respectively. UC-MSC and their CM significantly accelerated wound closure compared to PBS-treated wounds, and it was most rapid in CM-injected wounds. In day-14 wounds, significant difference in capillary densities among the three groups was noted (n = 6; P < 0.05), and higher levels of VEGF, PDGF, and KGF expression in the CM- and UC-MSC-injected wounds compared to the PBS-treated wounds were seen. The expression levels of PDGF-β and KGF were higher in CM-treated wounds than those in UC-MSC-treated wounds. Conclusion. Both the transplantation of UC-MSC and their CM are beneficial to diabetic wound healing, and CM has been shown to be therapeutically better than UC-MSC, at least in the context of diabetic wound healing. PMID:24089612

  4. Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro

    PubMed Central

    Huang, Tonglie; Zhang, Kuo; Sun, Lijuan; Xue, Xiaochang; Zhang, Cun; Shu, Zhen; Mu, Nan; Gu, Jintao; Zhang, Wangqian; Wang, Yukun; Zhang, Yingqi; Zhang, Wei

    2015-01-01

    Chemical burns take up a high proportion of burns admissions and can penetrate deep into tissues. Various reagents have been applied in the treatment of skin chemical burns; however, no optimal reagent for skin chemical burns currently exists. The present study investigated the effect of topical body protective compound (BPC)-157 treatment on skin wound healing, using an alkali burn rat model. Topical treatment with BPC-157 was shown to accelerate wound closure following an alkali burn. Histological examination of skin sections with hematoxylin–eosin and Masson staining showed better granulation tissue formation, reepithelialization, dermal remodeling, and a higher extent of collagen deposition when compared to the model control group on the 18th day postwounding. BPC-157 could promote vascular endothelial growth factor expression in wounded skin tissues. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell cycle analysis demonstrated that BPC-157 enhanced the proliferation of human umbilical vein endothelial cells (HUVECs). Transwell assay and wound healing assay showed that BPC-157 significantly promoted migration of HUVECs. We also observed that BPC-157 upregulated the expression of VEGF-a and accelerated vascular tube formation in vitro. Moreover, further studies suggested that BPC-157 regulated the phosphorylation level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) as well as its downstream targets, including c-Fos, c-Jun, and Egr-1, which are key molecules involved in cell growth, migration, and angiogenesis. Altogether, our results indicated that BPC-157 treatment may accelerate wound healing in a model of alkali burn-induced skin injury. The therapeutic mechanism may be associated with accelerated granulation tissue formation, reepithelialization, dermal remodeling, and collagen deposition through ERK1/2 signaling pathway. PMID:25995620

  5. Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro.

    PubMed

    Huang, Tonglie; Zhang, Kuo; Sun, Lijuan; Xue, Xiaochang; Zhang, Cun; Shu, Zhen; Mu, Nan; Gu, Jintao; Zhang, Wangqian; Wang, Yukun; Zhang, Yingqi; Zhang, Wei

    2015-01-01

    Chemical burns take up a high proportion of burns admissions and can penetrate deep into tissues. Various reagents have been applied in the treatment of skin chemical burns; however, no optimal reagent for skin chemical burns currently exists. The present study investigated the effect of topical body protective compound (BPC)-157 treatment on skin wound healing, using an alkali burn rat model. Topical treatment with BPC-157 was shown to accelerate wound closure following an alkali burn. Histological examination of skin sections with hematoxylin-eosin and Masson staining showed better granulation tissue formation, reepithelialization, dermal remodeling, and a higher extent of collagen deposition when compared to the model control group on the 18th day postwounding. BPC-157 could promote vascular endothelial growth factor expression in wounded skin tissues. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell cycle analysis demonstrated that BPC-157 enhanced the proliferation of human umbilical vein endothelial cells (HUVECs). Transwell assay and wound healing assay showed that BPC-157 significantly promoted migration of HUVECs. We also observed that BPC-157 upregulated the expression of VEGF-a and accelerated vascular tube formation in vitro. Moreover, further studies suggested that BPC-157 regulated the phosphorylation level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) as well as its downstream targets, including c-Fos, c-Jun, and Egr-1, which are key molecules involved in cell growth, migration, and angiogenesis. Altogether, our results indicated that BPC-157 treatment may accelerate wound healing in a model of alkali burn-induced skin injury. The therapeutic mechanism may be associated with accelerated granulation tissue formation, reepithelialization, dermal remodeling, and collagen deposition through ERK1/2 signaling pathway.

  6. The healing effects of autologous platelet gel on acute human skin wounds.

    PubMed

    Hom, David B; Linzie, Bradley M; Huang, Trevor C

    2007-01-01

    To compare the healing of full-thickness skin punch wounds treated with topical autologous platelet gel (APG) vs conventional therapy (antibiotic ointment and/or occlusive dressings) in healthy volunteers. A prospective, single-blind, pilot study comprising 80 full-thickness skin punch wounds (4 mm diameter) was conducted on the thighs of 8 healthy volunteers. With each subject serving as his or her own control (5 punch sites per leg), APG was applied topically on one thigh, and an antibiotic ointment and/or a semiocclusive dressing was applied on the other thigh. Healing was monitored for spontaneous wound closure by clinical assessment and by digital photographs over 6 months. Over 35 days, 64 serial dermal biopsy specimens (6 mm diameter) were analyzed (using hematoxylin-eosin, Mason trichrome, CD-34, and Ki-67 stains) to measure differences between treated and control sites for cellularity, granulation formation, vascularity, epithelialization, and cellular replication. Over a 42-day period, the APG-treated sites had statistically increased wound closure compared with controls by visual clinical assessment and by digital planimetry photographic measurements (Pclosure was 81.1% +/- 2.5% (mean +/- SE) for the APG-treated sites and 57.2% +/- 5.9% for the control sites. Also, the APG wound closure velocities were significantly faster than those of the controls (P = .001). Histologically, over time, the APG-treated sites had similar cellularity, cellular replication, granulation tissue, vascularity, and epithelialization compared with controls. However, when the platelet count in the gel was more than 6 times the baseline intravascular platelet count in some subjects, epithelialization and granulation formation appeared 3 days earlier in the APG-treated group. Furthermore, in vitro testing of supplemental APG showed increased endothelial cell proliferation compared with controls (P<.04). This pilot study provides preliminary

  7. Facial gunshot wound debridement: debridement of facial soft tissue gunshot wounds.

    PubMed

    Shvyrkov, Michael B

    2013-01-01

    Over the period 1981-1985 the author treated 1486 patients with facial gunshot wounds sustained in combat in Afghanistan. In the last quarter of 20th century, more powerful and destructive weapons such as M-16 rifles, AK-47 and Kalashnikov submachine guns, became available and a new approach to gunshot wound debridement is required. Modern surgeons have little experience in treatment of such wounds because of rare contact with similar pathology. This article is intended to explore modern wound debridement. The management of 502 isolated soft tissue injuries is presented. Existing principles recommend the sparing of damaged tissues. The author's experience was that tissue sparing lead to a high rate of complications (47.6%). Radical primary surgical debridement (RPSD) of wounds was then adopted with radical excision of necrotic non-viable wound margins containing infection to the point of active capillary bleeding and immediate primary wound closure. After radical debridement wound infection and breakdown decreased by a factor of 10. Plastic operations with local and remote soft tissue were made on 14, 7% of the wounded. Only 0.7% patients required discharge from the army due to facial muscle paralysis and/or facial skin impregnation with particles of gunpowder from mine explosions. Gunshot face wound; modern debridement. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  8. [Vacuum-assisted therapy for various wound types including diabetic foot ulcer].

    PubMed

    Farah, Raymond; Gantus, Maher; Kogan, Leonid

    2011-03-01

    Vacuum is a noninvasive system that creates a localized controlled negative pressure environment. In this study, vacuum was provided by the V.A.C. Therapy system, which promotes wound healing by delayed primary or secondary intention through creating a moist wound environment, preparing the wound bed for closure, reducing edema, and promoting formation and perfusion of granulation tissue. Vacuum-assisted closure therapy is indicated for use in all care settings and for a variety of wound types including diabetic foot ulcers. The purpose of this study was to evaluate safety and clinical efficacy of negative pressure wound therapy (NPWT) compared with advanced moist wound therapy and standard treatment to treat foot ulcers in diabetic patients. This trial enrolled 43 patients; most of them were diabetic patients at any age with various skin ulcers and diabetic foot. These patients were divided into two groups, 17 patients were treated with vacuum and the 26 patients in the control group were treated with standard therapy including debridement. A greater proportion of foot and skin ulcers achieved complete ulcer closure with vacuum-assisted therapy p<0.001 compared with the standard therapy. Vacuum therapy significantly decreased the duration and frequency of admission p=0.032 and decreased the rate of amputation p<0.001. Results of our trial support other studies and demonstrate that vacuum is as safe as and more efficacious than standard therapy in the treatment of diabetic foot ulcers. A significantly greater number of patients achieved complete ulcer closure and granulation tissue formation with this therapy. The study group showed a significant reduction in the median time needed to heal ulcers, reduction of the number of admissions and amputation frequency.

  9. Novel nanofibrous dressings containing rhEGF and Aloe vera for wound healing applications.

    PubMed

    Garcia-Orue, Itxaso; Gainza, Garazi; Gutierrez, Franciso Borja; Aguirre, Jose Javier; Evora, Carmen; Pedraz, Jose Luis; Hernandez, Rosa Maria; Delgado, Araceli; Igartua, Manoli

    2017-05-25

    Nanofibrous membranes produced by electrospinning possess a large surface area-to-volume ratio, which mimics the three-dimensional structure of the extracellular matrix. Thus, nanofibrous dressings are a promising alternative for chronic wound healing, since they can replace the natural ECM until it is repaired. Therefore, in this study we have developed a PLGA nanofibrous membrane that contains recombinant human Epidermal Growth Factor (rhEGF) and Aloe vera (AV) extract. Both of them promote wound healing, as EGF is a wound healing mediator and AV stimulates the proliferation and activity of fibroblast. The obtained membranes were composed of uniform and randomly oriented fibers with an average diameter of 356.03±112.05nm, they presented a porosity of 87.92±11.96% and the amount of rhEGF was 9.76±1.75μg/mg. The in vitro viability assay demonstrated that the membranes containing rhEGF and AV improved fibroblast proliferation, revealing the beneficial effect of the combination. Furthermore, these membranes accelerated significantly wound closure and reepithelisation in an in vivo full thickness wound healing assay carried out in db/db mice. Overall, these findings demonstrated the potential of PLGA nanofibers containing rhEGF and AV for the treatment of chronic wounds. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. An ordinary differential equation model for full thickness wounds and the effects of diabetes.

    PubMed

    Bowden, L G; Maini, P K; Moulton, D E; Tang, J B; Wang, X T; Liu, P Y; Byrne, H M

    2014-11-21

    Wound healing is a complex process in which a sequence of interrelated phases contributes to a reduction in wound size. For diabetic patients, many of these processes are compromised, so that wound healing slows down. In this paper we present a simple ordinary differential equation model for wound healing in which attention focusses on the dominant processes that contribute to closure of a full thickness wound. Asymptotic analysis of the resulting model reveals that normal healing occurs in stages: the initial and rapid elastic recoil of the wound is followed by a longer proliferative phase during which growth in the dermis dominates healing. At longer times, fibroblasts exert contractile forces on the dermal tissue, the resulting tension stimulating further dermal tissue growth and enhancing wound closure. By fitting the model to experimental data we find that the major difference between normal and diabetic healing is a marked reduction in the rate of dermal tissue growth for diabetic patients. The model is used to estimate the breakdown of dermal healing into two processes: tissue growth and contraction, the proportions of which provide information about the quality of the healed wound. We show further that increasing dermal tissue growth in the diabetic wound produces closure times similar to those associated with normal healing and we discuss the clinical implications of this hypothesised treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Wound healing properties of jojoba liquid wax: an in vitro study.

    PubMed

    Ranzato, Elia; Martinotti, Simona; Burlando, Bruno

    2011-03-24

    The wound healing properties of jojoba (Simmondsia chinensis) liquid wax (JLW) were studied in vitro on HaCaT keratinocytes and human dermal fibroblasts, which are involved in wounded skin repair. JLW cytotoxicity was evaluated by the crystal violet staining and the neutral red uptake endpoint. Induction of wound healing by JLW was assessed by scratch wound assay on cell monolayers. The involvement of signaling pathways was evaluated by the use of the Ca(2+) chelator BAPTA and of kinase inhibitors, and by Western blot analysis of cell lysates using anti-phospho antibodies. Collagen and gelatinase secretion by cells were assayed by in-cell ELISA and zymography analysis, respectively. Cytotoxicity assays showed that the toxic effects of JLW to these cells are extremely low. Scratch wound experiments showed that JLW notably accelerates the wound closure of both keratinocytes and fibroblasts. The use of inhibitors and Western blot revealed that the mechanism of action of JLW is strictly Ca(2+) dependent and requires the involvement of the PI3K-Akt-mTOR pathway and of the p38 and ERK1/2 MAPKs. In addition, JLW was found to stimulate collagen I synthesis in fibroblasts, while no effect was detected on the secretion of MMP-2 and MMP-9 gelatinases by HaCaT or fibroblasts. Taken together, data provide a pharmacological characterization of JLW properties on skin cells and suggest that it could be used in the treatment of wounds in clinical settings. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Evaluation of dermal wound healing activity and in vitro antibacterial and antioxidant activities of a new exopolysaccharide produced by Lactobacillus sp.Ca6.

    PubMed

    Trabelsi, Imen; Ktari, Naourez; Ben Slima, Sirine; Triki, Mehdi; Bardaa, Sana; Mnif, Hela; Ben Salah, Riadh

    2017-10-01

    The present study aimed to evaluate the in vitro antibacterial and antioxidant activities and the in vivo wound healing performance of a noval exopolysaccharides (EPS-Ca 6 ) produced by Lactobacillus sp.Ca 6 strain. The results showed that EPS-Ca 6 had a potential antioxidant activity determined through four different assays: DPPH scavenging activity, reducing power, β-carotene bleaching by linoleic acid assay, and Metal chelating activities. It also exhibited significant antibacterial activity against pathogenic bacteria Salmonella enterica and Micrococcus luteus. The wound healing activity of the EPS-Ca 6 , using excision wound model in rats, showed that this novel EPS accelerated significantly wound healing activity as compared to the control group, and a total closure was achieved after 14days of wound induction. Furthermore, histological examination of biopsies showed fully re-epithelialized wound with a complete epidermal regeneration. Overall the finding indicates that the EPS-Ca 6 might be useful as a wound healing agent in modern medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Expectation-induced placebo responses fail to accelerate wound healing in healthy volunteers: results from a prospective controlled experimental trial.

    PubMed

    Vits, Sabine; Dissemond, Joachim; Schadendorf, Dirk; Kriegler, Lisa; Körber, Andreas; Schedlowski, Manfred; Cesko, Elvir

    2015-12-01

    Placebo responses have been shown to affect the symptomatology of skin diseases. However, expectation-induced placebo effects on wound healing processes have not been investigated yet. We analysed whether subjects' expectation of receiving an active drug accelerates the healing process of experimentally induced wounds. In 22 healthy men (experimental group, n = 11; control group, n = 11) wounds were induced by ablative laser on both thighs. Using a deceptive paradigm, participants in the experimental group were informed that an innovative 'wound gel' was applied on one of the two wounds, whereas a 'non-active gel' was applied on the wound of the other thigh. In fact, both gels were identical hydrogels without any active components. A control group was informed to receive a non-active gel on both wounds. Progress in wound healing was documented via planimetry on days 1, 4 and 7 after wound induction. From day 9 onwards wound inspections were performed daily accompanied by a change of the dressing and a new application of the gel. No significant differences could be observed with regard to duration or process of wound healing, either by intraindividual or by interindividual comparisons. These data document no expectation-induced placebo effect on the healing process of experimentally induced wounds in healthy volunteers. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  14. Topical Erythropoietin Treatment Accelerates the Healing of Cutaneous Burn Wounds in Diabetic Pigs Through an Aquaporin-3-Dependent Mechanism.

    PubMed

    Hamed, Saher; Ullmann, Yehuda; Egozi, Dana; Keren, Aviad; Daod, Essam; Anis, Omer; Kabha, Hoda; Belokopytov, Mark; Ashkar, Manal; Shofti, Rona; Zaretsky, Asaph; Schlesinger, Michal; Teot, Luc; Liu, Paul Y

    2017-08-01

    We have previously reported that the topical application of erythropoietin (EPO) to cutaneous wounds in rats and mice with experimentally induced diabetes accelerates their healing by stimulating angiogenesis, reepithelialization, and collagen deposition, and by suppressing the inflammatory response and apoptosis. Aquaporins (AQPs) are integral membrane proteins whose function is to regulate intracellular fluid hemostasis by enabling the transport of water and glycerol. AQP3 is the AQP that is expressed in the skin where it facilitates cell migration and proliferation and re-epithelialization during wound healing. In this report, we provide the results of an investigation that examined the contribution of AQP3 to the mechanism of EPO action on the healing of burn wounds in the skin of pigs with experimentally induced type 1 diabetes. We found that topical EPO treatment of the burns accelerated their healing through an AQP3-dependent mechanism that activates angiogenesis, triggers collagen and hyaluronic acid synthesis and the formation of the extracellular matrix (ECM), and stimulates reepithelialization by keratinocytes. We also found that incorporating fibronectin, a crucial constituent of the ECM, into the topical EPO-containing gel, can potentiate the accelerating action of EPO on the healing of the burn injury. © 2017 by the American Diabetes Association.

  15. Electrical Stimulation Technologies for Wound Healing

    PubMed Central

    Kloth, Luther C.

    2014-01-01

    Objective: To discuss the physiological bases for using exogenously applied electric field (EF) energy to enhance wound healing with conductive electrical stimulation (ES) devices. Approach: To describe the types of electrical currents that have been reported to enhance chronic wound-healing rate and closure. Results: Commercial ES devices that generate direct current (DC), and mono and biphasic pulsed current waveforms represent the principal ES technologies which are reported to enhance wound healing. Innovation: Wafer-thin, disposable ES technologies (wound dressings) that utilize mini or micro-batteries to deliver low-level DC for wound healing and antibacterial wound-treatment purposes are commercially available. Microfluidic wound-healing chips are currently being used with greater accuracy to investigate the EF effects on cellular electrotaxis. Conclusion: Numerous clinical trials described in subsequent sections of this issue have demonstrated that ES used adjunctively with standard wound care (SWC), enhances wound healing rate faster than SWC alone. PMID:24761348

  16. P311 Accelerates Skin Wound Reepithelialization by Promoting Epidermal Stem Cell Migration Through RhoA and Rac1 Activation.

    PubMed

    Yao, Zhihui; Li, Haisheng; He, Weifeng; Yang, Sisi; Zhang, Xiaorong; Zhan, Rixing; Xu, Rui; Tan, Jianglin; Zhou, Junyi; Wu, Jun; Luo, Gaoxing

    2017-03-15

    P311 is a newly discovered functional gene, and it has been proved to play a key role in blood pressure homeostasis, glioblastoma invasion, renal fibrosis, hypertrophic scar formation, and others. In this study, for the first time, we found that P311 could enhance reepithelialization during wound healing via promoting epidermal stem cell (EpSC) migration through Rho GTPases. P311 expression was highly increased in neo-epidermal cells during human and mouse skin wound healing, and P311was co-localized with 5-bromo-2'-deoxyuridine positive label-retaining cells in a mouse superficial second-degree burn wound model. Furthermore, transfection of human EpSCs with adenovirus encoding P311 significantly accelerated the cell migration in vitro. Moreover, highly expressed P311 could enhance the activities of the Rho GTPases (RhoA, Rac1, and Cdc42) in cultured human EpSCs. P311-knockout mouse EpSCs showed dramatically decreased cell migration and activities of Rho GTPases (RhoA, Rac1, and Cdc42). Besides, both the RhoA-specific inhibitor and the Rac1 inhibitor, not the Cdc42 inhibitor, could significantly suppress P311-induced human EpSC migration. In vivo, the reepithelialization was markedly impaired during wound healing after P311 was knocked out. Together, our results suggested that P311 could accelerate skin wound reepithelialization by promoting the migration of EpSCs through RhoA and Rac1 activation. P311 could serve as a novel target for regulation of EpSC migration during cutaneous wound healing.

  17. Does omphalocele major undergo spontaneous closure?

    PubMed Central

    Emordi, Victor C.; Osifo, David O.

    2017-01-01

    Abstract The early surgical management of omphalocele major in Africa predisposes neonates to surgical complications which are often worsened by the presence of associated anomalies. Conservative management using available escharotics results in early skin cover by secondary wound healing. This delays the need for fascial closure and avoids neonatal surgical risks thus improving survival. We present a case of omphalocele major that underwent spontaneous closure during conservative management with honey dressing without surgical intervention. PMID:28928917

  18. Circadian rhythms accelerate wound healing in female Siberian hamsters

    PubMed Central

    Cable, Erin J.; Onishi, Kenneth G.; Prendergast, Brian J.

    2017-01-01

    Circadian rhythms (CRs) provide temporal regulation and coordination of numerous physiological traits, including immune function. CRs in multiple aspects of immune function are absent in rodents that have been rendered circadian-arrhythmic through various methods. In Siberian hamsters, circadian arrhythmia can be induced by disruptive light treatments (DPS). Here we examined CRs in wound healing, and the effects of circadian disruption on wound healing in DPS-arrhythmic hamsters. Circadian entrained/rhythmic (RHYTH) and behaviorally-arrhythmic (ARR) female hamsters were administered a cutaneous wound either 3 h after light onset (ZT03) or 2 h after dark onset (ZT18); wound size was quantified daily using image analyses. Among RHYTH hamsters, ZT03 wounds healed faster than ZT18 wounds, whereas in ARR hamsters, circadian phase did not affect wound healing. In addition, wounds healed slower in ARR hamsters. The results document a clear CR in wound healing, and indicate that the mere presence of organismal circadian organization enhances this aspect of immune function. Faster wound healing in CR-competent hamsters may be mediated by CR-driven coordination of the temporal order of mechanisms (inflammation, leukocyte trafficking, tissue remodeling) underlying cutaneous wound healing. PMID:27998755

  19. Proline-Rich Peptide Mimics Effects of Enamel Matrix Derivative on Rat Oral Mucosa Incisional Wound Healing.

    PubMed

    Villa, Oscar; Wohlfahrt, Johan C; Mdla, Ibrahimu; Petzold, Christiane; Reseland, Janne E; Snead, Malcolm L; Lyngstadaas, Staale P

    2015-12-01

    Proline-rich peptides have been shown to promote periodontal regeneration. However, their effect on soft tissue wound healing has not yet been investigated. The aim of this study is to evaluate the effect of enamel matrix derivative (EMD), tyrosine-rich amelogenin peptide (TRAP), and a synthetic proline-rich peptide (P2) on acute wound healing after a full-thickness flap procedure in an incisional rat model. This experimental study has a split-mouth, randomized, placebo-controlled design. Test and control wounds were created on the palatal mucosa of 54 Sprague-Dawley rats. Wounds were histologically processed, and reepithelialization, leukocyte infiltration, and angiogenesis were assessed at days 1, 3, and 7 post-surgery. EMD and P2 significantly promoted early wound closure at day 1 (P <0.001 and P = 0.004, respectively). EMD maintained a significant acceleration of reepithelialization at day 3 (P = 0.004). Wounds treated by EMD and P2 showed increased angiogenesis during the first 3 days of healing (P = 0.03 and 0.001, respectively). Leukocyte infiltration was decreased in EMD-treated wounds at day 1 (P = 0.03), and P2 and TRAP induced a similar effect at days 3 (P = 0.002 and P <0.0001, respectively) and 7 (P = 0.005 and P <0.001). EMD and P2 promoted reepithelialization and neovascularization in full-thickness surgical wounds on rat oral mucosa.

  20. Aerogels made of chitosan and chondroitin sulfate at high degree of neutralization: Biological properties toward wound healing.

    PubMed

    Concha, Miguel; Vidal, Alejandra; Giacaman, Annesi; Ojeda, Javier; Pavicic, Francisca; Oyarzun-Ampuero, Felipe A; Torres, César; Cabrera, Marcela; Moreno-Villoslada, Ignacio; Orellana, Sandra L

    2018-02-09

    In this study, highly neutralized, highly porous, and ultralight polymeric aerogels prepared from aqueous colloidal suspensions of chitosan (CS) and chondroitin sulfate (ChS) nanocomplexes, formulated as quasi-equimolar amounts of both, are described. These aerogels were designed as healing agents under the inspiration of minimizing the amount of matter applied to wounds, reducing the electrostatic potential of the material and avoiding covalent cross-linkers in order to decrease metabolic stress over wounds. Aerogels synthesized under these criteria are biocompatible and provide specific properties for the induction of wound healing. They do not affect neither the metabolic activity of cultured 3T3 fibroblasts nor the biochemical parameters of experimental animals, open wounds close significantly faster and, unlike control wounds, complete reepithelialization and scarring can be attained 14 days after surgery. Because of its hydration abilities, rapid adaptation to the wound bed and the early accelerator effect of wound closure, the CS/ChS aerogels appear to be functional inducers of the healing. Previous information show that CS/ChS aerogels improve wound bed quality, increase granulation tissue and have pain suppressive effect. CS/ChS aerogels are useful as safe, inexpensive and easy to handle materials for topical applications, such as skin chronic wounds. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc.

  1. Smoke Extract Impairs Adenosine Wound Healing. Implications of Smoke-Generated Reactive Oxygen Species

    PubMed Central

    Zimmerman, Matthew C.; Zhang, Hui; Castellanos, Glenda; O’Malley, Jennifer K.; Alvarez-Ramirez, Horacio; Kharbanda, Kusum; Sisson, Joseph H.; Wyatt, Todd A.

    2013-01-01

    Adenosine concentrations are elevated in the lungs of patients with asthma and chronic obstructive pulmonary disease, where it balances between tissue repair and excessive airway remodeling. We previously demonstrated that the activation of the adenosine A2A receptor promotes epithelial wound closure. However, the mechanism by which adenosine-mediated wound healing occurs after cigarette smoke exposure has not been investigated. The present study investigates whether cigarette smoke exposure alters adenosine-mediated reparative properties via its ability to induce a shift in the oxidant/antioxidant balance. Using an in vitro wounding model, bronchial epithelial cells were exposed to 5% cigarette smoke extract, were wounded, and were then stimulated with either 10 μM adenosine or the specific A2A receptor agonist, 5′-(N-cyclopropyl)–carboxamido–adenosine (CPCA; 10 μM), and assessed for wound closure. In a subset of experiments, bronchial epithelial cells were infected with adenovirus vectors encoding human superoxide dismutase and/or catalase or control vector. In the presence of 5% smoke extract, significant delay was evident in both adenosine-mediated and CPCA-mediated wound closure. However, cells pretreated with N-acetylcysteine (NAC), a nonspecific antioxidant, reversed smoke extract–mediated inhibition. We found that cells overexpressing mitochondrial catalase repealed the smoke extract inhibition of CPCA-stimulated wound closure, whereas superoxide dismutase overexpression exerted no effect. Kinase experiments revealed that smoke extract significantly reduced the A2A-mediated activation of cyclic adenosine monophosphate–dependent protein kinase. However, pretreatment with NAC reversed this effect. In conclusion, our data suggest that cigarette smoke exposure impairs A2A-stimulated wound repair via a reactive oxygen species–dependent mechanism, thereby providing a better understanding of adenosine signaling that may direct the development of

  2. May Dietary Supplementation Augment Respiratory Burst in Wound-Site Inflammatory Cells?

    PubMed

    Das, Amitava; Dickerson, Ryan; Ghatak, Piya Das; Gordillo, Gayle M; Chaffee, Scott; Saha, Abhijoy; Khanna, Savita; Roy, Sashwati

    2018-02-10

    Persistent infection contributes to wound chronicity. At the wound site, NADPH oxidase (NOX) activity in immune cells fights infection to enable the healing process. Fermented papaya preparation (FPP) is a carbohydrate-rich nutritional supplement that has demonstrated ability to bolster respiratory burst in experimental rodent systems. In FPP, glucose coexists with fructose and maltose in addition to multiple other sugar alcohols such as inositol. We have previously reported that FPP supplementation augments wound healing in diabetic mice via improvement of respiratory burst activity of wound innate immune cells. In this clinical study ( clinicaltrials.gov : NCT02332993), chronic wound patients were orally supplemented with FPP daily. Inducible production of reactive oxygen species was significantly higher in wound-site immune cells from patients supplemented with FPP and on standard of care (SoC) for wound management compared with those patients receiving SoC alone. Wound closure in FPP-supplemented patients showed improvement. Importantly, the consumption of this mixture of carbohydrates, including significant amounts of glucose, did not increase HbA1c. These observations warrant a full-length clinical trial testing the hypothesis that FPP improves wound closure by augmenting NOX activity in immune cells at the wound site. Antioxid. Redox Signal. 28, 401-405.

  3. Co-delivery of a growth factor and a tissue-protective molecule using elastin biopolymers accelerates wound healing in diabetic mice.

    PubMed

    Devalliere, Julie; Dooley, Kevin; Hu, Yong; Kelangi, Sarah S; Uygun, Basak E; Yarmush, Martin L

    2017-10-01

    Growth factor therapy is a promising approach for chronic diabetic wounds, but strategies to efficiently and cost-effectively deliver active molecules to the highly proteolytic wound environment remain as major obstacles. Here, we re-engineered keratinocyte growth factor (KGF) and the cellular protective peptide ARA290 into a protein polymer suspension with the purpose of increasing their proteolytic resistance, thus their activity in vivo. KGF and ARA290 were fused with elastin-like peptide (ELP), a protein polymer derived from tropoelastin, that confers the ability to separate into a colloidal suspension of liquid-like coacervates. ELP fusion did not diminish peptides activities as demonstrated by ability of KGF-ELP to accelerate keratinocyte proliferation and migration, and ARA290-ELP to protect cells from apoptosis. We examined the healing effect of ARA290-ELP and KGF-ELP alone or in combination, in a full-thickness diabetic wound model. In this model, ARA290-ELP was found to accelerate healing, notably by increasing angiogenesis in the wound bed. We further showed that co-delivery of ARA290 and KGF, with the 1:4 KGF-ELP to ARA290-ELP ratio, was the most effective wound treatment with the fastest healing rate, the thicker granulation tissue and regenerated epidermis after 28 days. Overall, this study shows that ARA290-ELP and KGF-ELP constitute promising new therapeutics for treatment of chronic wounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Methods and apparatus for microwave tissue welding for wound closure

    NASA Technical Reports Server (NTRS)

    Ngo, Phong H. (Inventor); Dusl, John R. (Inventor); Arndt, G. Dickey (Inventor); Phan, Chau T. (Inventor); Byerly, Diane L. (Inventor); Sognier, Marguerite A. (Inventor); Carl, James R. (Inventor)

    2013-01-01

    Methods and apparatus for joining biological tissue together are provided. In at least one specific embodiment, a method for joining biological tissue together can include applying a biological solder on a wound. A barrier layer can be disposed on the biological solder. An antenna can be located in proximate spatial relationship to the barrier layer. An impedance of the antenna can be matched to an impedance of the wound. Microwaves from a signal generator can be transmitted through the antenna to weld two or more biological tissue pieces of the wound together. A power of the microwaves can be adjusted by a control circuit disposed between the antenna and the signal generator. The heating profile within the tissue may be adjusted and controlled by the placement of metallic microspheres in or around the wound.

  5. Tenofovir Inhibits Wound Healing of Epithelial Cells and Fibroblasts from the Upper and Lower Human Female Reproductive Tract

    PubMed Central

    Rodriguez-Garcia, Marta; Patel, Mickey V.; Shen, Zheng; Bodwell, Jack; Rossoll, Richard M.; Wira, Charles R.

    2017-01-01

    Disruption of the epithelium in the female reproductive tract (FRT) is hypothesized to increase HIV infection risk by interfering with barrier protection and facilitating HIV-target cell recruitment. Here we determined whether Tenofovir (TFV), used vaginally in HIV prevention trials, and Tenofovir alafenamide (TAF), an improved prodrug of TFV, interfere with wound healing in the human FRT. TFV treatment of primary epithelial cells and fibroblasts from the endometrium (EM), endocervix (CX) and ectocervix (ECX) significantly delayed wound closure. Reestablishment of tight junctions was compromised in EM and CX epithelial cells even after wound closure occurred. In contrast, TAF had no inhibitory effect on wound closure or tight junction formation following injury. TAF accumulated inside genital epithelial cells as TFV-DP, the active drug form. At elevated levels of TAF treatment to match TFV intracellular TFV-DP concentrations, both equally impaired barrier function, while wound closure was more sensitive to TFV. Furthermore, TFV but not TAF increased elafin and MIP3a secretion following injury, molecules known to be chemotactic for HIV-target cells. Our results highlight the need of evaluating antiretroviral effects on genital wound healing in future clinical trials. A possible link between delayed wound healing and increased risk of HIV acquisition deserves further investigation. PMID:28368028

  6. Anterior gradient 2 is induced in cutaneous wound and promotes wound healing through its adhesion domain.

    PubMed

    Zhu, Qi; Mangukiya, Hitesh Bhagavanbhai; Mashausi, Dhahiri Saidi; Guo, Hao; Negi, Hema; Merugu, Siva Bharath; Wu, Zhenghua; Li, Dawei

    2017-09-01

    Anterior gradient 2 (AGR2), a member of protein disulfide isomerase (PDI) family, is both located in cytoplasm and secreted into extracellular matrix. The orthologs of AGR2 have been linked to limb regeneration in newt and wound healing in zebrafish. In mammals, AGR2 influences multiple cell signaling pathways in tumor formation and in normal cell functions related to new tissue formation like angiogenesis. However, the function of AGR2 in mammalian wound healing remains unknown. This study aimed to investigate AGR2 expression and its function during skin wound healing and the possible application of external AGR2 in cutaneous wound to accelerate the healing process. Our results showed that AGR2 expression was induced in the migrating epidermal tongue and hyperplastic epidermis after skin excision. Topical application of recombinant AGR2 significantly accelerated wound-healing process by increasing the migration of keratinocytes (Kera.) and the recruitment of fibroblasts (Fibro.) near the wounded area. External AGR2 also promoted the migration of Kera. and Fibro. in vitro in a dose-dependent manner. The adhesion domain of AGR2 was required for the formation of focal adhesions in migrating Fibro., leading to the directional migration along AGR2 gradient. These results indicate that recombinant AGR2 accelerates skin wound healing through regulation of Kera. and Fibro. migration, thus demonstrating its potential utility as an alternative strategy of the therapeutics to accelerate the healing of acute or chronic skin wounds. © 2017 Federation of European Biochemical Societies.

