Differentiation of mesenchymal stem cells into neuronal cells on fetal bovine acellular dermal matrix as a tissue engineered nerve scaffold

PubMed Central

Feng, Yuping; Wang, Jiao; Ling, Shixin; Li, Zhuo; Li, Mingsheng; Li, Qiongyi; Ma, Zongren; Yu, Sijiu

2014-01-01

The purpose of this study was to assess fetal bovine acellular dermal matrix as a scaffold for supporting the differentiation of bone marrow mesenchymal stem cells into neural cells following induction with neural differentiation medium. We performed long-term, continuous observation of cell morphology, growth, differentiation, and neuronal development using several microscopy techniques in conjunction with immunohistochemistry. We examined specific neuronal proteins and Nissl bodies involved in the differentiation process in order to determine the neuronal differentiation of bone marrow mesenchymal stem cells. The results show that bone marrow mesenchymal stem cells that differentiate on fetal bovine acellular dermal matrix display neuronal morphology with unipolar and bi/multipolar neurite elongations that express neuronal-specific proteins, including βIII tubulin. The bone marrow mesenchymal stem cells grown on fetal bovine acellular dermal matrix and induced for long periods of time with neural differentiation medium differentiated into a multilayered neural network-like structure with long nerve fibers that was composed of several parallel microfibers and neuronal cells, forming a complete neural circuit with dendrite-dendrite to axon-dendrite to dendrite-axon synapses. In addition, growth cones with filopodia were observed using scanning electron microscopy. Paraffin sectioning showed differentiated bone marrow mesenchymal stem cells with the typical features of neuronal phenotype, such as a large, round nucleus and a cytoplasm full of Nissl bodies. The data suggest that the biological scaffold fetal bovine acellular dermal matrix is capable of supporting human bone marrow mesenchymal stem cell differentiation into functional neurons and the subsequent formation of tissue engineered nerve. PMID:25598779

The use of acellular dermal matrix membrane for vertical soft tissue augmentation during submerged implant placement: a case series.

PubMed

Puisys, Algirdas; Vindasiute, Egle; Linkevciene, Laura; Linkevicius, Tomas

2015-04-01

To evaluate the efficiency of acellular dermal matrix membrane to augment vertical peri-implant soft tissue thickness during submerged implant placement. Forty acellular dermal matrix-derived allogenic membranes (AlloDerm, BioHorizons, Birmingham, AL, USA) and 42 laser-modified surface internal hex implants (BioHorizons Tapered Laser Lok, Birmingham, AL, USA) were placed in submerged approach in 40 patients (15 males and 25 females, mean age 42.5 ± 1.7) with a thin vertical soft tissue thickness of 2 mm or less. After 3 months, healing abutments were connected to implants, and the augmented soft tissue thickness was measured with periodontal probe. The gain in vertical soft tissue volume was calculated. Mann-Whitney U-test was applied and significance was set to 0.05. All 40 allografts healed successfully. Thin soft tissue before augmentation had an average thickness of 1.54 ± 0.51 mm SD (range, 0.5-2.0 mm, median 1.75 mm), and after soft tissue augmentation with acellular dermal matrix, thickness increased to 3.75 ± 0.54 mm SD (range, 3.0-5.0 mm, median 4.0 mm) at 3 months after placement. This difference between medians was found to be statistically significant (P < 0.001). Mean increase in soft tissue thickness was 2.21 ± 0.85 mm SD (range, 1.0-4.5 mm, median 2.0 mm). It can be concluded that acellular dermal matrix membrane can be successfully used for vertical soft tissue augmentation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

440 Consecutive immediate, implant-based, single-surgeon breast reconstructions in 281 patients: a comparison of early outcomes and costs between SurgiMend fetal bovine and AlloDerm human cadaveric acellular dermal matrices.

PubMed

Butterfield, Jennifer L

2013-05-01

A 2010 nationwide survey of plastic and reconstructive surgeons indicated that approximately 83 percent performed predominantly implant-based breast reconstruction, with acellular dermal matrix used by approximately half of those practitioners. Although the medical literature documents well over 2000 cases of breast reconstruction with matrices, relatively few cases using other than human cadaveric acellular dermal matrices have been reported. The author compared complications and costs using SurgiMend fetal bovine and AlloDerm human cadaveric acellular dermal matrices. A retrospective review of a single surgeon's 5-year experience was performed for consecutive, nonrandomized immediate breast reconstructions with acellular dermal matrix from 2005 to 2010. Two hundred eighty-one patients had 440 implant-based reconstructions using SurgiMend [222 patients (79.0 percent)] or AlloDerm [59 patients (21.0 percent)]. No significant differences in complication rates were observed between SurgiMend and AlloDerm for hematoma, infection, major skin necrosis, or breast implant removal. Seroma was the most prevalent complication; the seroma rate for AlloDerm (15.7 percent) was significantly greater than that for SurgiMend (8.3 percent). Using recent product costs for equivalently sized AlloDerm and SurgiMend units, the cost of SurgiMend was $1024 less per breast than AlloDerm. SurgiMend fetal bovine and AlloDerm human cadaveric acellular dermal matrices demonstrate similar rates of major early complications in breast reconstruction in this study. This similarity in complication rates between SurgiMend and AlloDerm and the cost savings seen with the use of SurgiMend are factors for the surgeon to consider in choosing a matrix for breast reconstruction. : Therapeutic, III.

Non-cross-linked porcine acellular dermal matrices for abdominal wall reconstruction.

PubMed

Burns, Nadja K; Jaffari, Mona V; Rios, Carmen N; Mathur, Anshu B; Butler, Charles E

2010-01-01

Non-cross-linked porcine acellular dermal matrices have been used clinically for abdominal wall repair; however, their biologic and mechanical properties and propensity to form visceral adhesions have not been studied. The authors hypothesized that their use would result in fewer, weaker visceral adhesions than polypropylene mesh when used to repair ventral hernias and form a strong interface with the surrounding musculofascia. Thirty-four guinea pigs underwent inlay repair of surgically created ventral hernias using polypropylene mesh, porcine acellular dermal matrix, or a composite of the two. The animals were killed at 4 weeks, and the adhesion tenacity grade and surface area of the repair site involved by adhesions were measured. Sections of the repair sites, including the implant-musculofascia interface, underwent histologic analysis and uniaxial mechanical testing. The incidence of bowel adhesions to the repair site was significantly lower with the dermal matrix (8 percent, p < 0.01) and the matrix/mesh combination (0 percent, p < 0.001) than with polypropylene mesh alone (70 percent). The repairs made with the matrix or the matrix/mesh combination, compared with the polypropylene mesh repairs, had significantly lower mean adhesion surface areas [12.8 percent (p < 0.001), 9.2 percent (p < 0.001), and 79.9 percent] and grades [0.6 (p < 0.001), 0.6 (p < 0.001), and 2.9]. The dermal matrix underwent robust cellular and vascular infiltration. The ultimate tensile strength at the implant-musculofascia interface was similar in all groups. Porcine acellular dermal matrix becomes incorporated into the host tissue and causes fewer adhesions to repair sites than does polypropylene mesh, with similar implant-musculofascia interface strength. It also inhibits adhesions to adjacent dermal matrix in the combination repairs. It has distinct advantages over polypropylene mesh for complex abdominal wall repairs, particularly when material placement directly over bowel is unavoidable.

[Autogenous platelet-rich plasma gel with acellular xenogeneic dermal matrix for treatment of deep II degree burns].

PubMed

Hao, Tianzhi; Zhu, Jingmin; Hu, Wenbo; Zhang, Hua; Gao, Zhenhui; Wen, Xuehui; Zhou, Zhi; Lu, Gang; Liu, Jingjie; Li, Wen

2010-06-01

To investigate the effectiveness of autogenous platelet-rich plasma (PRP) gel with acellular xenogeneic dermal matrix in the treatment of deep II degree burns. From January 2007 to December 2009, 30 cases of deep II degree burns were treated. There were 19 males and 11 females with an average age of 42.5 years (range, 32-57 years). The burn area was 10% to 48% of total body surface area. The time from burn to hospitalization was 30 minutes to 8 hours. All patients were treated with tangential excision surgery, one side of the wounds were covered with autogenous PRP gel and acellular xenogeneic dermal matrix (PRP group), the other side of the wounds were covered with acellular xenogeneic dermal matrix only (control group). The healing rate, healing time, infection condition, and scar formation were observed. At 7 days after operation, the infection rate in PRP group (6.7%, 2/30) was significantly lower than that in control group (16.7%, 5/30, P < 0.05). The healing times were (18 +/- 4) days and (22 +/- 4) days respectively in PRP group and control group, showing significant difference (P < 0.05). The healing rates at 14 days and 21 days were 75% +/- 7% and 88% +/- 5% in PRP group, were 62% +/- 15% and 73% +/- 7% in control group, showing significant difference (P < 0.05). RPR group was superior to control group in elasticity, color, appearance, softness, scar formation, and healing quality. Autogenous PRP gel with acellular xenogeneic dermal matrix can accelerate the wound healing of deep II degree burns as well as alleviate the scar proliferation.

Development of a tissue-engineered human oral mucosa equivalent based on an acellular allogeneic dermal matrix: a preliminary report of clinical application to burn wounds.

PubMed

Iida, Takuya; Takami, Yoshihiro; Yamaguchi, Ryo; Shimazaki, Shuji; Harii, Kiyonori

2005-01-01

Tissue-engineered skin equivalents composed of epidermal and dermal components have been widely investigated for coverage of full-thickness skin defects. We developed a tissue-engineered oral mucosa equivalent based on an acellular allogeneic dermal matrix and investigated its characteristics. We also tried and assessed its preliminary clinical application. Human oral mucosal keratinocytes were separated from a piece of oral mucosa and cultured in a chemically-defined medium. The keratinocytes were seeded on to the acellular allogeneic dermal matrix and cultured. Histologically, the mucosa equivalent had a well-stratified epithelial layer. Immunohistochemical study showed that it was similar to normal oral mucosa. We applied this equivalent in one case with an extensive burn wound. The equivalent was transplanted three weeks after the harvest of the patient's oral mucosa and about 30% of the graft finally survived. We conclude that this new oral mucosa equivalent could become a therapeutic option for the treatment of extensive burns.

Use of the tunnel technique and an acellular dermal matrix in the treatment of multiple adjacent teeth with gingival recession in the esthetic zone.

PubMed

Mahn, Douglas H

2010-12-01

The proper management of gingival recession is critical to the establishment of a natural-appearing soft tissue architecture. Subepithelial connective tissue grafts have been considered the "gold standard" but are limited by the availability of palatal donor tissue. Tunnel techniques have improved the esthetic results of connective tissue grafting. Acellular dermal matrices have been successful in the treatment of gingival recession and are not limited by the palatal anatomy. The aim of this report is to describe the application of the tunnel technique, with use of an acellular dermal matrix, in the correction of gingival recession affecting multiple adjacent teeth in the esthetic zone.

A novel surgical procedure for coronally repositioning of the buccal implant mucosa using acellular dermal matrix: a case report.

PubMed

Mareque-Bueno, Santiago

2011-01-01

This case report describes a surgical procedure for coronally advancing the peri-implant mucosa to treat a soft tissue dehiscence in a single-tooth implant-supported restoration in combination with an acellular dermal matrix graft. The patient was a 41-year-old systemically healthy, non-smoking female. Her chief complaint pertained to the unesthetic appearance of her right lateral upper incisor, caused by recession of the mucosal margin. On examination, a 3-mm recession could be observed. The periodontium was classified as thin. A 2-mm band of keratinized peri-implant mucosa was present. Keratinized gingiva was approximately 6 mm at adjacent areas. The surgical technique included a novel incision design to coronally position the flap over an acellular dermal matrix graft. Partial coverage of the recession was achieved. After a 6-month period, tissues appeared thicker than preoperatively, with no bleeding on probing and no probing depth >2 mm. The patient was satisfied with the overall treatment result. This case report shows the possibility of achieving partial soft tissue coverage over an implant-supported restoration with the combined use of an acellular dermal matrix and a coronally positioned flap. A novel technique is presented that allowed advancing the flap over the graft in a single-tooth restoration where enough keratinized tissue was present preoperatively.

Acellular dermal matrix allograft used to gain attached gingiva in a case of epidermolysis bullosa.

PubMed

Buduneli, Eralp; Ilgenli, Tunç; Buduneli, Nurcan; Ozdemir, Fezal

2003-11-01

Epidermolysis bullosa (EB) is an acquired disease or inherited as either autosomal dominant or recessive with an incidence of 1/50,000. The prominent clinical characteristic of the disease is the development of bullae or vesicles in mucosa or skin in response to minor trauma. A female patient with a dystrophic type of EB had been put in a maintenance regimen after completion of the initial phase of periodontal therapy and followed for 7 years. The purpose of this report is to document acellular dermal matrix allograft application to increase the width of the attached gingiva in this patient experiencing difficulty in chewing and performing plaque control due to the dramatic loss of attached gingiva after 7 years of supportive periodontal therapy. Under local anaesthesia and antibiotic coverage, the acellular dermal matrix allograft was applied in the anterior region of the upper jaw in order to increase the width of attached gingiva, thereby improving patient comfort. The healing was uneventful and a significant gain in attached gingiva dimensions was observed 9 months after the periodontal surgery. The procedure avoided a second surgical site, provided satisfactory results from an aesthetic point of view, and improved patient comfort. Acellular dermal matrix allograft may be regarded as an alternative in the treatment of EB cases to increase the width of attached gingiva and facilitate maintenance of the dentition.

What happens to an acellular dermal matrix after implantation in the human body? A histological and electron microscopic study.

PubMed

Boháč, Martin; Danišovič, Ľuboš; Koller, Ján; Dragúňová, Jana; Varga, Ivan

2018-01-22

Acellular matrices are used for various purposes and they have been studied extensively for their potential roles in regenerating tissues or organs. The acellular matrix generates physiological cues that mimic the native tissue microenvironment. Acellular dermal matrix (ADM) is a soft connective tissue graft generated by a decellularization process that preserves the intact extracellular skin matrix. Upon implantation, this structure serves as a scaffold for donor-side cells to facilitate subsequent incorporation and revascularization. In breast reconstruction, ADM is used mainly for lower pole coverage and the shaping of a new breast. It helps control the positioning of the implant in the inframammary fold, and prevent the formation of contractile pseudocapsule around the breast implant. In this study, we provide a comprehensive histological description of ADM used for human breast reconstruction over the course of several months following implementation. Using immunohistochemical methods (a panel of 12 antibodies) coupled with optical and transmission electron microscopy, we confirmed that the original acellular dermal matrix became recolonized by fibroblasts and myofibroblasts, and also by various other free cells of the connective tissue (lymphocytes, macrophages and multinucleated giant cells, granulocytes, mast cells) after implantation into the patient's body. Within the implanted ADM, there was a relatively rapid ingrowth of blood vessels. Lymphatic vessels were only detected in one case 9 months after the implantation of the ADM. These results suggest that lymphangiogenesis is a longer process than angiogenesis.

Full-mouth esthetic rehabilitation with acellular dermal matrix.

PubMed

Clozza, Emanuele; Suzuki, Takanori; Engebretson, Steven P

2014-01-01

Treatment of multiple recession defects with the adjunct use of a connective tissue graft (CTG) represents a challenge when diagnosed in several teeth of the mouth. The amount of CTG harvested from the palate may not be adequate to address this condition. In such scenarios, alternative sources such as acellular dermal matrix (ADM) are preferred due to the unlimited availability. A case report is presented, dealing with the treatment of multiple gingival recessions affecting the majority of dentition using ADM, with a 6-month follow-up.

Bovine versus Porcine Acellular Dermal Matrix: A Comparison of Mechanical Properties.

PubMed

Adelman, David M; Selber, Jesse C; Butler, Charles E

2014-05-01

Porcine and bovine acellular dermal matrices (PADM and BADM, respectively) are the most commonly used biologic meshes for ventral hernia repair. A previous study suggests a higher rate of intraoperative device failures using PADM than BADM. We hypothesize that this difference is, in part, related to intrinsic mechanical properties of the matrix substrate and source material. The following study directly compares these 2 matrices to identify any potential differences in mechanical properties that may relate to clinical outcomes. Sections of PADM (Strattice; Lifecell, Branchburg, N.J.) and BADM (SurgiMend; TEI Biosciences, Boston, Mass.) were subjected to a series of biomechanical tests, including suture retention, tear strength, and uniaxial tensile strength. Results were collected and compared statistically. In all parameters, BADM exhibited a superior mechanical strength profile compared with PADM of similar thickness. Increased BADM thickness correlated with increased mechanical strength. In suture tear-through testing with steel wire, failure of the steel wire occurred in the 4-mm-thick BADM, whereas the matrix material failed in all other thicknesses of BADM and PADM. Before implantation, BADM is inherently stronger than PADM at equivalent thicknesses and considerably stronger at increased thicknesses. These results corroborate clinical data from a previous study in which PADM was associated with a higher intraoperative device failure rate. Although numerous properties of acellular dermal matrix contribute to clinical outcomes, surgeons should consider initial mechanical strength properties when choosing acellular dermal matrices for load-bearing applications such as hernia repair.

Prospective randomized comparison of scar appearances between cograft of acellular dermal matrix with autologous split-thickness skin and autologous split-thickness skin graft alone for full-thickness skin defects of the extremities.

PubMed

Yi, Ju Won; Kim, Jae Kwang

2015-03-01

The purpose of this study was to evaluate the clinical outcomes of cografting of acellular dermal matrix with autologous split-thickness skin and autologous split-thickness skin graft alone for full-thickness skin defects on the extremities. In this prospective randomized study, 19 consecutive patients with full-thickness skin defects on the extremities following trauma underwent grafting using either cograft of acellular dermal matrix with autologous split-thickness skin graft (nine patients, group A) or autologous split-thickness skin graft alone (10 patients, group B) from June of 2011 to December of 2012. The postoperative evaluations included observation of complications (including graft necrosis, graft detachment, or seroma formation) and Vancouver Scar Scale score. No statistically significant difference was found regarding complications, including graft necrosis, graft detachment, or seroma formation. At week 8, significantly lower Vancouver Scar Scale scores for vascularity, pliability, height, and total score were found in group A compared with group B. At week 12, lower scores for pliability and height and total scores were identified in group A compared with group B. For cases with traumatic full-thickness skin defects on the extremities, a statistically significant better result was achieved with cograft of acellular dermal matrix with autologous split-thickness skin graft than with autologous split-thickness skin graft alone in terms of Vancouver Scar Scale score. Therapeutic, II.

Human acellular dermal wound matrix: evidence and experience.

PubMed

Kirsner, Robert S; Bohn, Greg; Driver, Vickie R; Mills, Joseph L; Nanney, Lillian B; Williams, Marie L; Wu, Stephanie C

2015-12-01

A chronic wound fails to complete an orderly and timely reparative process and places patients at increased risk for wound complications that negatively impact quality of life and require greater health care expenditure. The role of extracellular matrix (ECM) is critical in normal and chronic wound repair. Not only is ECM the largest component of the dermal skin layer, but also ECM proteins provide structure and cell signalling that are necessary for successful tissue repair. Chronic wounds are characterised by their inflammatory and proteolytic environment, which degrades the ECM. Human acellular dermal matrices, which provide an ECM scaffold, therefore, are being used to treat chronic wounds. The ideal human acellular dermal wound matrix (HADWM) would support regenerative healing, providing a structure that could be repopulated by the body's cells. Experienced wound care investigators and clinicians discussed the function of ECM, the evidence related to a specific HADWM (Graftjacket(®) regenerative tissue matrix, Wright Medical Technology, Inc., licensed by KCI USA, Inc., San Antonio, TX), and their clinical experience with this scaffold. This article distills these discussions into an evidence-based and practical overview for treating chronic lower extremity wounds with this HADWM. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Interposition Ankle Arthroplasty Using Acellular Dermal Matrix: A Small Series.

PubMed

Carpenter, Brian; Duncan, Kyle; Ernst, Jordan; Ryba, Dalton; Suzuki, Sumihiro

Although ankle arthrodesis is the reference standard for end-stage ankle arthritis, loss of mobility and adjacent joint arthritis are consequences that alternatives to arthrodesis attempt to avoid. The purpose of the present study was to report the clinical results of interpositional arthroplasty using acellular dermal matrix in 4 patients (age 32 to 42 years) for the treatment of advanced ankle osteoarthritis. The primary findings included relief of pain, with improvement in tibiotalar joint range of motion from a mean of 16.5° (range 0° to 24°) preoperatively to a mean of 31° (range 25° to 40°) postoperatively. All 4 patients underwent open arthrotomy of the anterior and posterior tibiotalar capsule with plafond exostectomy and debridement of all deleterious tissue within the ankle capsule. The articular surface of the talar dome was denuded down to smooth subchondral bone, and microfracture was performed. Autologous calcaneal bone marrow aspirate was applied, and talar resurfacing was achieved using an acellular dermal matrix. Knotless anchors placed medially and laterally within the anterior and posterior dome were used to affix the dermal matrix. The follow-up period ranged from 12 to 18 (mean 14) months. The mean pre- and 12-month postoperative Association of Orthopaedic Foot and Ankle Society hindfoot-ankle scale scores were 35 and 88.5, respectively. These outcomes suggest that interpositional tibiotalar arthroplasty using an acellular dermal matrix is successful in improving function and range of motion and decreasing pain. As an alternative to tibiotalar arthrodesis, interpositional tibiotalar arthroplasty might be the procedure of choice for young patients with end-stage ankle arthritis. Longer follow-up periods, histologic testing, and arthroscopic evaluations would be advantageous to further assess the durability of this procedure. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Repair of Postoperative Abdominal Hernia in a Child with Congenital Omphalocele Using Porcine Dermal Matrix

PubMed Central

Mylona, E.; Tsakalidis, C.; Spyridakis, I.; Mitsiakos, G.; Karagianni, P.

2016-01-01

Introduction. Incisional hernias are a common complication appearing after abdominal wall defects reconstruction, with omphalocele and gastroschisis being the most common etiologies in children. Abdominal closure of these defects represents a real challenge for pediatric surgeons with many surgical techniques and various prosthetic materials being used for this purpose. Case Report. We present a case of repair of a postoperative ventral hernia occurring after congenital omphalocele reconstruction in a three-and-a-half-year-old child using an acellular, sterile, porcine dermal mesh. Conclusion. Non-cross-linked acellular porcine dermal matrix is an appropriate mesh used for the reconstruction of abdominal wall defects and their postoperative complications like large ventral hernias with success and preventing their recurrence. PMID:27110247

Repair of Postoperative Abdominal Hernia in a Child with Congenital Omphalocele Using Porcine Dermal Matrix.

PubMed

Lambropoulos, V; Mylona, E; Mouravas, V; Tsakalidis, C; Spyridakis, I; Mitsiakos, G; Karagianni, P

2016-01-01

Introduction. Incisional hernias are a common complication appearing after abdominal wall defects reconstruction, with omphalocele and gastroschisis being the most common etiologies in children. Abdominal closure of these defects represents a real challenge for pediatric surgeons with many surgical techniques and various prosthetic materials being used for this purpose. Case Report. We present a case of repair of a postoperative ventral hernia occurring after congenital omphalocele reconstruction in a three-and-a-half-year-old child using an acellular, sterile, porcine dermal mesh. Conclusion. Non-cross-linked acellular porcine dermal matrix is an appropriate mesh used for the reconstruction of abdominal wall defects and their postoperative complications like large ventral hernias with success and preventing their recurrence.

A modified tensionless gingival grafting technique using acellular dermal matrix.

PubMed

Taylor, John B; Gerlach, Robert C; Herold, Robert W; Bisch, Frederick C; Dixon, Douglas R

2010-10-01

Conventional surgical procedures designed for autogenous tissue material may not be appropriate when using acellular dermal matrix (ADM) for the treatment of gingival recessions. This article describes a new surgical technique that addresses the unique and sensitive aspects of ADM specifically to improve esthetic outcomes and gain increased clinical predictability when treating Miller Class I and II gingival recession defects. In this paper, a root coverage case is described and the specific steps and rationale for this new technique are explained. This technique has been predictable clinically, with results comparable to those achieved using autogenous tissue.

A comparative clinical study of the efficacy of subepithelial connective tissue graft and acellular dermal matrix graft in root coverage: 6-month follow-up observation

PubMed Central

Thomas, Libby John; Emmadi, Pamela; Thyagarajan, Ramakrishnan; Namasivayam, Ambalavanan

2013-01-01

Aims: The purpose of this study was to compare the clinical efficacy of subepithelial connective tissue graft and acellular dermal matrix graft associated with coronally repositioned flap in the treatment of Miller's class I and II gingival recession, 6 months postoperatively. Settings and Design: Ten patients with bilateral Miller's class I or class II gingival recession were randomly divided into two groups using a split-mouth study design. Materials and Methods: Group I (10 sites) was treated with subepithelial connective tissue graft along with coronally repositioned flap and Group II (10 sites) treated with acellular dermal matrix graft along with coronally repositioned flap. Clinical parameters like recession height and width, probing pocket depth, clinical attachment level, and width of keratinized gingiva were evaluated at baseline, 90th day, and 180th day for both groups. The percentage of root coverage was calculated based on the comparison of the recession height from 0 to 180th day in both Groups I and II. Statistical Analysis Used: Intragroup parameters at different time points were measured using the Wilcoxon signed rank test and Mann–Whitney U test was employed to analyze the differences between test and control groups. Results: There was no statistically significant difference in recession height and width, gain in CAL, and increase in the width of keratinized gingiva between the two groups on the 180th day. Both procedures showed clinically and statistically significant root coverage (Group I 96%, Group II 89.1%) on the 180th day. Conclusions: The results indicate that coverage of denuded root with both subepithelial connective tissue autograft and acellular dermal matrix allograft are very predictable procedures, which were stable for 6 months postoperatively. PMID:24174728

Healing Rates in a Multicenter Assessment of a Sterile, Room Temperature, Acellular Dermal Matrix Versus Conventional Care Wound Management and an Active Comparator in the Treatment of Full-Thickness Diabetic Foot Ulcers.