  7. Significant skin-tightening by closure of fractional ablative laser holes.

    PubMed

    Russe, Elisabeth; Purschke, Martin; Limpiangkanan, Wikunda; Farinelli, William A; Wang, Ying; Doukas, Apostolos G; Sakamoto, Fernanda H; Wechselberger, Gottfried; Anderson, Richard Rox

    2018-01-01

    Ablative fractional laser treatment uses thousands of very small laser beam wounds to damage a fraction of the skin, which stimulates tissue remodeling. Each open micro-wound heals without scarring, but the amount of skin tightening achieved is limited. This animal study was performed to test the hypothesis that immediate temporary closure of fractional laser wounds could increase skin tightening after fractional ablative laser treatment. Four adult swine were used for the study; 98 square test sites (3 × 3 cm) were tattooed on the abdomen and flanks of each pig. An ablative fractional Erbium:YAG laser (Sciton Profile, Sciton Inc, Palo Alto, CA) was used to treat the test areas. A laser micro-spot fluence of 375 J/cm 2 was delivered in 150-250 microseconds pulses, resulting in an array of ablation channels extending 1.5 mm deep into the skin, with a spot size of 250 µm, with 10% treatment density. Immediately following laser exposure the resulting holes were closed using a stretched elastic adhesive dressing, which, when applied, recoiled and compressed the diameter of the ablation holes. The compressive dressings were removed after 7 days. This procedure was compared to removing the same amount of skin (10%) mechanically by specially designed 19 gauge coring needles, as well as to the same laser and coring methods without compression closure. Area and shape of test sites were measured by digital photography before and 28 days after treatment. Data analysis included compensation for animal growth, as measured by increase in the area of the untreated control sites. All treated and control sites healed within a week, without scarring evident at 28 days. Laser treatment combined with compressive wound closure caused significant shrinkage at 28 days compared with untreated control sites. The treated skin area was reduced by 11.5% (P = 0.0001). Needle coring with wound closure produced similar, significant shrinkage (8%, P < 0.0021), whereas laser

  8. Fidgetin-like 2: a microtubule-based regulator of wound healing

    PubMed Central

    Charafeddine, Rabab A.; Makdisi, Joy; Schairer, David; O’Rourke, Brian P.; Diaz-Valencia, Juan D.; Chouake, Jason; Kutner, Allison; Krausz, Aimee; Adler, Brandon; Nacharaju, Parimala; Liang, Hongying; Mukherjee, Suranjana; Friedman, Joel M.; Friedman, Adam; Nosanchuk, Joshua D.; Sharp, David J.

    2015-01-01

    Wound healing is a complex process driven largely by the migration of a variety of distinct cell types from the wound margin into the wound zone. In this study, we identify the previously uncharacterized microtubule-severing enzyme, Fidgetin-like 2 (FL2), as a fundamental regulator of cell migration that can be targeted in vivo using nanoparticle-encapsulated siRNA to promote wound closure and regeneration. In vitro, depletion of FL2 from mammalian tissue culture cells results in a more than two-fold increase in the rate of cell movement, due in part to a significant increase in directional motility. Immunofluorescence analyses indicate that FL2 normally localizes to the cell edge, importantly to the leading edge of polarized cells, where it regulates the organization and dynamics of the microtubule cytoskeleton. To clinically translate these findings, we utilized a nanoparticle-based siRNA delivery platform to locally deplete FL2 in both murine full-thickness excisional and burn wounds. Topical application of FL2 siRNA nanoparticles to either wound type results in a significant enhancement in the rate and quality of wound closure both clinically and histologically relative to controls. Taken together, these results identify FL2 as a promising therapeutic target to promote the regeneration and repair of cutaneous wounds. PMID:25756798

  9. Topically applied connective tissue growth factor/CCN2 improves diabetic preclinical cutaneous wound healing: potential role for CTGF in human diabetic foot ulcer healing.

    PubMed

    Henshaw, F R; Boughton, P; Lo, L; McLennan, S V; Twigg, S M

    2015-01-01

    Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1 μg rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulation tissue. In the human study across 32 subjects, serial CTGF regulation was analyzed longitudinally in postdebridement diabetic wound fluid. CTGF treated diabetic wounds had an accelerated closure rate compared with vehicle treated diabetic wounds. Healed skin withstood more strain before breaking in CTGF treated rat wounds. Granulation tissue from CTGF treatment in diabetic wounds showed collagen IV accumulation compared with nondiabetic animals. Wound α-smooth muscle actin was increased in CTGF treated diabetic wounds compared with untreated diabetic wounds, as was macrophage infiltration. Endogenous wound fluid CTGF protein rate of increase in human diabetic foot ulcers correlated positively with foot ulcer healing rate (r = 0.406; P < 0.001). These data collectively increasingly substantiate a functional role for CTGF in human diabetic foot ulcers.

  10. Blue light does not impair wound healing in vitro.

    PubMed

    Masson-Meyers, Daniela Santos; Bumah, Violet Vakunseh; Enwemeka, Chukuka Samuel

    2016-07-01

    Irradiation with red or near infrared light promotes tissue repair, while treatment with blue light is known to be antimicrobial. Consequently, it is thought that infected wounds could benefit more from combined blue and red/infrared light therapy; but there is a concern that blue light may slow healing. We investigated the effect of blue 470nm light on wound healing, in terms of wound closure, total protein and collagen synthesis, growth factor and cytokines expression, in an in vitro scratch wound model. Human dermal fibroblasts were cultured for 48h until confluent. Then a linear scratch wound was created and irradiated with 3, 5, 10 or 55J/cm(2). Control plates were not irradiated. Following 24h of incubation, cells were fixed and stained for migration and fluorescence analyses and the supernatant collected for quantification of total protein, hydroxyproline, bFGF, IL-6 and IL-10. The results showed that wound closure was similar for groups treated with 3, 5 and 10J/cm(2), with a slight improvement with the 5J/cm(2) dose, and slower closure with 55J/cm(2) p<0.001). Total protein concentration increased after irradiation with 3, 5 and 10J/cm(2), reaching statistical significance at 5J/cm(2) compared to control (p<0.0001). However, hydroxyproline levels did not differ between groups. Similarly, bFGF and IL-10 concentrations did not differ between groups, but IL-6 concentration decreased progressively as fluence increased (p<0.0001). Fluorescence analysis showed viable cells regardless of irradiation fluence. We conclude that irradiation with blue light at low fluence does not impair in vitro wound healing. The significant decrease in IL-6 suggests that 470nm light is anti-inflammatory. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. The immediate use of a silicone sheet wound closure device in scar reduction and prevention.

    PubMed

    Parry, James R; Stupak, Howard D; Johnson, Calvin M

    2016-02-01

    Silicone has been used successfully postoperatively in the prevention of hypertrophic and other types of adverse scars. The Silicone Suture Plate (SSP) is a new, minimally invasive, sterile wound closure device that is applied intraoperatively to prevent adverse scarring. The SSP device permits immediate application of silicone while concurrently allowing for wound-edge tension redistribution. In this prospective, controlled, single-blinded clinical study, 8 consecutive patients undergoing deep-plane rhytidectomy were selected. SSP devices were placed on the patients' posterior rhytidectomy hairline incision; the mirror-image control site underwent standard suturing techniques. Three blinded, independent raters assessed the treatment and control sides at 6-week and 4-month follow-up visits, using the Objective Scar Assessment Scale (OSAS), a validated scar assessment tool. The 6-week OSAS scores revealed an 18.4% improvement on the side with the SSP device (13.3) when compared to the control side (16.3). The 4-month OSAS scores showed a 27.3% improvement on the treatment side from 12.7 (control) to 9.2 (SSP). These OSAS results were found to be statistically significant when taken as an aggregate of the observers' scores, but not when observers' scores were measured individually (p < 0.05). In our series of patients, we showed promising results with the use of the SSP device. Early silicone application and tissue tension distribution contributed to an overall more aesthetically pleasing scar compared to those seen with standard suturing techniques, although more testing is required.

  12. Glu-Trp-ONa or its acylated analogue (R-Glu-Trp-ONa) administration enhances the wound healing in the model of chronic skin wounds in rabbits.

    PubMed

    Shevtsov, Maxim A; Smagina, Larisa V; Kudriavtceva, Tatiana A; Petlenko, Sergey V; Voronkina, Irina V

    2015-01-01

    The management of chronic skin wounds represents a major therapeutic challenge. The synthesized dipeptide (Glu-Trp-ONa) and its acylated analogue (R-Glu-Trp-ONa) were assessed in the model of nonhealing dermal wounds in rabbits in relation to their healing properties in wound closure. Following wound modeling, the rabbits received a course of intraperitoneal injections of Glu-Trp-ONa or R-Glu-Trp-ONa. Phosphate-buffered saline and Solcoseryl® were applied as negative and positive control agents, respectively. An injection of Glu-Trp-ONa and R-Glu-Trp-ONa decreased the period of wound healing in animals in comparison to the control and Solcoseryl-treated groups. Acylation of Glu-Trp-ONa proved to be beneficial as related to the healing properties of the dipeptide. Subsequent zymography analyses showed that the applied peptides decreased the proteolytic activity of matrix metalloproteinases MMP-9, MMP-8, and MMP-2 in the early inflammatory phase and reversely increased the activity of MMP-9, MMP-8, and MMP-1 in the remodeling phase. Histological analyses of the wound sections (hematoxylin-eosin, Mallory's staining) confirmed the enhanced formation of granulation tissue and re-epithelialization in the experimental groups. By administering the peptides, wound closures increased significantly through the modulation of the MMPs' activity, indicating their role in wound healing.

  13. Post-surgical wound management of pilonidal cysts with a haemoglobin spray: a case series.

    PubMed

    Mustafi, N; Engels, P

    2016-04-01

    Painful acute cysts in the natal cleft or lower back, known as pilonidal sinus disease, are a severe burden to many younger patients. Although surgical intervention is the preferred first line treatment, postsurgical wound healing disturbances are frequently reported due to infection or other complications. Different treatment options of pilonidal cysts have been discussed in the literature, however, no standardised guideline for the postsurgical wound treatment is available. After surgery, a common recommended treatment to patients is rinsing the wound with clean water and dressing with a sterile compress. We present a case series of seven patients with wounds healing by secondary intention after surgical intervention of a pilonidal cyst. The average age of the patients was 40 years old. Of the seven patients, three had developed a wound healing disturbance, one wound had started to develop a fibrin coating and three were in a good condition. The applied wound care regimens comprised appropriate mechanical or autolytic debridement, rinsing with an antimicrobial solution, haemoglobin application, and primary and secondary dressings. In all seven cases a complete wound closure was achieved within an average of 76 days with six out of seven wounds achieving wound closure within 23-98 days. Aesthetic appearance was deemed excellent in five out of seven cases excellent and acceptable in one. Treatment of one case with a sustained healing disturbance did result in wound closure but with a poor aesthetic outcome and an extensive cicatrisation of the new tissue. Based on these results we recommend that to avoid healing disturbances of wounds healing by secondary intention after surgical pilonidal cyst intervention, an adequate wound care regime comprising appropriate wound debridement, rinsing, topically applied haemoglobin and adequate wound dressing is recommendable as early as possible after surgery.

  14. Honey/Chitosan Nanofiber Wound Dressing Enriched with Allium sativum and Cleome droserifolia: Enhanced Antimicrobial and Wound Healing Activity.

    PubMed

    Sarhan, Wessam A; Azzazy, Hassan M E; El-Sherbiny, Ibrahim M

    2016-03-01

    Two natural extracts were loaded within fabricated honey, poly(vinyl alcohol), chitosan nanofibers (HPCS) to develop biocompatible antimicrobial nanofibrous wound dressing. The dried aqueous extract of Cleome droserifolia (CE) and Allium sativum aqueous extract (AE) and their combination were loaded within the HPCS nanofibers in the HPCS-CE, HPCS-AE, and HPCS-AE/CE nanofiber mats, respectively. It was observed that the addition of AE resulted in the least fiber diameter (145 nm), whereas the addition of the AE and CE combination resulted in the least swelling ability and the highest weight loss. In vitro antibacterial testing against Staphylococcus aureus, Escherichia coli, Methicillin-resistant S. aureus (MRSA), and multidrug-resistant Pseudomonas aeruginosa was performed in comparison with the commercial dressing AquacelAg and revealed that the HPCS-AE and HPCS-AE/CE nanofiber mats allowed complete inhibition of S. aureus and the HPCS-AE/CE exhibited mild antibacterial activity against MRSA. A preliminary in vivo study revealed that the developed nanofiber mats enhanced the wound healing process as compared to the untreated control as proved by the enhanced wound closure rates in mice and by the histological examination of the wounds. Moreover, comparison with the commercial dressing Aquacel Ag, the HPCS, and HPCS-AE/CE demonstrated similar effects on the wound healing process, whereas the HPCS/AE allowed an enhanced wound closure rate. Cell culture studies proved the biocompatibility of the developed nanofiber mats in comparison with the commercial Aquacel Ag, which exhibited noticeable cytotoxicity. The developed natural nanofiber mats hold potential as promising biocompatible antibacterial wound dressing.

  15. Clinical Experience and Best Practices Using Epidermal Skin Grafts on Wounds.

    PubMed

    Kirsner, Robert S; Bernstein, Brent; Bhatia, Animesh; Lantis, John; Le, Lam; Lincoln, Katherine; Liu, Paul; Rodgers, Lee; Shaw, Mark; Young, David

    2015-11-01

    Over the years, autologous skin grafting has been used extensively to achieve wound closure, optimize a functional scar, and improve aesthetic outcomes for the patient. Although a vast majority of the literature is on the use of full-thickness and split-thickness skin grafts, epidermal skin grafts (ESGs) have emerged as a viable option in the reconstructive ladder when only the epidermal layer is needed. These grafts are distinct from other types of autologous skin grafts in that they can be harvested without anesthesia and leave minimal or no scarring at the donor site. In order to explore the use of ESGs in the continuum of primary wound closure, a multidisciplinary expert panel convened in October 2014, in Las Vegas, NV, to review the scientific basis and clinical uses of epidermal grafting. This publication provides an overview of epidermal grafting, recommendations for graft application, and potential roles for its use in wound care and closure.

  16. Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds

    NASA Astrophysics Data System (ADS)

    Seow, Wei Yang; Salgado, Giorgiana; Lane, E. Birgitte; Hauser, Charlotte A. E.

    2016-09-01

    Wound healing is a major burden of healthcare systems worldwide and hydrogel dressings offer a moist environment conducive to healing. We describe cysteine-containing ultrashort peptides that self-assemble spontaneously into hydrogels. After disulfide crosslinking, the optically-transparent hydrogels became significantly stiffer and exhibited high shape fidelity. The peptide sequence (LIVAGKC or LK6C) was then chosen for evaluation on mice with full-thickness excision wounds. Crosslinked LK6C hydrogels are handled easily with forceps during surgical procedures and offer an improvement over our earlier study of a non-crosslinked peptide hydrogel for burn wounds. LK6C showed low allergenic potential and failed to provoke any sensitivity when administered to guinea pigs in the Magnusson-Kligman maximization test. When applied topically as a dressing, the medium-infused LK6C hydrogel accelerated re-epithelialization compared to controls. The peptide hydrogel is thus safe for topical application and promotes a superior rate and quality of wound healing.

  17. Electrospun tilapia collagen nanofibers accelerating wound healing via inducing keratinocytes proliferation and differentiation.

    PubMed

    Zhou, Tian; Wang, Nanping; Xue, Yang; Ding, Tingting; Liu, Xin; Mo, Xiumei; Sun, Jiao

    2016-07-01

    The development of biomaterials with the ability to induce skin wound healing is a great challenge in biomedicine. In this study, tilapia skin collagen sponge and electrospun nanofibers were developed for wound dressing. The collagen sponge was composed of at least two α-peptides. It did not change the number of spleen-derived lymphocytes in BALB/c mice, the ratio of CD4(+)/CD8(+) lymphocytes, and the level of IgG or IgM in Sprague-Dawley rats. The tensile strength and contact angle of collagen nanofibers were 6.72±0.44MPa and 26.71±4.88°, respectively. They also had good thermal stability and swelling property. Furthermore, the nanofibers could significantly promote the proliferation of human keratinocytes (HaCaTs) and stimulate epidermal differentiation through the up-regulated gene expression of involucrin, filaggrin, and type I transglutaminase in HaCaTs. The collagen nanofibers could also facilitate rat skin regeneration. In the present study, electrospun biomimetic tilapia skin collagen nanofibers were succesfully prepared, were proved to have good bioactivity and could accelerate rat wound healing rapidly and effectively. These biological effects might be attributed to the biomimic extracellular matrix structure and the multiple amino acids of the collagen nanofibers. Therefore, the cost-efficient tilapia collagen nanofibers could be used as novel wound dressing, meanwhile effectively avoiding the risk of transmitting animal disease in the future clinical apllication. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. A modified collagen gel enhances healing outcome in a preclinical swine model of excisional wounds.

    PubMed

    Elgharably, Haytham; Roy, Sashwati; Khanna, Savita; Abas, Motaz; Dasghatak, Piya; Das, Amitava; Mohammed, Kareem; Sen, Chandan K

    2013-01-01

    Collagen-based dressings are of great interest in wound care. However, evidence supporting their mechanism of action is scanty. This work provides first results from a preclinical swine model of excisional wounds, elucidating the mechanism of action of a modified collagen gel (MCG) dressing. Following wounding, wound-edge tissue was collected at specific time intervals (3, 7, 14, and 21 days postwounding). On day 7, histological analysis showed significant increase in the length of rete ridges, suggesting improved biomechanical properties of the healing wound tissue. Rapid and transient mounting of inflammation is necessary for efficient healing. MCG significantly accelerated neutrophil and macrophage recruitment to the wound site on day 3 and day 7 with successful resolution of inflammation on day 21. MCG induced monocyte chemotactic protein-1 expression in neutrophil-like human promyelocytic leukemia-60 cells in vitro. In vivo, MCG-treated wound tissue displayed elevated vascular endothelial growth factor expression. Consistently, MCG-treated wounds displayed significantly higher abundance of endothelial cells with increased blood flow to the wound area indicating improved vascularization. This observation was explained by the finding that MCG enhanced proliferation of wound-site endothelial cells. In MCG-treated wound tissue, Masson's trichrome and picrosirius red staining showed higher abundance of collagen and increased collagen type I:III ratio. This work presents first evidence from a preclinical setting explaining how a collagen-based dressing may improve wound closure by targeting multiple key mechanisms. The current findings warrant additional studies to determine whether the responses to the MCG are different from other collagen-based products used in clinical setting. © 2013 by the Wound Healing Society.

  19. Multichannel Negative Pressure Wound Therapy Vacuum Assisted Closure (V.A.C.)

    DTIC Science & Technology

    2016-10-01

    Concepts, Inc. (KCI) Innovation & Strategic Marketing 12930 W Interstate 10 San Antonio, TX 78249-2248 8. PERFORMING ORGANIZATION REPORT...canisters. It was also designed to have four independently controlled NPWT channels . 15. SUBJECT TERMS Wound therapy, multichannel negative...wound dressings and wound exudate canisters. It was also designed to have four independently controlled NPWT channels . 2.0 INTRODUCTION The

  20. EVALUATION OF EFFECTIVENESS IN A NOVEL WOUND HEALING OINTMENT-CROCODILE OIL BURN OINTMENT

    PubMed Central

    Li, Hua-Liang; Deng, Yi-Tao; Zhang, Zi-Ran; Fu, Qi-Rui; Zheng, Ya-Hui; Cao, Xing-Mei; Nie, Jing; Fu, Li-Wen; Chen, Li-Ping; Xiong, You-Xiong; Shen, Dong-Yan; Chen, Qing-Xi

    2017-01-01

    Background: Crocodile oil and its products are used as ointments for burns and scalds in traditional medicines. A new ointment formulation - crocodile oil burn ointment (COBO) was developed to provide more efficient wound healing activity. The purpose of the study was to evaluate the burn healing efficacy of this new formulation by employing deep second-degree burns in a Wistar rat model. The analgesic and anti-inflammatory activities of COBO were also studied to provide some evidences for its further use. Materials and methods: The wound healing potential of this formulation was evaluated by employing a deep second-degree burn rat model and the efficiency was comparatively assessed against a reference ointment - (1% wt/wt) silver sulfadiazine (SSD). After 28 days, the animals were euthanized and the wounds were removed for transversal and longitudinal histological studies. Acetic acid-induced writhing in mice was used to evaluate the analgesic activity and its anti-inflammatory activity was observed in xylene -induced edema in mice. Results: COBO enhanced the burn wound healing (20.5±1.3 d) as indicated by significant decrease in wound closure time compared with the burn control (25.0±2.16 d) (P<0.01). Hair follicles played an importance role in the physiological functions of the skin, and their growth in the wound could be revealed for the skin regeneration situation. Histological results showed that the hair follicles were well-distributed in the post-burn skin of COBO treatment group, and the amounts of total, active, primary and secondary hair follicles in post-burn 28-day skin of COBO treatment groups were more than those in burn control and SSD groups. On the other hand, the analgesic and anti-inflammatory activity of COBO were much better than those of control group, while they were very close to those of moist exposed burn ointment (MEBO). Conclusions: COBO accelerated wound closure, reduced inflammation, and had analgesic effects compared with SSD in

  1. EVALUATION OF EFFECTIVENESS IN A NOVEL WOUND HEALING OINTMENT-CROCODILE OIL BURN OINTMENT.

    PubMed

    Li, Hua-Liang; Deng, Yi-Tao; Zhang, Zi-Ran; Fu, Qi-Rui; Zheng, Ya-Hui; Cao, Xing-Mei; Nie, Jing; Fu, Li-Wen; Chen, Li-Ping; Xiong, You-Xiong; Shen, Dong-Yan; Chen, Qing-Xi

    2017-01-01

    Crocodile oil and its products are used as ointments for burns and scalds in traditional medicines. A new ointment formulation - crocodile oil burn ointment (COBO) was developed to provide more efficient wound healing activity. The purpose of the study was to evaluate the burn healing efficacy of this new formulation by employing deep second-degree burns in a Wistar rat model. The analgesic and anti-inflammatory activities of COBO were also studied to provide some evidences for its further use. The wound healing potential of this formulation was evaluated by employing a deep second-degree burn rat model and the efficiency was comparatively assessed against a reference ointment - (1% wt/wt) silver sulfadiazine (SSD). After 28 days, the animals were euthanized and the wounds were removed for transversal and longitudinal histological studies. Acetic acid-induced writhing in mice was used to evaluate the analgesic activity and its anti-inflammatory activity was observed in xylene -induced edema in mice. COBO enhanced the burn wound healing (20.5±1.3 d) as indicated by significant decrease in wound closure time compared with the burn control (25.0±2.16 d) ( P <0.01). Hair follicles played an importance role in the physiological functions of the skin, and their growth in the wound could be revealed for the skin regeneration situation. Histological results showed that the hair follicles were well-distributed in the post-burn skin of COBO treatment group, and the amounts of total, active, primary and secondary hair follicles in post-burn 28-day skin of COBO treatment groups were more than those in burn control and SSD groups. On the other hand, the analgesic and anti-inflammatory activity of COBO were much better than those of control group, while they were very close to those of moist exposed burn ointment (MEBO). COBO accelerated wound closure, reduced inflammation, and had analgesic effects compared with SSD in deep second degree rat burn model. These findings suggest

  2. Skin closure with dye-enhanced laser welding and fibrinogen.

    PubMed

    Wider, T M; Libutti, S K; Greenwald, D P; Oz, M C; Yager, J S; Treat, M R; Hugo, N E

    1991-12-01

    The topical application of wavelength-specific dye and fibrinogen has been used to enhance laser closure of vascular anastomoses. We compared the closure of skin incisions by two different dye-enhanced, fibrinogen-based laser welding systems [argon laser (power density 4.78 W/cm2) with fluorescein isothiocyanate dye (n = 32) and diode laser (power density 9.55 W/cm2) with indocyanine green dye (n = 32)] with closure by interrupted 5-0 nylon suture (n = 64) and examined tensile strength, hydroxyproline production, histology, and cosmesis. Two 3-cm full-thickness incisions were made on the shaved backs of 64 rats. One incision was closed with suture, whereas the other, after treatment with the appropriate dye, was welded with either argon- or diode-lasered fibrinogen. At postoperative days 5, 10, 15, and 28, the closure sites were harvested and sectioned for analysis. Initially, wounds closed with argon-lasered fibrinogen showed less inflammatory response, greater collagen production (34.61 +/- 0.74 mg/gm), and greater mean peak stress at rupture (64.85 lbs/in2) than those closed with suture (16.42 +/- 3.20 mg/gm, 26.68 lbs/in2) (p less than 0.05). By 15 days, both argon and diode laser closures are superior in strength and collagen production to suture closure (p less than 0.05). At 28 days, diode laser closures (1315.60 lbs/in2) are stronger than suture closures (998.09 lbs/in2), whereas both are stronger than argon laser closures (813.16 lbs/in2) (p less than 0.05). Cosmetically, argon-welded wounds consistently appeared finer and lacked cross-hatched suture scars.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Wound healing potential of adipose tissue stem cell extract

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Na, You Kyung; Ban, Jae-Jun; Lee, Mijung

    Adipose tissue stem cells (ATSCs) are considered as a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using stem cells, intercellular molecule exchange by stem cell secretory factors showed beneficial effects by reducing tissue damage and augmentation of endogenous repair. Delayed cutaneous wound healing is implicated in many conditions such as diabetes, aging, stress and alcohol consumption. However, the effects of cell-free extract of ATSCs (ATSC-Ex) containing secretome on wound healing process have not been investigated. In this study, ATSC-Ex was topically applied on the cutaneous wound and healing speed wasmore » examined. As a result, wound closure was much faster in the cell-free extract treated wound than control wound at 4, 6, 8 days after application of ATSC-Ex. Dermal fibroblast proliferation, migration and extracellular matrix (ECM) production are critical aspects of wound healing, and the effects of ATSC-Ex on human dermal fibroblast (HDF) was examined. ATSC-Ex augmented HDF proliferation in a dose-dependent manner and migration ability was enhanced by extract treatment. Representative ECM proteins, collagen type I and matrix metalloproteinase-1, are significantly up-regulated by treatment of ATSC-Ex. Our results suggest that the ATSC-Ex have improving effect of wound healing and can be the potential therapeutic candidate for cutaneous wound healing. - Highlights: • Topical application of ATSC-Ex results in faster wound closure than normal wound in vivo. • ATSC-Ex enhances dermal fibroblast proliferation, migration and extracellular matrix production. • This study suggests that ATSC-Ex is an effective source to augment wound healing.« less

  4. Oral administration of antioxidants improves skin wound healing in diabetic mice.

    PubMed

    Pessoa, Ana Flávia Marçal; Florim, Juliana Costa; Rodrigues, Hosana Gomes; Andrade-Oliveira, Vinicius; Teixeira, Simone A; Vitzel, Kaio Fernando; Curi, Rui; Saraiva Câmara, Niels Olsen; Muscará, Marcelo N; Lamers, Marcelo Lazzaron; Santos, Marinilce Fagundes

    2016-11-01

    Oxidative stress aggravates several long-term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan-induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post-wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b + and Ly6G + cells) and reduced levels of KC, TNF-α, IL-1β, and IL-12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG + /CD206 - macrophages whereas CD206 + /MIG - macrophages were decreased. Cytokines IL-12p40, TNF-α, IL-1β, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia. © 2016 by the Wound Healing Society.

  5. Wound ballistics and blast injuries.

    PubMed

    Prat, N J; Daban, J-L; Voiglio, E J; Rongieras, F

    2017-12-01

    Wounds due to gunshot and explosions, while usually observed during battlefield combat, are no longer an exceptional occurrence in civilian practice in France. The principles of wound ballistics are based on the interaction between the projectile and the human body as well as the transfer of energy from the projectile to tissues. The treatment of ballistic wounds relies on several principles: extremity wound debridement and absence of initial closure, complementary medical treatment, routine immobilization, revision surgery and secondary closure. Victims of explosions usually present with a complex clinical picture since injuries are directly or indirectly related to the shock wave (blast) originating from the explosion. These injuries depend on the type of explosive device, the environment and the situation of the victim at the time of the explosion, and are classed as primary, secondary, tertiary or quaternary. Secondary injuries due to flying debris and bomb fragments are generally the predominant presenting symptoms while isolated primary injuries (blast) are rare. The resulting complexity of the clinical picture explains why triage of these victims is particularly difficult. Certain myths, such as inevitable necrosis of the soft tissues that are displaced by the formation of the temporary cavitation by the projectile, or sterilization of the wounds by heat generated by the projectile should be forgotten. Ballistic-protective body armor and helmets are not infallible, even when they are not perforated, and can even be at the origin of injuries, either due to missile impact, or to the blast. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. MicroRNA miR-27b rescues bone marrow-derived angiogenic cell function and accelerates wound healing in type 2 diabetes mellitus.

    PubMed

    Wang, Jie-Mei; Tao, Jun; Chen, Dan-Dan; Cai, Jing-Jing; Irani, Kaikobad; Wang, Qinde; Yuan, Hong; Chen, Alex F

    2014-01-01

    Vascular precursor cells with angiogenic potentials are important for tissue repair, which is impaired in diabetes mellitus. MicroRNAs are recently discovered key regulators of gene expression, but their role in vascular precursor cell-mediated angiogenesis in diabetes mellitus is unknown. We tested the hypothesis that the microRNA miR-27b rescues impaired bone marrow-derived angiogenic cell (BMAC) function in vitro and in vivo in type 2 diabetic mice. BMACs from adult male type 2 diabetic db/db and from normal littermate db/+ mice were used. miR-27b expression was decreased in db/db BMACs. miR-27b mimic improved db/db BMAC function, including proliferation, adhesion, tube formation, and delayed apoptosis, but it did not affect migration. Elevated thrombospondin-1 (TSP-1) protein in db/db BMACs was suppressed on miR-27b mimic transfection. Inhibition of miR-27b in db/+ BMACs reduced angiogenesis, which was reversed by TSP-1 small interfering RNA (siRNA). miR-27b suppressed the pro-oxidant protein p66(shc) and mitochondrial oxidative stress, contributing to its protection of BMAC function. miR-27b also suppressed semaphorin 6A to improve BMAC function in diabetes mellitus. Luciferase binding assay suggested that miR-27b directly targeted TSP-1, TSP-2, p66(shc), and semaphorin 6A. miR-27b improved topical cell therapy of diabetic BMACs on diabetic skin wound closure, with a concomitant augmentation of wound perfusion and capillary formation. Normal BMAC therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice. miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice.

  7. Office management of minor wounds.

    PubMed Central

    Gouin, S.; Patel, H.

    2001-01-01

    OBJECTIVE: To review office interventions for minor wounds not requiring sutures, such as abrasions, bites, and lacerations. QUALITY OF EVIDENCE: Most information on minor wound management comes from descriptive studies. Few comparative studies examine the effectiveness of topical antisepsis for minor wounds. Several clinical trials have demonstrated that tissue adhesives produce short- and long-term cosmetic results equivalent to those achieved with suture materials. MAIN MESSAGE: Sterile saline is the least toxic solution for wound irrigation. Chlorhexidine (2%) and povidone iodine (10%) have been the most investigated antiseptic solutions. Systemic antibiotics are unnecessary for wounds unlikely to be infected. All bite wounds require special attention. Primary closure of bite wounds is indicated in certain circumstances: less than 12-hour-old nonpuncture wounds, uninfected wounds, and low-risk lesions (such as on the face). In spite of their many advantages, skin tapes should be used for low-tension wounds only. The popularity of tissue adhesives has greatly increased. Since the advent of newer products (with increased bonding strength and flexibility), adhesives are used to manage most lacerations except those in areas of high tension (e.g., joints) and on mucosal surfaces. CONCLUSION: Minor wounds not requiring sutures can be managed easily in the office. PMID:11340758

  8. Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Kant, Vinay; Kumar, Dinesh; Kumar, Dhirendra; Prasad, Raju; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surender K

    2015-05-01

    Substance P (SP) is known to stimulate angiogenesis, fibroblasts proliferation and expressions of cytokines and growth factors involved in wound healing. However, SP level reduces in dermis in diabetics and, hence, it was hypothesized that exogenously applied SP could be helpful in improving wound healing in diabetic rats. Excision skin wound was created on the back of diabetic rats and rats were divided into three groups i.e. (i) saline-, (ii) gel- and (iii) SP-treated. Normal saline, pluronic gel and SP (10(-6)M) in gel were topically applied once daily for 19days. SP treatment significantly increased the wound closure, levels of interleukin-10, and expressions of vascular endothelial growth factor, transforming growth factor-beta1, heme oxygenase-1 and endothelial nitric oxide synthase, whereas it significantly decreased the expression of tumor necrosis factor-alpha, interleukin-1beta and matrix metalloproteinases-9 in the granulation/healing tissue. The inflammatory cells were present for long time in normal saline-treated group. Histological evaluation revealed better extracellular matrix formation with marked fibroblast proliferation and collagen deposition in SP-treated group. Early epithelial layer formation, increased microvessel density and greater growth associated protein-43 positive nerve fibers were also evidenced in SP-treated group. In conclusion, SP treatment markedly accelerated cutaneous wound healing in diabetic rats. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Alteration of skin wound healing in keratinocyte-specific mediator complex subunit 1 null mice.