PubMed

Walters, Jodi; Cazzell, Shawn; Pham, Hau; Vayser, Dean; Reyzelman, Alexander

2016-01-01

The purpose of this 16-week, multicenter, randomized, controlled trial was to assess the healed ulcer rate of a human acellular dermal matrix, DermACELL, compared with conventional care and a second acellular dermal matrix, Graftjacket, in the treatment of full-thickness diabetic foot ulcers. One hundred sixty-eight patients were randomized into DermACELL, conventional care, and Graftjacket treatment arms in a 2:2:1 ratio. Patients in the acellular dermal matrix groups received either 1 or 2 applications of the graft at the discretion of the investigator. Weekly follow-up visits were conducted until the ulcer healed or the endpoint was reached. At 16 weeks, the DermACELL arm had a significantly higher proportion of completely healed ulcers than the conventional care arm (67.9% vs 48.1%; P = .0385) and a nonsignificantly higher proportion than the Graftjacket arm (67.9% vs 47.8%; P = .1149). The DermACELL arm also exhibited a greater average percent reduction in wound area than the conventional care arm (91.4% vs 80.3%; P = .0791) and the Graftjacket arm (91.4% vs 73.5%; P = .0762). The proportion of severe adverse events and the proportion of overall early withdrawals were similar among the 3 groups based on relative population size (P ≥ .05). The results presented here indicate that DermACELL is an appropriate clinical option in the treatment of diabetic foot ulcers, with significant increases in healing rates and rate of percentage wound closure as compared with conventional care options.

Reconstruction of Traumatic Defect of the Lower Third of the Leg Using a Combined Therapy: Negative Pressure Wound Therapy, Acellular Dermal Matrix, and Skin Graft

PubMed Central

Brongo, Sergio; Campitiello, Nicola; Rubino, Corrado

2014-01-01

The reconstruction of lower third of the leg is one of the most challenging problems for plastic and reconstructive surgeons and current approaches are still disappointing. We show an easy option to obtain a coverage of traumatic pretibial defects with good aesthetic and functional results: the association of negative pressure wound therapy, acellular dermal matrix, and skin graft. The choice of this combined therapy avoids other surgical procedures such as local perforator flaps and free flaps that require more operating time, special equipment, and adequate training. PMID:25177509

Reconstruction of attached soft tissue around dental implants by acelluar dermal matrix grafts and resin splint

PubMed Central

Liu, Changying; Su, Yucheng; Tan, Baosheng; Ma, Pan; Wu, Gaoyi; Li, Jun; Geng, Wei

2014-01-01

Objectives: The purpose of this study was to recommend a new method using acellular dermal matrix graft and resin splint to reconstruct the attached soft tissue around dental implants in patients with maxillofacial defects. Materials and methods: Total 8 patients (3 male and 5 female patients) diagnosed with maxillofacial defects and dentition defects caused by tumors, fractures or edentulous jaw, were selected for this study. Dental implants were routinely implanted at the edentulous area. Acellular dermal matrix heterografts and resin splint were used to increase the attached soft tissue. The width of attached gingiva in the labial or buccal surface at edentulous area was measured before surgical procedures and after the completion of superstructures. Paired t-test was applied to assess the change of quantitative variables. All tests were 2-tailed, and P < 0.05 was considered statistically significant. Results: The dense connective tissue around implants could be reconstructed one month after the completion of surgical procedures, and the epithelial cuff around the implant neck established very well. The width of attached gingival tissue in the patients increased significantly from a mean of 0.61 ± 0.75 mm to 6.25 ± 1.04 mm. The patients were fully satisfied with the esthetic and functional results achieved. Conclusions: The acellular dermal matrix graft could be used to increase the attached gingiva around dental implants in these patients with maxillofacial defects. The resin splint could facilitate the healing of graft. PMID:25663964

Efficacy of micronized acellular dermal graft for use in interproximal papillae regeneration.

PubMed

Geurs, Nico C; Romanos, Alain H; Vassilopoulos, Philip J; Reddy, Michael S

2012-02-01

The aim of this study was to evaluate interdental papillary reconstruction based on a micronized acellular dermal matrix allograft technique. Thirty-eight papillae in 12 patients with esthetic complaints of insufficient papillae were evaluated. Decreased gingival recession values were found postoperatively (P < .001). Chi-square analysis showed significantly higher postoperative Papilla Index values (chi-square = 43, P < .001), further supported by positive symmetry statistical analysis values (positive kappa and weighted kappa values). This procedure shows promise as a method for papillary reconstruction.

A novel dermal matrix generated from burned skin as a promising substitute for deep-degree burns therapy

PubMed Central

YU, GUANYING; YE, LAN; TAN, WEI; ZHU, XUGUO; LI, YAONAN; JIANG, DUYIN

2016-01-01

The extensive skin defects induced by severe burns are dangerous and can be fatal. Currently, the most common therapy is tangential excision to remove the necrotic or denatured areas of skin, followed by skin grafting. Xenogeneic dermal substitutes, such as porcine acellular dermal matrix (ADM), are typically used to cover the burn wounds, and may accelerate wound healing. It is assumed that burned skin that still maintains partial biological activity may be recycled to construct an autologous acellular dermal matrix, termed 'deep-degree burned dermal matrix (DDBDM)'. In theory, DDBDM may avoid the histoincompatibility issues associated with foreign or xenogeneic dermal matrices, and reduce therapy costs by making full use of discarded skin. In the present study, the collagens within prepared DDBDM were thickened, disorganized and partially fractured, however, they still maintained their reticular structure and tensile strength (P<0.01). Through microarray analysis of the cytokines present in ADM and DDBDM, it was determined that the DDBDM did not produce excessive levels of harmful burn toxins. Following 4 weeks of subcutaneous implantation, ADM and DDBDM were incompletely degraded and maintained good integrity. No significant inflammatory reaction or rejection were observed, which indicated that ADM and DDBDM have good histocompatibility. Therefore, DDBDM may be a useful material for the treatment of deep-degree burns. PMID:26846279

Usefulness of Cross-Linked Human Acellular Dermal Matrix as an Implant for Dorsal Augmentation in Rhinoplasty.

PubMed

Yang, Chae Eun; Kim, Soo Jung; Kim, Ji Hee; Lee, Ju Hee; Roh, Tai Suk; Lee, Won Jai

2018-02-01

Asian noses are relatively small and flat compared to Caucasians; therefore, rhinoplasty procedures often focus on dorsal augmentation and tip projection rather than reduction in the nasal framework. Various autologous and alloplastic implant materials have been used for dorsal augmentation. Recently, human acellular dermal matrices have been introduced as an implant material for dorsal augmentation, camouflaging autologous implants without an additional donor site. Here, we introduce a cross-linked human acellular dermal matrix as an implant material in augmentation rhinoplasty and share the clinical experiences. Eighteen patients who underwent augmentation rhinoplasty using acellular dermal matrix from April 2014 to November 2015 were reviewed retrospectively. Clinical outcomes and complications were assessed at the outpatient clinic during the follow-up period ranging from 8 to 38 months. Contour changes were assessed through comparison of preoperative and postoperative photographs by two independent plastic surgeons. Patient satisfaction was assessed at the outpatient clinic by six questions regarding aesthetic and functional aspects. Postoperative photographs demonstrated the height of the nasal dorsum did not decrease over time except two patients whose ADM was grafted into a subperiosteal pocket. Others who underwent supraperiosteal implantation showed acceptable maintenance of dorsal height. No major complication was reported. Overall, patient satisfaction scored 81.02 out of 100. Cross-linked human ADM has advantages of both autogenous and alloplastic materials. The surgical results remain stable without complications. Therefore, it is a suitable alternative implant material for dorsal augmentation in rhinoplasty. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Application of the xenogenic acellular dermal matrix membrane application used in the postoperative tissue shortage repair].

PubMed

Bai, Yanxia; Yan, Liying; Zhang, Shaoqiang; Shao, Yuan; Yao, Xiaobao; Li, Honghui; Zhao, Ruimin; Zhao, Qian; Zhang, Pengfei; Yang, Qi

2014-09-01

To observe the short-term and long-term curative effect of the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer) application used in the 82 cases postoperative tissue shortage repair that after the head neck carcinoma resection. To held the 82 cases head neck carcinoma postoperative mucosa shortage repaired after resection by the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer), 65 cases mucosa shortage wound be directly covered by the repair membrane and the other 17 cases mucosa shortage wound be repaired by the tranfered muscle tissue flap with the repair membrane covered; 53 cases underwent additional postoperative radiotherapy between 2-4 weeks and follow-up in 1, 3, 6, 12, 18, 24, 30, 36, 48, 60 months and observed the operation site repair process through the electronic laryngoscope, observed the patients respiration, swallow, phonation function. Seventy-seven cases patients operation incision reached I phase healing standard, another 5 cases patients operation incision reached II phase healing standard because of the wound infection and fully-recovered through the local wound drainage,dressing process. All the patients tracheal cannula,the stomach tube be extubated successfully and without the local cicatricial constriction occurred. Seventy-eight cases follow up period reached 1 year including 53 cases who underwent postoperative radiotherapy, 49 cases follow up period reached 3 years including 32 cases who underwent postoperative radiotherapy, 14 cases follow up period reached 5 years including 12 cases who underwent postoperative radiotherapy. The patients with static local lesions discovered no reaction such as exclusion, allergy. The application of xenogenic acellular dermal matrix membrane (or joint muscle flap transfer used in in the postoperative tissue shortage repair that after the head neck carcinoma resection have several advantage such as comparatively easily implementation, operation safety edge enough,well preserved organ function, comparatively low incidence about the laryngeal stenosis, the short-term and long-term repair effect are all exact.

Yeasts from skin colonization are able to cross the acellular dermal matrix.

PubMed

Jarros, Isabele Carrilho; Okuno, Érika; Costa, Maiara Ignacio; Veiga, Flávia Franco; de Souza Bonfim-Mendonça, Patricia; Negri, Melyssa Fernanda Norman; Svidzinski, Terezinha Inez Estivalet

2018-04-01

In recent decades, the prognosis for burn patients has improved considerably with the development of specialized care. The acellular dermal matrix (ADM) is a totally artificial acellular device that functions to control water loss, prevent penetration by bacteria and allow migration of endothelial cells and fibroblasts from patient tissues. However, little is known about its effectiveness against yeasts. The present study evaluated the capacity of colonization and migration of some human commensal yeasts. Three clinical isolates from skin scales, identified as Candida parapsilosis, Candida glabrata and Rhodotorula mucilaginosa, were used. Their ability to cross the ADM was evaluated. After three days, all isolates had crossed the ADM. C. parapsilosis showed the lowest growth, while R. mucilaginosa showed intermediate and C. glabrata the highest growth. In the plates incubated for seven days, the growth of C. parapsilosis and C. glabrata increased by 1 log over the third day. All isolates have the capacity to colonize and migrate through the matrix, increasing the potential risk to burn patients, who can develop severe and even fatal infections by invasive fungi. Copyright © 2018 Elsevier Ltd. All rights reserved.

Repair of Primary Cleft Palate and Oronasal Fistula With Acellular Dermal Matrix: A Systematic Review and Surgeon Survey.

PubMed

Simpson, Andrew; Samargandi, Osama A; Wong, Alison; Graham, M Elise; Bezuhly, Michael

2018-01-01

The current review and survey aim to assess the effectiveness of acellular dermal matrix (ADM) in the repair of cleft palate and oronasal fistula and to evaluate the current trends of ADM use in palate surgery. A systematic review of English articles was conducted using MEDLINE (1960 to July 1, 2016), the Cochrane Controlled Trials Register (1960 to July 1, 2016), and EMBASE (1991 to July 1, 2016). Additional studies were identified through a review of references cited in initially identified articles. Search terms included "cleft palate," "palatal," "oronasal fistula," "acellular dermal matrix," and "Alloderm®." An online survey was disseminated to members of the American Cleft Palate-Craniofacial Association to assess current trends in ADM use in palate surgery. All studies evaluating the outcome of primary palate repair or repair of oronasal fistula with the use of aceullar dermal matrix products were included in the review. Twelve studies met inclusion criteria for review. Studies were generally of low quality, as indicated by methodological index for non-randomized studies (MINORS) scores ranging from 7 to 14. The pooled estimate for fistula formation after primary palatoplasty following ADM use was 7.1%. The pooled estimate for recurrence of fistula after attempted repair using ADM was 11%. Thirty-six cleft surgeons responded to the online survey study. Of these, 45% used ADM in primary cleft palate repair, while 67% used ADM for repair of oronasal fistulae. Use of ADM products is commonplace in palate surgery. Despite this, there is a paucity of high-quality data demonstrating benefit. Further randomized controlled trials examining ADM in palate surgery are required to help develop structured guidelines and improve care.

Combined periodontal and restorative approach to the treatment of gingival recessions with noncarious cervical lesions: a case treated with acellular dermal matrix allograft and compomer restorations.

PubMed

Efeoğlu, Ahmet; Hanzade, Mete; Sari, Esra; Alpay, Hande; Karakaş, Ozan; Koray, Fatma

2012-08-01

Treatment of gingival recessions has become one of the most challenging procedures in periodontal plastic surgery. Various surgical options with predictable outcomes are available, but in cases with cervical lesions or restorations, optimal functional and esthetic results may require the combination of periodontal and restorative procedures. In this case report, one patient treated with acellular dermal matrix allograft and a coronally positioned flap in combination with compomer cervical restorations is presented. Clinical parameters were recorded immediately prior to surgery and after 12 months. Postoperatively, significant root coverage, reductions in probing depths, and gains in clinical attachment were observed. The final clinical results, esthetics, color match, and tissue contours were acceptable to both the patient and clinicians.