    PubMed

    Noguchi, Fumihito; Nakajima, Takeshi; Inui, Shigeki; Reddy, Janardan K; Itami, Satoshi

    2014-01-01

    MED1 (Mediator complex subunit 1) is a co-activator of various transcription factors that function in multiple transcriptional pathways. We have already established keratinocyte-specific MED1 null mice (Med1(epi-/-)) that develop epidermal hyperplasia. Herein, to investigate the function(s) of MED1 in skin wound healing, full-thickness skin wounds were generated in Med1(epi-/-) and age-matched wild-type mice and the healing process was analyzed. Macroscopic wound closure and the re-epithelialization rate were accelerated in 8-week-old Med1(epi-/-) mice compared with age-matched wild-type mice. Increased lengths of migrating epithelial tongues and numbers of Ki67-positive cells at the wounded epidermis were observed in 8-week-old Med1(epi-/-) mice, whereas wound contraction and the area of α-SMA-positive myofibroblasts in the granulation tissue were unaffected. Migration was enhanced in Med1(epi-/-) keratinocytes compared with wild-type keratinocytes in vitro. Immunoblotting revealed that the expression of follistatin was significantly decreased in Med1(epi-/-) keratinocytes. Moreover, the mitogen-activated protein kinase pathway was enhanced before and after treatment of Med1(epi-/-) keratinocytes with activin A in vitro. Cell-cycle analysis showed an increased ratio of S phase cells after activin A treatment of Med1(epi-/-) keratinocytes compared with wild-type keratinocytes. These findings indicate that the activin-follistatin system is involved in this acceleration of skin wound healing in 8-week-old Med1(epi-/-) mice. On the other hand, skin wound healing in 6-month-old Med1(epi-/-) mice was significantly delayed with decreased numbers of Ki67-positive cells at the wounded epidermis as well as BrdU-positive label retaining cells in hair follicles compared with age-matched wild-type mice. These results agree with our previous observation that hair follicle bulge stem cells are reduced in older Med1(epi-/-) mice, indicating a decreased contribution of hair

  10. Human endothelial progenitor cells-derived exosomes accelerate cutaneous wound healing in diabetic rats by promoting endothelial function.

    PubMed

    Li, Xiaocong; Jiang, Chunyu; Zhao, Jungong

    2016-08-01

    Wound healing is deeply dependent on neovascularization to restore blood flow. The neovascularization of endothelial progenitor cells (EPCs) through paracrine secretion has been reported in various tissue repair models. Exosomes, key components of cell paracrine mechanism, have been rarely reported in wound healing. Exosomes were isolated from the media of EPCs obtained from human umbilical cord blood. Diabetic rats wound model was established and treated with exosomes. The in vitro effects of exosomes on the proliferation, migration and angiogenic tubule formation of endothelial cells were investigated. We revealed that human umbilical cord blood EPCs derived exosomes transplantation could accelerate cutaneous wound healing in diabetic rats. We also showed that exosomes enhanced the proliferation, migration and tube formation of vascular endothelial cells in vitro. Furthermore, we found that endothelial cells stimulated with these exosomes would increase expression of angiogenesis-related molecules, including FGF-1, VEGFA, VEGFR-2, ANG-1, E-selectin, CXCL-16, eNOS and IL-8. Taken together, our findings indicated that EPCs-derived exosomes facilitate wound healing by positively modulating vascular endothelial cells function. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Experimental closure of gunshot wounds by fibrin glue with antibiotics in pigs.

    PubMed

    Djenić, Nebojša; Višnjić, Milan; Dragović, Saša; Bojanić, Vladmila; Bojanić, Zoran; Djurdjević, Dragan; Djindjić, Boris; Kostov, Miloš

    2015-09-01

    Gunshot wounds caused by the automatic rifle M70AB2 (AK-47) 7.62 mm, after the primary surgical management, were closed with delayed primary suture during the next four to seven days. This period coincides with the fibroblastic phase of wound healing. Fibrin glue is used as a local hemostatic and as a matrix for the local dosed release of antibiotics. Antibiotics addition to fibrin glue resulted in continuous diffusion into the surrounding next 4 to 7 days. The aim of this study was to create the preconditions for gunshot wounds closing without complications by the application of fibrin glue with antibiotics 24 h after primary surgical treatment. A total of 14 pigs were wounded in the gluteofemoral region by the bullet M67, initial velocity of 720 m/s. All wounded animals were surgically treated according to the principles of the war-surgery doctrine. Seven wounds were closed with primary delayed suture four days after the primary surgical treatment (traditional approach). Fibrin glue with antibiotics was introduced in seven wounds during the primary surgical treatment and primary delayed suture was done after 24 h. The macroscopic appearance and the clinical assessment of the wound were done during the primary surgical treatment and during its revision after 24 h, as well as histopathological findings at the days 4 and 7 after wounding. Gunshot wounds caused by the automatic rifle M70AB2 (AK-47) 7.62 mm, and treated with fibrin glue with antibiotics after primary surgical management, were closed with primary delayed suture after 24 h. In further wound evolution there were no complications. Uncomplicated soft-tissue wounds caused by an automatic M70AB2 rifle may be closed primarily with delayed suture without the risk of developing complications if on revision, 24 h after primary surgery, there were no present necrotic tissues, hematoma, and any signs of infection when fibrin glue with antibiotics (ceftriaxone and clindamycin) was applied. The use of this method

  12. The use of urinary bladder matrix in the treatment of complicated open wounds.

    PubMed

    Lanteri Parcells, Alexis; Abernathie, Brenon; Datiashvili, Ramazi

    2014-07-01

    Management of complicated open wounds represents a challenge when reconstructive options are not applicable. Urinary bladder matrix (UBM) provides a biocompatible material that allows inductivetissue remodeling. The use of urinary bladder matrix inthe treatment of 5 patients with complicated open wounds that failed toheal with conventional therapy is presented. A 3-year old male sustained a second-degree oil burn measuring 8 cm x 4 cm to his dorsal forearm; UBM was applied weekly and the wound epithelialized in 3 weeks. A 52-year old male sustained massive second and third degree burns to his leg after a fire; UBM was applied weekly and the wound epithelialized in 28 weeks. A 61-year old female sustained a severe crushing injury to her right knee. A gastrocnemius muscle transfer and rectus abdominus muscle free flap transfer both failed, then UBM and vacuum-assisted closure therapy were applied and the wound epithelialized in 24 weeks. A 54-year old female underwent a breast mastectomy and immediate reconstruction with pedicled transverse rectus abdominus flap. The patient developed partial necrosis and the wound was managed with UBM and vacuum-assisted closure therapy. The wound epithelialized in 12 weeks. A 36-year old female sustained severe degloving injuries to both hands with exposed metacarpals. Weekly application of UBM provided tissue remodeling over the bones, which allowed successful skin grafting and closure. These experiences show UBM to be an effective method in management of complicated open wounds in select cases. Further studies need to be implemented to confirm this conclusion.

  13. Effects of High Estrogen Levels on Monocyte Chemoattractant Protein-1 and Wound Healing

    PubMed Central

    Plackett, Timothy P.; Gregory, Meredith S.; Kovacs, Elizabeth J.

    2015-01-01

    Objective: Herein, we tested the effects of high levels of supplemental estrogen treatment on cutaneous wound healing. Approach: Female mice were implanted with a 17β-estradiol (E2) secreting pellet or placebo before receiving a full-thickness dermal excisional wound. Mice receiving the E2 pellet attained hormone levels that are comparable to those achieved during pregnancy. At 1, 3, and 5 days after injury, the dermal excision wound was examined for their histologic appearance, rate of closure, and chemokine levels. Results: Wound closure, assessed by percent reepithelialization, was slower in E2-treated mice relative to placebo (42.6%±6.6% vs. 70.0%±5.3%, respectively, 3 days after injury). In addition, there was a marked reduction in the subepithelial inflammatory infiltrate and granulation tissue in E2-treated mice relative to placebo. Wound levels of monocyte chemoattractant protein-1 (MCP-1) were increased by 3 days after injury and continued to rise at 5 days after injury in placebo-treated mice (p<0.01). By contrast, MCP-1 levels were significantly reduced at 3 and 5 days after injury in E2-treated mice relative to placebo-treated controls (p<0.01). This attenuation could be reversed by treatment with an estrogen receptor antagonist. Innovation: High levels of estrogen are able to suppress normal wound closure. Conclusion: Dermal wound healing can be altered by manipulating the gonadal steroid hormone levels. In particular, high levels of estrogen can be utilized to slow down the rate of wound healing through a reduction in the inflammatory response. PMID:25713751

  14. Upper Blepharoplasty and Lateral Wound Dehiscence.

    PubMed

    Kashkouli, Mohsen Bahmani; Jamshidian-Tehrani, Mansooreh; Sharzad, Sahab; Sanjari, Mostafa Soltan

    2015-01-01

    To report the frequency of lateral wound dehiscence (LWD) after upper blepharoplasty (UB), a technique and its outcome to prevent LWD. A retrospective review was performed for cases of LWD after UB presenting between 2003 and 2009, and then a prospective comparative study was performed between February 2009 and March 2013. For the comparison, subjects were divided into two groups based on intraoperative assessment of lateral wound tension (same technique and surgeon). Group 1 received 1-3 orbicularis/subcutaneous buried sutures (6-0 polyglactin) before interrupted 6-0 nylon skin closure. Group 2 underwent skin closure only. Subjects, who had re-operation, skin healing disorders, and incomplete follow-up (<6 months), were excluded. P < 0.05 was considered as statistically significant. There were 14 (14/678, 2%) cases with LWD with a mean age of 36.2 years in the audit (2003-2009). The prospective study included 68 subjects (68/293, 23.2%) in Group 1 and 225 in Group 2. Gender and simultaneous forehead and eyebrow procedures were similar between groups (P = 0.3 and P = 0.4 respectively). Group 1 was statistically significantly younger at mean age of 41.4 years, compared to Group 2 at 56.1 years (P = 0.000). The frequency of LWD significantly (P = 0.04) decreased to 0.3% (1/293). In the presence of wound tension on skin closure (intraoperative assessment), tension relieving buried orbicularis/subcutaneous 6-0 polyglactin suturing of the lateral UB incision could prevent LWD.

  15. Progressive Tightening of Pulley Sutures for Primary Repair of Large Scalp Wounds

    PubMed Central

    McLaughlin, Jillian M.; Ross, Lindy S.; Phillips, Linda G.; Wagner, Richard F.

    2017-01-01

    Summary: Scalp defects greater than 2 cm in diameter are not usually amenable to primary closure and require local tissue rearrangement, grafting, tissue expansion, or prolonged second intention healing. Scalp flap reconstruction is a significant undertaking that requires elevation of a total flap surface area that is 3–6 times the size of the defect, often involves profuse bleeding, and can be challenging to perform without conscious sedation or general anesthesia. Anticoagulated and medically complex patients pose additional challenges and limit options for treatment. The pulley suture uses the mechanical advantage of the pulley to distribute tension across a wound and is useful in areas of high tension such as scalp wounds. For scalp wounds greater than 2 cm, pulley sutures are placed along the length of the wound. An assistant exerts equal tension on the pulley sutures, and the surgeon sequentially ties the sutures. The sutures are tightened and retied weekly until complete scalp closure is achieved. The pulley sutures can be used for rapid primary closure of scalp wounds up to 2.5–3.0 cm in diameter under local anesthesia. For scalp wounds larger than 3 cm, we have also found that pulley sutures can be progressively tightened yielding additional tissue expansion every week. Scalp wounds greater than 3.0 cm can be easily closed via primary repair and weekly tightening of pulley sutures without the need for flap reconstruction, traditional tissue expander placement, or second intention healing. PMID:29632771

  16. Abbreviated closure for remote damage control laparotomy in extreme environments: A randomized trial of sutures versus wound clamps comparing terrestrial and weightless conditions.

    PubMed

    Kirkpatrick, Andrew W; McKee, Jessica Lynn; Tien, Colonel Homer; LaPorta, Anthony J; Lavell, Kit; Leslie, Tim; McBeth, Paul B; Roberts, Derek J; Ball, Chad G

    2017-05-01

    Far-Forward Damage Control Laparotomies (DCLs) might provide direct-compression of visceral hemorrhage, however, suturing is a limiting factor, especially for non-physicians. We thus compared abbreviated skin closures comparing skin-suture (SS) versus wound-clamp (WC), on-board a research aircraft in weightlessness (0g) and normal gravity (1g). Surgeons conducted DCLs on a surgical-simulator; onboard the hangered-aircraft (1g), or during parabolic flight (0g), randomized to either WC or SS. Ten surgeons participated. Two (40%) surgeons randomized to suture in 0g were incapacitated with motion-sickness, and none were able to close in either 1 or 0g. With WC, two completely closed in 1g as did three in 0g, despite having longer incisions (p = 0.016). Overall skin-closure with WC was significantly greater in both 1g (p = 0.016) and 0g (p = 0.008). WC was more effective in 1g and particularly 0g. Future studies should address the utility of abbreviated WC abdominal closure to facilitate potential Far-Forward DCL. ID ISRCTN/77929274. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Development of ethyl alcohol-precipitated silk sericin/polyvinyl alcohol scaffolds for accelerated healing of full-thickness wounds.

    PubMed

    Siritienthong, Tippawan; Ratanavaraporn, Juthamas; Aramwit, Pornanong

    2012-12-15

    Silk sericin has been recently reported for its advantageous biological properties to promote wound healing. In this study, we established that the ethyl alcohol (EtOH) could be used to precipitate sericin and form the stable sericin/polyvinyl alcohol (PVA) scaffolds without the crosslinking. The sericin/PVA scaffolds were fabricated via freeze-drying and subsequently precipitating in various concentrations of EtOH. The EtOH-precipitated sericin/PVA scaffolds showed denser structure, higher compressive modulus, but lower water swelling ability than the non-precipitated scaffolds. Sericin could be released from the EtOH-precipitated sericin/PVA scaffolds in a sustained manner. After cultured with L929 mouse fibroblasts, the 70 vol% EtOH-precipitated sericin/PVA scaffolds showed the highest potential to promote cell proliferation. After applied to the full-thickness wounds of rats, the 70 vol% EtOH-precipitated sericin/PVA scaffolds showed significantly higher percentage of wound size reduction and higher extent of type III collagen formation and epithelialization, compared with the control scaffolds without sericin. The accelerated wound healing by the 70 vol% EtOH-precipitated sericin/PVA scaffolds was possibly due to (1) the bioactivity of sericin itself to promote wound healing, (2) the sustained release of precipitated sericin from the scaffolds, and (3) the activation and recruitment of wound healing-macrophages by sericin to the wounds. This finding suggested that the EtOH-precipitated sericin/PVA scaffolds were more effective for the wound healing, comparing with the EtOH-precipitated PVA scaffolds without sericin. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Radiation combined injury models to study the effects of interventions and wound biomechanics.

    PubMed

    Zawaski, Janice A; Yates, Charles R; Miller, Duane D; Kaffes, Caterina C; Sabek, Omaima M; Afshar, Solmaz F; Young, Daniel A; Yang, Yunzhi; Gaber, M Waleed

    2014-12-01

    In the event of a nuclear detonation, a considerable number of projected casualties will suffer from combined radiation exposure and burn and/or wound injury. Countermeasure assessment in the setting of radiation exposure combined with dermal injury is hampered by a lack of animal models in which the effects of interventions have been characterized. To address this need, we used two separate models to characterize wound closure. The first was an open wound model in mice to study the effect of wound size in combination with whole-body 6 Gy irradiation on the rate of wound closure, animal weight and survival (morbidity). In this model the addition of interventions, wound closure, subcutaneous vehicle injection, topical antiseptic and topical antibiotics were studied to measure their effect on healing and survival. The second was a rat closed wound model to study the biomechanical properties of a healed wound at 10 days postirradiation (irradiated with 6 or 7.5 Gy). In addition, complete blood counts were performed and wound pathology by staining with hematoxylin and eosin, trichrome, CD68 and Ki67. In the mouse open wound model, we found that wound size and morbidity were positively correlated, while wound size and survival were negatively correlated. Regardless of the wound size, the addition of radiation exposure delayed the healing of the wound by approximately 5-6 days. The addition of interventions caused, at a minimum, a 30% increase in survival and improved mean survival by ∼9 days. In the rat closed wound model we found that radiation exposure significantly decreased all wound biomechanical measurements as well as white blood cell, platelet and red blood cell counts at 10 days post wounding. Also, pathological changes showed a loss of dermal structure, thickening of dermis, loss of collagen/epithelial hyperplasia and an increased density of macrophages. In conclusion, we have characterized the effect of a changing wound size in combination with radiation

  19. Targeted treatment of invasive fungal infections accelerates healing of foot wounds in patients with Type 2 diabetes.

    PubMed

    Chellan, G; Neethu, K; Varma, A K; Mangalanandan, T S; Shashikala, S; Dinesh, K R; Sundaram, K R; Varma, N; Jayakumar, R V; Bal, A; Kumar, H

    2012-09-01

    To test the hypothesis that fluconazole plus standard care is superior to the standard care for diabetic foot wounds infected with deep-seated fungal infections. We carried out a randomized, controlled, open-label, parallel-arm study in 75 patients with both fungal and bacterial infections in deep tissues of diabetic foot wounds. Thirty-seven patients (control group) were given standard care (surgical debridement + culture-specific antibiotics + offloading + glycaemic control) and 38 patients (treatment group) were given fluconazole 150 mg daily plus standard care. Wound surface area was measured every 2 weeks until the endpoints (complete epithelialization or skin grafting) were met. By week 4, the mean wound surface area reduced to 27.3 from 111.5 cm(2) in the treatment group, as opposed to 67.1 from 87.3 cm(2) in the control group. Subsequently, the mean wound surface areas were remarkably smaller in the treatment group compared with the control group, and statistically significant differences (P ≤ 0.05) in mean wound surface area were observed between the treatment group and the control group at week 6. However, no statistically significant (P ≤ 0.47) difference in complete healing was observed between the treatment group and the control group, 20 vs. 24. The mean wound healing time for the treatment group was 7.3 weeks, whereas for the control group it was 11.3 weeks (P ≤ 0.022). Similarly, the probability of wound healing in the treatment group was 50 vs. 20% in the control group at week 10. Fluconazole plus standard care was superior to standard care alone in accelerating wound reduction among patients with diabetes with deep-seated fungal infections in diabetic foot wounds. Those in the treatment group who did heal, healed more quickly (P ≤ 0.022), but overall healing was not different. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  20. Poly (3-hydroxyalkanoates)-co-(6-hydroxyhexanoate) hydrogel promotes angiogenesis and collagen deposition during cutaneous wound healing in rats.

    PubMed

    Gumel, Ahmad Mohammed; Razaif-Mazinah, Mohd Rafais Mohd; Anis, Siti Nor Syairah; Annuar, Mohamad Suffian Mohamad

    2015-07-08

    Wound management and healing in several physiological or pathological conditions, particularly when comorbidities are involved, usually proves to be difficult. This presents complications leading to socio-economic and public health burdens. The accelerative wound healing potential of biocompatible poly(3-hydroxyalkanoates)-co-(6-hydroxyhexanoate) (PHA-PCL) composite hydrogel is reported herein. The biosynthesized PHA-PCL macromer was cross-linked with PEGMA to give a hydrogel. Twenty-four rats weighing 200-250 g each were randomly assigned to four groups of six rats. Rats in group I (negative control) were dressed with sterilized gum acacia paste in 10% normal saline while PEGMA-alone hydrogel (PH) was used to dress group II (secondary control) rats. Group III rats were dressed with PHAs-PCL cross-linked PEGMA hydrogel (PPH). For the positive control (group IV), the rats were dressed with Intrasite(®) gel. Biochemical, histomorphometric and immunohistomorphometric analyses revealed a significant difference in area closure and re-epithelialization on days 7 and 14 in PPH or Intrasite(®) gel groups compared to gum acacia or PEGMA-alone groups. Furthermore, wounds dressed with PPH or Intrasite(®) gel showed evident collagen deposition, enhanced fibrosis and extensively organized angiogenesis on day 14 compared to the negative control group. While improvement in wound healing of the PH dressed group could be observed, there was no significant difference between the negative control group and the PH dressed group in any of the tests. The findings suggested that topical application of PPH accelerated the rats' wound healing process by improving angiogenesis attributed to the increased microvessel density (MVD) and expressions of VEGF-A in tissue samples. Thus, PPH has been demonstrated to be effective in the treatment of cutaneous wounds in rats, and could be a potential novel agent in the management and acceleration of wound healing in humans and animals.

  1. Do inflammatory markers portend heterotopic ossification and wound failure in combat wounds?

    PubMed

    Forsberg, Jonathan A; Potter, Benjamin K; Polfer, Elizabeth M; Safford, Shawn D; Elster, Eric A

    2014-09-01

    After a decade of war in Iraq and Afghanistan, we have observed an increase in combat-related injury survival and a paradoxical increase in injury severity, mainly because of the effects of blasts. These severe injuries have a devastating effect on each patient's immune system resulting in massive upregulation of the systemic inflammatory response. By examining inflammatory mediators, preliminary data suggest that it may be possible to correlate complications such as wound failure and heterotopic ossification (HO) with distinct systemic and local inflammatory profiles, but this is a relatively new topic. We asked whether systemic or local markers of inflammation could be used as an objective means, independent of demographic and subjective factors, to estimate the likelihood of (1) HO and/or (2) wound failure (defined as wounds requiring surgical débridement after definitive closure, or wounds that were not closed or covered within 21 days of injury) in patients sustaining combat wounds. Two hundred combat wounded active-duty service members who sustained high-energy extremity injuries were prospectively enrolled between 2008 and 2012. Of these 200 patients, 189 had adequate followups to determine the presence or absence of HO, and 191 had adequate followups to determine the presence or absence of wound failure. In addition to injury-specific and demographic data, we quantified 24 cytokines and chemokines during each débridement. Patients were followed clinically for 6 weeks, and radiographs were obtained 3 months after definitive wound closure. Associations were investigated between these markers and wound failure or HO, while controlling for known confounders. The presence of an amputation (p < 0.001; odds ratio [OR], 6.1; 95% CI. 1.63-27.2), Injury Severity Score (p = 0.002; OR, 33.2; 95% CI, 4.2-413), wound surface area (p = 0.001; OR, 1.01; 95% CI, 1.002-1.009), serum interleukin (IL)-3 (p = 0.002; OR, 2.41; 95% CI, 1.5-4.5), serum IL-12p70 (p = 0.01; OR, 0

  2. Aloe vera oral administration accelerates acute radiation-delayed wound healing by stimulating transforming growth factor-β and fibroblast growth factor production.

    PubMed

    Atiba, Ayman; Nishimura, Mayumi; Kakinuma, Shizuko; Hiraoka, Takeshi; Goryo, Masanobu; Shimada, Yoshiya; Ueno, Hiroshi; Uzuka, Yuji

    2011-06-01

    Delayed wound healing is a significant clinical problem in patients who have had previous irradiation. This study investigated the effectiveness of Aloe vera (Av) on acute radiation-delayed wound healing. The effect of Av was studied in radiation-exposed rats compared with radiation-only and control rats. Skin wounds were excised on the back of rats after 3 days of local radiation. Wound size was measured on days 0, 3, 6, 9, and 12 after wounding. Wound tissues were examined histologically and the expressions of transforming growth factor β-1 (TGF-β-1) and basic fibroblast growth factor (bFGF) were examined by immunohistochemistry and reverse-transcription polymerase chain reaction. Wound contraction was accelerated significantly by Av on days 6 and 12 after wounding. Furthermore, the inflammatory cell infiltration, fibroblast proliferation, collagen deposition, angiogenesis, and the expression levels of TGF-β-1 and bFGF were significantly higher in the radiation plus Av group compared with the radiation-only group. These data showed the potential application of Av to improve the acute radiation-delayed wound healing by increasing TGF-β-1 and bFGF production. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. SCF increases in utero-labeled stem cells migration and improves wound healing.

    PubMed

    Zgheib, Carlos; Xu, Junwang; Mallette, Andrew C; Caskey, Robert C; Zhang, Liping; Hu, Junyi; Liechty, Kenneth W

    2015-01-01

    Diabetic skin wounds lack the ability to heal properly and constitute a major and significant complication of diabetes. Nontraumatic lower extremity amputations are the number one complication of diabetic skin wounds. The complexity of their pathophysiology requires an intervention at many levels to enhance healing and wound closure. Stem cells are a promising treatment for diabetic skin wounds as they have the ability to correct abnormal healing. Stem cell factor (SCF), a chemokine expressed in the skin, can induce stem cells migration, however the role of SCF in diabetic skin wound healing is still unknown. We hypothesize that SCF would correct the impairment and promote the healing of diabetic skin wounds. Our results show that SCF improved wound closure in diabetic mice and increased HIF-1α and vascular endothelial growth factor (VEGF) expression levels in these wounds. SCF treatment also enhanced the migration of red fluorescent protein (RFP)-labeled skin stem cells via in utero intra-amniotic injection of lenti-RFP at E8. Interestingly these RFP+ cells are present in the epidermis, stain negative for K15, and appear to be distinct from the already known hair follicle stem cells. These results demonstrate that SCF improves diabetic wound healing in part by increasing the recruitment of a unique stem cell population present in the skin. © 2015 by the Wound Healing Society.

  4. A Modified Collagen Gel Enhances Healing Outcome in a Pre-Clinical Swine Model of Excisional Wounds

    PubMed Central

    Elgharably, Haytham; Roy, Sashwati; Khanna, Savita; Abas, Motaz; DasGhatak, Piya; Das, Amitava; Mohammed, Kareem; Sen, Chandan K.

    2013-01-01

    Collagen-based dressings are of great interest in wound care. However, evidence supporting their mechanism of action in a wound setting in vivo is scanty. This work providesfirst results from a pre-clinical swine model of excisional wounds elucidating the mechanism of action of a modified collagen gel (MCG) dressing. Following wounding, wound-edge tissue was collected at specific time intervals (3, 7, 14, and 21 days post-wounding). On day 7, histological analysis showed significant increase in the length of rete ridges suggesting improved biomechanical properties of the healing wound tissue. Rapid and transient mounting of inflammation is necessary for efficient healing. MCG significantly accelerated neutrophil and macrophages recruitment to the wound site on day 3 and day 7 with successful resolution of inflammation on day 21. MCG induced MCP-1 expression in neutrophil-like HL-60 cells in vitro. In vivo, MCG treated wound tissue displayed elevated VEGF expression. Consistently, MCG-treated wounds displayed significantly higher abundance of endothelial cells with increased blood flow to the wound area indicating improved vascularization. This observation was explained by the finding that MCG enhanced proliferation of wound-site endothelial cells. In MCG-treated wound tissue, Masson’s Trichrome and Picrosirius red staining showed higher abundance of collagen and increased collagen type I:III ratio. This work presents first evidence from a pre-clinical experimental setting explaining how a collagen-based dressing may improve wound closure by targeting multiple key mechanisms as compared to standard of care i.e., Tegadem treated wounds. The current findings warrant additional studies to determine whether the responses to the MCG are different from other modified or unmodified collagen based products used in clinical setting. PMID:23607796

  5. Angiopoietin-like 4 Stimulates STAT3-mediated iNOS Expression and Enhances Angiogenesis to Accelerate Wound Healing in Diabetic Mice

    PubMed Central

    Chong, Han Chung; Chan, Jeremy Soon Kiat; Goh, Chi Qin; Gounko, Natalia V; Luo, Baiwen; Wang, Xiaoling; Foo, Selin; Wong, Marcus Thien Chong; Choong, Cleo; Kersten, Sander; Tan, Nguan Soon

    2014-01-01

    Impaired wound healing is a major source of morbidity in diabetic patients. Poor outcome has, in part, been related to increased inflammation, poor angiogenesis, and deficiencies in extracellular matrix components. Despite the enormous impact of these chronic wounds, effective therapies are lacking. Here, we showed that the topical application of recombinant matricellular protein angiopoietin-like 4 (ANGPTL4) accelerated wound reepithelialization in diabetic mice, in part, by improving angiogenesis. ANGPTL4 expression is markedly elevated upon normal wound injury. In contrast, ANGPTL4 expression remains low throughout the healing period in diabetic wounds. Exogenous ANGPTL4 modulated several regulatory networks involved in cell migration, angiogenesis, and inflammation, as evidenced by an altered gene expression signature. ANGPTL4 influenced the expression profile of endothelial-specific CD31 in diabetic wounds, returning its profile to that observed in wild-type wounds. We showed ANGPTL4-induced nitric oxide production through an integrin/JAK/STAT3-mediated upregulation of inducible nitric oxide synthase (iNOS) expression in wound epithelia, thus revealing a hitherto unknown mechanism by which ANGPTL4 regulated angiogenesis via keratinocyte-to-endothelial-cell communication. These data show that the replacement of ANGPTL4 may be an effective adjunctive or new therapeutic avenue for treating poor healing wounds. The present finding also confirms that therapeutic angiogenesis remains an attractive treatment modality for diabetic wound healing. PMID:24903577

  6. Promotion of Wound Healing by an Agonist of Adenosine A2A Receptor Is Dependent on Tissue Plasminogen Activator.

    PubMed

    Montesinos, M Carmen; Desai-Merchant, Avani; Cronstein, Bruce N

    2015-12-01

    Impaired wound healing, as it occurs in diabetes mellitus or long-term corticoid treatment, is commonly associated with disability, diminished quality of life, and high economic costs. Selective agonists of the A2A receptor subtype of adenosine, an endogenous regulator of inflammation, promote tissue repair in animal models, both healthy and with impaired healing. Plasmin-mediated proteolysis of fibrin and other matrix proteins is essential for cell migration at sites of injury. Since adenosine A2A receptor activation increases plasminogen activator release from macrophages and mast cells, we studied the effect of a selective agonist, CGS-21680, on full-thickness excisional wound closure in wild-type, urokinase plasminogen activator (uPA)-deficient, and tissue plasminogen activator (tPA)-deficient mice. Wound closure was impaired in tPA- and uPA-deficient mice as compared with wild-type mice, and topical application of CGS-21680 significantly increased the rate at which wounds closed in wild-type mice and uPA-deficient mice, but not in tPA-deficient mice. Immunostaining of tissue sections showed that tPA was present in endothelial cells and histiocytes by day 3 post-wound and also by day 6. In contrast, uPA was more prominent in these cell types only by day 6 post-wound. Our results confirm that plasminogen activation contributes to wound repair and are consistent with the hypothesis that adenosine A2A receptor activation promotes wound closure by a mechanism that depends upon tPA, but not uPA. Moreover, our results suggest that topical adenosine A2A receptor agonists may be useful in promotion of wound closure in patients with impaired wound healing.

  7. The Effect of Combined Ultrasound and Electric Field Stimulation on Wound Healing in Chronic Ulcerations.

    PubMed

    Avrahami, Ram; Rosenblum, Jonathan; Gazes, Michael; Rosenblum, Sean; Litman, Leib

    2015-07-01

    Ultrasound and electric stimulation are known therapies for the treatment of chronic ulcerations. Combined modulated ultrasound and electric field stimulation (CUSEFS) have never been studied as a single modality. The authors evaluate the results of CUSEFS (BRH Medical Ltd, Jerusalem, Israel) on a variety of wound types in a number of clinics. This retrospective analysis looked at ulcers treated with CUSEFS in 4 clinics. Wounds were evaluated by an independent assessor and data was evaluated by an independent statistician. Of the 300 wounds treated with the CUSEFS device, only those classified as diabetic foot ulcers (DFUs) or venous leg ulcers (VLUs) were evaluated. A treatment was deemed successful if the wound was 50% closed within 4 weeks. Subjects were then followed to see if their wounds completely closed within 16 weeks. Of the 27 DFUs treated, 59.3% (16) achieved 50% closure within 4 weeks. Of the 38 VLUs treated, 71.1% (27) achieved 50% closure within 4 weeks. It was found that variables such as gender, size of the wound at presentation, and longevity of the wound had no bearing on the outcome. The age of the patient had an effect on the outcome of the VLUs. The wound healing trajectory was supported in that there was a significant difference in the achievement of total closure between those subjects who had a successful trial and those who did not. Combined modulated ultrasound and electric field stimulation has a place as adjunct therapy that aids wound healing and provides an effective noninvasive treatment option.