Nerve Wrapping of the Sciatic Nerve With Acellular Dermal Matrix in Chronic Complete Proximal Hamstring Ruptures and Ischial Apophyseal Avulsion Fractures

PubMed Central

Haus, Brian M.; Arora, Danny; Upton, Joseph; Micheli, Lyle J.

2016-01-01

Background: Patients with chronic injuries of the proximal hamstring can develop significant impairment because of weakness of the hamstring muscles, sciatic nerve compression from scar formation, or myositis ossificans. Purpose: To describe the surgical outcomes of patients with chronic injury of the proximal hamstrings who were treated with hamstring repair and sciatic neurolysis supplemented with nerve wrapping with acellular dermal matrix. Study Design: Retrospective case series; Level of evidence, 4. Methods: Fifteen consecutive patients with a diagnosis of chronic complete proximal hamstring rupture or chronic ischial tuberosity apophyseal avulsion fracture (mean age, 39.67 years; range, 14-69 years) were treated with proximal hamstring repair and sciatic neurolysis supplemented with nerve wrapping with acellular dermal matrix. Nine patients had preoperative sciatica, and 6 did not. Retrospective chart review recorded clinical outcomes measured by the degree of pain relief, the rate of return to activities, and associated postoperative complications. Results: All 15 patients were followed in the postoperative period for an average of 16.6 months. Postoperatively, there were 4 cases of transient sciatic nerve neurapraxia. Four patients (26%) required postoperative betamethasone sodium phosphate (Celestone Soluspan) injectable suspension USP 6 mg/mL. Among the 9 patients with preoperative sciatica, 6 (66%) had a good or excellent outcome and were able to return to their respective activities/sports; 3 (33%) had persistent chronic pain. One of these had persistent sciatic neuropathy that required 2 surgical reexplorations and scar excision after development of recurrent extraneural scar formation. Among the 6 without preoperative sciatica, 100% had a good or excellent outcomes and 83% returned to their respective activities/sports. Better outcomes were observed in younger patients, as the 3 cases of persistent chronic sciatic pain were in patients older than 45 years. Conclusion: This study suggests that when used as an adjunct to sciatic neurolysis, nerve wrapping with acellular dermal matrix can be a safe and effective method of treating younger patients with and preventing the development of sciatic neuropathic pain after chronic injury of the proximal hamstrings. PMID:27081655

Co-Graft of Acellular Dermal Matrix and Autogenous Microskin in a Child with Extensive Burns

PubMed Central

Chen, X.L.; Xia, Z.F.; Fang, L.S.; Wang, Y.J.; Wang, C.H.

2008-01-01

Summary A 6-yr-old boy was the victim of a burns accident in a public bathhouse. The burns involved the face, neck, upper and lower extremities, anterior and posterior trunk, and both buttocks, covering 72% of the total body surface area (TBSA). The lesions in the lower extremities and parts of the right upper extremity were deep partial-thickness, comprising 40% TBSA. On day 5 post-burn, the lesions in both lower extremities were excised to the extent of the fascia under general anaesthesia. Meshed J1 Jayya Acellular Dermis®, a kind of acellular allodermal (ADM) matrix, was then placed on the left knee joint. The right knee joint served as control. The wounds in both lower extremities were then overlaid with microskin autografting. At 19 days post-application, the lesions in both lower extremities had almost completely resurfaced. Follow-up at six months revealed well-healed and stable skin of acellular ADM and microskin autografts on the left knee. However, the skin of the right knee was unstable and there was a chronic residual ulcer. Both legs showed some significant hypertrophic scars. The left knee joint (acellular ADM grafted site) showed mild contractures, while the right knee joint developed a significant contracture. The "skin" of the co-graft covered site appeared thicker and more elastic. The movement range of the left knee joint was much larger than that of the right knee joint. These results suggest that co-graft of acellular dermal matrix and autogenous microskin may be an effective way to repair this functional site in children with extensive burns and to improve the functional and cosmetic results. PMID:21991120

Cost minimisation analysis of using acellular dermal matrix (Strattice™) for breast reconstruction compared with standard techniques.

PubMed

Johnson, R K; Wright, C K; Gandhi, A; Charny, M C; Barr, L

2013-03-01

We performed a cost analysis (using UK 2011/12 NHS tariffs as a proxy for cost) comparing immediate breast reconstruction using the new one-stage technique of acellular dermal matrix (Strattice™) with implant versus the standard alternative techniques of tissue expander (TE)/implant as a two-stage procedure and latissimus dorsi (LD) flap reconstruction. Clinical report data were collected for operative time, length of stay, outpatient procedures, and number of elective and emergency admissions in our first consecutive 24 patients undergoing one-stage Strattice reconstruction. Total cost to the NHS based on tariff, assuming top-up payments to cover Strattice acquisition costs, was assessed and compared to the two historical control groups matched on key variables. Eleven patients having unilateral Strattice reconstruction were compared to 10 having TE/implant reconstruction and 10 having LD flap and implant reconstruction. Thirteen patients having bilateral Strattice reconstruction were compared to 12 having bilateral TE/implant reconstruction. Total costs were: unilateral Strattice, £3685; unilateral TE, £4985; unilateral LD and implant, £6321; bilateral TE, £5478; and bilateral Strattice, £6771. The cost analysis shows a financial advantage of using acellular dermal matrix (Strattice) in unilateral breast reconstruction versus alternative procedures. The reimbursement system in England (Payment by Results) is based on disease-related groups similar to that of many countries across Europe and tariffs are based on reported hospital costs, making this analysis of relevance in other countries. Copyright © 2013 Elsevier Ltd. All rights reserved.

A comparative study of root coverage using two different acellular dermal matrix products.

PubMed

Barker, Thomas S; Cueva, Marco A; Rivera-Hidalgo, Francisco; Beach, M Miles; Rossmann, Jeffrey A; Kerns, David G; Crump, T Bradley; Shulman, Jay D

2010-11-01

Gingival recession remains an important problem in dental esthetics. A new dermal matrix material has been introduced, but its effectiveness has not been studied and compared to current dermal matrix material. The aim of this study is to compare the healing associated with a coronally advanced flap for root coverage in areas of localized tissue recession when using Alloderm (ADM) and Puros Dermis (PDM). A split-mouth design was used for this study, with 52 contralateral sites in 14 patients with Miller Class I or III facial tissue recession. Twenty-six sites were treated with coronally advanced flap using PDM, and 26 sites were treated with coronally advanced flap using ADM, all followed for 6 months. Clinical measurements of vertical recession, keratinized tissue, probing depths, and attachment levels were made initially, at 3 months, and at 6 months. Both groups had significant improvement in the amount of recession coverage with means of 2.83 mm for the PDM and 3.13 mm for the ADM. The percentage of root coverage was 81.4% for the PDM and 83.4% for the ADM; differences between the materials were not statistically significant. Based on the results of this study, there was no statistical or clinical difference in the amount of root coverage, probing depth, or keratinized tissue in coronally advanced flaps for root coverage with either of the two acellular dermal matrix materials. Both materials were successful in achieving root coverage.

Placement of a Non–Cross-Linked Porcine-Derived Acellular Dermal Matrix During Preperitoneal Laparoscopic Inguinal Hernia Repair

PubMed Central

Alshkaki, Giath

2013-01-01

This retrospective chart review evaluated outcomes following laparoscopic inguinal herniorrhaphies with non–cross-linked intact porcine-derived acellular dermal matrix (PADM) by one surgeon in a community teaching facility hospital. Mesh was sutured and/or tacked in the preperitoneal space. Postoperative visits were scheduled at 2 weeks, 3 months, and 6 months, and then at 6-month intervals up to 2 years. PADM was placed in 14 male patients (mean age, 41.1 years). Seven patients had bilateral hernias. One patient required intraoperative conversion to open herniorrhaphy based on diagnostic laparoscopy findings. PADM sizes were 6 × 10 to 12 × 16 cm; mean operative time was 102 minutes. All patients were discharged on the day of surgery and resumed full activity. This treatment approach was effective, with no recurrence or complications during a median follow-up period of 18 months (range, 13–25 months). PMID:23701148

Placement of a non-cross-linked porcine-derived acellular dermal matrix during preperitoneal laparoscopic inguinal hernia repair.

PubMed

Alshkaki, Giath

2013-01-01

This retrospective chart review evaluated outcomes following laparoscopic inguinal herniorrhaphies with non-cross-linked intact porcine-derived acellular dermal matrix (PADM) by one surgeon in a community teaching facility hospital. Mesh was sutured and/or tacked in the preperitoneal space. Postoperative visits were scheduled at 2 weeks, 3 months, and 6 months, and then at 6-month intervals up to 2 years. PADM was placed in 14 male patients (mean age, 41.1 years). Seven patients had bilateral hernias. One patient required intraoperative conversion to open herniorrhaphy based on diagnostic laparoscopy findings. PADM sizes were 6 × 10 to 12 × 16 cm; mean operative time was 102 minutes. All patients were discharged on the day of surgery and resumed full activity. This treatment approach was effective, with no recurrence or complications during a median follow-up period of 18 months (range, 13-25 months).

Healing rate and autoimmune safety of full-thickness wounds treated with fish skin acellular dermal matrix versus porcine small-intestine submucosa: a noninferiority study.

PubMed

Baldursson, Baldur Tumi; Kjartansson, Hilmar; Konrádsdóttir, Fífa; Gudnason, Palmar; Sigurjonsson, Gudmundur F; Lund, Sigrún Helga

2015-03-01

A novel product, the fish skin acellular dermal matrix (ADM) has recently been introduced into the family of biological materials for the treatment of wounds. Hitherto, these products have been produced from the organs of livestock. A noninferiority test was used to compare the effect of fish skin ADM against porcine small-intestine submucosa extracellular matrix in the healing of 162 full-thickness 4-mm wounds on the forearm of 81 volunteers. The fish skin product was noninferior at the primary end point, healing at 28 days. Furthermore, the wounds treated with fish skin acellular matrix healed significantly faster. These results might give the fish skin ADM an advantage because of its environmental neutrality when compared with livestock-derived products. The study results on these acute full-thickness wounds might apply for diabetic foot ulcers and other chronic full-thickness wounds, and the shorter healing time for the fish skin-treated group could influence treatment decisions. To test the autoimmune reactivity of the fish skin, the participants were tested with the following ELISA (enzyme-linked immunosorbent assay) tests: RF, ANA, ENA, anti ds-DNA, ANCA, anti-CCP, and anticollagen I and II. These showed no reactivity. The results demonstrate the claims of safety and efficacy of fish skin ADM for wound care. © The Author(s) 2015.

Histologic analysis of fetal bovine derived acellular dermal matrix in tissue expander breast reconstruction.

PubMed

Gaster, Richard S; Berger, Aaron J; Monica, Stefanie D; Sweeney, Robert T; Endress, Ryan; Lee, Gordon K

2013-04-01

This study seeks to determine human host response to fetal bovine acellular dermal matrix (ADM) in staged implant-based breast reconstruction. A prospective study was performed for patients undergoing immediate breast reconstruction with tissue expander placement and SurgiMend acellular fetal bovine dermis. At the time of exchange for permanent implant, we obtained tissue specimens of SurgiMend and native capsule. Histological and immunohistochemical assays were performed to characterize the extent of ADM incorporation/degradation, host cell infiltration, neovascularization, inflammation, and host replacement of acellular fetal bovine collagen. Seventeen capsules from 12 patients were included in our study. The average "implantation" time of SurgiMend was 7.8 months (range, 2-23 months). Histological analysis of the biopsy of tissue revealed rare infiltration of host inflammatory cells, even at 23 months. One patient had an infection requiring removal of the tissue expander at 2 months. Contracture, inflammatory changes, edema, and polymorphonuclear leukocyte infiltration were rare in the ADM. An acellular capsule was seen in many cases, at the interface of SurgiMend with the tissue expander. SurgiMend demonstrated a very infrequent inflammatory response. An antibody specific to bovine collagen allowed for direct identification of bovine collagen separate from human collagen. Cellular infiltration and neovascularization of SurgiMend correlated with the quality of the mastectomy skin flap rather than the duration of implantation. Future studies are needed to further characterize the molecular mechanisms underlying tissue incorporation of this product.

Surgical Outcomes of Deep Superior Sulcus Augmentation Using Acellular Human Dermal Matrix in Anophthalmic or Phthisis Socket.

PubMed

Cho, Won-Kyung; Jung, Su-Kyung; Paik, Ji-Sun; Yang, Suk-Woo

2016-07-01

Patients with anophthalmic or phthisis socket suffer from cosmetic problems. To resolve those problems, the authors present the surgical outcomes of deep superior sulcus (DSS) augmentation using acellular dermal matrix in patients with anophthalmic or phthisis socket. The authors retrospectively reviewed anophthalmic or phthisis patients who underwent surgery for DSS augmentation using acellular dermal matrix. To evaluate surgical outcomes, the authors focused on 3 aspects: the possibility of wearing contact prosthesis, the degree of correction of the DSS, and any surgical complications. The degree of correction of DSS was classified as excellent: restoration of superior sulcus enough to remove sunken sulcus shadow; fair: gain of correction effect but sunken shadow remained; or fail: no effect of correction at all. Ten eyes of 10 patients were included. There was a mean 21.3 ± 37.1-month period from evisceration or enucleation to the operation for DSS augmentation. All patients could wear contact prosthesis after the operation (100%). The degree of correction was excellent in 8 patients (80%) and fair in 2. Three of 10 (30%) showed complications: eyelid entropion, upper eyelid multiple creases, and spontaneous wound dehiscence followed by inflammation after stitch removal. Uneven skin surface and paresthesia in the forehead area of the affected eye may be observed after surgery. The overall surgical outcomes were favorable, showing an excellent degree of correction of DSS and low surgical complication rates. This procedure is effective for patients who have DSS in the absence or atrophy of the eyeball.