  8. Substance P accelerates wound healing in type 2 diabetic mice through endothelial progenitor cell mobilization and Yes-associated protein activation

    PubMed Central

    Um, Jihyun; Yu, Jinyeong; Park, Ki-Sook

    2017-01-01

    Wound healing is delayed in diabetes due to a number of factors, including impaired angiogenesis and poor dermal healing. The present study demonstrated that subcutaneous administration of substance P (SP) accelerates wound healing in db/db type 2 diabetic mice (db/db mice). SP injection (10 nM/kg, subcutaneously) enhanced angiogenesis, induced the mobilization of endothelial progenitor cells (EPCs) and increased the number of EPC-colony forming units (EPC-CFUs) in the bone marrow of db/db mice. Immunohistochemistry was performed to check the effects of SP on the cellular proliferation and the subcellular localization of Yes-associated protein (YAP) in the wound dermis. SP also upregulated cellular proliferation in the injured dermis of db/db mice. Compared with the control group, an increased number of cells in the wound dermis of SP-treated mice exhibited nuclear localization of YAP, which induces cellular proliferation. The results of the current study indicate that subcutaneous administration of SP may be a promising therapeutic strategy to treat diabetic wounds exhibiting impaired angiogenesis and dysfunctional dermal wound healing. PMID:28339006

  9. Wound healing effects of deoxyshikonin isolated from Jawoongo: In vitro and in vivo studies.

    PubMed

    Park, Jun Yeon; Kwak, Jin Ho; Kang, Ki Sung; Jung, Eun Bee; Lee, Dong-Soo; Lee, Sanghyun; Jung, Yujung; Kim, Ki Hyun; Hwang, Gwi Seo; Lee, Hye Lim; Yamabe, Noriko; Kim, Su-Nam

    2017-03-06

    Jawoongo is a traditional drug ointment (with a traditional botanic formula) used for the treatment of burns and wounds in Korea. One of the components of Jawoongo is Lithospermi Radix (LR, the dried root of Lithospermum erythrorhizon Siebold & Zucc., also known as Zicao or Gromwell), which contains deoxyshikonin and its derivatives. The aim of the present study was to investigate the effects of deoxyshikonin on wound healing. The effects of LR extract and deoxyshikonin on tube formation and migration were measured in human umbilical vein vascular endothelial cells (HUVEC) and HaCaT cells, respectively. We evaluated protein expression of mitogen-activated protein kinase (MAPK) activation by Western blotting. The wound healing effects of deoxyshikonin was assessed in a mouse model of cutaneous wounds. The results showed that deoxyshikonin enhanced tube formation in HUVEC and migration in HaCaT cells. From the western blot analysis, we found that deoxyshikonin stimulated the phosphorylation of p38 and extracellular signal-regulated kinase (ERK) in HaCaT cells. Moreover, 20µm deoxyshikonin-treated groups showed accelerated wound closure compared with the controls in a mouse model of cutaneous wounds. In conclusion, the current data indicate that deoxyshikonin treatment elevated tube formation in HUVECs, and that deoxyshikonin-induced proliferation and migration in HaCaT cells were mediated by the activation of ERK and p38 MAPKs, respectively. Collectively, these data suggest that deoxyshikonin in Jawoongo must be an active compound for may be wound healing. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  10. Comparative analysis of angiogenic gene expression in normal and impaired wound healing in diabetic mice: effects of extracorporeal shock wave therapy.

    PubMed

    Zins, Stephen R; Amare, Mihret F; Tadaki, Douglas K; Elster, Eric A; Davis, Thomas A

    2010-12-01

    Impaired wound healing is a persistent clinical problem which has been treated with mixed results. Studies aimed at elucidating the mechanism of impaired wound healing have focused on small cohorts of genes which leave an incomplete picture of the wound healing process. We aimed to investigate impaired wound healing via a comprehensive panel of angiogenic/inflammation-related genes and wound closure kinetics with and without the application of extracorporeal shock wave therapy (ESWT), which has been demonstrated to improve wound healing. Full-thickness skin from the dorsal surface of "normal" (BALB/c) and "impaired" (db (+)/db (+)) mice was excised, and wound margin tissue was harvested 2, 7, and 10 days post injury. A separate, but identical wound model was established over 40 days in order to measure wound closure kinetics. Over time, the normal non-ESWT treated wounds exhibited varying patterns of elevated expression of 25-30 genes, whereas wounds with impaired healing displayed prolonged elevated expression of only a few genes (CXCL2, CXCL5, CSF3, MMP9, TGF-α). In response to ESWT, gene expression was augmented in both types of wounds, especially in the expression of PECAM-1; however, ESWT had no effect on wound closure in either model. In addition, multiple doses of ESWT exacerbated the delayed wound healing, and actually caused the wounds to initially increase in size. These data provide a more complete picture of impaired wound healing, and a way to evaluate various promising treatments.

  11. Topical N-Acetylcysteine Accelerates Wound Healing in Vitro and in Vivo via the PKC/Stat3 Pathway

    PubMed Central

    Tsai, Min-Ling; Huang, Hui-Pei; Hsu, Jeng-Dong; Lai, Yung-Rung; Hsiao, Yu-Ping; Lu, Fung-Jou; Chang, Horng-Rong

    2014-01-01

    N-Acetylcysteine (Nac) is an antioxidant administered in both oral and injectable forms. In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing activities and the epithelialization-related proteins, matrixmetalloproteinase-1 (MMP-1) and proteins involved in regulating the expression of MMP-1 in CCD-966SK cells treated with Nac. Various Nac concentrations (0.1, 0.5, and 1.0 mM) increased glutathione levels, cell viability, scratch-wound healing activities and migration abilities of CCD-966SK cells in a dose-dependent manner. The MMP-1 expression of CCD-966SK cells treated with 1.0 mM Nac for 24 h was significantly increased. Levels of phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos and Jun, but not extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), were also significantly increased in a dose-dependent manner compared to the controls. In addition, Nac induced collagenous expression of MMP-1 via the PKC/Stat3 signaling pathway. In vivo, a burn wound healing rat model was applied to assess the stimulation activity and histopathological effects of Nac, with 3.0% Nac-treated wounds being found to show better characteristics on re-epithelialization. Our results demonstrated that Nac can potentially promote wound healing activity, and may be a promising drug to accelerate burn wound healing. PMID:24798751

  12. Boric Acid Reduces the Formation of DNA Double Strand Breaks and Accelerates Wound Healing Process.

    PubMed

    Tepedelen, Burcu Erbaykent; Soya, Elif; Korkmaz, Mehmet

    2016-12-01

    Boron is absorbed by the digestive and respiratory system, and it was considered that it is converted to boric acid (BA), which was distributed to all tissues above 90 %. The biochemical essentiality of boron element is caused by boric acid because it affects the activity of several enzymes involved in the metabolism. DNA damage repair mechanisms and oxidative stress regulation is quite important in the transition stage from normal to cancerous cells; thus, this study was conducted to investigate the protective effect of boric acid on DNA damage and wound healing in human epithelial cell line. For this purpose, the amount of DNA damage occurred with irinotecan (CPT-11), etoposide (ETP), doxorubicin (Doxo), and H 2 O 2 was determined by immunofluorescence through phosphorylation of H2AX (Ser139) and pATM (Ser1981) in the absence and presence of BA. Moreover, the effect of BA on wound healing has been investigated in epithelial cells treated with these agents. Our results demonstrated that H2AX (Ser139) foci numbers were significantly decreased in the presence of BA while wound healing was accelerated by BA compared to that in the control and only drug-treated cells. Eventually, the results indicate that BA reduced the formation of DNA double strand breaks caused by agents as well as improving the wound healing process. Therefore, we suggest that boric acid has important therapeutical effectiveness and may be used in the treatment of inflammatory diseases where oxidative stress and wound healing process plays an important role.

  13. Upper Blepharoplasty and Lateral Wound Dehiscence

    PubMed Central

    Kashkouli, Mohsen Bahmani; Jamshidian-Tehrani, Mansooreh; Sharzad, Sahab; Sanjari, Mostafa Soltan

    2015-01-01

    Purpose: To report the frequency of lateral wound dehiscence (LWD) after upper blepharoplasty (UB), a technique and its outcome to prevent LWD. Materials and Methods: A retrospective review was performed for cases of LWD after UB presenting between 2003 and 2009, and then a prospective comparative study was performed between February 2009 and March 2013. For the comparison, subjects were divided into two groups based on intraoperative assessment of lateral wound tension (same technique and surgeon). Group 1 received 1-3 orbicularis/subcutaneous buried sutures (6-0 polyglactin) before interrupted 6-0 nylon skin closure. Group 2 underwent skin closure only. Subjects, who had re-operation, skin healing disorders, and incomplete follow-up (<6 months), were excluded. P < 0.05 was considered as statistically significant. Results: There were 14 (14/678, 2%) cases with LWD with a mean age of 36.2 years in the audit (2003–2009). The prospective study included 68 subjects (68/293, 23.2%) in Group 1 and 225 in Group 2. Gender and simultaneous forehead and eyebrow procedures were similar between groups (P = 0.3 and P = 0.4 respectively). Group 1 was statistically significantly younger at mean age of 41.4 years, compared to Group 2 at 56.1 years (P = 0.000). The frequency of LWD significantly (P = 0.04) decreased to 0.3% (1/293). Conclusion: In the presence of wound tension on skin closure (intraoperative assessment), tension relieving buried orbicularis/subcutaneous 6-0 polyglactin suturing of the lateral UB incision could prevent LWD. PMID:26692716

  14. Oral administration of marine collagen peptides from Chum Salmon skin enhances cutaneous wound healing and angiogenesis in rats.

    PubMed

    Zhang, Zhaofeng; Wang, Junbo; Ding, Ye; Dai, Xiaoqian; Li, Yong

    2011-09-01

    A wound is a clinical entity which often poses problems in clinical practice. The present study was aimed to investigate the wound healing potential of administering marine collagen peptides (MCP) from Chum Salmon skin by using two wound models (incision and excision) in rats. Ninety-six animals were equally divided into the two wound models and then within each model animals were randomly divided into two groups: vehicle-treated group and 2 g kg(-1) MCP-treated group. Wound closure and tensile strength were calculated. Collagen deposition was assessed by Masson staining and hydroxyproline measurement. Angiogenesis was assessed by immunohistological methods. MCP-treated rats showed faster wound closure and improved tissue regeneration at the wound site, which was supported by histopathological parameters pertaining to wound healing. MCP treatment improved angiogenesis and helped form thicker and better organised collagen fibre deposition compared to vehicle-treated group. The results show the efficacy of oral MCP treatment on wound healing in animals. Copyright © 2011 Society of Chemical Industry.

  15. Age-dependent Impairment of HIF-1α̣Expression in Diabetic Mice: Correction with Electroporation-facilitated Gene Therapy Increases Wound Healing, Angiogenesis, and Circulating Angiogenic Cells

    PubMed Central

    Liu, Lixin; Marti, Guy P.; Wei, Xiaofei; Zhang, Xianjie; Zhang, Huafeng; Liu, Ye V.; Nastai, Manuel; Semenza, Gregg L.; Harmon, John W.

    2009-01-01

    Wound healing is impaired in elderly patients with diabetes mellitus. We hypothesized that age-dependent impairment of cutaneous wound healing in db/db diabetic mice: (a) would correlate with reduced expression of the transcription factor hypoxia-inducible factor 1α (HIF-1α) as well as its downstream target genes; and (b) could be overcome by HIF-1α replacement therapy. Wound closure, angiogenesis, and mRNA expression in excisional skin wounds were analyzed and circulating angiogenic cells were quantified in db/db mice that were untreated or received electroporation-facilitated HIF-1α gene therapy. HIF-1α mRNA levels in wound tissue were significantly reduced in older (4–6 months) as compared to younger (1.5–2 months) db/db mice. Expression of mRNAs encoding the angiogenic cytokines vascular endothelial growth factor (VEGF), angiopoietin 1 (ANGPT1), ANGPT2, platelet derived growth factor B (PDGF-B), and placental growth factor (PLGF) was also impaired in wounds of older db/db mice. Intradermal injection of plasmid gWIZ-CA5, which encodes a constitutively active form of HIF-1α, followed by electroporation, induced increased levels of HIF-1α mRNA at the injection site on day 3 and increased levels of VEGF, PLGF, PDGF-B, and ANGPT2 mRNA on day 7. Circulating angiogenic cells in peripheral blood increased 10-fold in mice treated with gWIZ-CA5. Wound closure was significantly accelerated in db/db mice treated with gWIZ-CA5 as compared to mice treated with empty vector. Thus, HIF-1α gene therapy corrects the age-dependent impairment of HIF-1α expression, angiogenic cytokine expression, and circulating angiogenic cells that contribute to the age-dependent impairment of wound healing in db/db mice. PMID:18506785

  16. Thiol-ene Michael-type formation of gelatin/poly(ethylene glycol) biomatrices for three-dimensional mesenchymal stromal/stem cell administration to cutaneous wounds

    PubMed Central

    Xu, Kedi; Cantu, David Antonio; Fu, Yao; Kim, Jaehyup; Zheng, Xiaoxiang; Hematti, Peiman; Kao, W. John

    2013-01-01

    Mesenchymal stromal/stem cells (MSCs) are considered promising cellular therapeutics in the fields of tissue engineering and regenerative medicine. MSCs secrete high concentrations of immunomodulatory cytokines and growth factors, which exert paracrine effects on infiltrating immune and resident cells of the wound microenvironment that could favorably promote healing after acute injury. However, better spatial delivery and improved retention at the site of injury are two factors that could improve the clinical application of MSCs. In this study, we utilized thiol-ene Michael-type addition for rapid encapsulation of MSCs within a gelatin/poly(ethylene glycol) biomatrix; this biomatrix was also applied as a provisional dressing to full-thickness wounds in Sprague-Dawley rats. The three-way interaction of MSCs, gelatin/poly(ethylene glycol) biomatrices, and host immune cells and adjacent resident cells of the wound microenvironment favorably modulated wound progression and host response. In this model we observed attenuated immune cell infiltration, lack of foreign giant cell (FBGC) formation, accelerated wound closure and re-epithelialization, as well as enhanced neovascularization and granulation tissue formation by 7 days. The MSC-entrapped gelatin/poly(ethylene glycol) biomatrix localized the presentation of MSCs adjacent to the wound microenvironment and thus, mediated early resolution of inflammatory events and facilitated proliferative phases in wound healing. PMID:23811217

  17. Finasteride accelerates prostate wound healing after thulium laser resection through DHT and AR signalling.

    PubMed

    Zhao, Ruizhe; Wang, Xingjie; Jiang, Chenyi; Shi, Fei; Zhu, Yiping; Yang, Boyu; Zhuo, Jian; Jing, Yifeng; Luo, Guangheng; Xia, Shujie; Han, Bangmin

    2018-06-01

    Urinary tract infection, urinary frequency, urgency, urodynia and haemorrhage are common post-operative complications of thulium laser resection of the prostate (TmLRP). Our study mainly focuses on the role of finasteride in prostate wound healing through AR signalling. TmLRP beagles were randomly distributed into different treatment groups. Serum and intra-prostatic testosterone and DHT level were determined. Histological analysis was conducted to study the re-epithelialization and inflammatory response of the prostatic urethra in each group. We investigated the role of androgen in proliferation and inflammatory response in prostate. In addition, the effects of TNF-α on prostate epithelium and stromal cells were also investigated. Testosterone and DHT level increased in testosterone group and DHT decreased in finasteride group. Accelerated wound healing of prostatic urethra was observed in the finasteride group. DHT suppressed proliferation of prostate epithelium and enhanced inflammatory response in prostate. We confirmed that DHT enhanced macrophages TNF-α secretion through AR signalling. TNF-α suppressed proliferation of prostate epithelial cells and retarded cell migration. TNF-α also played a pivotal role in suppressing fibroblasts activation and contraction. Testosterone treatment repressed re-epithelialization and wound healing of prostatic urethra. Finasteride treatment may be an effective way to promote prostate re-epithelialization. © 2017 John Wiley & Sons Ltd.

  18. Topical application of Acheflan on rat skin injury accelerates wound healing: a histopathological, immunohistochemical and biochemical study.

    PubMed

    Perini, Jamila Alessandra; Angeli-Gamba, Thais; Alessandra-Perini, Jessica; Ferreira, Luiz Claudio; Nasciutti, Luiz Eurico; Machado, Daniel Escorsim

    2015-06-30

    with TF. These ointments seem to accelerate wound healing, probably due to their involvement with the increase of angiogenesis and dermal remodeling.

  19. Vitamin D ameliorates impaired wound healing in streptozotocin-induced diabetic mice by suppressing NF-κB-mediated inflammatory genes.

    PubMed

    Yuan, YiFeng; Das, Sushant K; Li, MaoQuan

    2018-04-27

    Diabetic wounds are characterized by delayed wound healing due to persistent inflammation and excessive production of reactive oxygen species. Vitamin D, which is well acknowledged to enhance intestinal calcium absorption and increase in plasma calcium level, has recently been shown to display beneficial effects in various vascular diseases by promoting angiogenesis and inhibiting inflammatory responses. However, the role of Vitamin D in diabetic wound healing is still unclear. In the present study, we investigated the role of Vitamin D in cutaneous wound healing in streptozotocin (STZ)-induced diabetic mice. Four weeks after injection of STZ, a full thickness excisional wound was created with a 6-mm diameter sterile biopsy punch on the dorsum of the mice. Vitamin D was given consecutively for 14 days by intraperitoneal injection. Vitamin D supplementation significantly accelerated wound healing in diabetic mice and improved the healing quality as assessed by measuring the wound closure rate and histomorphometric analyses. By monitoring the level of pro-inflammatory cytokines tumor necrosis factor-α ( TNF-α ), interleukin (IL) 6 ( IL-6 ), IL-1β ) in the wounds, reduced inflammatory response was found in VD treatment group. Furthermore, nuclear factor κB (NF-κB) pathway was found to be involved in the process of diabetic wound healing by assessing the relative proteins in diabetic wounds. Vitamin D supplementation obviously suppressed NF-κB pathway activation. These results demonstrated that Vitamin D improves impaired wound healing in STZ-induced diabetic mice through suppressing NF-κB-mediated inflammatory gene expression. © 2018 The Author(s).

  20. Temporary Rectal Stenting for Management of Severe Perineal Wounds in Two Dogs.

    PubMed

    Skinner, Owen T; Cuddy, Laura C; Coisman, James G; Covey, Jennifer L; Ellison, Gary W

    Perineal wounds in dogs present a challenge due to limited local availability of skin for closure and constant exposure to fecal contaminants. This report describes temporary rectal stenting in two dogs following severe perineal wounds. Dog 1 presented with a 4 × 4 cm full-thickness perineal slough secondary to multiple rectal perforations. A 12 mm internal diameter endotracheal tube was placed per-rectum as a temporary stent to minimize fecal contamination. The stent was removed 18 days after placement, and the perineal wound had healed at 32 days post-stent placement, when a minor rectal stricture associated with mild, intermittent tenesmus was detected. Long-term outcome was deemed good. Dog 2 presented with multiple necrotic wounds with myiasis, circumferentially surrounding the anus and extending along the tail. A 14 mm internal diameter endotracheal tube was placed per-rectum. The perineal and tail wounds were managed with surgical debridement and wet-to-dry and honey dressings prior to caudectomy and negative pressure wound therapy (NPWT). Delayed secondary wound closure and stent removal were performed on day six without complication. Long-term outcome was deemed excellent. Temporary rectal stenting may be a useful technique for fecal diversion to facilitate resolution of complex perineal injuries, including rectal perforation.

  1. Successful treatment of complex traumatic and surgical wounds with a foetal bovine dermal matrix.

    PubMed

    Hayn, Ernesto

    2014-12-01

    A foetal bovine dermal repair scaffold (PriMatrix, TEI Biosciences) was used to treat complex surgical or traumatic wounds where the clinical need was to avoid skin flaps and to build new tissue in the wound that could be reepithelialised from the wound margins or closed with a subsequent application of a split-thickness skin graft (STSG). Forty-three consecutive cases were reviewed having an average size of 79·3 cm(2) , 50% of which had exposed tendon and/or bone. In a subset of wounds (44·7%), the implantation of the foetal dermal collagen scaffold was also augmented with negative pressure wound therapy (NPWT). Complete wound healing was documented in over 80% of the wounds treated, whether the wound was treated with the foetal bovine dermal scaffold alone (95·2%) or when supplemented with NPWT (82·4%). The scaffold successfully incorporated into wounds with exposed tendon and/or bone to build vascularised, dermal-like tissue. The new tissue in the wound supported STSGs however, in the majority of the cases (88·3%); wound closure was achieved through reepithelialisation of the incorporated dermal scaffold by endogenous wound keratinocytes. The foetal bovine dermal repair scaffold was found to offer an effective alternative treatment strategy for definitive closure of challenging traumatic or surgical wounds on patients who were not suitable candidates for tissue flaps. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  2. Tumors Alter Inflammation and Impair Dermal Wound Healing in Female Mice

    PubMed Central

    Pyter, Leah M.; Husain, Yasmin; Calero, Humberto; McKim, Daniel B.; Lin, Hsin-Yun; Godbout, Jonathan P.; Sheridan, John F.; Engeland, Christopher G.; Marucha, Phillip T.

    2016-01-01

    Tissue repair is an integral component of cancer treatment (e.g., due to surgery, chemotherapy, radiation). Previous work has emphasized the immunosuppressive effects of tumors on adaptive immunity and has shown that surgery incites cancer metastases. However, the extent to which and how tumors may alter the clinically-relevant innate immune process of wound healing remains an untapped potential area of improvement for treatment, quality of life, and ultimately, mortality of cancer patients. In this study, 3.5 mm full-thickness dermal excisional wounds were placed on the dorsum of immunocompetent female mice with and without non-malignant flank AT-84 murine oral squamous cell carcinomas. Wound closure rate, inflammatory cell number and inflammatory signaling in wounds, and circulating myeloid cell concentrations were compared between tumor-bearing and tumor-free mice. Tumors delayed wound closure, suppressed inflammatory signaling, and altered myeloid cell trafficking in wounds. An in vitro scratch “wounding” assay of adult dermal fibroblasts treated with tumor cell-conditioned media supported the in vivo findings. This study demonstrates that tumors are sufficient to disrupt fundamental and clinically-relevant innate immune functions. The understanding of these underlying mechanisms provides potential for therapeutic interventions capable of improving the treatment of cancer while reducing morbidities and mortality. PMID:27548621

  3. The utilization of an ocular wound chamber on corneal epithelial wounds

    PubMed Central

    McDaniel, Jennifer S; Holt, Andrew W; Por, Elaine D; Eriksson, Elof; Johnson, Anthony J; Griffith, Gina L

    2018-01-01

    Purpose Currently available ocular moisture chambers are not adequate to manage the treatment of periocular burns, corneal injuries, and infection. The purpose of these studies was to demonstrate that a flexible, semi-transparent ocular wound chamber device adapted from technology currently used on dermal wounds is safe for use on corneal epithelial injuries. Materials and methods A depilatory cream (Nair™, 30 seconds) was utilized to remove the excess hair surrounding the left eyes of anesthetized Institute Armand Frappier (IAF) hairless, female guinea pigs (Crl:HA-Hrhr). A 4 mm corneal epithelium defect was created using a corneal rust ring remover (Algerbrush®II). Epithelial defects were either left untreated or the eyes were fitted with an ocular wound chamber and 0.5 mL of hydroxypropyl methylcellulose (HPMC) gel (GenTeal®) or HPMC liquid (GenTeal®) was injected into each chamber (N=5 per group). At 0, 24, 48, and 72 hours fluorescein and optical coherence tomography imaging was collected and the intraocular pressure (IOP) was measured. H&E staining was performed on corneal and eyelid skin samples and evaluated by a veterinary pathologist. Results Corneal epithelial wounds demonstrated 100% closure rates when left untreated or treated with an ocular wound chamber containing HPMC gel at 72 hours while wounds treated with an ocular wound chamber containing HPMC liquid were 98% healed. No significant differences were found in corneal thickness and wound healing, IOP, or eyelid skin pathology in any treatment group when compared to controls. Conclusions This study indicates that adapted wound chamber technology can be safely used on sterile, corneal epithelial wounds without adverse effects on periocular or ocular tissue when filled with a liquid or gel. PMID:29785086

  4. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts.

    PubMed

    Hu, Li; Wang, Juan; Zhou, Xin; Xiong, Zehuan; Zhao, Jiajia; Yu, Ran; Huang, Fang; Zhang, Handong; Chen, Lili

    2016-09-12

    Prolonged healing and scar formation are two major challenges in the treatment of soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role in tissue regeneration, and recent studies have suggested that exosomes secreted by stem cells may contribute to paracrine signaling. In this study, we investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound healing. We found that ASCs-Exos could be taken up and internalized by fibroblasts to stimulate cell migration, proliferation and collagen synthesis in a dose-dependent manner, with increased genes expression of N-cadherin, cyclin-1, PCNA and collagen I, III. In vivo tracing experiments demonstrated that ASCs-Exos can be recruited to soft tissue wound area in a mouse skin incision model and significantly accelerated cutaneous wound healing. Histological analysis showed increased collagen I and III production by systemic administration of exosomes in the early stage of wound healing, while in the late stage, exosomes might inhibit collagen expression to reduce scar formation. Collectively, our findings indicate that ASCs-Exos can facilitate cutaneous wound healing via optimizing the characteristics of fibroblasts. Our results provide a new perspective and therapeutic strategy for the use of ASCs-Exos in soft tissue repair.

  5. Wound healing properties of ethyl acetate fraction of Moringa oleifera in normal human dermal fibroblasts.

    PubMed

    Gothai, Sivapragasam; Arulselvan, Palanisamy; Tan, Woan Sean; Fakurazi, Sharida

    2016-01-01

    Wounds are the outcome of injuries to the skin that interrupt the soft tissue. Healing of a wound is a complex and long-drawn-out process of tissue repair and remodeling in response to injury. A large number of plants are used by folklore traditions for the treatment of cuts, wounds and burns. Moringa oleifera (MO) is an herb used as a traditional folk medicine for the treatment of various skin wounds and associated diseases. The underlying mechanisms of wound healing activity of ethyl acetate fraction of MO leaves extract are completely unknown. In the current study, ethyl acetate fraction of MO leaves was investigated for its efficacy on cell viability, proliferation and migration (wound closure rate) in human normal dermal fibroblast cells. Results revealed that lower concentration (12.5 µg/ml, 25 µg/ml, and 50 µg/ml) of ethyl acetate fraction of MO leaves showed remarkable proliferative and migratory effect on normal human dermal fibroblasts. This study suggested that ethyl acetate fraction of MO leaves might be a potential therapeutic agent for skin wound healing by promoting fibroblast proliferation and migration through increasing the wound closure rate corroborating its traditional use.

  6. Biomimetic hydrogel loaded with silk and l-proline for tissue engineering and wound healing applications.

    PubMed

    Thangavel, Ponrasu; Ramachandran, Balaji; Kannan, Ramya; Muthuvijayan, Vignesh

    2017-08-01

    The aim of this article was to develop silk protein (SF) and l-proline (LP) loaded chitosan-(CS) based hydrogels via physical cross linking for tissue engineering and wound healing applications. Silk fibroin, a biodegradable and biocompatible protein, and l-proline, an important imino acid that is required for collagen synthesis, were added to chitosan to improve the wound healing properties of the hydrogel. Characterization of these hydrogels revealed that CS/SF/LP hydrogels were blended properly and LP incorporated hydrogels showed excellent thermal stability and good surface morphology. Swelling study showed the water holding efficiency of the hydrogels to provide enough moisture at the wound surface. In vitro biodegradation results demonstrated that the hydrogels had good degradation rate in PBS with lysozyme. LP loaded hydrogels showed approximately a twofold increase in antioxidant activity. In vitro cytocompatibility studies using NIH 3T3 L1 cells showed increased cell viability (p < 0.01), migration, proliferation and wound healing activity (p < 0.001) in LP loaded hydrogels compared to CS and CS/SF hydrogels. Cell adhesion on SF and LP hydrogels were observed using SEM and compared to CS hydrogel. LP incorporation showed 74-78% of wound closure compared to 35% for CS/SF and 3% for CS hydrogels at 48 h. These results suggest that incorporation of LP can significantly accelerate wound healing process compared to pure CS and SF-loaded CS hydrogels. Hence, CS/LP hydrogels could be a potential wound dressing material for the enhanced wound tissue regeneration and repair. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1401-1408, 2017. © 2016 Wiley Periodicals, Inc.

  7. Computational and Experimental Study of the Mechanics of Embryonic Wound Healing

    PubMed Central

    Varner, Victor D.; Taber, Larry A.

    2013-01-01

    Wounds in the embryo show a remarkable ability to heal quickly without leaving a scar. Previous studies have found that an actomyosin ring (“purse string”) forms around the wound perimeter and contracts to close the wound over the course of several dozens of minutes. Here, we report experiments that reveal an even faster mechanism which remarkably closes wounds by more than 50% within the first 30 seconds. Circular and elliptical wounds (~100 µm in size) were made in the blastoderm of early chick embryos and allowed to heal, with wound area and shape characterized as functions of time. The closure rate displayed a biphasic behavior, with rapid constriction lasting about a minute, followed by a period of more gradual closure to complete healing. Fluorescent staining suggests that both healing phases are driven by actomyosin contraction, with relatively rapid contraction of fibers at cell borders within a relatively thick ring of tissue (several cells wide) around the wound followed by slower contraction of a thin supracellular actomyosin ring along the margin, consistent with a purse string mechanism. Finite-element modeling showed that this idea is biophysically plausible, with relatively isotropic contraction within the thick ring giving way to tangential contraction in the thin ring. In addition, consistent with experimental results, simulated elliptical wounds heal with little change in aspect ratio, and decreased membrane tension can cause these wounds to open briefly before going on to heal. These results provide new insight into the healing mechanism in embryonic epithelia. PMID:23973771

  8. Wound Complications in Preoperatively Irradiated Soft-Tissue Sarcomas of the Extremities

    PubMed Central

    Rosenberg, Lewis A.; Esther, Robert J.; Erfanian, Kamil; Green, Rebecca; Kim, Hong Jin; Sweeting, Raeshell; Tepper, Joel E.

    2014-01-01

    Purpose To determine whether the involvement of plastic surgery and the use of vascularized tissue flaps reduces the frequency of major wound complications after radiation therapy for soft-tissue sarcomas (STS) of the extremities. Methods and Materials This retrospective study evaluated patients with STS of the extremities who underwent radiation therapy before surgery. Major complications were defined as secondary operations with anesthesia, seroma/hematoma aspirations, readmission for wound complications, or persistent deep packing. Results Between 1996 and 2010, 73 patients with extremity STS were preoperatively irradiated. Major wound complications occurred in 32% and secondary operations in 16% of patients. Plastic surgery closed 63% of the wounds, and vascularized tissue flaps were used in 22% of closures. When plastic surgery performed closure the frequency of secondary operations trended lower (11% vs 26%; P =.093), but the frequency of major wound complications was not different (28% vs 38%; P =.43). The use of a vascularized tissue flap seemed to have no effect on the frequency of complications. The occurrence of a major wound complication did not affect disease recurrence or survival. For all patients, 3-year local control was 94%, and overall survival was 72%. Conclusions The rates of wound complications and secondary operations in this study were very similar to previously published results. We were not able to demonstrate a significant relationship between the involvement of plastic surgery and the rate of wound complications, although there was a trend toward reduced secondary operations when plastic surgery was involved in the initial operation. Wound complications were manageable and did not compromise outcomes. PMID:22677371

  9. The use of negative pressure wound therapy in the treatment of infected wounds. Case studies.

    PubMed

    Jones, Daniel de Alcântara; Neves Filho, Wilson Vasconcelos; Guimarães, Janice de Souza; Castro, Daniel de Araújo; Ferracini, Antonio Marcos

    2016-01-01

    To evaluate the results and benefits obtained from the topical use of negative pressure wound therapy (NPWT) in patients with infected wounds. This was a retrospective study of 20 patients (17 males and three females, mean age 42 years) with infected wounds treated using NPWT. The infected wounds were caused by trauma. The treatment system used was VAC. ® (Vacuum Assisted Closure, KCI, San Antonio, United States) applied to the wound in continuous mode from 100 to 125 mmHg. The parameters related to the wounds (location, number of VAC changes, the size of the defects in the soft parts, and the evolution of the state of the wound), length of hospital stay, length of intravenous antibiotic therapy, and complications related to the use of this therapy were evaluated. The mean length of the hospital stay, use of NPWT, and antibacterial therapy were 41 days, 22.5 days, and 20 days respectively. The use of the VAC led to a mean reduction of 29% in the wound area (95.65-68.1 cm 2 ; p  < 0.05). Only one patient did not show any improvement in the final appearance of the wound with complete eradication of the infection. No complication directly caused by NPWT was observed. NPWT stimulates infection-free scar tissue formation in a short time, and is a quick and comfortable alternative to conventional infected wounds treatment methods.