Dermal Papilla Cells Improve the Wound Healing Process and Generate Hair Bud-Like Structures in Grafted Skin Substitutes Using Hair Follicle Stem Cells

PubMed Central

Leirós, Gustavo José; Kusinsky, Ana Gabriela; Drago, Hugo; Bossi, Silvia; Sturla, Flavio; Castellanos, María Lía; Stella, Inés Yolanda

2014-01-01

Tissue-engineered skin represents a useful strategy for the treatment of deep skin injuries and might contribute to the understanding of skin regeneration. The use of dermal papilla cells (DPCs) as a dermal component in a permanent composite skin with human hair follicle stem cells (HFSCs) was evaluated by studying the tissue-engineered skin architecture, stem cell persistence, hair regeneration, and graft-take in nude mice. A porcine acellular dermal matrix was seeded with HFSCs alone and with HFSCs plus human DPCs or dermal fibroblasts (DFs). In vitro, the presence of DPCs induced a more regular and multilayered stratified epidermis with more basal p63-positive cells and invaginations. The DPC-containing constructs more accurately mimicked the skin architecture by properly stratifying the differentiating HFSCs and developing a well-ordered epithelia that contributed to more closely recapitulate an artificial human skin. This acellular dermal matrix previously repopulated in vitro with HFSCs and DFs or DPCs as the dermal component was grafted in nude mice. The presence of DPCs in the composite substitute not only favored early neovascularization, good assimilation and remodeling after grafting but also contributed to the neovascular network maturation, which might reduce the inflammation process, resulting in a better healing process, with less scarring and wound contraction. Interestingly, only DPC-containing constructs showed embryonic hair bud-like structures with cells of human origin, presence of precursor epithelial cells, and expression of a hair differentiation marker. Although preliminary, these findings have demonstrated the importance of the presence of DPCs for proper skin repair. PMID:25161315

Fetal Bovine Dermal Repair Scaffold Used for the Treatment of Difficult-to- Heal Complex Wounds.

PubMed

Strauss, Neil H; Brietstein, Richard J

2012-11-01

 Introduction. Treating difficult-to-heal wounds with complexities, including those with exposed tendon/bone or infection, is a challenge that regularly confronts practitioners in a variety of clinical environments. The purpose of this study was to review the effectiveness of an acellular fetal bovine dermal repair scaffold (PriMatrix Dermal Repair Scaffold, TEI Biosciences, Inc, Boston, MA) used to treat complex difficult-to-heal wounds presenting in the authors' practice. A retrospective chart review was conducted of a single practice with multiple practicing physicians between 2008 and 2010. Over this time period, 70 patients with 83 wounds were treated with the acellular fetal bovine dermis following surgical debridement of the wound. Forty-nine patients (58 wounds) met established inclusion/exclusioncriteria and were critically evaluated. Wounds treated with the acellular fetal bovine dermis included chronic diabetic wounds, venous wounds, and pressure ulcers, as well as wounds caused by trauma and surgery. Additionally, the patients treated had comorbidities commonly associated with recalcitrant wounds. Of the wounds evaluated in this study, 75.9% successfully healed; 63.8% reepithelialized, and 12.1% were closed with a skin graft subsequent to treatment. Notably, the majority (58.6%) of the wounds reepithelialized by 12 weeks following a single application of the dermal repair scaffold. In the subset of challenging wounds with exposed tendon/bone, 80.8% of the wounds were treated successfully (61.5% reepithelialized, and 19.3% were skin grafted), indicating the successful regeneration and reepithelialization of new vascularized tissue by fetal dermal collagen in relatively avascular wound defects. The acellular fetal bovine dermal repair scaffold can be used as part of an effective treatment regimen to heal complex wounds with exposed tendon/bone caused by varying etiologies. The product actively participates in the generation of a new, vascularized tissue capable of reepithelializing, or successfully supporting, a split-thickness skin graft in defects where initial grafting or living skin substitutes are not viable options. .

Comparison of acellular dermal matrix and synthetic mesh for lateral chest wall reconstruction in a rabbit model.

PubMed

Holton, Luther H; Chung, Thomas; Silverman, Ronald P; Haerian, Hafez; Goldberg, Nelson H; Burrows, Whitney M; Gobin, Andrea; Butler, Charles E

2007-04-01

Synthetic mesh is used for chest wall reconstruction, but infection or exposure can occur and necessitate removal. Human acellular dermal matrix (AlloDerm) has been used to reconstruct musculofascial defects in the trunk with low infection and herniation rates. AlloDerm may have advantages over synthetic mesh for chest wall reconstruction. This study compared outcomes and repair strengths of AlloDerm to expanded polytetrafluoroethylene mesh used for repair of rib cage defects. A 3 x 3-cm, full-thickness, lateral rib cage defect was created in each rabbit and repaired with expanded polytetrafluoroethylene (n = 8) or acellular dermal matrix (n = 9). At 4 weeks, the animals were euthanized and evaluated for lung herniation/dehiscence, strength of adhesions between the implant and intrapleural structures, and breaking strength of the implant materials and the implant-fascia interface. Tissue sections were analyzed with histologic and immunohistochemical staining to evaluate cellular infiltration and vascularization. No herniation or dehiscence occurred with either material. The incidence and strength of adhesions was similar between materials. The mean breaking strength of the AlloDerm-fascia interface (14.5 +/- 8.9 N) was greater than the expanded polytetrafluoroethylene-fascia interface (8.7 +/- 4.4 N; p = 0.027) and similar to the rib-intercostal-rib interface of the contralateral native chest wall (14.0 +/- 5.6 N). The AlloDerm grafts became infiltrated with cells and vascularized after implantation. AlloDerm used for chest wall reconstruction results in greater implant-defect interface strength than expanded polytetrafluoroethylene. The ability of AlloDerm to become vascularized and remodeled by autologous cells and to resist infection may be advantageous for chest wall reconstruction.

Human versus non-cross-linked porcine acellular dermal matrix used for ventral hernia repair: comparison of in vivo fibrovascular remodeling and mechanical repair strength.

PubMed

Campbell, Kristin Turza; Burns, Nadja K; Rios, Carmen N; Mathur, Anshu B; Butler, Charles E

2011-06-01

Human acellular dermal matrix (HADM) and non-cross-linked porcine acellular dermal matrix (ncl-PADM) are clinically useful for complex ventral hernia repair. Direct comparisons between the two in vivo are lacking, however. This study compared clinically relevant early outcomes with these bioprosthetic materials when used for ventral hernia repair. Seventy-two guinea pigs underwent inlay repair of surgically created hernias with HADM (n = 37) or ncl-PADM (n = 35). Repair sites were harvested at 1, 2, or 4 weeks postoperatively. Adhesions were graded and quantified. Mechanical testing and histologic and immunohistologic (factor VIII) analyses of cellular and vascular infiltration were performed. No infections or recurrent hernias occurred. No difference was observed in mean adhesion surface area or tenacity between groups. Mean cellular infiltration (p < 0.002, weeks 1 and 4; p < 0.006, week 2) and vascular infiltration (p < 0.0003, week 1; p < 0.0001, weeks 2 and 4) were greater in HADM. Ultimate tensile strength at the implant-musculofascia interface increased over time with both materials, but no difference was observed at 4 weeks. The mean ultimate tensile strength of explanted ncl-PADM itself was consistently greater than that of HADM. The elastic modulus (stiffness) did not differ between groups at the interface but was greater in explanted ncl-PADM (p < 0.0001, weeks 1 and 2; p < 0.02, week 4). Both HADM and ncl-PADM become infiltrated with host cells and blood vessels within 4 weeks and have similar musculofascia-bioprosthetic interface strength. However, HADM has greater cellular and vascular infiltration. Longer-term studies will help determine whether later differences in material strength, stiffness, and remodeling affect hernia and/or bulge incidence.

Bovine Acellular Dermal Matrix for Levator Lengthening in Thyroid-Related Upper-Eyelid Retraction.

PubMed

Sun, Jing; Liu, Xingtong; Zhang, Yidan; Huang, Yazhuo; Zhong, Sisi; Fang, Sijie; Zhuang, Ai; Li, Yinwei; Zhou, Huifang; Fan, Xianqun

2018-05-02

BACKGROUND Eyelid retraction is the most common and often the first sign of thyroid eye disease (TED). Upper-eyelid retraction causes both functional and cosmetic problems. In order to correct the position of the upper eyelid, surgery is required. Many procedures have demonstrated good outcomes in mild and moderate cases; however, unpredictable results have been obtained in severe cases. Dryden introduced an upper-eyelid-lengthening procedure, which used scleral grafts, but outcomes were unsatisfactory. A new technique is introduced in this study as a reasonable alternative for TED-related severe upper-eyelid retraction correction. MATERIAL AND METHODS An innovative technique for levator lengthening using bovine acellular dermal matrix as a spacer graft is introduced for severe upper-eyelid retraction secondary to TED. Additionally, 2 modifications were introduced: the fibrous cords scattered on the surface of the levator aponeurosis were excised and the orbital fat pad anterior to the aponeurosis was dissected and sutured into the skin closure in a "skin-tarsus-fat-skin" fashion. RESULTS The modified levator-lengthening surgery was performed on 32 eyelids in 26 patients consisting of 21 women and 5 men (mean age, 37.8 years; age range, 19-67 years). After corrective surgery, the average upper margin reflex distance was lowered from 7.7±0.85 mm to 3.3±0.43 mm. Eighteen cases (69%) had perfect results, while 6 cases (23%) had acceptable results. CONCLUSIONS A modified levator-lengthening procedure using bovine acellular dermal matrix as a spacer graft ameliorated both the symptoms and signs of severe upper-eyelid retraction secondary to TED. This procedure is a reasonable alternative for correction of TED-related severe upper-eyelid retraction.

Bovine Acellular Dermal Matrix for Levator Lengthening in Thyroid-Related Upper-Eyelid Retraction

PubMed Central

Sun, Jing; Liu, Xingtong; Zhang, Yidan; Huang, Yazhuo; Zhong, Sisi; Fang, Sijie; Zhuang, Ai; Li, Yinwei; Zhou, Huifang

2018-01-01

Background Eyelid retraction is the most common and often the first sign of thyroid eye disease (TED). Upper-eyelid retraction causes both functional and cosmetic problems. In order to correct the position of the upper eyelid, surgery is required. Many procedures have demonstrated good outcomes in mild and moderate cases; however, unpredictable results have been obtained in severe cases. Dryden introduced an upper-eyelid-lengthening procedure, which used scleral grafts, but outcomes were unsatisfactory. A new technique is introduced in this study as a reasonable alternative for TED-related severe upper-eyelid retraction correction. Material/Methods An innovative technique for levator lengthening using bovine acellular dermal matrix as a spacer graft is introduced for severe upper-eyelid retraction secondary to TED. Additionally, 2 modifications were introduced: the fibrous cords scattered on the surface of the levator aponeurosis were excised and the orbital fat pad anterior to the aponeurosis was dissected and sutured into the skin closure in a “skin-tarsus-fat-skin” fashion. Results The modified levator-lengthening surgery was performed on 32 eyelids in 26 patients consisting of 21 women and 5 men (mean age, 37.8 years; age range, 19–67 years). After corrective surgery, the average upper margin reflex distance was lowered from 7.7±0.85 mm to 3.3±0.43 mm. Eighteen cases (69%) had perfect results, while 6 cases (23%) had acceptable results. Conclusions A modified levator-lengthening procedure using bovine acellular dermal matrix as a spacer graft ameliorated both the symptoms and signs of severe upper-eyelid retraction secondary to TED. This procedure is a reasonable alternative for correction of TED-related severe upper-eyelid retraction. PMID:29718902

The high failure rate of biologic resurfacing of the glenoid in young patients with glenohumeral arthritis.

PubMed

Strauss, Eric J; Verma, Nikhil N; Salata, Michael J; McGill, Kevin C; Klifto, Christopher; Nicholson, Gregory P; Cole, Brian J; Romeo, Anthony A

2014-03-01

The current study evaluated the outcomes of biologic resurfacing of the glenoid using a lateral meniscus allograft or human acellular dermal tissue matrix at intermediate-term follow-up. Forty-five patients (mean age, 42.2 years) underwent biologic resurfacing of the glenoid, and 41 were available for follow-up at a mean of 2.8 years. Lateral meniscal allograft resurfacing was used in 31 patients and human acellular dermal tissue matrix interposition in 10. Postoperative range of motion and clinical outcomes were assessed at the final follow-up. The overall clinical failure rate was 51.2%. The lateral meniscal allograft cohort had a failure rate of 45.2%, with a mean time to failure of 3.4 years. Human acellular dermal tissue matrix interposition had a failure rate of 70.0%, with a mean time to failure of 2.2 years. Overall, significant improvements were seen compared with baseline with respect to the visual analog pain score (3.0 vs. 6.3), American Shoulder and Elbow Surgeons score (62.0 vs. 36.8), and Simple Shoulder Test score (7.0 vs. 4.0). Significant improvements were seen for forward elevation (106° to 138°) and external rotation (31° to 51°). Despite significant improvements compared with baseline values, biologic resurfacing of the glenoid resulted in a high rate of clinical failure at intermediate follow-up. Our results suggest that biologic resurfacing of the glenoid may have a minimal and as yet undefined role in the management of glenohumeral arthritis in the young active patient over more traditional methods of hemiarthroplasty or total shoulder arthroplasty. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Histologic analysis of the acellular dermal matrix graft incorporation process: a pilot study in dogs.