  10. Serum and Wound Vancomycin Levels After Intrawound Administration in Primary Total Joint Arthroplasty.

    PubMed

    Johnson, Jeremiah D; Nessler, Joseph M; Horazdovsky, Ryan D; Vang, Sandy; Thomas, Avis J; Marston, Scott B

    2017-03-01

    Periprosthetic joint infection is the most common cause of readmissions after total joint arthroplasty (TJA). Intrawound vancomycin powder (VP) has reduced infection rates in spine surgery; however, there are no data regarding VP in primary TJA. Thirty-four TJA patients received 2 g of VP intraoperatively to investigate VP's pharmacokinetics. Serum and wound concentrations were measured at multiple intervals over 24 hours after closure. All serum concentrations were subtherapeutic (<15μg/mL) and peaked 12 hours after closure (4.7μg/mL; standard deviation [SD], 3.2). Wound concentrations were 922 μg/mL (SD, 523) 3 hours after closure and 207 μg/mL (SD, 317) at 24 hours. VP had a half-life of 7.2 hours (95% confidence interval, 7.0-9.3) in TJA wounds. VP produced highly therapeutic intrawound concentrations while yielding low systemic levels in TJA. VP may serve as a safe adjunct in the prevention of periprosthetic joint infection. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Adenoviral Mediated Gene Transfer of IGF-1 Enhances Wound Healing and Induces Angiogenesis

    PubMed Central

    Balaji, S.; LeSaint, M.; Bhattacharya, S. S.; Moles, C.; Dhamija, Y.; Kidd, M.; Le, L.D.; King, A.; Shaaban, A.; Crombleholme, T. M.; Bollyky, P.; Keswani, S. G.

    2014-01-01

    Background Chronic wounds are characterized by a wound healing and neovascularization deficit. Strategies to increase neovascularization can significantly improve chronic wound healing. Insulin like growth factor (IGF-1) is reported to be a keratinocyte mitogen and is believed to induce angiogenesis via a vascular endothelial growth factor (VEGF) dependent pathway. Using a novel ex vivo human dermal wound model and a diabetic impaired wound healing murine model, we hypothesized that adenoviral over expression of IGF-1 (Ad-IGF-1) will enhance wound healing and induce angiogenesis through a VEGF dependent pathway. Methods Ex vivo: 6 mm full thickness punch biopsies were obtained from normal human skin, and 3 mm full thickness wounds were created at the center. Skin explants were maintained at air liquid interface. Db/db murine model: 8 mm full thickness dorsal wounds in diabetic (db/db) mice were created. Treatment groups in both human ex vivo and in vivo db/db wound models include 1×108 PFU of Ad-IGF-1 or Ad-LacZ, and PBS (n=4–5/group). Cytotoxicity (LDH) was quantified at days 3, 5 and 7 for the human ex vivo wound model. Epithelial gap closure (H&E; Trichrome), VEGF expression (ELISA) and capillary density (CD 31+ CAPS/HPF) were analyzed at day 7. Results In the human ex vivo organ culture, the adenoviral vectors did not demonstrate any significant difference in cytotoxicity compared to PBS. Ad-IGF-1 over expression significantly increases basal keratinocyte migration, with no significant effect on epithelial gap closure. There was a significant increase in capillary density in the Ad-IGF-1 wounds. However, there was no effect on VEGF levels in Ad-IGF-1 samples compared to controls. In db/db wounds, Ad-IGF-1 over expression significantly improves epithelial gap closure and granulation tissue with a dense cellular infiltrate compared to controls. Ad-IGF-1 also increases capillary density, again with no significant difference in VEGF levels in the wounds compared

  12. Assessment of antimicrobial and wound healing effects of Brevinin-2Ta against the bacterium Klebsiella pneumoniae in dermally-wounded rats

    PubMed Central

    Liu, Siqin; Long, Qilin; Xu, Yang; Wang, Jun; Xu, Zhongwei; Wang, Lei; Zhou, Mei; Wu, Yuxin; Chen, Tianbao; Shaw, Chris

    2017-01-01

    Antimicrobial peptides (AMPs) are regarded as promising alternatives for antibiotics due to their inherent capacity to prevent microbial drug resistance. Amphibians are rich source of bioactive molecules, which provide numerous AMPs with various structures as drug candidates. Here, we isolated and identified a novel AMP Brevinin-2Ta (B-2Ta) from the skin secretion of the European frog, Pelophylax kl. esculentus. In vitro studies revealed that it showed broad antimicrobial activities against S. aureus, E. coli and C. albicans with low cytotoxicity to erythrocytes. Furthermore, we examined the anti-inflammation effect in vivo by using Klebsiella pneumoniae-infected Sprague-Dawley (SD) rats. The wound closure outcomes revealed that B-2Ta effectively restrained the bacterial infection at a dose of 10 times minimal inhibitory concentration (MIC) during the 14 days of the wound healing process. Ultra-structure analyses showed that B-2Ta caused structural damage to the microorganism, and bacterial culture found that the number of microbes was significantly reduced by the end of treatment. Immunohistochemistry for the inflammatory marker IL-10 and the endothelial cell marker CD31 suggested positive effects on inflammatory status and epithelial migration and angiogenesis following treatment of the infected granulation tissues with B-2Ta. These results exhibited the continuous phase of inflammation reduction and wound healing acceleration in the B-2Ta-modulated re-epithelialisation of K. pneumoniae infected rats. Taken together, these data demonstrated that B-2Ta has great potential to be developed as antibacterial agents in clinic. PMID:29340060

  13. Negative pressure wound therapy reduces incidence of postoperative wound infection and dehiscence after long-segment thoracolumbar spinal fusion: a single institutional experience.

    PubMed

    Adogwa, Owoicho; Fatemi, Parastou; Perez, Edgar; Moreno, Jessica; Gazcon, Gustavo Chagoya; Gokaslan, Ziya L; Cheng, Joseph; Gottfried, Oren; Bagley, Carlos A

    2014-12-01

    Wound dehiscence and surgical site infections (SSIs) can have a profound impact on patients as they often require hospital readmission, additional surgical interventions, lengthy intravenous antibiotic administration, and delayed rehabilitation. Negative pressure wound therapy (NPWT) exposes the wound site to negative pressure, resulting in the improvement of blood supply, removal of excess fluid, and stimulation of cellular proliferation of granulation tissue. To assess the incidence of wound infection and dehiscence in patients undergoing long-segment thoracolumbar fusion before and after the routine use of NPWT. Retrospective study. One hundred sixty patients undergoing long-segment thoracolumbar spine fusions were included in this study. Postoperative incidence of wound infection and dehiscence. All adult patients undergoing thoracolumbar fusion for spinal deformity over a 6-year period at Duke University Medical Center by the senior author (CB) were included in this study. In 2012, a categorical change was made by the senior author (CB) that included the postoperative routine use of incisional NPWT devices after primary wound closure in all long-segment spine fusions. Before 2012, NPWT was not used. After primary wound closure, a negative pressure device is contoured to the size of the incision and placed over the incision site for 3 postoperative days. We retrospectively review the first 46 cases in which NPWT was used and compared them with the immediately preceding 114 cases to assess the incidence of wound infection and dehiscence. One hundred sixty (NPWT: 46 cases, non-NPWT: 114 cases) long-segment thoracolumbar spine fusions were performed for deformity correction. Baseline characteristics were similar between both cohorts. Compared with the non-NPWT cohort, a 50% decrease in the incidence of wound dehiscence was observed in the NPWT patient cohort (6.38% vs. 12.28%, p=.02). Similarly, compared with the non-NPWT cohort, the incidence of postoperative

  14. Lipid Emulsion Enriched in Omega-3 PUFA Accelerates Wound Healing: A Placebo-Controlled Animal Study.

    PubMed

    Peng, Yi-Chi; Yang, Fwu-Lin; Subeq, Yi-Maun; Tien, Chin-Chieh; Chao, Yann-Fen C; Lee, Ru-Ping

    2018-06-01

    The Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) generate bioactive lipid mediators that reduce inflammation. The present study evaluated the effect of SMOFlipid containing ω-3 PUFAs on wound healing. Rats were divided into a SMOFlipid (SMOF) group and a 0.9% saline (placebo) group, with eight rats in each group. Wound excision was performed on the dorsal surface of each rat. In the SMOF group, 1 gm/kg SMOFlipid was dissolved in 3 mL saline as a treatment; in the placebo group, 3 mL saline was prepared as a treatment. The treatments were administered intravenously at an initial rate of 0.2 mL/kg body weight/h immediately after wounding, for 72 h. Blood samples were collected for white blood cell, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 measurements at the baseline and at 1, 6, 12, 24, 48, and 72 h after intervention. Wound areas were measured over a 2-week period after excision, and a histological examination was performed. Compared with the placebo group, SMOFlipid supplementation engendered significant decreases in the wound area on day 3 (78.28 ± 5.25 vs. 105.86 ± 8.89%), day 5 (72.20 ± 4.31 vs. 96.39 ± 4.72%), day 10 (20.78 ± 1.28 vs. 39.80 ± 10.38%), and day 14 (7.56 ± 0.61 vs. 15.10 ± 2.42%). The placebo group had a higher TNF-α level than the SMOF group at 72 h. The IL-10 level was higher in the SMOF group than in the placebo group at 48 h. Histological analysis revealed a higher rate of fibroblast distribution and collagen fiber organization in the SMOF group (P = 0.01). SMOFlipid enriched in ω-3 PUFA accelerates wound healing.

  15. Epigallocatechin-3-gallate augments therapeutic effects of mesenchymal stem cells in skin wound healing.

    PubMed

    Li, Min; Xu, Jingxing; Shi, Tongxin; Yu, Haiyang; Bi, Jianping; Chen, Guanzhi

    2016-11-01

    In non-healing wounds, mesenchymal stem cell (MSC)-based therapies have the potential to activate a series of coordinated cellular processes, including angiogenesis, inflammation, cell migration, proliferation and epidermal terminal differentiation. As pro-inflammatory reactions play indispensable roles in initiating wound repair, sustained and prolonged inflammation exhibit detrimental effects on skin wound closure. We investigated the feasibility of using an antioxidant agent epigallocatechin-3-gallate (EGCG), along with MSCs, to improve wound repair through their immunomodulatory actions. In a rat model of wound healing, a single dose of EGCG at 10 mg/kg increased the efficiency of MSC-induced skin wound closure. Twenty days after the wound induction, MSC treatment significantly enhanced the epidermal thickness, which was further increased by EGCG administration. Consistently, the highest extent of growth factors upregulation for neovascularization induction was seen in the animals treated by both MSCs and EGCG, associated with a potent anti-scarring effect throughout the healing process. Finally, expression levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6, in the wound area were reduced by MSCs, and this reduction was further potentiated by EGCG co-administration. EGCG, together with MSCs, can promote skin wound healing likely through their combinational effects in modulating chronic inflammation. © 2016 John Wiley & Sons Australia, Ltd.

  16. Preclinical efficacy and safety of herbal formulation for management of wounds.

    PubMed

    Ogwang, P E; Nyafuono, J; Agwaya, Moses; Omujal, F; Tumusiime, H R; Kyakulaga, A H

    2011-09-01

    Medicinal plants in Uganda and other developing countries have been scientifically demonstrated to have medicinal benefits but few or none have been translated to products for clinical use. Most herbal products developed by local herbalists and sold to the public are not standardized and lack efficacy and safety data to support use. To formulate from two Ugandan medicinal plants a herbal product for wound management and test its preclinical safety and efficacy using rat models. Thirty (30) Wistar albino rats were randomly divided into three groups and wounds were surgically created on the mid-dorsal region. The wounds were treated topically with distilled water (group I), Jena(®) (group II)and Neomycin sulfate cream (group III). The effects of the treatments on rate of wound closure, epithelialisation time and histological organization of tissue were assessed. The herbal formulation (Jena) had a significantly higher rate of wound closure than neomycin (p<0.05) which itself was better than distilled water. Epithelialisation time was also significantly shorter for the herbal product (p<0.01). Histological picture revealed more collagen fibers, less inflammation and better tissue remodeling for rats treated with herbal product. The herbal formulation Jena(®) systematically designed and formulated based on two Ugandan medicinal plants is according to this study better than neomycin and probably other imported products for wound management in Uganda. We recommend its trial in a clinical setting as an alternative in wound management.

  17. Low-Magnitude High-Frequency Vibration Accelerated the Foot Wound Healing of n5-streptozotocin-induced Diabetic Rats by Enhancing Glucose Transporter 4 and Blood Microcirculation.

    PubMed

    Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Jiang, Jonney Lei; Wang, Tina Bai-Yan; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

    2017-09-14

    Delayed wound healing is a Type 2 diabetes mellitus (DM) complication caused by hyperglycemia, systemic inflammation, and decreased blood microcirculation. Skeletal muscles are also affected by hyperglycemia, resulting in reduced blood flow and glucose uptake. Low Magnitude High Frequency Vibration (LMHFV) has been proven to be beneficial to muscle contractility and blood microcirculation. We hypothesized that LMHFV could accelerate the wound healing of n5-streptozotocin (n5-STZ)-induced DM rats by enhancing muscle activity and blood microcirculation. This study investigated the effects of LMHFV in an open foot wound created on the footpad of n5-STZ-induced DM rats (DM_V), compared with no-treatment DM (DM), non-DM vibration (Ctrl_V) and non-DM control rats (Ctrl) on Days 1, 4, 8 and 13. Results showed that the foot wounds of DM_V and Ctrl_V rats were significantly reduced in size compared to DM and Ctrl rats, respectively, at Day 13. The blood glucose level of DM_V rats was significantly reduced, while the glucose transporter 4 (GLUT4) expression and blood microcirculation of DM_V rats were significantly enhanced in comparison to those of DM rats. In conclusion, LMHFV can accelerate the foot wound healing process of n5-STZ rats.

  18. Changes in the management of deep sternal wound infections: a 12-year review.

    PubMed

    Lonie, Sarah; Hallam, Jane; Yii, Michael; Davis, Philip; Newcomb, Andrew; Nixon, Ian; Rosalion, Alexander; Ricketts, Sophie

    2015-11-01

    Deep sternal wound infection (DSWI) is a rare but life-threatening complication following cardiac surgery associated with increased morbidity and mortality. Management of these patients has evolved over the years and can include sternal rewiring, mediastinal irrigation, negative-pressure wound therapy (NPWT) dressing or repair with flaps. We reviewed changes in our management of DSWI and outcomes. Using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database, 5472 underwent cardiac surgery at St Vincent's Hospital, Melbourne, and 42 were identified as developing DSWI requiring re-operation between June 2002 and September 2014. Data were collected pertaining to risk factors for DSWI, management strategies and outcomes. Patients were compared from a period prior to NPWT dressing use (June 2002-February 2006, n = 14) and since the NPWT has been used regularly in the management of DSWI (from March 2006, n = 28). Patients were also compared based on the requirement for flap closure of their sternal wound. Because of the widespread use of NPWT dressings, there is a trend towards fewer sternal infections requiring flap closure (25 versus 42.8%) and less post-operative complications after definitive closure (7.1 versus 28.6%). Before and after widespread NPWT use, patients require similar number of re-operations before closure and have no significant differences in time to definitive closure or length of hospital stay. The use of NPWT dressings as a bridge to definitive closure may reduce the need for more burdensome flap reconstruction, does not delay definitive reconstruction or prolong hospital stay and may reduce post-reconstruction complications requiring re-operation. © 2015 Royal Australasian College of Surgeons.

  19. Can Methicillin-resistant Staphylococcus aureus Silently Travel From the Gut to the Wound and Cause Postoperative Infection? Modeling the "Trojan Horse Hypothesis".

    PubMed

    Krezalek, Monika A; Hyoju, Sanjiv; Zaborin, Alexander; Okafor, Emeka; Chandrasekar, Laxmi; Bindokas, Vitas; Guyton, Kristina; Montgomery, Christopher P; Daum, Robert S; Zaborina, Olga; Boyle-Vavra, Susan; Alverdy, John C

    2018-04-01

    To determine whether intestinal colonization with methicillin-resistant Staphylococcus aureus (MRSA) can be the source of surgical site infections (SSIs). We hypothesized that gut-derived MRSA may cause SSIs via mechanisms in which circulating immune cells scavenge MRSA from the gut, home to surgical wounds, and cause infection (Trojan Horse Hypothesis). MRSA gut colonization was achieved by disrupting the microbiota with antibiotics, imposing a period of starvation and introducing MRSA via gavage. Next, mice were subjected to a surgical injury (30% hepatectomy) and rectus muscle injury and ischemia before skin closure. All wounds were cultured before skin closure. To control for postoperative wound contamination, reiterative experiments were performed in mice in which the closed wound was painted with live MRSA for 2 consecutive postoperative days. To rule out extracellular bacteremia as a cause of wound infection, MRSA was injected intravenously in mice subjected to rectus muscle ischemia and injury. All wound cultures were negative before skin closure, ruling out intraoperative contamination. Out of 40 mice, 4 (10%) developed visible abscesses. Nine mice (22.5%) had MRSA positive cultures of the rectus muscle without visible abscesses. No SSIs were observed in mice injected intravenously with MRSA. Wounds painted with MRSA after closure did not develop infections. Circulating neutrophils from mice captured by flow cytometry demonstrated MRSA in their cytoplasm. Immune cells as Trojan horses carrying gut-derived MRSA may be a plausible mechanism of SSIs in the absence of direct contamination.

  20. Ratio-driven resuscitation predicts early fascial closure in the combat wounded.

    PubMed

    Glaser, Jacob; Vasquez, Matthew; Cardarelli, Cassandra; Dunne, James; Elster, Eric; Hathaway, Emily; Bograd, Benjamin; Safford, Shawn; Rodriguez, Carlos

    2015-10-01

    Operation Iraqi Freedom and Operation Enduring Freedom have seen the highest rates of combat casualties since Vietnam. These casualties often require massive transfusion (MT) and immediate surgical attention to control hemorrhage. Clinical practice guidelines dictate ratio-driven resuscitation (RDR) for patients requiring MT. With the transition from crystalloid to blood product resuscitation, we have seen fewer open abdomens in combat casualties. We sought to determine the effect RDR has on achieving early definitive abdominal fascial closure in combat casualties undergoing exploratory laparotomy. Records of 1,977 combat casualties admitted to a single US military hospital from April 2003 to December 2011 were reviewed. Patients receiving an MT and laparotomy in theater constituted the study cohort. The cohort was divided into RDR, defined as a ratio of 0.8-U to 1.2-U packed red blood cells to 1-U fresh frozen plasma, and No-RDR groups. Age, injury patterns, mechanism of injury, injury severity, blood products, number of laparotomies, and days to fascial closure were collected. Assessed outcomes were number of days (early ≤ 2 days) and number of laparotomies to achieve fascial closure. The mean age of the study cohort (n = 172) was 24.0 years, and mean Injury Severity Score (ISS) was 24.8. Improvised explosive device blast was the most common mechanism of injury (74.4%). The cohort was divided into RDR patients (n = 73) and no RDR (n = 99). There was no difference in mean age, mean ISS, or rate of nontherapeutic exploratory laparotomies between the groups. RDR patients had a significantly lower abdominal injury rate (34.2% vs. 72.7%, p < 0.01), had fewer laparotomies (2.7 vs. 4.3, p = 0.003), and achieved primary fascial closure faster (2.4 days vs. 7.2 days, p = 0.004). On multivariate analysis, RDR (2.74; 95% confidence interval, 1.44-5.2) was an independent predictor for early fascial closure. Adherence to RDR guidelines resulted in significantly decreased

  1. MFG-E8 Reprogramming of Macrophages Promotes Wound Healing by Increased bFGF Production and Fibroblast Functions.

    PubMed

    Laplante, Patrick; Brillant-Marquis, Frédéric; Brissette, Marie-Joëlle; Joannette-Pilon, Benjamin; Cayrol, Romain; Kokta, Victor; Cailhier, Jean-François

    2017-09-01

    Macrophages are essential for tissue repair. They have a crucial role in cutaneous wound healing, participating actively in the inflammation phase of the process. Unregulated macrophage activation may, however, represent a source of excessive inflammation, leading to abnormal wound healing and hypertrophic scars. Our research group has shown that apoptotic endothelial and epithelial cells secrete MFG-E8, which has the ability to reprogram macrophages from an M1 (proinflammatory) to an M2 (anti-inflammatory, pro-repair) phenotype. Hence, we tested whether modulation of macrophage reprogramming would promote tissue repair. Using a mouse model of wound healing, we showed that the presence and/or addition of MFG-E8 favors wound closure associated with an increase in CD206-positive cells and basic fibroblast growth factor production in healing tissues. More importantly, adoptive transfer of ex vivo MFG-E8-treated macrophages promoted wound closure. We also observed that MFG-E8-treated macrophages produced basic fibroblast growth factor that is responsible for fibroblast migration and proliferation. Taken together, our results strongly suggest that MFG-E8 plays a key role in macrophage reprogramming in tissue healing through induction of an anti-inflammatory M2 phenotype and basic fibroblast growth factor production, leading to fibroblast migration and wound closure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Wound Complications in Preoperatively Irradiated Soft-Tissue Sarcomas of the Extremities

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rosenberg, Lewis A.; Esther, Robert J.; Erfanian, Kamil

    2013-02-01

    Purpose: To determine whether the involvement of plastic surgery and the use of vascularized tissue flaps reduces the frequency of major wound complications after radiation therapy for soft-tissue sarcomas (STS) of the extremities. Methods and Materials: This retrospective study evaluated patients with STS of the extremities who underwent radiation therapy before surgery. Major complications were defined as secondary operations with anesthesia, seroma/hematoma aspirations, readmission for wound complications, or persistent deep packing. Results: Between 1996 and 2010, 73 patients with extremity STS were preoperatively irradiated. Major wound complications occurred in 32% and secondary operations in 16% of patients. Plastic surgery closedmore » 63% of the wounds, and vascularized tissue flaps were used in 22% of closures. When plastic surgery performed closure the frequency of secondary operations trended lower (11% vs 26%; P=.093), but the frequency of major wound complications was not different (28% vs 38%; P=.43). The use of a vascularized tissue flap seemed to have no effect on the frequency of complications. The occurrence of a major wound complication did not affect disease recurrence or survival. For all patients, 3-year local control was 94%, and overall survival was 72%. Conclusions: The rates of wound complications and secondary operations in this study were very similar to previously published results. We were not able to demonstrate a significant relationship between the involvement of plastic surgery and the rate of wound complications, although there was a trend toward reduced secondary operations when plastic surgery was involved in the initial operation. Wound complications were manageable and did not compromise outcomes.« less

  3. Platelet Lysate-Modified Porous Silicon Microparticles for Enhanced Cell Proliferation in Wound Healing Applications.

    PubMed

    Fontana, Flavia; Mori, Michela; Riva, Federica; Mäkilä, Ermei; Liu, Dongfei; Salonen, Jarno; Nicoletti, Giovanni; Hirvonen, Jouni; Caramella, Carla; Santos, Hélder A

    2016-01-13

    The new frontier in the treatment of chronic nonhealing wounds is the use of micro- and nanoparticles to deliver drugs or growth factors into the wound. Here, we used platelet lysate (PL), a hemoderivative of platelets, consisting of a multifactorial cocktail of growth factors, to modify porous silicon (PSi) microparticles and assessed both in vitro and ex vivo the properties of the developed microsystem. PL-modified PSi was assessed for its potential to induce proliferation of fibroblasts. The wound closure-promoting properties of the microsystem were then assessed in an in vitro wound healing assay. Finally, the PL-modified PSi microparticles were evaluated in an ex vivo experiment over human skin. It was shown that PL-modified PSi microparticles were cytocompatible and enhanced the cell proliferation in different experimental settings. In addition, this microsystem promoted the closure of the gap between the fibroblast cells in the wound healing assay, in periods of time comparable with the positive control, and induced a proliferation and regeneration process onto the human skin in an ex vivo experiment. Overall, our results show that PL-modified PSi microparticles are suitable microsystems for further development toward applications in the treatment of chronic nonhealing wounds.

  4. Injectable hyperbranched poly(β-amino ester) hydrogels with on-demand degradation profiles to match wound healing processes† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc03913a

    PubMed Central

    Xu, Qian; Guo, Linru; A, Sigen; Gao, Yongsheng; Zhou, Dezhong; Greiser, Udo; Creagh-Flynn, Jack; Zhang, Hong; Dong, Yixiao; Cutlar, Lara; Wang, Fagang; Liu, Wenguang

    2018-01-01

    Adjusting biomaterial degradation profiles to match tissue regeneration is a challenging issue. Herein, biodegradable hyperbranched poly(β-amino ester)s (HP-PBAEs) were designed and synthesized via “A2 + B4” Michael addition polymerization, and displayed fast gelation with thiolated hyaluronic acid (HA-SH) via a “click” thiol–ene reaction. HP-PBAE/HA-SH hydrogels showed tunable degradation profiles both in vitro and in vivo using diamines with different alkyl chain lengths and poly(ethylene glycol) diacrylates with varied PEG spacers. The hydrogels with optimized degradation profiles encapsulating ADSCs were used as injectable hydrogels to treat two different types of humanized excisional wounds – acute wounds with faster healing rates and diabetic wounds with slower healing and neo-tissue formation. The fast-degrading hydrogel showed accelerated wound closure in acute wounds, while the slow-degrading hydrogel showed better wound healing for diabetic wounds. The results demonstrate that the new HP-PBAE-based hydrogel in combination with ADSCs can be used as a well-controlled biodegradable skin substitute, which demonstrates a promising approach in the treatment of various types of skin wounds. PMID:29719691

  5. Open abdomen with vacuum-assisted wound closure and mesh-mediated fascial traction in patients with complicated diffuse secondary peritonitis: A single-center 8-year experience.

    PubMed

    Tolonen, Matti; Mentula, Panu; Sallinen, Ville; Rasilainen, Suvi; Bäcklund, Minna; Leppäniemi, Ari

    2017-06-01

    Open abdomen (OA) treatment in patients with peritonitis is increasing worldwide. Various temporary abdominal closure devices are being used. This study included patients with complicated diffuse secondary peritonitis, OA, and vacuum-assisted wound closure and mesh-mediated fascial traction (VAWCM). The aim of this study was to describe mortality and major morbidity in terms of delayed primary fascial closure and enteroatmospheric fistula rates. This was a single-academic-center retrospective study of consecutive patients with diffuse peritonitis, OA, and VAWCM between years 2008 and 2016. Descriptive and univariate analyses were performed. Forty-one patients were identified and analyzed. Median age was 59 years, preoperative septic shock was diagnosed in 54% (n = 22), and 59% (n = 24) had a postoperative peritonitis. Mortality was 29% (n = 12), and 76% (n = 31) of patients were admitted in the intensive care unit. The median duration of OA was 7 days with a median of two dressing changes. Delayed primary fascial closure rate among survivors was 92% (n = 33), and enteroatmospheric fistulas developed in 7% (n = 3). In a subgroup analysis, patients with OA in the primary laparotomy for peritonitis (n = 27) were compared with patients with OA in the subsequent laparotomies (n = 14). There were no significant differences between groups. The VAWCM technique in patients with complicated secondary diffuse peritonitis and OA yields excellent results in terms of delayed primary fascial closure rate and a low number of enteroatmospheric fistulas. It seems to be safe to close the abdomen at the index laparotomy, if possible, even if there is a risk of a need of OA later. Therapeutic/care management study, level IV.

  6. Wound healing properties of ethyl acetate fraction of Moringa oleifera in normal human dermal fibroblasts

    PubMed Central

    Gothai, Sivapragasam; Arulselvan, Palanisamy; Tan, Woan Sean; Fakurazi, Sharida

    2016-01-01

    Background/Aim: Wounds are the outcome of injuries to the skin that interrupt the soft tissue. Healing of a wound is a complex and long-drawn-out process of tissue repair and remodeling in response to injury. A large number of plants are used by folklore traditions for the treatment of cuts, wounds and burns. Moringa oleifera (MO) is an herb used as a traditional folk medicine for the treatment of various skin wounds and associated diseases. The underlying mechanisms of wound healing activity of ethyl acetate fraction of MO leaves extract are completely unknown. Materials and Methods: In the current study, ethyl acetate fraction of MO leaves was investigated for its efficacy on cell viability, proliferation and migration (wound closure rate) in human normal dermal fibroblast cells. Results: Results revealed that lower concentration (12.5 µg/ml, 25 µg/ml, and 50 µg/ml) of ethyl acetate fraction of MO leaves showed remarkable proliferative and migratory effect on normal human dermal fibroblasts. Conclusion: This study suggested that ethyl acetate fraction of MO leaves might be a potential therapeutic agent for skin wound healing by promoting fibroblast proliferation and migration through increasing the wound closure rate corroborating its traditional use. PMID:27069722

  7. Expression of synaptopodin in endothelial cells exposed to laminar shear stress and its role in endothelial wound healing.

    PubMed

    Mun, Gyeong In; Park, Soojin; Kremerskothen, Joachim; Boo, Yong Chool

    2014-03-18

    We examined the hypothesis that certain actin binding proteins might be upregulated by laminar shear stress (LSS) and could contribute to endothelial wound healing. Analysis of mRNA expression profiles of human umbilical vein endothelial cells under static and LSS-exposed conditions provided a list of LSS-induced actin binding proteins including synaptopodin (SYNPO) whose endothelial expression has not been previously reported. Additional studies demonstrated that SYNPO is a key mediator of endothelial wound healing because small interfering RNA-mediated suppression of SYNPO attenuated wound closure under LSS whereas overexpression of exogenous SYNPO enhanced endothelial wound closure in the absence of LSS. This study suggests that LSS-induced actin binding proteins including SYNPO may play a critical role in the endothelial wound healing stimulated by LSS. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Polyurethane foam containing rhEGF as a dressing material for healing diabetic wounds: Synthesis, characterization, in vitro and in vivo studies.

    PubMed

    Pyun, Do Gi; Choi, Hyun Jun; Yoon, Hyoung Soon; Thambi, Thavasyappan; Lee, Doo Sung

    2015-11-01

    Diabetic wounds are a major health issue associated with diabetes mellitus. To surmount this issue, we developed polyurethane foams (PUFs) incorporating varying amounts of recombinant human epidermal growth factor (rhEGF) (rhEGF-PUFs) as a wound dressing for diabetic wounds. From electron microscopy images, it was found that the pore size of the rhEGF-PUFs surface (the wound contact layer) was less than 100μm, regardless of rhEGF content. The release of rhEGF from the PUFs was evaluated using an enzyme-linked immunosorbent assay. The result showed that the release of rhEGF was time and concentration dependent, i.e., the amount of released rhEGF significantly increased as the immersion time and the rhEGF content of the PUFs increased. In vitro cytotoxicity testing showed that rhEGF-PUFs increased the viability of HaCaT human keratinocytes and CCD986-sk human fibroblasts, which indicated that the incorporated rhEGF maintained its biological activity. In an in vitro scratch wound healing assay, the wound closure rate was faster in CCD986-sk human fibroblasts than in HaCaT human keratinocytes. Finally, the rhEGF-PUFs were evaluated as an in vivo treatment in a full-thickness wound model in diabetized Sprague-Dawley rats. The result indicated that compared with PUFs, rhEGF-PUFs accelerated wound healing by promoting wound contraction, re-epithelialization, collagen deposition and the formation of a skin appendage. These findings demonstrate that rhEGF-PUFs are a promising dressing for diabetic wounds. Copyright © 2015. Published by Elsevier B.V.

  9. Conflicts in wound classification of neonatal operations.

    PubMed

    Vu, Lan T; Nobuhara, Kerilyn K; Lee, Hanmin; Farmer, Diana L

    2009-06-01

    This study sought to determine the reliability of wound classification guidelines when applied to neonatal operations. This study is a cross-sectional web-based survey of pediatric surgeons. From a random sample of 22 neonatal operations, participants classified each operation as "clean," "clean-contaminated," "contaminated," or "dirty or infected," and specified duration of perioperative antibiotics as "none," "single preoperative," "24 hours," or ">24 hours." Unweighted kappa score was calculated to estimate interrater reliability. Overall interrater reliability for wound classification was poor (kappa = 0.30). The following operations were classified as clean: pyloromyotomy, resection of sequestration, resection of sacrococcygeal teratoma, oophorectomy, and immediate repair of omphalocele; as clean-contaminated: Ladd procedure, bowel resection for midgut volvulus and meconium peritonitis, fistula ligation of tracheoesophageal fistula, primary esophageal anastomosis of esophageal atresia, thoracic lobectomy, staged closure of gastroschisis, delayed repair and primary closure of omphalocele, perineal anoplasty and diverting colostomy for imperforate anus, anal pull-through for Hirschsprung disease, and colostomy closure; and as dirty: perforated necrotizing enterocolitis. There is poor consensus on how neonatal operations are classified based on contamination. An improved classification system will provide more accurate risk assessment for development of surgical site infections and identify neonates who would benefit from antibiotic prophylaxis.

  10. Cold Plasma Welding System for Surgical Skin Closure: In Vivo Porcine Feasibility Assessment.

    PubMed

    Harats, Moti; Lam, Amnon; Maller, Michael; Kornhaber, Rachel; Haik, Josef

    2016-09-29

    Cold plasma skin welding is a novel technology that bonds skin edges through soldering without the use of synthetic materials or conventional wound approximation methods such as sutures, staples, or skin adhesives. The cold plasma welding system uses a biological solder applied to the edges of a skin incision, followed by the application of cold plasma energy. The objectives of this study were to assess the feasibility of a cold plasma welding system in approximating and fixating skin incisions compared with conventional methods and to evaluate and define optimal plasma welding parameters and histopathological tissue response in a porcine model. The cold plasma welding system (BioWeld1 System, IonMed Ltd, Yokneam, Israel) was used on porcine skin incisions using variable energy parameters. Wound healing was compared macroscopically and histologically to incisions approximated with sutures. When compared to sutured skin closure, cold plasma welding in specific system parameters demonstrated comparable and favorable wound healing results histopathologically as well as macroscopically. No evidence of epidermal damage, thermal or otherwise, was encountered in the specified parameters. Notably, bleeding, infection, and wound dehiscence were not detected at incision sites. Skin incisions welded at extreme energy parameters presented second-degree burns. Implementation of cold plasma welding has been shown to be feasible for skin closure. Initial in vivo results suggest cold plasma welding might provide equal, if not better, healing results than traditional methods of closure.