PubMed

Luczyszyn, Sonia M; Grisi, Márcio F M; Novaes, Arthur B; Palioto, Daniela B; Souza, Sérgio L S; Taba, Mario

2007-08-01

Clinical results with acellular dermal matrix graft (ADMG) in periodontal surgeries suggest that the material is incorporated by the host tissues. However, histologic studies of the ADMG incorporation process are limited. The objective of this study was to evaluate the incorporation of ADMG into gingival tissues in a dog model. Gingival recession-type defects were created at the canines of six dogs. After 6 weeks, periodontal surgeries to repair the defects were performed using ADMG. Two animals each were sacrificed after 4, 8, and 12 weeks. At 4 weeks, thick collagen fibers from the ADMG were clearly seen in the connective tissue, and some blood vessels were penetrating into the ADMG. At 8 weeks, blood vessel penetration was enhanced, and collagen fiber bundles from the ADMG were seen sending branches into the connective tissue in all directions. After 12 weeks, the ADMG and the connective tissue seemed to be well integrated into a single highly vascularized structure, indicating almost complete incorporation of the ADMG.

Use of latissimus dorsi muscle onlay patch alternative to acellular dermal matrix in implant-based breast reconstruction

PubMed Central

Lee, Jeeyeon

2015-01-01

Background An acellular dermal matrix (ADM) is applied to release the surrounding muscles and prevent dislocation or rippling of the implant. We compared implant-based breast reconstruction using the latissimus dorsi (LD) muscle, referred to as an “LD muscle onlay patch,” with using an ADM. Method A total of 56 patients (60 breasts) underwent nipple sparing mastectomy with implant-based breast reconstruction using an ADM or LD muscle onlay patch. Cosmetic outcomes were assessed 4 weeks after chemotherapy or radiotherapy, and statistical analyses were performed. Results Mean surgical time and hospital stay were significantly longer in the LD muscle onlay patch group than the ADM group. However, there were no statistically significant differences between groups in postoperative complications. Cosmetic outcomes for breast symmetry and shape were higher in the LD muscle onlay patch group. Conclusions Implant-based breast reconstruction with an LD muscle onlay patch would be a feasible alternative to using an ADM. PMID:26161312

Predictable root recession coverage.

PubMed

Hoexter, David L

2006-01-01

Gingival recession, exposure of the tooth's root, is undesirable and, in many situations, contrary to normal physiology. Today's root coverage is predictable. With the use of an acellular dermal matrix membrane (Fasciablast), we can achieve a new blood supply and predictable coverage, with no second surgical procedure. Youth, esthetics and physiology are restored.

Acellular dermal matrix graft with or without enamel matrix derivative for root coverage in smokers: a randomized clinical study.

PubMed

Alves, Luciana B; Costa, Priscila P; Scombatti de Souza, Sérgio Luís; de Moraes Grisi, Márcio F; Palioto, Daniela B; Taba, Mario; Novaes, Arthur B

2012-04-01

The aim of this randomized controlled clinical study was to compare the use of an acellular dermal matrix graft (ADMG) with or without the enamel matrix derivative (EMD) in smokers to evaluate which procedure would provide better root coverage. Nineteen smokers with bilateral Miller Class I or II gingival recessions ≥3 mm were selected. The test group was treated with an association of ADMG and EMD, and the control group with ADMG alone. Probing depth, relative clinical attachment level, gingival recession height, gingival recession width, keratinized tissue width and keratinized tissue thickness were evaluated before the surgeries and after 6 months. Wilcoxon test was used for the statistical analysis at significance level of 5%. No significant differences were found between groups in all parameters at baseline. The mean gain recession height between baseline and 6 months and the complete root coverage favored the test group (p = 0.042, p = 0.019 respectively). Smoking may negatively affect the results achieved through periodontal plastic procedures; however, the association of ADMG and EMD is beneficial in the root coverage of gingival recessions in smokers, 6 months after the surgery. © 2012 John Wiley & Sons A/S.

Reconstruction of the pelvic floor and perineum with human acellular dermal matrix and thigh flaps following pelvic exenteration.

PubMed

Said, Hakim K; Bevers, Michael; Butler, Charles E

2007-12-01

Patients who undergo pelvic floor resection as treatment for recurrent cancer following radiation therapy have increased rates of complications, particularly if permanent prosthetic mesh is used for reconstruction. Human acellular dermal matrix (HADM), commonly used for reconstruction in other torso locations, is associated with lower rates of complications (including infection, adhesions and cutaneous exposure) than synthetic mesh. We describe an effective technique to reconstruct the pelvic floor and perineum with HADM and thigh-based flaps following pelvic exenteration and radical vulvectomy. A 75-year-old woman underwent radical resection of the pelvic floor and perineum to treat recurrent vulvar squamous cell carcinoma and osteoradionecrosis. The pelvic floor and perineal soft tissue defect were reconstructed with HADM (AlloDerm; LifeCell Corporation, Branchburg, NJ) and bilateral, thigh-based tissue flaps, respectively. Despite a large resection, previous irradiation therapy and bacterial contamination the wounds healed without complications. Reconstruction of pelvic floor defects using HADM is an option when wound conditions are unfavorable for the use of permanent prosthetic meshes.

Hospital readmission following open, single-stage, elective abdominal wall reconstructions using acellular dermal matrix affects long-term hernia recurrence rate.

PubMed

Giordano, Salvatore A; Garvey, Patrick B; Baumann, Donald P; Liu, Jun; Butler, Charles E

2018-02-05

We evaluated the incidence of and the risk factors for readmission in patients who underwent abdominal wall reconstruction (AWR) using acellular dermal matrix (ADM) and assess whether readmission affects AWR long-term outcomes. A retrospective, single-center study of patients underwent AWR with ADM was conducted. The primary outcome was the incidence of unplanned readmission within 30 days after the initial discharge post-AWR. Secondary outcomes were surgical site occurrence (SSO) and hernia recurrence at follow-up. Of 452 patients (mean age, 59 years; mean follow-up, 35 months), 29 (6.4%) were readmitted within 30 days. Most readmissions were due to SSO (44.8%) or wound infections (12.8%). The hernia recurrence rate was significantly higher in readmitted patients (17.2% vs 9.9%; P = 0.044). Wider defects, prolonged operative time, and coronary artery disease were independent predictors of readmission. Readmission is associated with hernia recurrence on long-term follow-up. SSO is the most common cause for readmission. Copyright © 2018 Elsevier Inc. All rights reserved.

Tunneling procedure for root coverage using acellular dermal matrix: a case series.

PubMed

Modaressi, Marmar; Wang, Hom-Lay

2009-08-01

This study was designed to demonstrate the use of the relatively novel tunneling technique for root coverage with acellular dermal matrix (ADM) to treat Miller Class I and II gingival recession defects. Five subjects with two to five adjacent buccal gingival recession defects were treated with ADM using the tunneling technique for root coverage. A calibrated, blinded examiner measured clinical parameters, including probing depth, clinical attachment level, width of keratinized tissue, recession depth, recession width at 1 mm apical to the cementoenamel junction, gingival tissue thickness at 1 mm and 3 mm apical to the gingival margin, Plaque Index, Gingival Index, and Wound Healing Index, at different time intervals. Patient discomfort was recorded 14 days postoperatively, and an overall quality assessment was recorded 180 days postoperatively. Results showed an average of 61% defect coverage (equal to 93.5% root coverage), and a 0.15-mm gain in tissue thickness was achieved 1 year postoperatively. This suggested that root coverage with ADM using the tunneling technique can be a viable alternative to traditional techniques, especially for multiple recession defects in maxillary premolar and anterior teeth.

Acellular dermal matrix allograft. The results of controlled randomized clinical studies.

PubMed

Novaes, Arthur Belém; de Barros, Raquel Rezende Martins

2008-10-01

The aim of this presentation was to discuss the effectiveness of the acellular dermal matrix in root coverage therapy and in alveolar ridge augmentation, based on three controlled randomized clinical trials conducted by our research team (Novaes Jr et al., 2001; Barros et al., 2005; Luczyszyn et al., 2005). The first and second studies highlight the allograft's performance in the treatment of gingival recession. In both studies, clinical parameters were assessed prior to surgery and 6 or 12 months post-surgery. The first one compared the use of the acellular dermal matrix with the subepithelial connective tissue graft and showed 1.83 and 2.10 mm of recession reduction, respectively. Because no statistically significant differences between the groups were observed, it was concluded that the allograft can be used as a substitute for the autograft. In the second study, a new surgical approach was compared to a conventional surgical procedure described by Langer and Langer in 1985. A statistically significant greater recession reduction favoring the test procedure was achieved. The percentage of root coverage was 82.5% and 62.3% for test and control groups. Thus the new technique was considered more suitable for the treatment of gingival recessions with the allograft. Finally, the third study evaluated the allograft as a membrane, associated or not with a resorbable hydroxyapatite in bone regeneration to prevent ridge deformities. In one group the extraction sockets were covered only by the allograft and in the other, the alveoli were also filled with the resorbable hydroxyapatite. After six months, both treatments were able to preserve ridge thickness, considering the pre-operative values. In conclusion, no adverse healing events were noted with the use of allograft in site preservation procedures, and sites treated with the combination of allograft plus resorbable hydroxyapatite showed significantly greater ridge thickness preservation at six months when compared to sites treated with allograft alone (6.8 +/- 1.26 and 5.53 +/- 1.06 respectively).

A new system for cultivation of human keratinocytes on acellular dermal matrix substitute with the use of human fibroblast feeder layer.

PubMed

Xiao, S; Zhu, S; Ma, B; Xia, Z-F; Yang, J; Wang, G

2008-01-01

To improve the proliferative potential of human keratinocytes (HK) cultured on acellular dermal matrix (ADM), HK and mitomycin C-treated human fibroblasts (MMC-HF) were seeded onto ADM to form four types of composite skin: type I, HK were seeded onto the epidermal side of ADM; type II, both HK and MMC-HF were seeded onto the epidermal side; type III, MMC-HF were preseeded onto the dermal side of ADM, and then HK were seeded onto the epidermal side, and type IV, where MMC-HF were preseeded onto both sides, and then HK were seeded onto the epidermal side. Compared with type I and III, the proliferative potential of HK of type II and IV was significantly higher on day 3, 5, 7 and 9 in vitro. In type I and III, HK grew into one layer on day 7-9, while in type II and IV keratinocytes grew into a confluent monolayer by day 4-6. The adherence to ADM of HK in types II and IV was stronger than that in type I and III. The take rate of type II and IV composite skin was also significantly higher. In conclusion, when MMC-HF and HK were cocultured on the epidermal side of ADM, MMC-HF could serve as excellent feeder cells. Copyright 2007 S. Karger AG, Basel.

Periodontal plastic surgery of gingival recessions at single and multiple teeth.

PubMed

Cairo, Francesco

2017-10-01

This manuscript aims to review periodontal plastic surgery for root coverage at single and multiple gingival recessions. Techniques are assessed based on biological principles, surgical procedures, prognosticative factors and expected clinical and esthetic outcomes. The use of coronally advanced flap, laterally sliding flap, free gingival graft, the tunnel grafting technique, barrier membranes, enamel matrix derivative, collagen matrix and acellular dermal matrix are evaluated. The clinical scenario and practical implications are analyzed according to a modern evidence-based approach. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Advanced age does not affect abdominal wall reconstruction outcomes using acellular dermal matrix: A comparative study using propensity score analysis.

PubMed

Giordano, Salvatore; Schaverien, Mark; Garvey, Patrick B; Baumann, Donald P; Liu, Jun; Butler, Charles E

2017-06-01

We hypothesized that elderly patients (≥65 years) experience worse outcomes following abdominal wall reconstruction (AWR) for hernia or oncologic resection. We included all consecutive patients who underwent complex AWR using acellular dermal matrix (ADM) between 2005 and 2015. Propensity score analysis was performed for risk adjustment in multivariable analysis and for one-to-one matching. The primary outcome was hernia recurrence; the secondary outcomes included surgical site occurrence (SSO) and bulging. Mean follow-up for the 511 patients was 31.4 months; 184 (36%) patients were elderly. The elderly and non-elderly groups had similar rates of hernia recurrence (7.6% vs 10.1%, respectively; p = 0.43) and SSO (24.5% vs 23.5%, respectively; p = 0.82). Bulging occurred significantly more often in elderly patients (6.5% vs 2.8%, respectively; p = 0.04). After adjustment through the propensity score, which included 130 pairs, these results persisted. Contrary to our hypothesis, elderly patients did not have worse outcomes in AWR with ADM. Surgeons should not deny elderly patients AWR solely because of their age. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison between two surgical techniques for root coverage with an acellular dermal matrix graft.

PubMed

Andrade, Patrícia F; Felipe, Maria Emília M C; Novaes, Arthur B; Souza, Sérgio L S; Taba, Mário; Palioto, Daniela B; Grisi, Márcio F M

2008-03-01

The aim of this randomized, controlled, clinical study was to compare two surgical techniques with the acellular dermal matrix graft (ADMG) to evaluate which technique could provide better root coverage. Fifteen patients with bilateral Miller Class I gingival recession areas were selected. In each patient, one recession area was randomly assigned to the control group, while the contra-lateral recession area was assigned to the test group. The ADMG was used in both groups. The control group was treated with a broader flap and vertical-releasing incisions, and the test group was treated with the proposed surgical technique, without releasing incisions. The clinical parameters evaluated before the surgeries and after 12 months were: gingival recession height, probing depth, relative clinical attachment level and the width and thickness of keratinized tissue. There were no statistically significant differences between the groups for all parameters at baseline. After 12 months, there was a statistically significant reduction in recession height in both groups, and there was no statistically significant difference between the techniques with regard to root coverage. Both surgical techniques provided significant reduction in gingival recession height after 12 months, and similar results in relation to root coverage.

Acellular fetal bovine dermal matrix for treatment of chronic ulcerations of the midfoot associated with Charcot neuroarthropathy.

PubMed

Kavros, Steven J

2012-08-01

Gross deformity of the foot in Charcot neuroarthropathy can lead to collapse and subsequent ulceration, infection, amputation, or premature death. This study evaluated healing of midfoot ulcerations of Charcot neuroarthropathy using PriMatrix, a novel acellular fetal bovine dermal matrix. In this retrospective analysis, 20 patients with ulcerations of the midfoot associated with Charcot neuroarthropathy were treated with either PriMatrix in addition to standard wound care (PriMatrix group,n = 12) or standard wound care alone (control group, n = 8). All patients had chronic, nonhealing foot ulcerations of at least 2250 mm(3) for a minimum of 30 days duration. All foot ulcerations were full thickness with subcutaneous involvement. Ankle brachial index ≥0.90 and/or transcutaneous oximetry (TcPo(2)) ≥40 mm Hg at the periulcer site was necessary for inclusion. Patients were excluded if they had acute or chronic osteomyelitis of the foot. Demography, risk factors, baseline severity of Charcot neuroarthropathy, and wound volume (control 4078 mm(3), PriMatrix 3737.5 mm(3), P = nonsignificant) were similar between treatment groups. Mean time to healing in the PriMatrix group (116 days, 95% CI = 109-123) was significantly shorter than in the control group (180 days, 95% confidence interval [CI] = 171-188); P < .0001. A significantly faster rate of healing was observed with PriMatrix (87.9 mm(3)/wk, 95% CI = 115.2% to 60.6%) compared with control (59.0 mm(3)/wk, 95% CI = 72.8% to 45.3%); P < .0001). The significantly faster rate of healing and steeper slope of volume reduction in the PriMatrix group warrants further investigation into its effects on healing of neuropathic ulcerations and potential limb salvage.

The scarless latissimus dorsi flap provides effective lower pole prosthetic coverage in breast reconstruction.

PubMed

Lee, Mark A; Miteff, Kirstin G

2014-05-01

The evolution of surgical breast cancer treatment has led to the oncologically safe preservation of greater amounts of native skin, yet we are still often using flaps with large skin paddles, thereby resulting in significant donor-site scars. This explains the increasing appeal of acellular dermal matrix reconstructions. Acellular dermal matrices can, however, have significant problems, particularly if there is any vascular compromise of the mastectomy skin flaps. We have developed a method of raising the latissimus dorsi flap through the anterior mastectomy incisions without requiring special instruments or repositioning. This can provide autologous vascularized cover of the prosthesis. A clear surgical description of the scarless latissimus dorsi flap harvest is provided, and our results of a retrospective cohort review of 20 consecutive patients with 27 traditional latissimus dorsi breast reconstructions were compared with those of 20 consecutive patients with 30 scarless latissimus dorsi breast reconstructions. Operative time, length of stay, and complication rates were reduced in the scarless group. Patients Breast-Q scores were equivalent in each group. The aesthetic assessment was good/excellent in 77% of both groups; however, subscale assessment was better in the scarless group. This was statistically significant (P = 0.0). Breast reconstruction using the scarless latissimus dorsi flap is time effective, requires no patient repositioning, and uses standard breast instrumentation. It is safe and versatile while reducing the risk of exposed prosthesis if native skin necrosis occurs. It is a vascularized alternative to acellular dermal matrices.

The Scarless Latissimus Dorsi Flap Provides Effective Lower Pole Prosthetic Coverage in Breast Reconstruction

PubMed Central

Miteff, Kirstin G.

2014-01-01

Background: The evolution of surgical breast cancer treatment has led to the oncologically safe preservation of greater amounts of native skin, yet we are still often using flaps with large skin paddles, thereby resulting in significant donor-site scars. This explains the increasing appeal of acellular dermal matrix reconstructions. Acellular dermal matrices can, however, have significant problems, particularly if there is any vascular compromise of the mastectomy skin flaps. We have developed a method of raising the latissimus dorsi flap through the anterior mastectomy incisions without requiring special instruments or repositioning. This can provide autologous vascularized cover of the prosthesis. Methods: A clear surgical description of the scarless latissimus dorsi flap harvest is provided, and our results of a retrospective cohort review of 20 consecutive patients with 27 traditional latissimus dorsi breast reconstructions were compared with those of 20 consecutive patients with 30 scarless latissimus dorsi breast reconstructions. Results: Operative time, length of stay, and complication rates were reduced in the scarless group. Patients Breast-Q scores were equivalent in each group. The aesthetic assessment was good/excellent in 77% of both groups; however, subscale assessment was better in the scarless group. This was statistically significant (P = 0.0). Conclusions: Breast reconstruction using the scarless latissimus dorsi flap is time effective, requires no patient repositioning, and uses standard breast instrumentation. It is safe and versatile while reducing the risk of exposed prosthesis if native skin necrosis occurs. It is a vascularized alternative to acellular dermal matrices. PMID:25289340

The use of PriMatrix, a fetal bovine acellular dermal matrix, in healing chronic diabetic foot ulcers: a prospective multicenter study.

PubMed

Kavros, Steven J; Dutra, Timothy; Gonzalez-Cruz, Renier; Liden, Brock; Marcus, Belinda; McGuire, James; Nazario-Guirau, Luis

2014-08-01

The objective of this multicenter study was to prospectively evaluate the healing outcomes of chronic diabetic foot ulcers (DFUs) treated with PriMatrix (TEI Biosciences, Boston, Massachusetts), a fetal bovine acellular dermal matrix. Inclusion criteria required the subjects to have a chronic DFU that ranged in area from 1 to 20 cm² and failed to heal more than 30% during a 2-week screening period when treated with moist wound therapy. For qualifying subjects, PriMatrix was secured into a clean, sharply debrided wound; dressings were applied to maintain a moist wound environment, and the DFU was pressure off-loaded. Wound area measurements were taken weekly for up to 12 weeks, and PriMatrix was reapplied at the discretion of the treating physician. A total of 55 subjects were enrolled at 9 US centers with 46 subjects progressing to study completion. Ulcers had been in existence for an average of 286 days, and initial mean ulcer area was 4.34 cm². Of the subjects completing the study, 76% healed by 12 weeks with a mean time to healing of 53.1 ± 21.9 days. The mean number of applications for these healed wounds was 2.0 ± 1.4, with 59.1% healing with a single application of PriMatrix and 22.9% healing with 2 applications. For subjects not healed by 12 weeks, the average wound area reduction was 71.4%. The results of this multicenter prospective study demonstrate that the use of PriMatrix integrated with standard-of-care therapy is a successful treatment regimen to heal DFUs.

Interposition Dermal Matrix Xenografts: A Successful Alternative to Traditional Treatment of Massive Rotator Cuff Tears.

PubMed

Neumann, Julie A; Zgonis, Miltiadis H; Rickert, Kathleen D; Bradley, Kendall E; Kremen, Thomas J; Boggess, Blake R; Toth, Alison P

2017-05-01

Management of massive rotator cuff tears in shoulders without glenohumeral arthritis remains problematic for surgeons. Repairs of massive rotator cuff tears have failure rates of 20% to 94% at 1 to 2 years postoperatively as demonstrated with arthrography, ultrasound, and magnetic resonance imaging. Additionally, inconsistent outcomes have been reported with debridement alone of massive rotator cuff tears, and limitations have been seen with other current methods of operative intervention, including arthroplasty and tendon transfers. The use of interposition porcine acellular dermal matrix xenograft in patients with massive rotator cuff tears will result in improved subjective outcomes, postoperative pain, function, range of motion, and strength. Case series; Level of evidence, 4. Sixty patients (61 shoulders) were prospectively observed for a mean of 50.3 months (range, 24-63 months) after repair of massive rotator cuff tears with porcine acellular dermal matrix xenograft as an interposition graft. Subjective outcome data were obtained with visual analog scale for pain score (0-10, 0 = no pain) and Modified American Shoulder and Elbow Surgeons (MASES) score. Active range of motion in flexion, external rotation, and internal rotation were recorded. Strength in the supraspinatus and infraspinatus muscles was assessed manually on a 10-point scale and by handheld dynamometer. Ultrasound was used to assess the integrity of the repair during latest follow-up. Mean visual analog scale pain score decreased from 4.0 preoperatively to 1.0 postoperatively ( P < .001). Mean active forward flexion improved from 140.7° to 160.4° ( P < .001), external rotation at 0° of abduction from 55.6° to 70.1° ( P = .001), and internal rotation at 90° of abduction from 52.0° to 76.2° ( P < .001). Supraspinatus manual strength increased from 7.7 to 8.8 ( P < .001) and infraspinatus manual strength from 7.7 to 9.3 ( P < .001). Mean dynamometric strength in forward flexion was 77.7 N in nonoperative shoulders (shoulder that did not undergo surgery) and 67.8 N ( P < .001) in operative shoulders (shoulder that underwent rotator cuff repair with interposition porcine dermal matrix xenograft). Mean dynamometric strength in external rotation was 54.5 N in nonoperative shoulders and 50.1 N in operative shoulders ( P = .04). Average postoperative MASES score was 87.8. Musculoskeletal ultrasound showed that 91.8% (56 of 61) of repairs were fully intact; 3.3% (2 of 61), partially intact; and 4.9% (3 of 61), not intact. Patients who underwent repair of massive rotator cuff tears with interposition porcine acellular dermal matrix graft have good subjective function as assessed by the MASES score. Patients have significant improvement in pain, range of motion, and manual muscle strength. Postoperative ultrasound demonstrated that the repair was completely intact in 91.8% of patients, a vast improvement compared with results previously reported for primary repairs of massive rotator cuff tears.

Comparison of acellular dermal graft and palatal autograft in the reconstruction of keratinized gingiva around dental implants: a case report.

PubMed

Yan, Ji-Jong; Tsai, Alex Yi-Min; Wong, Man-Ying; Hou, Lein-Tuan

2006-06-01

The use of autogenous gingival grafts has proved to be an effective and predictable way to increase the amount of keratinized gingiva. However, discomfort and pain at the donor site are unavoidable. Acellular dermal matrix (ADM) allograft can be used as a donor tissue to eliminate the need for another surgical site and alleviate pain and trauma. The purpose of this study was to evaluate the effectiveness of ADM allograft in increasing the width of keratinized gingiva around dental implants. A patient with inadequate keratinized gingiva around dental implants in maxillary and mandibular anterior regions received either an ADM graft or palatal autograft by random allocation. The width of keratinized gingiva and other clinical periodontal parameters were recorded initially and at 3 and 6 months after surgery. Both grafts provided satisfactory results. The width of keratinized tissues was increased by using the ADM allograft, but by a lesser amount than seen with the autogenous gingival graft.

Primary fascial closure with biologic mesh reinforcement results in lesser complication and recurrence rates than bridged biologic mesh repair for abdominal wall reconstruction: A propensity score analysis.