  11. Dual effects of atmospheric pressure plasma jet on skin wound healing of mice.

    PubMed

    Xu, Gui-Min; Shi, Xing-Min; Cai, Jing-Fen; Chen, Si-Le; Li, Ping; Yao, Cong-Wei; Chang, Zheng-Shi; Zhang, Guan-Jun

    2015-01-01

    Cold plasma has become an attractive tool for promoting wound healing and treating skin diseases. This article presents an atmospheric pressure plasma jet (APPJ) generated in argon gas through dielectric barrier discharge, which was applied to superficial skin wounds in BALB/c mice. The mice (n = 50) were assigned randomly into five groups (named A, B, C, D, E) with 10 animals in each group. Natural wound healing was compared with stimulated wound healing treated daily with APPJ for different time spans (10, 20, 30, 40, and 50 seconds) on 14 consecutive days. APPJ emission spectra, morphological changes in animal wounds, and tissue histological parameters were analyzed. Statistical results revealed that wound size changed over the duration of the experimental period and there was a significant interaction between experimental day and group. Differences between group C and other groups at day 7 were statistically significant (p < 0.05). All groups had nearly achieved closure of the untreated control wounds at day 14. The wounds treated with APPJ for 10, 20, 30, and 40 seconds showed significantly enhanced daily improvement compared with the control and almost complete closure at day 12, 10, 7, and 13, respectively. The optimal results of epidermal cell regeneration, granulation tissue hyperplasia, and collagen deposition in histological aspect were observed at day 7. However, the wounds treated for 50 seconds were less well healed at day 14 than those of the control. It was concluded that appropriate doses of cold plasma could inactivate bacteria around the wound, activate fibroblast proliferation in wound tissue, and eventually promote wound healing. Whereas, over doses of plasma suppressed wound healing due to causing cell death by apoptosis or necrosis. Both positive and negative effects may be related to the existence of reactive oxygen and nitrogen species (ROS and RNS) in APPJ. © 2015 by the Wound Healing Society.

  12. Microfluidic wound bandage: localized oxygen modulation of collagen maturation.

    PubMed

    Lo, Joe F; Brennan, Martin; Merchant, Zameer; Chen, Lin; Guo, Shujuan; Eddington, David T; DiPietro, Luisa A

    2013-01-01

    Restoring tissue oxygenation has the potential to improve poorly healing wounds with impaired microvasculature. Compared with more established wound therapy using hyperbaric oxygen chambers, topical oxygen therapy has lower cost and better patient comfort, although topical devices have provided inconsistent results. To provide controlled topical oxygen while minimizing moisture loss, a major issue for topical oxygen, we have devised a novel wound bandage based on microfluidic diffusion delivery of oxygen. In addition to modulating oxygen from 0 to 100% in 60 seconds rise time, the microfluidic oxygen bandage provides a conformal seal around the wound. When 100% oxygen is delivered, it penetrates wound tissues as measured in agar phantom and in vivo wounds. Using this microfluidic bandage, we applied the oxygen modulation to 8 mm excisional wounds prepared on diabetic mice. Treatment with the microfluidic bandage demonstrated improved collagen maturity in the wound bed, although only marginal differences were observed in total collagen, microvasculature, and external closure rates. Our results show that proper topical oxygen can improve wound parameters underneath the surface. Because of the ease of fabrication, the oxygen bandage represents an economical yet practical method for oxygen wound research. © 2013 by the Wound Healing Society.

  13. Activation of MRTF-A–dependent gene expression with a small molecule promotes myofibroblast differentiation and wound healing

    PubMed Central

    Velasquez, Lissette S.; Sutherland, Lillian B.; Liu, Zhenan; Grinnell, Frederick; Kamm, Kristine E.; Schneider, Jay W.; Olson, Eric N.; Small, Eric M.

    2013-01-01

    Myocardin-related transcription factors (MRTFs) regulate cellular contractility and motility by associating with serum response factor (SRF) and activating genes involved in cytoskeletal dynamics. We reported previously that MRTF-A contributes to pathological cardiac remodeling by promoting differentiation of fibroblasts to myofibroblasts following myocardial infarction. Here, we show that forced expression of MRTF-A in dermal fibroblasts stimulates contraction of a collagen matrix, whereas contractility of MRTF-A null fibroblasts is impaired under basal conditions and in response to TGF–β1 stimulation. We also identify an isoxazole ring-containing small molecule, previously shown to induce smooth muscle α-actin gene expression in cardiac progenitor cells, as an agonist of myofibroblast differentiation. Isoxazole stimulates myofibroblast differentiation via induction of MRTF-A–dependent gene expression. The MRTF-SRF signaling axis is activated in response to skin injury, and treatment of dermal wounds with isoxazole accelerates wound closure and suppresses the inflammatory response. These results reveal an important role for MRTF-SRF signaling in dermal myofibroblast differentiation and wound healing and suggest that targeting MRTFs pharmacologically may prove useful in treating diseases associated with inappropriate myofibroblast activity. PMID:24082095

  14. A Unique Application of Negative Pressure Wound Therapy Used to Facilitate Patient Engagement in the Amputation Recovery Process.

    PubMed

    Wise, Jessica; White, Alicia; Stinner, Daniel J; Fergason, John R

    2017-08-01

    Amputation rates during recent military conflicts were at an all-time high, but medical treatment of those amputations and attitudes of service members to get back to duty are also surging ahead. We present the cases of an active duty rescue C130 pilot with an above-the-knee amputation and a retired army sergeant with a below-the-knee amputation. Successful rehabilitation was augmented in both cases by using negative pressure incorporated in a custom prosthetic socket to accelerate incision closure, improve self-efficacy in wound care, and self-management, ultimately leading to faster recovery times, full engagement of the rehabilitation process, and return to active duty.

  15. What is important to patients in wound management.

    PubMed

    Keeton, Helen; Crouch, Robert; Lowe, Kate

    2015-02-01

    Traumatic wounds are a common reason for patients to attend emergency departments. There are many ways of managing these wounds from glue to suturing. The authors conducted a patient survey to identify the outcome measures most important to patients after closure of traumatic wounds. The results showed that having the least chance of infection was the most important outcome, followed by being looked after by caring staff and a quick recovery. These finding were consistent regardless of the anatomical location of the wound or age of the patient. This information is being used to guide the authors in the most appropriate outcome measures for further research. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Curcuma purpurascens BI. rhizome accelerates rat excisional wound healing: involvement of Hsp70/Bax proteins, antioxidant defense, and angiogenesis activity.

    PubMed

    Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Hajiaghaalipour, Fatemeh; Zahedifard, Maryam; Tayeby, Faezeh; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

    2015-01-01

    Curcuma purpurascens BI. is a member of Zingiberaceae family. The purpose of this study is to investigate the wound healing properties of hexane extract of C. purpurascens rhizome (HECP) against excisional wound healing in rats. Twenty four rats were randomly divided into 4 groups: A) negative control (blank placebo, acacia gum), B) low dose of HECP, C) high dose of HECP, and D) positive control, with 6 rats in each group. Full-thickness incisions (approximately 2.00 cm) were made on the neck area of each rat. Groups 1-4 were treated two-times a day for 20 days with blank placebo, HECP (100 mg/kg), HECP (200 mg/kg), and intrasite gel as a positive control, respectively. After 20 days, hematoxylin and eosin and Masson's trichrome stainings were employed to investigate the histopathological alterations. Protein expressions of Bax and Hsp70 were examined in the wound tissues using immunohistochemistry analysis. In addition, levels of enzymatic antioxidants and malondialdehyde representing lipid peroxidation were measured in wound tissue homogenates. Macroscopic evaluation of wounds showed conspicuous elevation in wound contraction after topical administration of HECP at both doses. Moreover, histopathological analysis revealed noteworthy reduction in the scar width correlated with the enhanced collagen content and fibroblast cells, accompanied by a reduction of inflammatory cells in the granulation tissues. At the molecular level, HECP facilitates wound-healing process by downregulating Bax and upregulating Hsp70 protein at the wound site. The formation of new blood vessel was observed in Masson's trichrome staining of wounds treated with HECP (100 and 200 mg/kg). In addition, HECP administration caused a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation. These findings suggested that HECP accelerated wound-healing process in rats via antioxidant activity, angiogenesis effect and anti-inflammatory responses involving Hsp70/Bax.

  17. Nondermal irritating hyperosmotic nanoemulsions reduce treatment times in a contamination model of wound healing.

    PubMed

    Connell, Sean; Li, Jianming; Durkes, Abigail; Zaroura, Mohammed; Shi, Riyi

    2016-07-01

    Increased microbial burden within the wound often complicates wound healing and may lead to subsequent infection or delayed healing. Here, we investigate a novel topical for addressing wound contamination that utilizes hyperosmotic saccharides with a cell membrane disrupting emulsion. These hyperosmotic nanoemulsions (HNE) were administered topically in a full-thickness biopsy model of wound healing. Results show that HNE were well tolerated in noninfected animals with no indications of dermal irritation or acute toxicity. Additionally, HNE was able to reduce bacterial bioburden (Escherichia coli and Enterococcus faecalis) levels by 3 logs within 24 h when wounds were inoculated with 5 × 10(6) total CFU. These bactericidal values were similar to wounds treated with silver sulfadiazine. Wound closure showed HNE wounds closed in 7.6 ± 0.2 days while SSD and control required 10.2 ± 0.4 and 10.4 ± 0.3 days, respectively. HNE maintained a moist wound environment, were well debrided, and exhibited improved hemostatic response. Further histological examination revealed enhanced granulation tissue as compared to silver sulfadiazine and control cohorts. These results were corroborated with 3D topographical imprints of the wounds at day 14 which qualitatively showed a smoother surface. In contrast, silver sulfadiazine appeared to delay wound closure. Finally, dermal sensitization and irritation studies conducted in guinea pig and rabbits did not reveal any acute dermal side effects from HNE exposure. The cumulative data indicates nonantibiotic-based HNEs may be a promising topical treatment for the management of contaminated wounds. © 2016 by the Wound Healing Society.

  18. Schinus terebinthifolius Raddi ( Aroeira) leaves oil attenuates inflammatory responses in cutaneous wound healing in mice 1.

    PubMed

    Estevão, Lígia Reis Moura; Simões, Ricardo Santos; Cassini-Vieira, Puebla; Canesso, Maria Cecilia Campos; Barcelos, Lucíola da Silva; Rachid, Milene Alvarenga; Câmara, Cláudio Augusto Gomes da; Evêncio-Neto, Joaquim

    2017-09-01

    To investigated the inflammatory, angiogenic and fibrogenic activities of the Schinus terebinthifolius Raddi leaves oil (STRO) on wound healing. The excisional wound healing model was used to evaluate the effects of STRO. The mice were divided into two groups: Control, subjected to vehicle solution (ointment lanolin/vaseline base), or STRO- treated group, administered topically once a day for 3, 7 and 14 days post-excision. We evaluated the macroscopic wound closure rate; the inflammation was evaluated by leukocytes accumulation and cytokine levels in the wounds. The accumulation of neutrophil and macrophages in the wounds were determined by assaying myeloperoxidase and N-acetyl-β-D-glucosaminidase activities. The levels of TNF-α, CXCL-1 and CCL-2 in wound were evaluated by ELISA assay. Angiogenesis and collagen fibers deposition were evaluated histologically. We observed that macroscopic wound closure rate was improved in wounds from STRO-group than Control-group. The wounds treated with STRO promoted a reduction in leucocyte accumulation and in pro-inflammatory cytokine. Moreover, STRO treatment increased significantly the number of blood vessels and collagen fibers deposition, as compared to control group. Topical application of STRO display anti-inflammatory and angiogenic effects, as well as improvement in collagen replacement, suggesting a putative use of this herb for the development of phytomedicines to treat inflammatory diseases, including wound healing.

  19. Effe0cts of porcine acellular dermal matrix treatment on wound healing and scar formation: role of Jag1 expression in epidermal stem cells.

    PubMed

    Chen, Xiao-Dong; Ruan, Shu-Bin; Lin, Ze-Peng; Zhou, Ziheng; Zhang, Feng-Gang; Yang, Rong-Hua; Xie, Ju-Lin

    2018-02-08

    Skin wound healing involves Notch/Jagged1 signaling. However, little is known how Jag1 expression level in epidermal stem cells (ESCs) contributes to wound healing and scar formation. We applied multiple cellular and molecular techniques to examine how Jag1 expression in ESCs modulates ESCs differentiation to myofibroblasts (MFB) in vitro, interpret how Jag1 expression in ESCs is involved in wound healing and scar formation in mice, and evaluate the effects of porcine acellular dermal matrix (ADM) treatment on wound healing and scar formation. We found that Jag1, Notch1 and Hes1 expression was up-regulated in the wound tissue during the period of wound healing. Furthermore, Jag1 expression level in the ESCs was positively associated with the level of differentiation to MFB. ESC-specific knockout of Jag1 delayed wound healing and promoted scar formation in vivo. In addition, we reported that porcine ADM treatment after skin incision could accelerate wound closure and reduce scar formation in vivo. This effect was associated with decreased expression of MFB markers, including α-SMA Col-1 and Col-III in wound tissues. Finally, we confirmed that porcine ADM treatment could increase Jag1, Notch1 and Hesl expression in wound tissues. Taken together, our results suggested that ESC-specific Jag1 expression levels are critical for wound healing and scar formation, and porcine ADM treatment would be beneficial in promoting wound healing and preventing scar formation by enhancing Notch/Jagged1 signaling pathway in ESCs.

  20. Fire scar growth and closure rates in white oak (Quercus alba) and the implications for prescribed burning

    Treesearch

    Michael C. Stambaugh; Kevin T. Smith; Daniel C. Dey

    2017-01-01

    In burned forestlands, fire scar wounds commonly occur on tree stems as a result of cambial heating. In hardwood forests in particular, wounding can lead to stem decay with the extent of decay being related to scar size and exposure time. Therefore, wound closure rates are important to understand in the context of fire management such that allowing sufficient time for...

  1. Syndecan-4 enhances PDGF-BB activity in diabetic wound healing.

    PubMed

    Das, Subhamoy; Majid, Marjan; Baker, Aaron B

    2016-09-15

    Non-healing ulcers are a common consequence of long-term diabetes and severe peripheral vascular disease. These non-healing wounds are a major source of morbidity in patients with diabetes and place a heavy financial burden on the healthcare system. Growth factor therapies are an attractive strategy for enhancing wound closure in non-healing wounds but have only achieved mixed results in clinical trials. Platelet derived growth factor-BB (PDGF-BB) is the only currently approved growth factor therapy for non-healing wounds. However, PDGF-BB therapy is not effective in many patients and requires high doses that increase the potential for side effects. In this work, we demonstrate that syndecan-4 delivered in a proteoliposomal formulation enhances PDGF-BB activity in diabetic wound healing. In particular, syndecan-4 proteoliposomes enhance the migration of keratinocytes derived from patients with diabetes. In addition, syndecan-4 proteoliposomes sensitize keratinocytes to PDGF-BB stimulation, enhancing the intracellular signaling response to PDGF-BB. We further demonstrated that co-therapy with syndecan-4 proteoliposomes enhanced wound closure in diabetic, hyperlipidemic ob/ob mice. Wounds treated with both syndecan-4 proteoliposomes and PDGF-BB had increased re-epithelization and angiogenesis in comparison to wounds treated with PDGF-BB alone. Moreover, the wounds treated with syndecan-4 proteoliposomes and PDGF-BB also had increased M2 macrophages and reduced M1 macrophages, suggesting syndecan-4 delivery induces immunomodulation within the healing wounds. Together our findings support that syndecan-4 proteoliposomes markedly improve PDGF-BB efficacy for wound healing and may be useful in enhancing treatments for non-healing wounds. Non-healing wounds are major healthcare issue for patients with diabetes and peripheral vascular disease. Growth factor therapies have potential for healing chronic wounds but have not been effective for many patients. PDGF-BB is

  2. Drug delivery systems and materials for wound healing applications.

    PubMed

    Saghazadeh, Saghi; Rinoldi, Chiara; Schot, Maik; Kashaf, Sara Saheb; Sharifi, Fatemeh; Jalilian, Elmira; Nuutila, Kristo; Giatsidis, Giorgio; Mostafalu, Pooria; Derakhshandeh, Hossein; Yue, Kan; Swieszkowski, Wojciech; Memic, Adnan; Tamayol, Ali; Khademhosseini, Ali

    2018-04-05

    Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Demonstration of the Rat Ischemic Skin Wound Model

    PubMed Central

    Sherwood, Jacob; Wu, Mack; Gould, Lisa J.

    2015-01-01

    The propensity for chronic wounds in humans increases with ageing, disease conditions such as diabetes and impaired cardiovascular function, and unrelieved pressure due to immobility. Animal models have been developed that attempt to mimic these conditions for the purpose of furthering our understanding of the complexity of chronic wounds. The model described herein is a rat ischemic skin flap model that permits a prolonged reduction of blood flow resulting in wounds that become ischemic and resemble a chronic wound phenotype (reduced vascularization, increased inflammation and delayed wound closure). It consists of a bipedicled dorsal flap with 2 ischemic wounds placed centrally and 2 non-ischemic wounds lateral to the flap as controls. A novel addition to this ischemic skin flap model is the placement of a silicone sheet beneath the flap that functions as a barrier and a splint to prevent revascularization and reduce contraction as the wounds heal. Despite the debate of using rats for wound healing studies due to their quite distinct anatomic and physiologic differences compared to humans (i.e., the presence of a panniculus carnosus muscle, short life-span, increased number of hair follicles, and their ability to heal infected wounds) the modifications employed in this model make it a valuable alternative to previously developed ischemic skin flap models. PMID:25866964

  4. Demonstration of the rat ischemic skin wound model.

    PubMed

    Trujillo, Andrea N; Kesl, Shannon L; Sherwood, Jacob; Wu, Mack; Gould, Lisa J

    2015-04-01

    The propensity for chronic wounds in humans increases with ageing, disease conditions such as diabetes and impaired cardiovascular function, and unrelieved pressure due to immobility. Animal models have been developed that attempt to mimic these conditions for the purpose of furthering our understanding of the complexity of chronic wounds. The model described herein is a rat ischemic skin flap model that permits a prolonged reduction of blood flow resulting in wounds that become ischemic and resemble a chronic wound phenotype (reduced vascularization, increased inflammation and delayed wound closure). It consists of a bipedicled dorsal flap with 2 ischemic wounds placed centrally and 2 non-ischemic wounds lateral to the flap as controls. A novel addition to this ischemic skin flap model is the placement of a silicone sheet beneath the flap that functions as a barrier and a splint to prevent revascularization and reduce contraction as the wounds heal. Despite the debate of using rats for wound healing studies due to their quite distinct anatomic and physiologic differences compared to humans (i.e., the presence of a panniculus carnosus muscle, short life-span, increased number of hair follicles, and their ability to heal infected wounds) the modifications employed in this model make it a valuable alternative to previously developed ischemic skin flap models.

  5. [COMPARISON OF REPAIR EFFECT BETWEEN CHIMERIC ANTEROLATERAL THIGH FLAP AND SERIES-WOUND FLAPS FOR DEFECT AFTER RESECTION OF ORAL AND MAXILLOFACIAL CANCER].

    PubMed

    Yang, Heping; Zhang, Hongwu; Chen, Haidi; Yang, Shuxiong; Wang, Jun; Hu, Dawang

    2016-04-01

    thigh-flap group were significantly better than those of the series-wound flaps group (P < 0.05), while there was no significant difference in diet, mouth opening degree, oral cavity holding water test, and occlusion scores between the 2 groups (P > 0.05). Using chimeric anterolateral thigh flap for defect repair after resection of oral and maxillofacial cancer can significantly shorten the operation time, accelerate postoperative rehabilitation, and help the functional recovery of oral closure, chewing, language performance, swallowing function when compared with the series-wound flaps.

  6. Oxygen in wound healing: nutrient, antibiotic, signaling molecule, and therapeutic agent.

    PubMed

    Eisenbud, David E

    2012-07-01

    Disturbances to healing observed under hypoxic conditions have given insights into the roles of oxygen. Wound hypoxia is more prevalent than generally appreciated, and occurs even in patients who are free of arterial occlusive disease. There is a strong scientific basis for oxygen treatment as prophylaxis against infection, to facilitate wound closure, and to prevent amputation in wounded patients. This article reviews extensive data from preclinical and human trials of supplemental inhaled oxygen, hyperbaric oxygen, and topical oxygen treatment. Oxygen supports biochemical metabolism and cellular function, and has roles in combating infection and facilitating the wound healing cascade. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Verapamil, a Calcium-Channel Blocker, Improves the Wound Healing Process in Rats with Excisional Full-Thickness Skin Wounds Based on Stereological Parameters.

    PubMed

    Ashkani-Esfahani, Soheil; Hosseinabadi, Omid Koohi; Moezzi, Parinaz; Moafpourian, Yalda; Kardeh, Sina; Rafiee, Shima; Fatheazam, Reza; Noorafshan, Ali; Nadimi, Elham; Mehrvarz, Shayan; Khoshneviszadeh, Mehdi; Khoshneviszadeh, Mahsima

    2016-08-01

    Calcium can play noticeable roles in the wound-healing process, such as its effects on organization of F-actinin collagen bundles by fibroblasts at the injury site. In addition, calcium-channel blockers such as verapamil have antioxidant activity by increasing nitric oxide production that promotes angiogenesis, proliferation of fibroblasts, and endothelial cells in the skin-regeneration process. Therefore, in this study, the authors' objective was to investigate the effects of verapamil on the process of wound healing in rat models according to stereological parameters. In this experimental study, 36 male Wistar rats were randomly divided into 3 groups (n = 12): the control group that received no treatment, gel-base-treated group, and the 5% verapamil gel-treated group. Treatments were done every 24 hours for 15 days. Wound closure rate, volume densities of the collagen bundles and the vessels, vessel's length density and mean diameter, and fibroblast populations were estimated using stereological methods and were analyzed by the Kruskal-Wallis and Mann-Whitney U tests; P < .05 was considered statistically significant. The verapamil-treated group showed a faster wound closure rate in comparison with control and gel-base groups (P = .007 and P = .011). The numerical density of fibroblasts, volume density of collagen bundles, mean diameter, and volume densities of the vessels in the verapamil group were significantly higher than those in the control and the base groups (P < .005). The authors showed that verapamil has the ability to improve wound healing by enhancing fibroblast proliferation, collagen bundle synthesis, and revascularization in skin injuries.

  8. Irradiation at 636 nm positively affects diabetic wounded and hypoxic cells in vitro.

    PubMed

    Sekhejane, Palesa R; Houreld, Nicolette N; Abrahamse, Heidi

    2011-08-01

    This study investigated the effect of low-intensity laser irradiation (LILI) on pro-inflammatory cytokines involved in wound healing processes in diabetes and hypoxia. Diabetes is associated with impaired wound healing and a prolonged inflammatory phase. Pro-inflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 are elevated in diabetes. LILI has been reported to accelerate wound healing and decrease inflammatory cytokines. A human skin fibroblast cell line (WS1) was used in vitro. Cells were exposed to various insults, namely, wounding, and a diabetic or hypoxic environment. Experimental cells were exposed to an energy density of 5  J/cm(2) using a continuous wave 636-nm diode laser at an average power of 95  mW, an illuminated area of 9.05  cm(2), and an irradiance of 11 mW/cm(2) (irradiation time, 476  sec). The effect of laser irradiation on cytokine expression was examined at 1 or 24  h post-irradiation. Cellular morphology, viability, proliferation, and cytokine expression (IL-1β, IL-6, and TNF-α) were investigated. Translocation of nuclear factor-kappa B (NF-κB) was also determined. There was a higher rate of migration in irradiated wounded cultures, and irradiated hypoxic cells showed an improvement in cellular morphology. All cell models showed an increase in proliferation. Normal wounded cells showed a decrease in apoptosis, TNF-α, and IL-1β. Diabetic wounded cells showed an increase in viability and a decrease in apoptosis and IL-1β, whereas hypoxic cells showed an increase in viability and IL-6, and a decrease in apoptosis and TNF-α. NF-κB was translocated into the nucleus post-irradiation. Phototherapy resulted in hastened wound closure, increased proliferation, and normalization of cellular function. The decrease in the different pro-inflammatory cytokines and NF-κB translocation was model and time dependent. Overall, laser irradiation resulted in a reduction in inflammatory cytokines and

  9. The extracellular adherence protein (Eap) of Staphylococcus aureus inhibits wound healing by interfering with host defense and repair mechanisms.

    PubMed

    Athanasopoulos, Athanasios N; Economopoulou, Matina; Orlova, Valeria V; Sobke, Astrid; Schneider, Darius; Weber, Holger; Augustin, Hellmut G; Eming, Sabine A; Schubert, Uwe; Linn, Thomas; Nawroth, Peter P; Hussain, Muzaffar; Hammes, Hans-Peter; Herrmann, Mathias; Preissner, Klaus T; Chavakis, Triantafyllos

    2006-04-01

    Staphylococcus aureus is a major human pathogen interfering with host-cell functions. Impaired wound healing is often observed in S aureus-infected wounds, yet, the underlying mechanisms are poorly defined. Here, we identify the extracellular adherence protein (Eap) of S aureus to be responsible for impaired wound healing. In a mouse wound-healing model wound closure was inhibited in the presence of wild-type S aureus and this effect was reversible when the wounds were incubated with an isogenic Eap-deficient strain. Isolated Eap also delayed wound closure. In the presence of Eap, recruitment of inflammatory cells to the wound site as well as neovascularization of the wound were prevented. In vitro, Eap significantly reduced intercellular adhesion molecule 1 (ICAM-1)-dependent leukocyte-endothelial interactions and diminished the consequent activation of the proinflammatory transcription factor nuclear factor kappaB (NFkappaB) in leukocytes associated with a decrease in expression of tissue factor. Moreover, Eap blocked alphav-integrin-mediated endothelial-cell migration and capillary tube formation, and neovascularization in matrigels in vivo. Collectively, the potent anti-inflammatory and antiangiogenic properties of Eap provide an underlying mechanism that may explain the impaired wound healing in S aureus-infected wounds. Eap may also serve as a lead compound for new anti-inflammatory and antiangiogenic therapies in several pathologies.

  10. Mechanics of epithelial closure over non-adherent environments

    NASA Astrophysics Data System (ADS)

    Vedula, Sri Ram Krishna; Peyret, Grégoire; Cheddadi, Ibrahim; Chen, Tianchi; Brugués, Agustí; Hirata, Hiroaki; Lopez-Menendez, Horacio; Toyama, Yusuke; Neves de Almeida, Luís; Trepat, Xavier; Lim, Chwee Teck; Ladoux, Benoit

    2015-01-01

    The closure of gaps within epithelia is crucial to maintain its integrity during biological processes such as wound healing and gastrulation. Depending on the distribution of extracellular matrix, gap closure occurs through assembly of multicellular actin-based contractile cables or protrusive activity of border cells into the gap. Here we show that the supracellular actomyosin contractility of cells near the gap edge exerts sufficient tension on the surrounding tissue to promote closure of non-adherent gaps. Using traction force microscopy, we observe that cell-generated forces on the substrate at the gap edge first point away from the centre of the gap and then increase in the radial direction pointing into the gap as closure proceeds. Combining with numerical simulations, we show that the increase in force relies less on localized purse-string contractility and more on large-scale remodelling of the suspended tissue around the gap. Our results provide a framework for understanding the assembly and the mechanics of cellular contractility at the tissue level.

  11. Yorkie regulates epidermal wound healing in Drosophila larvae independently of cell proliferation and apoptosis.

    PubMed

    Tsai, Chang-Ru; Anderson, Aimee E; Burra, Sirisha; Jo, Juyeon; Galko, Michael J

    2017-07-01

    Yorkie (Yki), the transcriptional co-activator of the Hippo signaling pathway, has well-characterized roles in balancing apoptosis and cell division during organ growth control. Yki is also required in diverse tissue regenerative contexts. In most cases this requirement reflects its well-characterized roles in balancing apoptosis and cell division. Whether Yki has repair functions outside of the control of cell proliferation, death, and growth is not clear. Here we show that Yki and Scalloped (Sd) are required for epidermal wound closure in the Drosophila larval epidermis. Using a GFP-tagged Yki transgene we show that Yki transiently translocates to some epidermal nuclei upon wounding. Genetic analysis strongly suggests that Yki interacts with the known wound healing pathway, Jun N-terminal kinase (JNK), but not with Platelet Derived Growth Factor/Vascular-Endothelial Growth Factor receptor (Pvr). Yki likely acts downstream of or parallel to JNK signaling and does not appear to regulate either proliferation or apoptosis in the larval epidermis during wound repair. Analysis of actin structures after wounding suggests that Yki and Sd promote wound closure through actin regulation. In sum, we found that Yki regulates an epithelial tissue repair process independently of its previously documented roles in balancing proliferation and apoptosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Notoginsenoside Ft1 Promotes Fibroblast Proliferation via PI3K/Akt/mTOR Signaling Pathway and Benefits Wound Healing in Genetically Diabetic Mice.

    PubMed

    Zhang, Eryun; Gao, Bo; Yang, Li; Wu, Xiaojun; Wang, Zhengtao

    2016-02-01

    Wound healing requires the essential participation of fibroblasts, which is impaired in diabetic foot ulcers (DFU). Notoginsenoside Ft1 (Ft1), a saponin from Panax notoginseng, can enhance platelet aggregation by activating signaling network mediated through P2Y12 and induce proliferation, migration, and tube formation in cultured human umbilical vein endothelial cells. However, whether it can accelerate fibroblast proliferation and benefit wound healing, especially DFU, has not been elucidated. In the present study on human dermal fibroblast HDF-a, Ft1 increased cell proliferation and collagen production via PI3K/Akt/mTOR signaling pathway. On the excisional wound splinting model established on db/db diabetic mouse, topical application of Ft1 significantly shortened the wound closure time by 5.1 days in contrast with phosphate-buffered saline (PBS) treatment (15.8 versus 20.9 days). Meanwhile, Ft1 increased the rate of re-epithelialization and the amount of granulation tissue at day 7 and day 14. The molecule also enhanced mRNA expressions of COL1A1, COL3A1, transforming growth factor (TGF)-β1 and TGF-β3 and fibronectin, the genes that contributed to collagen expression, fibroblast proliferation, and consequent scar formation. Moreover, Ft1 facilitated the neovascularization accompanied with elevated vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor at either mRNA or protein levels and alleviated the inflammation of infiltrated monocytes indicated by reduced tumor necrosis factor-α and interleukin-6 mRNA expressions in the diabetic wounds. Altogether, these results indicated that Ft1 might accelerate diabetic wound healing by orchestrating multiple processes, including promoting fibroblast proliferation, enhancing angiogenesis, and attenuating inflammatory response, which provided a great potential application of it in clinics for patients with DFU. Copyright © 2016 by The American Society for Pharmacology and

  13. Activin B regulates adipose-derived mesenchymal stem cells to promote skin wound healing via activation of the MAPK signaling pathway.

    PubMed

    Zhang, Lei; Xu, Pengcheng; Wang, Xueer; Zhang, Min; Yan, Yuan; Chen, Yinghua; Zhang, Lu; Zhang, Lin

    2017-06-01

    Adipose-derived stem cells (ADSCs) are multipotent stromal cells that can differentiate into a variety of cell types, including skin cells, and they can provide an abundant source of cells for skin tissue engineering and skin wound healing. The purpose of this study is to explore the therapeutic effects of activin B in combination with ADSCs and the possible signaling mechanism. In this study, we found that activin B was able to promote ADSC migration by inducing actin stress fiber formation in vitro. In vivo, activin B in combination with ADSCs was capable of enhancing α-SMA expression and wound closure. This combined treatment also promoted fibroblast and keratinocyte proliferation and accelerated re-epithelialization and collagen deposition. Moreover, activin B in combination with ADSCs boosted angiogenesis in the wound area. Further study of the mechanism revealed that activation of JNK and ERK signaling, but not p38 signaling, were required for activin B-induced ADSC actin stress fiber formation and cell migration. These results showed that activin B was able to activate JNK and ERK signaling pathways to induce actin stress fiber formation and ADSC migration to promote wound healing. These results suggest that combined treatment with activin B and ADSCs is a promising therapeutic strategy for the management of serious skin wounds. Copyright © 2017. Published by Elsevier Ltd.

  14. Copper Metal-Organic Framework Nanoparticles Stabilized with Folic Acid Improve Wound Healing in Diabetes.

    PubMed

    Xiao, Jisheng; Zhu, Yunxiao; Huddleston, Samantha; Li, Peng; Xiao, Baixue; Farha, Omar K; Ameer, Guillermo A

    2018-02-27

    The successful treatment of chronic nonhealing wounds requires strategies that promote angiogenesis, collagen deposition, and re-epithelialization of the wound. Copper ions have been reported to stimulate angiogenesis; however, several applications of copper salts or oxides to the wound bed are required, leading to variable outcomes and raising toxicity concerns. We hypothesized that copper-based metal-organic framework nanoparticles (Cu-MOF NPs), referred to as HKUST-1, which are rapidly degraded in protein solutions, can be modified to slowly release Cu 2+ , resulting in reduced toxicity and improved wound healing rates. Folic acid was added during HKUST-1 synthesis to generate folic-acid-modified HKUST-1 (F-HKUST-1). The effect of folic acid incorporation on NP stability, size, hydrophobicity, surface area, and copper ion release profile was measured. In addition, cytotoxicity and in vitro cell migration processes due to F-HKUST-1 and HKUST-1 were evaluated. Wound closure rates were assessed using the splinted excisional dermal wound model in diabetic mice. The incorporation of folic acid into HKUST-1 enabled the slow release of copper ions, which reduced cytotoxicity and enhanced cell migration in vitro. In vivo, F-HKUST-1 induced angiogenesis, promoted collagen deposition and re-epithelialization, and increased wound closure rates. These results demonstrate that folic acid incorporation into HKUST-1 NPs is a simple, safe, and promising approach to control Cu 2+ release, thus enabling the direct application of Cu-MOF NPs to wounds.

  15. Bromelain ameliorates the wound microenvironment and improves the healing of firearm wounds.

    PubMed

    Wu, Si-Yu; Hu, Wei; Zhang, Bo; Liu, Shuai; Wang, Jian-Min; Wang, Ai-Min

    2012-08-01

    In a previous study, we proposed a new therapy using topical bromelain as a supplement to simple wound-track incision for the debridement of firearm wounds. This enzymatic debridement greatly simplified the management of high-velocity gunshot wounds in a pig model, and bromelain was confirmed to improve wound healing. The purpose of the present study was to investigate the effect of bromelain on the microenvironment of firearm wounds. Sixteen Chinese landrace pigs wounded by high-velocity projectiles were divided randomly into four groups: wound incision (group I), incision + bromelain (group IB), wound excision (group E), and control. Blood perfusion, oxygen partial pressure (pO(2)), and the content of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β in wound-track tissue were measured. Wound healing was also noted. The recovery of blood perfusion in tissue and pO(2) in wound tracks was significantly more rapid in group IB and group E than in group I and control. The tissue level of TNF-α was significantly lower in group IB than in group I and control 48 h and 72 h post-wounding, and was lower than in group E 48 h post-wounding. The tissue level of TGF-β in group IB was sustained at a significantly higher level than in the other three groups. Wound healing time was also shorter in group IB. Enzymatic debridement using topical bromelain in incised wound tracks accelerates the recovery of blood perfusion, pO(2) in wound tissue, controls the expression of TNF-α and raises the expression of TGF-β. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. [The primary closure approach of dog bite injuries of the nose].

    PubMed

    Zieliński, Tomasz

    2010-01-01

    Biting of humans by domestic animals, especially by dogs, is common injury which causes suffering and pain, might be a cause of disability or even death. It is associated with high risk of bacterial infection of the wounds or even transfection of rabies virus. Bites are usually to the upper and lower limbs, while the face is third in a raw localization of bites. Within the face, the nose and lips are injured the most often. The goal of this paper is presentation selected methods and obtained results of primary closure of dog bite injures of the nose. There were 16 patients with dog bites injures of the nose treated in the Department of Plastic, Reconstructive and Aesthetic Surgery of the Medical University of Łódź in the years 2003-2008. The patients were 11 to 46 years old. Bites caused either superficial laceration of the skin, tearing of the nostril wing or even major defects of the tissues. In 7 patients superficial wounds a direct closure was done and antibiotic ointment was applied. In 7 patients a defect of the skin was covered with a skin graft taken from retroauricular area, but in 2 of the patients of this group repair of mucosa and alar cartilage was done. In two persons with full thickness defects of the nose reconstruction was performed with the use of a pedicled nosolabial flap. Complications occurred only in 1 patient who developed infection in the wound. In all other patients there were no complications. Good aesthetic results were obtained. Primary closure approach of bite injures with tissue defect is not associated with larger risk than in the case in secondary such approach, and should be implemented always whenever it is possible in order to avoid risk of wound and scars which require further reconstructive procedures in future.

  17. Fluorescence imaging of tryptophan and collagen cross-links to evaluate wound closure ex vivo

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Ortega-Martinez, Antonio; Farinelli, Bill; Anderson, R. R.; Franco, Walfre

    2016-02-01

    Wound size is a key parameter in monitoring healing. Current methods to measure wound size are often subjective, time-consuming and marginally invasive. Recently, we developed a non-invasive, non-contact, fast and simple but robust fluorescence imaging (u-FEI) method to monitor the healing of skin wounds. This method exploits the fluorescence of native molecules to tissue as functional and structural markers. The objective of the present study is to demonstrate the feasibility of using variations in the fluorescence intensity of tryptophan and cross-links of collagen to evaluate proliferation of keratinocyte cells and quantitate size of wound during healing, respectively. Circular dermal wounds were created in ex vivo human skin and cultured in different media. Two serial fluorescence images of tryptophan and collagen cross-links were acquired every two days. Histology and immunohistology were used to validate correlation between fluorescence and epithelialization. Images of collagen cross-links show fluorescence of the exposed dermis and, hence, are a measure of wound area. Images of tryptophan show higher fluorescence intensity of proliferating keratinocytes forming new epithelium, as compared to surrounding keratinocytes not involved in epithelialization. These images are complementary since collagen cross-links report on structure while tryptophan reports on function. HE and immunohistology show that tryptophan fluorescence correlates with newly formed epidermis. We have established a fluorescence imaging method for studying epithelialization processes during wound healing in a skin organ culture model, our approach has the potential to provide a non-invasive, non-contact, quick, objective and direct method for quantitative measurements in wound healing in vivo.

  18. Acceleration of skin wound healing by low-dose indirect ionizing radiation in male rats.

    PubMed

    Jabbari, Nasrollah; Farjah, Gholam Hossein; Ghadimi, Behnam; Zanjani, Hajar; Heshmatian, Behnam

    2017-08-01

    A recent hypothesis has revealed that low-dose irradiation (LDI) with ionizing radiation might have a promoting effect on fracture healing. The aim of this study was to investigate the influence of direct (electron beam) and indirect (gamma-ray) low-dose ionizing irradiations on the wound healing process in male rats. In 72 male rats, a full-thickness wound was incised. The animals were randomly assigned to three groups, each with 24 rats. The first two groups were named IG-I and IG-II and respectively exposed to electron and gamma-radiations (75 cGy) immediately after the surgical procedure. The third group was considered as the control (CG) and remained untreated. Skin biopsies from the subgroups were collected on days 3, 7, 15, and 21 after the operation and evaluated using histological and biomechanical methods. Data were analyzed by one-way ANOVA, followed by Tukey's post hoc test using SPSS 20 software. Histological studies of tissues showed that the mean number of fibroblasts, macrophages, blood vessel sections, and neutrophils on the third and seventh days after the surgery in the gamma-treated group was higher than that in both other groups. In contrast, on day 21, the mean number of mentioned cells in the gamma-treated group was lower than in the other two groups. In addition, the mean maximum stress value was significantly greater in the gamma-treated group. Results of this study showed that gamma-ray irradiation is effective in the acceleration of wound healing. Copyright © 2017. Published by Elsevier Taiwan.

  19. Evaluation of human amniotic membrane as a wound dressing for split-thickness skin-graft donor sites.

    PubMed

    Loeffelbein, Denys J; Rohleder, Nils H; Eddicks, Matthias; Baumann, Claudia M; Stoeckelhuber, Mechthild; Wolff, Klaus-D; Drecoll, Enken; Steinstraesser, Lars; Hennerbichler, Simone; Kesting, Marco R

    2014-01-01

    Human amniotic membrane (HAM) has been used as a biomaterial in various surgical procedures and exceeds some qualities of common materials. We evaluated HAM as wound dressing for split-thickness skin-graft (STSG) donor sites in a swine model (Part A) and a clinical trial (Part B). Part A: STSG donor sites in 4 piglets were treated with HAM or a clinically used conventional polyurethane (PU) foil (n = 8 each). Biopsies were taken on days 5, 7, 10, 20, 40, and 60 and investigated immunohistochemically for alpha-smooth muscle actin (αSMA: wound contraction marker), von Willebrand factor (vWF: angiogenesis), Ki-67 (cell proliferation), and laminin (basement membrane integrity). Part B: STSG donor sites in 45 adult patients (16 female/29 male) were treated with HAM covered by PU foam, solely by PU foam, or PU foil/paraffin gauze (n = 15 each). Part A revealed no difference in the rate of wound closure between groups. HAM showed improved esthetic results and inhibitory effects on cicatrization. Angioneogenesis was reduced, and basement membrane formation was accelerated in HAM group. Part B: no difference in re-epithelialization/infection rate was found. HAM caused less ichor exudation and less pruritus. HAM has no relevant advantage over conventional dressings but might be a cost-effective alternative.

  20. Osthole confers neuroprotection against cortical stab wound injury and attenuates secondary brain injury.

    PubMed

    Xia, Yang; Kong, Liang; Yao, Yingjia; Jiao, Yanan; Song, Jie; Tao, Zhenyu; You, Zhong; Yang, Jingxian

    2015-09-04

    Neuroendoscopy is an innovative technique for neurosurgery that can nonetheless result in traumatic brain injury. The accompanying neuroinflammation may lead to secondary tissue damage, which is the major cause of delayed neuronal death after surgery. The present study investigated the capacity of osthole to prevent secondary brain injury and the underlying mechanism of action in a mouse model of stab wound injury. A mouse model of cortical stab wound injury was established by inserting a needle into the cerebral cortex for 20 min to mimic neuroendoscopy. Mice received an intraperitoneal injection of osthole 30 min after surgery and continued for 14 days. Neurological severity was evaluated 12 h and up to 21 days after the trauma. Brains were collected 3-21 days post-injury for histological analysis, immunocytochemistry, quantitative real-time PCR, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and enzyme-linked immunosorbent assays. Neurological function improved in mice treated with osthole and was accompanied by reduced brain water content and accelerated wound closure relative to untreated mice. Osthole treatment reduced the number of macrophages/microglia and peripheral infiltrating of neutrophils and lowered the level of the proinflammatory cytokines interleukin-6 and tumor necrosis factor α in the lesioned cortex. Osthole-treated mice had fewer TUNEL+ apoptotic neurons surrounding the lesion than controls, indicating increased neuronal survival. Osthole reduced secondary brain damage by suppressing inflammation and apoptosis in a mouse model of stab wound injury. These results suggest a new strategy for promoting neuronal survival and function after neurosurgery to improve long-term patient outcome.

  1. Factors influencing wound dehiscence.

    PubMed

    Riou, J P; Cohen, J R; Johnson, H

    1992-03-01

    Thirty-one abdominal fascial wound dehiscences occurred in 2,761 patients undergoing major abdominal surgery during a 5-year period (1%). Twenty-two specific local and systemic risk factors were analyzed and compared with the risk factors of a control group of 38 patients undergoing similar procedures without dehiscence. Through multivariate analysis, each factor was assessed as an independent statistical variable. Significant factors (p less than 0.05) were found to include age over 65, wound infection, pulmonary disease, hemodynamic instability, and ostomies in the incision. Additional systemic risk factors that were found to be significant included hypoproteinemia, systemic infection, obesity, uremia, hyperalimentation, malignancy, ascites, steroid use, and hypertension. Risk factors not found to be important independent variables included sex, type of incision, type of closure, foreign body in the wound, anemia, jaundice, and diabetes. When dehiscence and control groups were combined, 30% of patients with at least five significant risk factors developed dehiscence, and all the patients with more than eight risk factors developed a wound dehiscence. There was an overall mortality of 29%, which was directly related to the number of significant risk factors. The co-existence of 9 risk factors portended death in one third of the patients, and all the patients with more than 10 risk factors died.

  2. Nutrition in Wound Care Management: A Comprehensive Overview.

    PubMed

    Quain, Angela M; Khardori, Nancy M

    2015-12-01

    Wound care is a multidisciplinary specialty requiring many physiologic and immunologic processes as well as physical, social, and societal factors to achieve successful wound closure. Most wounds are treated with combinations of antimicrobials, protective barriers, and topical growth agents, including skin and biologic grafts.The role of nutrition in wound healing may be overlooked in the wound care patient. Like the specialty, it is often multifaceted, with many nutritional components playing a variety of roles in the wound healing process. Suboptimal nutrition can alter immune function, collagen synthesis, and wound tensile strength, all of which are essential in the wound healing process. It is also important to remember that not all wounds are equal: a burn is different from a diabetic foot ulcer, which is different from a pressure ulcer. Nonetheless, nutrition is a common denominator for all wound patients, and what is studied in 1 wound population is often relevant in another. Due to the complexities of monitoring and measuring both wound healing and dietary intake, randomized, controlled trials of wound care patients are difficult to conduct, and much of the data concerning nutrition in wound care relies on combined supplements. In summary, it appears that some nutrients are necessary only if deficient, whereas others may become conditionally essential and serve a therapeutic role. All of the nutrients discussed should be viewed as a component of a broader, complete diet. This article is a summary of wound healing and the roles of a variety of macronutrients and micronutrients in the process.

  3. Accelerated wound healing of oral soft tissues and angiogenic effect induced by a pool of aminoacids combined to sodium hyaluronate (AMINOGAM).

    PubMed

    Favia, G; Mariggio, M A; Maiorano, F; Cassano, A; Capodiferro, S; Ribatti, D

    2008-01-01

    In this study we investigated the property of a new medical substance, in the form of a gel compound containing four aminoacids (glycine, leucine, proline, lysine) and sodium hyaluronate (AMINOGAM), to accelerate the wound healing process of the soft oral tissues and to promote angiogenesis in vivo in the vascular proliferation in chick embryo chorioallantoic membrane (CAM) assay. Furthermore, we investigated the capacity of AMINOGAM to induce the expression of an angiogenic cytokine, namely vascular endothelial growth factor (VEGF) in human fibroblasts in vitro. Results showed that AMINOGAM promoted wound healing in post-surgical wounds (after teeth extraction, oral laser surgery with secondary healing without direct suture of the surgical wound, and after dental implant insertion). Stimulated angiogenesis in vivo in the CAM assay and the response was similar to that obtained with vascular endothelial growth factor, a well-known angiogenic cytokine, tested in the same assay, and confirmed by clinical outcomes, which showed reduction of the healing time of oral soft tissues after three different kinds of surgery and also the absence of post-operative infections.

  4. Curcuma purpurascens BI. rhizome accelerates rat excisional wound healing: involvement of Hsp70/Bax proteins, antioxidant defense, and angiogenesis activity

    PubMed Central

    Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Hajiaghaalipour, Fatemeh; Zahedifard, Maryam; Tayeby, Faezeh; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

    2015-01-01

    Purpose Curcuma purpurascens BI. is a member of Zingiberaceae family. The purpose of this study is to investigate the wound healing properties of hexane extract of C. purpurascens rhizome (HECP) against excisional wound healing in rats. Materials and methods Twenty four rats were randomly divided into 4 groups: A) negative control (blank placebo, acacia gum), B) low dose of HECP, C) high dose of HECP, and D) positive control, with 6 rats in each group. Full-thickness incisions (approximately 2.00 cm) were made on the neck area of each rat. Groups 1–4 were treated two-times a day for 20 days with blank placebo, HECP (100 mg/kg), HECP (200 mg/kg), and intrasite gel as a positive control, respectively. After 20 days, hematoxylin and eosin and Masson’s trichrome stainings were employed to investigate the histopathological alterations. Protein expressions of Bax and Hsp70 were examined in the wound tissues using immunohistochemistry analysis. In addition, levels of enzymatic antioxidants and malondialdehyde representing lipid peroxidation were measured in wound tissue homogenates. Results Macroscopic evaluation of wounds showed conspicuous elevation in wound contraction after topical administration of HECP at both doses. Moreover, histopathological analysis revealed noteworthy reduction in the scar width correlated with the enhanced collagen content and fibroblast cells, accompanied by a reduction of inflammatory cells in the granulation tissues. At the molecular level, HECP facilitates wound-healing process by downregulating Bax and upregulating Hsp70 protein at the wound site. The formation of new blood vessel was observed in Masson’s trichrome staining of wounds treated with HECP (100 and 200 mg/kg). In addition, HECP administration caused a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation. Conclusion These findings suggested that HECP accelerated wound-healing process in rats via antioxidant activity, angiogenesis

  5. Hydrogen-Rich Water Intake Accelerates Oral Palatal Wound Healing via Activation of the Nrf2/Antioxidant Defense Pathways in a Rat Model

    PubMed Central

    Orihuela-Campos, Rita Cristina; Fukui, Makoto; Ito, Hiro-O

    2016-01-01

    The wound healing process attempts to restore the integrity and function of the injured tissue. Additionally, proinflammatory cytokines, growth factors, and oxidative stress play important roles in wound healing. The aim of this study was to determine whether hydrogen-rich water intake induces the activation of the Nrf2/antioxidant defense pathway in rat palatal tissue, thereby reducing systemic oxidative stress and proinflammatory cytokine levels and promoting healing-associated genes. A circular excisional wound was created in the oral palatal region, and the wound healing process was observed. The rats were divided into two experimental groups in which either hydrogen-rich water or distilled water was consumed. In the drinking hydrogen-rich water, the palatal wound healing process was accelerated compared to that in the control group. As molecular hydrogen upregulated the Nrf2 pathway, systemic oxidative stresses were decreased by the activation of antioxidant activity. Furthermore, hydrogen-rich water intake reduced proinflammatory cytokine levels and promoted the expression of healing-associated factors in rat palatal tissue. In conclusion, hydrogen-rich water intake exhibited multiple beneficial effects through activation of the Nrf2/antioxidant defense pathway. The results of this study support the hypothesis that oral administration of hydrogen-rich water benefits the wound healing process by decreasing oxidative stress and inflammatory responses. PMID:26798423

  6. Hydrogen-Rich Water Intake Accelerates Oral Palatal Wound Healing via Activation of the Nrf2/Antioxidant Defense Pathways in a Rat Model.

    PubMed

    Tamaki, Naofumi; Orihuela-Campos, Rita Cristina; Fukui, Makoto; Ito, Hiro-O

    2016-01-01

    The wound healing process attempts to restore the integrity and function of the injured tissue. Additionally, proinflammatory cytokines, growth factors, and oxidative stress play important roles in wound healing. The aim of this study was to determine whether hydrogen-rich water intake induces the activation of the Nrf2/antioxidant defense pathway in rat palatal tissue, thereby reducing systemic oxidative stress and proinflammatory cytokine levels and promoting healing-associated genes. A circular excisional wound was created in the oral palatal region, and the wound healing process was observed. The rats were divided into two experimental groups in which either hydrogen-rich water or distilled water was consumed. In the drinking hydrogen-rich water, the palatal wound healing process was accelerated compared to that in the control group. As molecular hydrogen upregulated the Nrf2 pathway, systemic oxidative stresses were decreased by the activation of antioxidant activity. Furthermore, hydrogen-rich water intake reduced proinflammatory cytokine levels and promoted the expression of healing-associated factors in rat palatal tissue. In conclusion, hydrogen-rich water intake exhibited multiple beneficial effects through activation of the Nrf2/antioxidant defense pathway. The results of this study support the hypothesis that oral administration of hydrogen-rich water benefits the wound healing process by decreasing oxidative stress and inflammatory responses.

  7. Enhancement of Wound Healing by Non-Thermal N2/Ar Micro-Plasma Exposure in Mice with Fractional-CO2-Laser-Induced Wounds.

    PubMed

    Shao, Pei-Lin; Liao, Jiunn-Der; Wong, Tak-Wah; Wang, Yi-Cheng; Leu, Steve; Yip, Hon-Kan

    2016-01-01

    Micro-plasma is a possible alternative treatment for wound management. The effect of micro-plasma on wound healing depends on its composition and temperature. The authors previously developed a capillary-tube-based micro-plasma system that can generate micro-plasma with a high nitric oxide-containing species composition and mild working temperature. Here, the efficacy of micro-plasma treatment on wound healing in a laser-induced skin wound mouse model was investigated. A partial thickness wound was created in the back skin of each mouse and then treated with micro-plasma. Non-invasive methods, namely wound closure kinetics, optical coherence tomography (OCT), and laser Doppler scanning, were used to measure the healing efficiency in the wound area. Neo-tissue growth and the expressions of matrix metallopeptidase-3 (MMP-3) and laminin in the wound area were assessed using histological and immunohistochemistry (IHC) analysis. The results show that micro-plasma treatment promoted wound healing. Micro-plasma treatment significantly reduced the wound bed region. The OCT images and histological analysis indicates more pronounced tissue regrowth in the wound bed region after micro-plasma treatment. The laser Doppler images shows that micro-plasma treatment promoted blood flow in the wound bed region. The IHC results show that the level of laminin increased in the wound bed region after micro-plasma treatment, whereas the level of MMP-3 decreased. Based on these results, micro-plasma has potential to be used to promote the healing of skin wounds clinically.

  8. Enhancement of Wound Healing by Non-Thermal N2/Ar Micro-Plasma Exposure in Mice with Fractional-CO2-Laser-Induced Wounds

    PubMed Central

    Shao, Pei-Lin; Liao, Jiunn-Der; Wong, Tak-Wah; Wang, Yi-Cheng; Leu, Steve; Yip, Hon-Kan

    2016-01-01

    Micro-plasma is a possible alternative treatment for wound management. The effect of micro-plasma on wound healing depends on its composition and temperature. The authors previously developed a capillary-tube-based micro-plasma system that can generate micro-plasma with a high nitric oxide-containing species composition and mild working temperature. Here, the efficacy of micro-plasma treatment on wound healing in a laser-induced skin wound mouse model was investigated. A partial thickness wound was created in the back skin of each mouse and then treated with micro-plasma. Non-invasive methods, namely wound closure kinetics, optical coherence tomography (OCT), and laser Doppler scanning, were used to measure the healing efficiency in the wound area. Neo-tissue growth and the expressions of matrix metallopeptidase-3 (MMP-3) and laminin in the wound area were assessed using histological and immunohistochemistry (IHC) analysis. The results show that micro-plasma treatment promoted wound healing. Micro-plasma treatment significantly reduced the wound bed region. The OCT images and histological analysis indicates more pronounced tissue regrowth in the wound bed region after micro-plasma treatment. The laser Doppler images shows that micro-plasma treatment promoted blood flow in the wound bed region. The IHC results show that the level of laminin increased in the wound bed region after micro-plasma treatment, whereas the level of MMP-3 decreased. Based on these results, micro-plasma has potential to be used to promote the healing of skin wounds clinically. PMID:27248979

  9. The Electrical Response to Injury: Molecular Mechanisms and Wound Healing

    PubMed Central

    Reid, Brian; Zhao, Min

    2014-01-01

    Significance: Natural, endogenous electric fields (EFs) and currents arise spontaneously after wounding of many tissues, especially epithelia, and are necessary for normal healing. This wound electrical activity is a long-lasting and regulated response. Enhancing or inhibiting this electrical activity increases or decreases wound healing, respectively. Cells that are responsible for wound closure such as corneal epithelial cells or skin keratinocytes migrate directionally in EFs of physiological magnitude. However, the mechanisms of how the wound electrical response is initiated and regulated remain unclear. Recent Advances: Wound EFs and currents appear to arise by ion channel up-regulation and redistribution, which are perhaps triggered by an intracellular calcium wave or cell depolarization. We discuss the possibility of stimulation of wound healing via pharmacological enhancement of the wound electric signal by stimulation of ion pumping. Critical Issues: Chronic wounds are a major problem in the elderly and diabetic patient. Any strategy to stimulate wound healing in these patients is desirable. Applying electrical stimulation directly is problematic, but pharmacological enhancement of the wound signal may be a promising strategy. Future Directions: Understanding the molecular regulation of wound electric signals may reveal some fundamental mechanisms in wound healing. Manipulating fluxes of ions and electric currents at wounds might offer new approaches to achieve better wound healing and to heal chronic wounds. PMID:24761358

  10. New Guar Biopolymer Silver Nanocomposites for Wound Healing Applications

    PubMed Central

    Abdullah, Md Farooque; Das, Suvadra; Roy, Partha; Datta, Sriparna; Mukherjee, Arup

    2013-01-01

    Wound healing is an innate physiological response that helps restore cellular and anatomic continuity of a tissue. Selective biodegradable and biocompatible polymer materials have provided useful scaffolds for wound healing and assisted cellular messaging. In the present study, guar gum, a polymeric galactomannan, was intrinsically modified to a new cationic biopolymer guar gum alkylamine (GGAA) for wound healing applications. Biologically synthesized silver nanoparticles (Agnp) were further impregnated in GGAA for extended evaluations in punch wound models in rodents. SEM studies showed silver nanoparticles well dispersed in the new guar matrix with a particle size of ~18 nm. In wound healing experiments, faster healing and improved cosmetic appearance were observed in the new nanobiomaterial treated group compared to commercially available silver alginate cream. The total protein, DNA, and hydroxyproline contents of the wound tissues were also significantly higher in the treated group as compared with the silver alginate cream (P < 0.05). Silver nanoparticles exerted positive effects because of their antimicrobial properties. The nanobiomaterial was observed to promote wound closure by inducing proliferation and migration of the keratinocytes at the wound site. The derivatized guar gum matrix additionally provided a hydrated surface necessary for cell proliferation. PMID:24175306

  11. New guar biopolymer silver nanocomposites for wound healing applications.

    PubMed

    Ghosh Auddy, Runa; Abdullah, Md Farooque; Das, Suvadra; Roy, Partha; Datta, Sriparna; Mukherjee, Arup

    2013-01-01

    Wound healing is an innate physiological response that helps restore cellular and anatomic continuity of a tissue. Selective biodegradable and biocompatible polymer materials have provided useful scaffolds for wound healing and assisted cellular messaging. In the present study, guar gum, a polymeric galactomannan, was intrinsically modified to a new cationic biopolymer guar gum alkylamine (GGAA) for wound healing applications. Biologically synthesized silver nanoparticles (Agnp) were further impregnated in GGAA for extended evaluations in punch wound models in rodents. SEM studies showed silver nanoparticles well dispersed in the new guar matrix with a particle size of ~18 nm. In wound healing experiments, faster healing and improved cosmetic appearance were observed in the new nanobiomaterial treated group compared to commercially available silver alginate cream. The total protein, DNA, and hydroxyproline contents of the wound tissues were also significantly higher in the treated group as compared with the silver alginate cream (P < 0.05). Silver nanoparticles exerted positive effects because of their antimicrobial properties. The nanobiomaterial was observed to promote wound closure by inducing proliferation and migration of the keratinocytes at the wound site. The derivatized guar gum matrix additionally provided a hydrated surface necessary for cell proliferation.

  12. The utility of midtrimester ultrasound assessment of the subcutaneous space in predicting cesarean wound complications

    PubMed Central

    Shainker, Scott A.; Raghuraman, Nandini; Modest, Anna M.; Schnettler, William T.; Hacker, Michele R.; Ralston, Steven J.

    2016-01-01

    Objective To evaluate the association between cesarean wound complications and thickness of the subcutaneous space within the anterior abdomen at the midtrimester fetal anatomical survey. Methods In this case-control study, cases were identified using an ICD9 code for wound complications of cesarean delivery. For each case, we identified the woman with the next consecutive midtrimester ultrasound who had a cesarean delivery without a wound complication, matched on age and race, as the control. A blinded investigator measured subcutaneous space at three distinct suprapubic levels in the midsagital plane. Results Of 7228 women with a cesarean delivery, 123 (1.7%) had a wound complication. Seventy-nine cases were eligible. Midline suprapubic subcutaneous thickness did not differ between cases and controls at the superior, middle or inferior locations (p ≥ 0.35). Body mass index was moderately correlated with ultrasound-derived measurements (r≥ 0.63; p<0.001). The incidence of vertical skin incision, stapled skin closure and classical hysterotomy differed between groups (p≤ 0.046). There was no significant increase in wound complication risk with increasing subcutaneous space thickness, even after adjustment (p≥ 0.34). Conclusion Prenatal ultrasound can quantify the subcutaneous space. Vertical skin incision, stapled wound closure, and a classical hysterotomy were associated with cesarean wound complication, but midtrimester subcutaneous thickness was not. PMID:25302863

  13. Novel nitric oxide producing probiotic wound healing patch: preparation and in vivo analysis in a New Zealand white rabbit model of ischaemic and infected wounds.

    PubMed

    Jones, Mitchell; Ganopolsky, Jorge G; Labbé, Alain; Gilardino, Mirko; Wahl, Christopher; Martoni, Christopher; Prakash, Satya

    2012-06-01

    The treatment of chronic wounds poses a significant challenge for clinicians and patients alike. Here we report design and preclinical efficacy of a novel nitric oxide gas (gNO)-producing probiotic patch for wound healing. Specifically, a wound healing patch using lactic acid bacteria in an adhesive gas permeable membrane has been designed and investigated for treating ischaemic and infected full-thickness dermal wounds in a New Zealand white rabbit model for ischaemic wound healing. Kaplan-Meier survival curves showed increased wound closure with gNO-producing patch-treated wounds over 21 days of therapy (log-rank P = 0·0225 and Wilcoxon P = 0·0113). Cox proportional hazard regression showed that gNO-producing patch-treated wounds were 2·52 times more likely to close compared with control patches (hazard P = 0·0375, score P = 0·032 and likelihood ratio P = 0·0355), and histological analysis showed improved wound healing in gNO-producing patch-treated animals. This study may provide an effective, safe and less costly alternative for treating chronic wounds. © 2012 The Authors. © 2012 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

  14. Novel Multivalent Wound-Healing Ointment Provides Bioburden Control and Moisture Management: A Retrospective Registry Data Analysis.

    PubMed

    Serena, Thomas; Connell, Heather; McConnell, Sharon; Patel, Keyur; Doner, Bryan; Sabo, Matthew; Miller, Michael; Serena, Laura; Le, Lam T; Goldsmith, David; Chung, Jane

    2016-10-01

    The purpose of this retrospective registry data analysis was to explore the effectiveness of a novel multivalent topical ointment (Terrasil Infection Control Wound Care Ointment; Aspiera Medical, Woonsocket, Rhode Island), containing a patented mineral complex and 0.2% benzethonium chloride in the treatment of nonhealing acute and chronic wounds. Aspiera Medical designed a registry to capture physician experiences and treatment results with Terrasil Infection Control Wound Care Ointment. Physicians were asked to enter deidentified patient data into an online registry. Wound clinics in the United States were asked to participate in the registry. Physicians at 4 wound clinics treated 30 patients (26 of whom completed the treatment) with various chronic wounds that had persisted for an average of 6 months and entered treatment data into the registry. Patients applied the ointment according to physician orders. Concurrent treatments used by patients included offloading, compression wraps, and dressings, such as collagen and calcium alginate. Patients were treated until complete wound closure or lost to follow-up. Physicians calculated each patient's percentage wound reduction at each visit. Thirty patients were entered into the registry. Pretreatment and posttreatment measurements were available for 26 of them. Patients achieved an average surface area reduction of 84% in a mean of 23 days' treatment. The antimicrobial and moisturizing ointment studied appears to be effective in promoting wound closure in a variety of acute and chronic wounds. Wounds studied included diabetic foot ulcers, venous leg ulcers, venous stasis ulcers, surgical infections, burns, and insect bites. The results of this registry data analysis will be used to inform planned clinical trials.

  15. Response of beech and oaks to wounds made at different times of the year

    Treesearch

    Dirk Dujesiefken; Walter Liese; Walter Shortle; Rakesh Minocha

    2005-01-01

    Tree care, expecially pruning, is still mostly done in the dormant time. Such treatments expose live inner bark, the vascular cambium, and functioning outer sapwood to harsh external influences followed often by infection of pathogens. Investigations about response reactions of beech and oak to wounding made in different times of the year showed that wound closure was...

  16. Peptide-modified chitosan hydrogels promote skin wound healing by enhancing wound angiogenesis and inhibiting inflammation

    PubMed Central

    Chen, Xionglin; Zhang, Min; Wang, Xueer; Chen, Yinghua; Yan, Yuan; Zhang, Lu; Zhang, Lin

    2017-01-01

    Cutaneous wound healing following trauma is a complex and dynamic process involving multiple overlapping events following trauma. Two critical elements affecting skin wound healing are neovascularization and inflammation. A nascent vessel can provide nutrition and oxygen to a healing wound. Therefore, treatments strategies that enhance angiogenesis and inhibit inflammation can promote skin wound healing. Previous studies have shown that the SIKVAV peptide (Ser-Ile-Lys-Val-Ala-Val) from laminin can promote angiogenesis in vitro. This study evaluated the effects of peptide SIKVAV-modified chitosan hydrogels on skin wound healing. We established skin wounds established in mice and treated them with SIKVAV-modified chitosan hydrogels. H&E staining showed that peptide-modified chitosan hydrogels accelerated the reepithelialization of wounds compared with the negative and positive controls. Immunohistochemistry analysis demonstrated that more myofibroblasts were deposited at wounds treated with peptide-modified chitosan hydrogels that at those treated with negative and positive controls. In addition, peptide-modified chitosan hydrogels promoted angiogenesis as well as keratinocyte proliferation and differentiation, but inhibited inflammation in skin wounds. Taken together, these results suggest that SIKVAV-modified chitosan hydrogels are a promising treatment component for healing-impaired wounds. PMID:28559985

  17. The Golden Spiral Flap: A New Flap Design that Allows for Closure of Larger Wounds under Reduced Tension – How Studying Nature’s Own Design Led to the Development of a New Surgical Technique

    PubMed Central

    Paul, Sharad P.

    2016-01-01

    This paper details the study of biodynamic excisional skin tension lines on the scalp and the development of a new flap technique for closure of scalp wounds. Recently, a study by this author, on pigskin, replicated whorls by placing tissue under rapid stretch using saline tissue expanders, by recreating rapid dermo-epidermal shear of skin – thereby concluding that the golden spiral pattern is nature’s own pattern for rapid expansion. Given the relationship between tissue expansion and stretch has been shown to cause deformation gradients that have both elastic and growth factors, the author set out to test the hypothesis that a golden spiral pattern therefore would be more efficient at closing wounds under less tension when compared with standard semicircular rotational flap patterns. The author conducted a series of experiments, both on pigskin (to first confirm the hypothesis, using a recently developed computerized tensiometer) and later a clinical study. This paper presents a new random pivotal flap technique for skin closures on the head and neck: the golden spiral flap. Biomechanics, planning, and advantages of this new flap are described in this paper. PMID:27900320

  18. Contributions of ocular surface components to matrix-metalloproteinases (MMP)-2 and MMP-9 in feline tears following corneal epithelial wounding.

    PubMed

    Petznick, Andrea; Madigan, Michele C; Garrett, Qian; Sweeney, Deborah F; Evans, Margaret D M

    2013-01-01

    This study investigated ocular surface components that contribute to matrix-metalloproteinase (MMP)-2 and MMP-9 found in tears following corneal epithelial wounding. Laboratory short-haired cats underwent corneal epithelial debridement in one randomly chosen eye (n = 18). Eye-flush tears were collected at baseline and during various healing stages. Procedural control eyes (identical experimental protocol as wounded eyes except for wounding, n = 5) served as controls for tear analysis. MMP activity was analyzed in tears using gelatin zymography. MMP staining patterns were evaluated in ocular tissues using immunohistochemistry and used to determine MMP expression sites responsible for tear-derived MMPs. The proMMP-2 and proMMP-9 activity in tears was highest in wounded and procedural control eyes during epithelial migration (8 to 36 hours post-wounding). Wounded eyes showed significantly higher proMMP-9 in tears only during and after epithelial restratification (day 3 to 4 and day 7 to 28 post-wounding, respectively) as compared to procedural controls (p<0.05). Tears from wounded and procedural control eyes showed no statistical differences for pro-MMP-2 and MMP-9 (p>0.05). Immunohistochemistry showed increased MMP-2 and MMP-9 expression in the cornea during epithelial migration and wound closure. The conjunctival epithelium exhibited highest levels of both MMPs during wound closure, while MMP-9 expression was reduced in conjunctival goblet cells during corneal epithelial migration followed by complete absence of the cells during wound closure. The immunostaining for both MMPs was elevated in the lacrimal gland during corneal healing, with little/no change in the meibomian glands. Conjunctival-associated lymphoid tissue (CALT) showed weak MMP-2 and intense MMP-9 staining. Following wounding, migrating corneal epithelium contributed little to the observed MMP levels in tears. The major sources assessed in the present study for tear-derived MMP-2 and MMP-9

  19. The Four-Herb Chinese Medicine Formula Tuo-Li-Xiao-Du-San Accelerates Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats through Reducing Inflammation and Increasing Angiogenesis

    PubMed Central

    Zhang, Xiao-na; Ma, Ze-jun; Wang, Ying; Li, Yu-zhu; Sun, Bei; Guo, Xin; Pan, Cong-qing; Chen, Li-ming

    2016-01-01

    Impaired wound healing in diabetic patients is a serious complication that often leads to amputation or even death with limited effective treatments. Tuo-Li-Xiao-Du-San (TLXDS), a traditional Chinese medicine formula for refractory wounds, has been prescribed for nearly 400 years in China and shows good efficacy in promoting healing. In this study, we explored the effect of TLXDS on healing of diabetic wounds and investigated underlying mechanisms. Four weeks after intravenous injection of streptozotocin, two full-thickness excisional wounds were created with a 10 mm diameter sterile biopsy punch on the back of rats. The ethanol extract of TLXDS was given once daily by oral gavage. Wound area, histological change, inflammation, angiogenesis, and collagen synthesis were evaluated. TLXDS treatment significantly accelerated healing of diabetic rats and improved the healing quality. These effects were associated with reduced neutrophil infiltration and macrophage accumulation, enhanced angiogenesis, and increased collagen deposition. This study shows that TLXDS improves diabetes-impaired wound healing. PMID:27057551

  20. Closure of skin incisions in rabbits by laser soldering II: Tensile strength.

    PubMed

    Brosh, Tamar; Simhon, David; Halpern, Marisa; Ravid, Avi; Vasilyev, Tamar; Kariv, Naam; Nevo, Zvi; Katzir, Abraham

    2004-01-01

    The basic characteristic property of wound closure is the immediate and long-term tensile strength (LTS). The objective of the current study was to compare tissue laser soldering to other available methods (i.e., cyanoacrylate glues and sutures) in the performance and outcome of wound closure and reparative healing process, with an emphasis on the immediate and LTS. The animals were divided into three groups according to the type and details of the closure procedure. Group A: laser treatments at different temperatures were compared to sutured incisions, emphasizing the LTS after 10 days. Group B: laser soldering at 65 +/- 5 degrees C was compared to chemical glues (i.e., Histoacryl and Dermabond), emphasizing the immediate tensile strength (ITS). Group C: LTS of laser soldered incisions was compared to that of sutured incisions at various time intervals emphasizing LTS (3, 7, 14, 28 days). Group A: LTS at 60 degrees C exhibited the highest values (0.48 MPa). Group B: no ITS difference was detected between laser soldering and chemical glues. Group C: soldered incisions at 65 degrees C exhibited higher LTS (1.81 MPa) than that of sutured incisions (1.08 MPa) (P < 0.043). Temperature-controlled laser soldering at 65 degrees C provided sufficient ITS and higher bonding LTS values compared with sutures, resulting in better wound healing characteristics. The laser soldering system presented here should be tested on larger animal models before adopting it for clinical usage.

  1. Inheritance of compartmentalization of wounds in sweetgum (Liquidambar styraciflua L.) and eastern cottonwood (Populus deltoides Bartr.)

    Treesearch

    P. W. Garrett; W. K. Randall; A. L. Shigo; W. C. Shortle

    1979-01-01

    Studies of half-sib progeny tests of sweetgum (Liquidambar styraciflua) and clonal plantings of eastern cottonwood (Populus deltoides) in Mississippi indicate that rate of wound closure and size of discolored columns associated with the wounds are both heritable traits. Both are independent of stem diameter, which was used as a...

  2. Effects of Epidermal Growth Factor-Loaded Mucoadhesive Films on Wounded Oral Tissue Rafts

    PubMed Central

    Ramineni, Sandeep K.; Fowler, Craig B.; Fisher, Paul D.; Cunningham, Larry L.; Puleo, David A.

    2015-01-01

    Current treatments for traumatic oral mucosal wounds include the gold standard of autologous tissue and alternative tissue engineered grafts. While use of autografts has disadvantages of minimal availability of oral keratinized tissue, second surgery, and donor site discomfort, tissue engineered grafts are limited by their unavailability as off-the-shelf products owing to their fabrication time of 4–8 weeks. Hence, the current work aimed to develop a potentially cost-effective, readily available device capable of enhancing native mucosal regeneration. Considering the key role of epidermal growth factor (EGF) in promoting mucosal wound regeneration and the advantages of mucoadhesive delivery systems, mucoadhesive films composed of polyvinylpyrrolidone and carboxymethylcellulose were developed to provide sustained release of EGF for minimum of 6 hours. Bioactivity of released EGF supernatants was then confirmed by its ability to promote proliferation of BALB/3T3 fibroblasts. Efficacy of the developed system was then investigated in vitro using buccal tissues (ORL 300-FT) as a potential replacement for small animal studies. Although the mucoadhesive films achieved their desired role of delivering bioactive EGF in a sustained manner, treatment with EGF, irrespective of its release from the films or solubilized in medium, caused a hyperparakeratotic response from in vitro tissues with distinguishable histological features including thickening of the spinous layer, intra- and intercellular edema, and pyknotic nuclei. These significant morphological changes were associated with no improvements in wound closure. These observations raise questions about the potential of using in vitro tissues as a wound healing model and substitute for small animal studies. The mucoadhesive delivery system developed, however, with its potential for sustained release of bioactive growth factors and small molecules, may be loaded with other desired compounds, with or without EGF, to

  3. Enhanced wound contraction in fresh wounds dressed with honey in Wistar rats (Rattus Novergicus).

    PubMed

    Osuagwu, F C; Oladejo, O W; Imosemi, I O; Aiku, A; Ekpos, O E; Salami, A A; Oyedele, O O; Akang, E U

    2004-01-01

    Due to reports that honey accelerates wound healing, an investigation on its role in wound contraction in fresh wounds inflicted on wistar rats was carried out. Twenty adult male wistar rats had 2cm by 2cm square wound inflicted on their right dorsolateral trunk. They were divided into two groups. The experimental group had their wounds dressed with honey while the control group had normal saline dressing. Wound dressing was done every five days and measurements taken at each dressing. Wound morphology was also assessed. Dressing with honey significantly enhanced percentage wound contraction on day 10 with value of 79.20+/-2.94 compared to control value of 53.50+/-4.32. p=0.0. The mean wound measurement on day 10 reduced significantly in honey group, 1.15+/-0.18 compared to control group 2.38+/-0.28. p=0.002. However, there was no significant difference in fibroblast count per high power field in honey group 68.0+/-2.59 compared to control 90.2+/-17.40, p=0.242. Honey dressing increased mean blood vessel count per high power field, 18.8+/-3.77 albeit non significantly when compared to control value of 13.4+/-2.44, p=0.264. Also honey dressing caused increased granulation tissue formation in wounds dressed with honey compared to control group. Our study suggests that honey dressing enhances wound contraction in fresh wounds which is one of the key features of wound healing.

  4. Pulsed radio frequency energy in the treatment of complex diabetic foot wounds: two cases.

    PubMed

    Larsen, Jerrie A; Overstreet, Julia

    2008-01-01

    The use of radio waves (pulsed radio frequency energy) has become well accepted in the treatment of chronic wounds. We present 2 cases of complex diabetic foot wounds treated adjunctively with outpatient pulsed radio frequency energy using a solid-state, 27.12 MHz fixed power output radio frequency generator that transmits a fixed dose of nonionizing, nonthermal electromagnetic energy through an applicator pad. This therapy, in combination with offloading, debridement and advanced dressings, resulted in closure of both wounds in approximately 16 weeks.

  5. Paracrine factors of human mesenchymal stem cells increase wound closure and reduce reactive oxygen species production in a traumatic brain injury in vitro model.

    PubMed

    Torrente, D; Avila, M F; Cabezas, R; Morales, L; Gonzalez, J; Samudio, I; Barreto, G E

    2014-07-01

    Traumatic brain injury (TBI) consists of a primary and a secondary insult characterized by a biochemical cascade that plays a crucial role in cell death in the brain. Despite the major improvements in the acute care of head injury victims, no effective strategies exist for preventing the secondary injury cascade. This lack of success might be due to that most treatments are aimed at targeting neuronal population, even if studies show that astrocytes play a key role after a brain damage. In this work, we propose a new model of in vitro traumatic brain-like injury and use paracrine factors released by human mesenchymal stem cells (hMSCs) as a neuroprotective strategy. Our results demonstrate that hMSC-conditioned medium increased wound closure and proliferation at 12 h and reduced superoxide production to control conditions. This was accompanied by changes in cell morphology and polarity index, as both parameters reflect the ability of cells to migrate toward the wound. These findings indicate that hMSC is an important regulator of oxidative stress production, enhances cells migration, and shall be considered as a useful neuroprotective approach for brain recovery following injury. © The Author(s) 2014.

  6. Studies of the effect of grasshopper abdominal secretion on wound healing with the use of murine model.

    PubMed

    Buszewska-Forajta, M; Siluk, D; Daghir-Wojtkowiak, E; Sejda, A; Staśkowiak, D; Biernat, W; Kaliszan, R

    2015-12-24

    Grasshopper, belonging to Chorthippus sp., is a widespread insect inhabiting Polish territory. According to folk knowledge and folk tales, the grasshopper abdominal secretion was used by villagers of Central and South-West Poland as a natural drug accelerating the wound healing process. In the reported study the hypothesis about beneficial properties of grasshopper abdominal secretion on hard to heal wounds was verified. The study was carried out with the use of a murine model (mice C57BL/6). In order to verify the beneficial properties of grasshopper abdominal secretion, the wounds of 8mm in diameter were formed on one side of each tested mouse. The influence of ethanolic extract of insects' secretion on healing process was evaluated in comparison to ethanolic solution of allantoin and 30% aqueous solution of ethanol (medium). The observation was carried out over a 14 day period. Finally the statistical analysis (ANOVA) was carried out to highlight the differences in wound healing rate between applied preparations. Moreover, qualitative composition of grasshoppers' secretion was studied with the use of GC/MS technique. During the first three days of observation, wounds treated with allantoin were healed with higher efficiency in comparison to ethanol and insect secretion preparations. The trend of healing changed from the 4th day of observation. Wounds treated with grasshoppers' abdominal secretion were closuring faster than wounds treated with allantoin or ethanol. In this part of observation, in the case of allantoin and ethanol application, the wound healing efficiency was similar. Since the 9th day of experiment the measurement of wounds size was problematic, due to crust formation. Finally at the 14th day of the study, wounds were totally healed. Morphological study enabled to observe all the phases of healing. In the 5th and 8th day, the infiltration of neutrophils and mononuclear cells in dermis was observed, which is characteristic for inflammatory phase

  7. Expression and Function of Connexin 43 in Human Gingival Wound Healing and Fibroblasts

    PubMed Central

    Tarzemany, Rana; Jiang, Guoqiao; Larjava, Hannu; Häkkinen, Lari

    2015-01-01

    Connexins (C×s) are a family of transmembrane proteins that form hemichannels and gap junctions (GJs) on the cell membranes, and transfer small signaling molecules between the cytoplasm and extracellular space and between connecting cells, respectively. Among C×s, suppressing C×43 expression or function promotes skin wound closure and granulation tissue formation, and may alleviate scarring, but the mechanisms are not well understood. Oral mucosal gingiva is characterized by faster wound closure and scarless wound healing outcome as compared to skin wounds. Therefore, we hypothesized that C×43 function is down regulated during human gingival wound healing, which in fibroblasts promotes expression of genes conducive for fast and scarless wound healing. Cultured gingival fibroblasts expressed C×43 as their major connexin. Immunostaining of unwounded human gingiva showed that C×43 was abundantly present in the epithelium, and in connective tissue formed large C×43 plaques in fibroblasts. At the early stages of wound healing, C×43 was strongly down regulated in wound epithelial cells and fibroblasts, returning to the level of normal tissue by day 60 post-wounding. Blocking of C×43 function by C×43 mimetic peptide Gap27 suppressed GJ-mediated dye transfer, promoted migration, and caused significant changes in the expression of wound healing-associated genes in gingival fibroblasts. In particular, out of 54 genes analyzed, several MMPs and TGF-β1, involved in regulation of inflammation and extracellular matrix (ECM) turnover, and VEGF-A, involved in angiogenesis, were significantly upregulated while pro-fibrotic ECM molecules, including Collagen type I, and cell contractility-related molecules were significantly down regulated. These responses involved MAPK, GSK3α/β and TGF-β signaling pathways, and AP1 and SP1 transcription factors. Thus, suppressed function of C×43 in fibroblasts promotes their migration, and regulates expression of wound healing

  8. Mechanics of epithelial closure over non-adherent environments

    PubMed Central

    Vedula, Sri Ram Krishna; Peyret, Grégoire; Cheddadi, Ibrahim; Chen, Tianchi; Brugués, Agustí; Hirata, Hiroaki; Lopez-Menendez, Horacio; Toyama, Yusuke; Neves de Almeida, Luís; Trepat, Xavier; Lim, Chwee Teck; Ladoux, Benoit

    2015-01-01

    The closure of gaps within epithelia is crucial to maintain its integrity during biological processes such as wound healing and gastrulation. Depending on the distribution of extracellular matrix, gap closure occurs through assembly of multicellular actin-based contractile cables or protrusive activity of border cells into the gap. Here we show that the supracellular actomyosin contractility of cells near the gap edge exerts sufficient tension on the surrounding tissue to promote closure of non-adherent gaps. Using traction force microscopy, we observe that cell-generated forces on the substrate at the gap edge first point away from the centre of the gap and then increase in the radial direction pointing into the gap as closure proceeds. Combining with numerical simulations, we show that the increase in force relies less on localized purse-string contractility and more on large-scale remodelling of the suspended tissue around the gap. Our results provide a framework for understanding the assembly and the mechanics of cellular contractility at the tissue level. PMID:25608921

  9. Subcostal closure technique for prevention of postthoracotomy pain syndrome.

    PubMed

    Hong, Kipyo; Bae, Mikyung; Han, Sora

    2016-09-01

    The purpose of this study was to evaluate the efficacy of our subcostal closure technique in prevention of postthoracotomy pain syndrome. From July 2012 to March 2015, 29 patients in whom a lobectomy was indicated underwent a thoracotomy. The thoracotomy wounds were closed using a subcostal closure technique (subcostal closure group) and outcomes were compared with 31 patients who underwent video-assisted thoracoscopic surgery (thoracoscopy group). The duration of oral opioid consumption was evaluated from medical records, and postoperative pain was evaluated by telephone interview conducted by a trained nurse practitioner who was unaware of the patient's group. Pain scores were higher in the thoracoscopy group compared to the subcostal closure group, reaching statistical significance (Numeric Rating Scale 0.55 ± 0.948 in the subcostal closure group vs. 1.84 ± 1.614 in the thoracoscopy group; p < 0.001, Clinical Pain Scale 0.24 ± 0.435 in the subcostal closure group vs. 0.81 ± 0.703 in the thoracoscopy group; p < 0.001). The number of patients who consumed oral opioids for longer than 2 months after the operation was significantly greater in the thoracoscopy group than the subcostal closure group (6.9% in the subcostal closure group vs. 32.3% in the thoracoscopy group; p = 0.022). The subcostal closure technique is useful to prevent postthoracotomy pain syndrome. © The Author(s) 2016.

  10. Biomechanical Testing and Histologic Examination of Intradermal Skin Closure in Dogs Using Barbed Suture Device and Non-Barbed Monofilament Suture.

    PubMed

    Law, Andy Y; Butler, James R; Patnaik, Sourav S; Cooley, James A; Elder, Steven H

    2017-01-01

    To compare the biomechanical strength and histologic features of 3-0 Glycomer™ 631 barbed suture (V-LOC™ 90 Absorbable Wound Closure Device, Covidien, Mansfield, MA) to non-barbed 3-0 Glycomer™ 631 suture (Biosyn™, Covidien) for intradermal skin wound closure in the dog. Randomized, factorial, in vivo. Eighteen purpose-bred, mature male, and female hound dogs. Eighteen adult hound dogs were randomly assigned to 1 of 3 groups designated by postoperative day of assessment. Six skin incisions were made along the dorsum in the thoracolumbar region of each dog with an equal number (n=3) randomly assigned to closure with barbed or non-barbed suture. Six dogs were euthanatized on postoperative days 3, 10, and 14, respectively. Two additional incisions were made on each dog after euthanasia for baseline data (Day 0). The skin incision specimens were harvested for biomechanical testing and histologic evaluation. Non-barbed closure had significantly higher maximum load at failure (P<.001) and stiffness (P<.001) than barbed closure regardless of day. The average tissue reaction score was significantly higher for barbed closure (P=.008), regardless of day. Suturing time for barbed closures was significantly shorter. There was no significant difference in frequency of complications between closures. Barbed Glycomer™ 631 closures had a significantly lower maximum load at failure and stiffness, and higher average tissue reaction scores, but showed no difference in short term outcome for intradermal closure of dorsally located skin incisions in dogs. © 2016 The American College of Veterinary Surgeons.

  11. The Use of Temporoparietal Fascial Flap to Eliminate Wound Breakdown in Subtotal Petrosectomy for Chronic Discharging Ears.

    PubMed

    Yung, Matthew

    2016-03-01

    To find out if the use of the vascularized temporo-parietal fascial flap (TPFF) reduces postoperative infection or wound breakdown in subtotal petrosectomy for chronic discharging ears. A retrospective review on 26 subtotal petrosectomies with blind pit closures on chronic discharging ears performed by a single surgeon between 2000 and 2015 was performed. All patients had a minimum follow-up period of 6 months. Eleven mastoid cavities were obliterated with abdominal fat, and 15 cavities were obliterated with TPFF. There was no concomitant cochlear implant or middle ear implant. All postoperative wound infections or delay in wound healing were recorded into a database. The complication rates of the fat obliteration group were compared using Fisher's exact test with those for the TPFF obliteration group. In the fat obliteration group, 4 out of 11 patients had documented postoperative complications. Three had wound breakdown with exposure of the fat that required revision surgery. Another patient had postauricular abscess without the wound actually broken down. On the other hand, all the ears in the TPFF obliteration group (100%) were completely free of wound infection, wound breakdown, or any complication. The difference between the two groups was statistically significant (p = 0.022). Many authors have encountered postoperative infection or wound breakdown in subtotal petrosectomy with fat obliteration in the treatment of chronic otitis media. Using a richly vascularized temporo-temporal fascial flap to protect the blind pit closure in such patients reduces postoperative infection and wound breakdown.

  12. A current affair: electrotherapy in wound healing

    PubMed Central

    Hunckler, Jerome; de Mel, Achala

    2017-01-01

    New developments in accelerating wound healing can have immense beneficial socioeconomic impact. The wound healing process is a highly orchestrated series of mechanisms where a multitude of cells and biological cascades are involved. The skin battery and current of injury mechanisms have become topics of interest for their influence in chronic wounds. Electrostimulation therapy of wounds has shown to be a promising treatment option with no-device-related adverse effects. This review presents an overview of the understanding and use of applied electrical current in various aspects of wound healing. Rapid clinical translation of the evolving understanding of biomolecular mechanisms underlying the effects of electrical simulation on wound healing would positively impact upon enhancing patient’s quality of life. PMID:28461755

  13. Wound management with compression therapy and topical hemoglobin solution in a patient with Budd-Chiari Syndrome.

    PubMed

    Babadagi-Hardt, Zeynep; Engels, Peter; Kanya, Susanne

    2014-03-31

    Although the underlying primary cause of chronic wounds may vary, a common etiology of this is a hypoxic or ischemic status of the affected tissue of the lower extremities. In particular, for rare diseases associated with disturbed blood flow a correlation between cause and effect is often diagnosed inappropriately. As a consequence, chronic wounds may develop and persist for years. We present a case of a patient with chronic venous insufficiency due to an occlusion of the inferior caval vein. Initially, a Budd-Chiari syndrome was diagnosed which is a thrombotic obstruction of the hepatic venous outflow. In addition, the patient developed an obstruction of the inferior caval vein and subsequently a chronic venous insufficiency. As a consequence, chronic leg ulcers developed with a history of more than 7 years. Various wound care approaches were performed without success in wound closure. Finally, a combination of compression therapy and topical application of a hemoglobin solution successfully led to fast and persistent wound closure. Chronic ulcers of the lower limb such as venous leg ulcers, even for patients with rare disorders like Budd-Chiari syndrome, are associated with oxygen supply disturbances resulting in a hypoxic status of the affected tissue. Therefore, an adequate oxygen supply to chronic wounds plays a pivotal role in successful wound healing. Compression therapy in combination with enhancement of the local oxygen supply by topically applied hemoglobin showed marked improvement of wound healing in the presented patient.

  14. Wound healing and antibacterial activities of chondroitin sulfate- and acharan sulfate-reduced silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Im, A.-Rang; Kim, Jee Young; Kim, Hyun-Seok; Cho, Seonho; Park, Youmie; Kim, Yeong Shik

    2013-10-01

    For topical applications in wound healing, silver nanoparticles (AgNPs) have attracted much attention as antibacterial agents. Herein, we describe a green-synthetic route for the production of biocompatible and crystalline AgNPs using two glycosaminoglycans, chondroitin sulfate (CS) and acharan sulfate (AS), as reducing agents. The synthetic approach avoids the use of toxic chemicals, and the yield of AgNPs formation is found to be 98.1% and 91.1% for the chondroitin sulfate-reduced silver nanoparticles (CS-AgNPs) and the acharan sulfate-reduced silver nanoparticles (AS-AgNPs), respectively. Nanoparticles with mostly spherical and amorphous shapes were observed, with an average diameter of 6.16 ± 2.26 nm for CS-AgNPs and 5.79 ± 3.10 nm for AS-AgNPs. Images of the CS-AgNPs obtained from atomic force microscopy revealed the self-assembled structure of CS was similar to a densely packed woven mat with AgNPs sprinkled on the CS. These nanoparticles were stable under cell culture conditions without any noticeable aggregation. An approximately 128-fold enhancement of the antibacterial activities of the AgNPs was observed against Enterobacter cloacae and Escherichia coli when compared to CS and AS alone. In addition, an in vivo animal model of wound healing activity was tested using mice that were subjected to deep incision wounds. In comparison to the controls, the ointments containing CS-AgNPs and AS-AgNPs stimulated wound closure under histological examination and accelerated the deposition of granulation tissue and collagen in the wound area. The wound healing activity of the ointments containing CS-AgNPs and AS-AgNPs are comparable to that of a commercial formulation of silver sulfadiazine even though the newly prepared ointments contain a lower silver concentration. Therefore, the newly prepared AgNPs demonstrate potential for use as an attractive biocompatible nanocomposite for topical applications in the treatment of wounds.

  15. Quantitative Methods for Measuring Repair Rates and Innate-Immune Cell Responses in Wounded Mouse Skin.

    PubMed

    Li, Zhi; Gothard, Elizabeth; Coles, Mark C; Ambler, Carrie A

    2018-01-01

    In skin wounds, innate-immune cells clear up tissue debris and microbial contamination, and also secrete cytokines and other growth factors that impact repair process such as re-epithelialization and wound closure. After injury, there is a rapid influx and efflux of immune cells at wound sites, yet the function of each innate cell population in skin repair is still under investigation. Flow cytometry is a valuable research tool for detecting and quantifying immune cells; however, in mouse back skin, the difficulty in extracting immune cells from small area of skin due to tissue complexity has made cytometric analysis an underutilized tool. In this paper, we provide detailed methods on the digestion of lesion-specific skin without disrupting antigen expression followed by multiplex cell staining that allows for identification of seven innate-immune populations, including rare subsets such as group-3 innate lymphoid cells (ILC3s), by flow-cytometry analysis. Furthermore, when studying the functions of immune cells to tissue repair an important metric to monitor is size of the wound opening. Normal wounds close steadily albeit at non-linear rates, while slow or stalled wound closure can indicate an underlying problem with the repair process. Calliper measurements are difficult and time-consuming to obtain and can require repeated sedation of experimental animals. We provide advanced methods for measuring of wound openness; digital 3D image capture and semi-automated image processing that allows for unbiased, reliable measurements that can be taken repeatedly over time.

  16. Developing a toolbox for analysis of warrior wound biopsies: vibrational spectroscopy

    NASA Astrophysics Data System (ADS)

    Crane, Nicole J.; O'Brien, Frederick P.; Forsberg, Jonathan A.; Potter, Benjamin K.; Elster, Eric A.

    2011-03-01

    The management of modern traumatic war wounds remains a significant challenge for clinicians. This is a reflection of the extensive osseous and soft-tissue damage caused by blasts and high-energy projectiles. The ensuing inflammatory response ultimately dictates the pace of wound healing and tissue regeneration. Consequently, the eventual timing of wound closure or definitive coverage is often subjectively based. Some wounds require an extended period of time to close or fail to remain closed, despite the use and application of novel wound-specific treatment modalities. Aside from impaired wound healing, additional wound complications include wound infection, biofilm formation, and heterotopic ossification (the pathological mineralization of soft tissues). An understanding of the molecular environment of acute wounds throughout the debridement process can provide valuable insight into the mechanisms associated with the eventual wound outcome. The analysis of Raman spectra of ex vivo wound biopsy tissue obtained from serial traumatic wound debridements reveals a decreased 1665 cm-1/1445 cm-1 band area ratio in impaired healing wounds, indicative of an impaired remodeling process, in addition to a decreased 1240 cm-1/1270cm-1. The examination of debrided tissue exhibits mineralization during the early development of heterotopic ossification. Finally, preliminary results suggest that Fourier transform infrared (FT-IR) images of wound effluent may be able to provide early microbiological information about the wound.

  17. Oil Body-Bound Oleosin-rhFGF-10: A Novel Drug Delivery System that Improves Skin Penetration to Accelerate Wound Healing and Hair Growth in Mice.

    PubMed

    Li, Wenqing; Yang, Jing; Cai, Jingbo; Wang, Hongyu; Tian, Haishan; Huang, Jian; Qiang, Weidong; Zhang, Linbo; Li, Haiyan; Li, Xiaokun; Jiang, Chao

    2017-10-18

    Recombinant human fibroblast growth factor 10 (rhFGF-10) is frequently used to treat patients with skin injuries. It can also promote hair growth. However, the effective application of rhFGF-10 is limited because of its poor stability and transdermal absorption. In this study, polymerase chain reaction (PCR) and Southern blotting were used to identify transgenic safflowers carrying a gene encoding an oleosin-rhFGF-10 fusion protein. The size and structural integrity of oleosin-rhFGF-10 in oil bodies extracted from transgenic safflower seeds was characterized by polyacrylamide gel electrophoresis and western blotting. Oil body extracts containing oleosin-rhFGF-10 were topically applied to mouse skin. The absorption of oleosin-rhFGF-10 was studied by immunohistochemistry. Its efficiency in promoting wound healing and hair regeneration were evaluated in full thickness wounds and hair growth assays. We identified a safflower line that carried the transgene and expressed a 45 kDa oleosin-rhFGF-10 protein. Oil body-bound oleosin-rhFGF-10 was absorbed by the skin with higher efficiency and speed compared with prokaryotically-expressed rhFGF-10. Oleosin-rhFGF-10 also enhanced wound closure and promoted hair growth better than rhFGF-10. The application of oleosin-rhFGF-10 in oil bodies promoted its delivery through the skin, providing a basis for improved therapeutic effects in enhancing wound healing and hair growth.

  18. Evaluation of aqueous leaves extract of Moringa oleifera Linn for wound healing in albino rats.

    PubMed

    Rathi, B S; Bodhankar, S L; Baheti, A M

    2006-11-01

    Aqueous extract of leaves of M. oleifera was investigated and rationalised for its wound healing activity. The aqueous extract was studied at dose level of 300 mg/kg body weight using resutured incision; excision and dead space wound models in rats. Significant increase in wound closure rate, skin-breaking strength, granuloma breaking strength, hydroxyproline content, granuloma dry weight and decrease in scar area was observed. The prohealing actions seem to be due to increased collagen deposition as well as better alignment and maturation. From the results obtained, it may be concluded that the aqueous extract of M. oleifera has significant wound healing property.

  19. Wound healing by topical application of antioxidant iron chelators: kojic acid and deferiprone.

    PubMed

    Mohammadpour, Mehrdad; Behjati, Mohaddeseh; Sadeghi, Amir; Fassihi, Afshin

    2013-06-01

    Kojic acid and deferiprone are iron chelators used for skin lightening and iron-overload treatment, respectively. As iron chelation and free radical scavenging are principal factors for wound healing, it was hypothesised that the local application of these compounds might accelerate wound healing in rats. Ointments of 3%, 6% and 9% of deferiprone and kojic acid were prepared and topical treatment was performed on in vivo wound models for 12 days twice in day for test and control groups. Topical treatment with 3%, 6% and 9% showed significant improvement in wound healing after 4 days (P < 0·001). Topical application of 3% and 6% deferiprone enhanced wound healing after 8 days (P < 0·026 and P < 0·001, respectively). Accelerated wound healing was seen using 3% and 6% deferiprone after 12 days (P = 0·003 and P < 0·001, respectively). DPPH scavenging assay was also performed to compare the antioxidant potencies of kojic acid and deferiprone. Deferiprone had more free radical scavenging power than kojic acid. Generally, deferiprone topical treatment, accelerated wound healing more than kojic acid because of its higher antioxidant and iron chelation abilities. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

  20. The Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Media Topically Delivered in Fibrin Glue on Chronic Wound Healing in Rats

    PubMed Central

    Mehanna, Radwa A.; Nabil, Iman; Attia, Noha; Bary, Amany A.; Razek, Khalid A.; Ahmed, Tamer A. E.; Elsayed, Fatma

    2015-01-01

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) represent a modern approach for management of chronic skin injuries. In this work, we describe BM-MSCs application versus their conditioned media (CM) when delivered topically admixed with fibrin glue to enhance the healing of chronic excisional wounds in rats. Fifty-two adult male rats were classified into four groups after induction of large-sized full-thickness skin wound: control group (CG), fibrin only group (FG), fibrin + MSCs group (FG + SCs), and fibrin + CM group (FG + CM). Healing wounds were evaluated functionally and microscopically. Eight days after injury, number of CD68+ macrophages infiltrating granulation tissue was considerably higher in the latter two groups. Although—later—none of the groups depicted a substantially different healing rate, the quality of regenerated skin was significantly boosted by the application of either BM-MSCs or their CM both (1) structurally as demonstrated by the obviously increased mean area percent of collagen fibers in Masson's trichrome-stained skin biopsies and (2) functionally as supported by the interestingly improved epidermal barrier as well as dermal tensile strength. Thus, we conclude that topically applied BM-MSCs and their CM—via fibrin vehicle—could effectively improve the quality of healed skin in chronic excisional wounds in rats, albeit without true acceleration of wound closure. PMID:26236740