PubMed

Giordano, Salvatore; Garvey, Patrick B; Baumann, Donald P; Liu, Jun; Butler, Charles E

2017-02-01

Previous studies suggest that bridged mesh repair for abdominal wall reconstruction may result in worse outcomes than mesh-reinforced, primary fascial closure, particularly when acellular dermal matrix is used. We compared our outcomes of bridged versus reinforced repair using ADM in abdominal wall reconstruction procedures. This retrospective study included 535 consecutive patients at our cancer center who underwent abdominal wall reconstruction either for an incisional hernia or for abdominal wall defects left after excision of malignancies involving the abdominal wall with underlay mesh. A total of 484 (90%) patients underwent mesh-reinforced abdominal wall reconstruction and 51 (10%) underwent bridged repair abdominal wall reconstruction. Acellular dermal matrix was used, respectively, in 98% of bridged and 96% of reinforced repairs. We compared outcomes between these 2 groups using propensity score analysis for risk-adjustment in multivariate analysis and for 1-to-1 matching. Bridged repairs had a greater hernia recurrence rate (33.3% vs 6.2%, P < .001), a greater overall complication rate (59% vs 30%, P = .001), and worse freedom from hernia recurrence (log-rank P <.001) than reinforced repairs. Bridged repairs also had a greater rate of wound dehiscence (26% vs 14%, P = .034) and mesh exposure (10% vs 1%, P = .003) than mesh-reinforced abdominal wall reconstruction. When the treatment method was adjusted for propensity score in the propensity-score-matched pairs (n = 100), we found that the rates of hernia recurrence (32% vs 6%, P = .002), overall complications (32% vs 6%, P = .002), and freedom from hernia recurrence (68% vs 32%, P = .001) rates were worse after bridged repair. We did not observe differences in wound healing and mesh complications between the 2 groups. In our population of primarily cancer patients at MD Anderson Cancer Center bridged repair for abdominal wall reconstruction is associated with worse outcomes than mesh-reinforced abdominal wall reconstruction. Particularly when employing acellular dermal matrix, reinforced repairs should be used for abdominal wall reconstruction whenever possible. Copyright © 2016 Elsevier Inc. All rights reserved.

[Study on preparation of laser micropore porcine acellular dermal matrix combined with split-thickness autograft and its application in wound transplantation].

PubMed

Liang, Li-Ming; Chai, Ji-Ke; Yang, Hong-Ming; Feng, Rui; Yin, Hui-Nan; Li, Feng-Yu; Sun, Qiang

2007-04-01

To prepare a porcine acellular dermal matrix (PADM), and to optimize the interpore distance between PADM and co-grafted split-thickness autologous skin. Porcine skin was treated with trypsin/Triton X-100 to prepare an acellular dermal matrix. Micropores were produced on the PADM with a laser punch. The distance between micropores varied as 0.8 mm, 1.0 mm, 1.2 mm and 1.5 mm. Full-thickness defect wounds were created on the back of 144 SD rats. The rats were randomly divided into 6 groups as follows, with 24 rats in each group. Micropore groups I -IV: the wounds were grafted with PADM with micropores in four different intervals respectively, and covered with split-thickness autologous skin graft. Mesh group: the wounds were grafted with meshed PADM and split-thickness autograft. with simple split-thickness autografting. The gross observation of wound healing and histological observation were performed at 2, 4, 6 weeks after surgery. The wound healing rate and contraction rate were calculated. Two and four weeks after surgery, the wound healing rate in micropore groups I and II was lower than that in control group (P < 0.05), but no obvious difference was between micropore groups I , II and mesh group (P > 0.05) until 6 weeks after grafting( P <0.05). The wound contraction rate in micropore groups I and II ([(16.0 +/- 2.6)%, (15.1 +/- 2.4)%] was remarkably lower than that in control group 4 and 6 weeks after grafting (P < 0.05), and it was significantly lower than that in mesh group [(19.3 +/- 2.4)%] 6 weeks after surgery (P <0.05). Histological examination showed good epithelization, regularly arranged collagenous fibers, and integral structure of basement membrane. Laser micropore PADM (0.8 mm or 1.0 mm in distance) grafting in combination with split-thickness autografting can improve the quality of wound healing. PADM with laser micropores in 1.0 mm distance is the best choice among them.

Effect of in vitro gingival fibroblast seeding on the in vivo incorporation of acellular dermal matrix allografts in dogs.

PubMed

Novaes, Arthur B; Marchesan, Julie Teresa; Macedo, Guilherme O; Palioto, Daniela B

2007-02-01

Acellular dermal matrix allograft (ADMA) has been used in various periodontal procedures with successful results. Because ADMA has no blood vessels or cells, slower healing and incorporation are observed compared to a subepithelial connective tissue graft. Fibroblasts accelerate the healing process by regulation of matrix deposition and synthesis of a variety of growth factors. Thus, the objective of this study was to evaluate histologically if gingival fibroblasts affect healing and incorporation of ADMA in dogs when used as a subepithelial allograft. Gingival fibroblasts were established from explant culture from the connective tissue of keratinized gingiva collected from the maxilla of seven mongrel dogs. ADMA was seeded with gingival fibroblasts and transferred to dogs. Surgery was performed bilaterally, and the regions were divided into two groups: ADMA+F (ADMA containing fibroblasts) and ADMA (ADMA only). Biopsies were performed after 2, 4, and 8 weeks of healing. The quantity of blood vessels was significantly higher in the ADMA+F group at 2 weeks of healing (Kruskal-Wallis; P <0.05). There was no statistical difference (P >0.05) in the number of cell layers, epithelial area, or inflammatory infiltrate between the two groups at any stage of healing. The enhanced vascularization in vivo in early stages supports the important role of fibroblasts in improving graft performance and wound healing of cultured graft substitutes.

Management of gingival recession by the use of an acellular dermal graft material: a 12-case series.

PubMed

Santos, A; Goumenos, G; Pascual, A

2005-11-01

Different soft tissue defects can be treated by a variety of surgical procedures. Most of these techniques require the palatal area as a donor site. Recently, an acellular dermal graft has become available that can substitute for palatal donor tissue. This study describes the surgical technique for gingival augmentation and root coverage and the results of 12 clinical cases. A comparison between the three most popular mucogingival procedures for root coverage is also presented. The results of the 12 patients and the 26 denuded surfaces have shown that we can obtain a mean root coverage of 74% with the acellular dermal graft. Thirteen out of the 26 denuded surfaces had complete root coverage. The average increase in keratinized tissue was 1.19 mm. It seems that the long-term results of the cases are stable. The proposed technique of root coverage with an acellular dermal graft can be a good alternative to soft tissue grafts for root coverage, and it should be part of our periodontal plastic surgery armamentarium.

Suppression of α Smooth Muscle Actin Accumulation by Bovine Fetal Dermal Collagen Matrix in Full Thickness Skin Wounds

PubMed Central

Lineaweaver, William; Bush, Katie; James, Kenneth

2015-01-01

Abstract The suppression of elements associated with wound contracture and unfavorable scarring is a potentially important strategy in clinical wound management. In this study, the presence of α smooth muscle actin (αSMA), a protein involved in wound contraction, was analyzed in a series of wounds in which bovine fetal collagen (BFC) acellular dermal matrix (PriMatrix) was used in staged split thickness skin graft procedures. The results obtained through histological and quantitative image analyses of incidental biopsies from these wounds demonstrated a suppression of αSMA in the wound regions occupied by assimilated BFC relative to increased levels of αSMA found in other areas of the wound. The αSMA levels found in assimilated BFC were similar to αSMA levels in uninjured human dermis. These findings suggest a mechanism by which application of BFC could decrease contraction of full thickness skin wounds. PMID:25695450

Suppression of α Smooth Muscle Actin Accumulation by Bovine Fetal Dermal Collagen Matrix in Full Thickness Skin Wounds.

PubMed

Lineaweaver, William; Bush, Katie; James, Kenneth

2015-06-01

The suppression of elements associated with wound contracture and unfavorable scarring is a potentially important strategy in clinical wound management. In this study, the presence of α smooth muscle actin (αSMA), a protein involved in wound contraction, was analyzed in a series of wounds in which bovine fetal collagen (BFC) acellular dermal matrix (PriMatrix) was used in staged split thickness skin graft procedures. The results obtained through histological and quantitative image analyses of incidental biopsies from these wounds demonstrated a suppression of αSMA in the wound regions occupied by assimilated BFC relative to increased levels of αSMA found in other areas of the wound. The αSMA levels found in assimilated BFC were similar to αSMA levels in uninjured human dermis. These findings suggest a mechanism by which application of BFC could decrease contraction of full thickness skin wounds.

High Throughput Assay for Bacterial Adhesion on Acellular Dermal Matrices and Synthetic Surgical Materials

PubMed Central

Nyame, Theodore T.; Lemon, Katherine P.; Kolter, Roberto; Liao, Eric C.

2013-01-01

Background There has been increasing use of various synthetic and biologically derived materials in surgery. Biologic surgical materials are used in many plastic surgery procedures, ranging from breast reconstruction to hernia repairs. In particular, acellular dermal matrix (ADM) material has gained popularity in these applications. There is a paucity of data on how ADM compares to other surgical materials as a substrate for bacterial adhesion, the first step in formation biofilm, which occurs in prosthetic wound infections. We have designed a high throughput assay to evaluate Staphylococcus aureus adherence on various synthetic and biologically derived materials. Methods Clinical isolates of Staphylococcus aureus (strains SC-1 and UAMS-1) were cultured with different materials and bacterial adherence was measured using a resazurin cell vitality reporter microtiter assay. Four materials that are commonly utilized in reconstructive procedures were evaluated: prolene mesh, vicryl mesh, and two different ADM preparations (AlloDerm®, FlexHD®). We were able to develop a high throughput and reliable assay for quantifying bacterial adhesion on synthetic and biologically derived materials. Results The resazurin vitality assay can be reliably used to quantify bacterial adherence to acellular dermal matrix material, as well as synthetic material. S. aureus strains SC-1 and UAMS-1 both adhered better to ADM materials (AlloDerm® vs. FlexHD®) than to the synthetic material prolene. S. aureus also adhered better to vicryl than to prolene. Strain UAMS-1 adhered better to vicryl and ADM materials than did strain SC-1. Conclusion Our results suggest that S. aureus adheres more readily to ADM material than to synthetic material. We have developed an assay to rapidly test bacterial formation on surgical materials, using two S. aureus bacterial strains. This provides a standard method to evaluate existing and new materials with regard to bacterial adherence and potential propensity for infection. This assay is particularly important in the clinical context of the severe sequelae of post-operative infection. PMID:22030489

Recellularizing of human acellular dermal matrices imaged by high-definition optical coherence tomography.

PubMed

Boone, Marc A L M; Draye, Jean Pierre; Verween, Gunther; Aiti, Annalisa; Pirnay, Jean-Paul; Verbeken, Gilbert; De Vos, Daniel; Rose, Thomas; Jennes, Serge; Jemec, Gregor B E; Del Marmol, Veronique

2015-05-01

High-definition optical coherence tomography (HD-OCT) permits real-time 3D imaging of the impact of selected agents on human skin allografts. The real-time 3D HD-OCT assessment of (i) the impact on morphological and cellular characteristics of the processing of human acellular dermal matrices (HADMs) and (ii) repopulation of HADMs in vitro by human fibroblasts and remodelling of the extracellular matrix by these cells. Four different skin decellularization methods, Dispase II/Triton X-100, Dispase II/SDS (sodium dodecyl sulphate), NaCl/Triton X-100 and NaCl/SDS, were analysed by HD-OCT. HD-OCT features of epidermal removal, dermo-epidermal junction (DEJ) integrity, cellularity and dermal architecture were correlated with reflectance confocal microscopy (RCM), histopathology and immunohistochemistry. Human adult dermal fibroblasts were in vitro seeded on the NaCl/Triton X-100 processed HADMs, cultured up to 19 days and evaluated by HD-OCT in comparison with MTT proliferation test and histology. Epidermis was effectively removed by all treatments. DEJ was best preserved after NaCl/Triton X-100 treatment. Dispase II/SDS treatment seemed to remove all cellular debris in comparison with NaCl/Triton X-100 but disturbed the DEJ severely. The dermal micro-architectural structure and vascular spaces of (sub)papillary dermis were best preserved with the NaCl/Triton X-100. The impact on the 3D structure and vascular holes was detrimental with Dispase II/SDS. Elastic fibre fragmentation was only observed after Dispase II incubation. HD-OCT showed that NaCl/Triton X-100 processed matrices permitted in vitro repopulation by human dermal fibroblasts (confirmed by MTT test and histology) and underwent remodelling upon increasing incubation time. Care must be taken in choosing the appropriate processing steps to maintain selected properties of the extracellular matrix in HADMs. Processing HADMs with NaCl/Triton X-100 permits in vitro the proliferation and remodelling activity of human dermal fibroblasts. HD-OCT provides unique real-time and non-invasive 3D imaging of tissue-engineered skin constructs and complementary morphological and cytological information. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Original technique for penile girth augmentation through porcine dermal acellular grafts: results in a 69-patient series.

PubMed

Alei, Giovanni; Letizia, Piero; Ricottilli, Francesco; Simone, Pierfranco; Alei, Lavinia; Massoni, Francesco; Ricci, Serafino

2012-07-01

Although different techniques for augmentation phalloplasty have been reported in the medical literature, this issue is still highly controversial, and none of the proposed procedures has been unanimously approved. The aim of this study is to describe an innovative surgical technique for penile girth augmentation with porcine dermal acellular grafts, through a small transverse incision at the penile base, along the penopubic junction. Between 2000 and 2009, 104 patients were referred to our institution for penile enhancement. After a preoperative psychosexual consultation and a general medical assessment, 69 patients were deemed suitable good candidates for surgery. The average penis circumference was measured at the mid-length of the penis and was 8.1 cm (5.4-10.7 cm) and 10.8 cm (6.5-15.8 cm) during flaccidity and erection, respectively. All patients received penile augmentation with porcine dermal acellular grafts. Results evaluation of an innovative technique for penile girth augmentation through exogenous porcine grafts and small penobubic incision. Postoperative measurements were performed at 6 and 12 months. At the 1-year follow-up, the average penis circumference was 11.3 cm (8.2-13.2 cm, 3.1 cm mean increase) during flaccidity and 13.2 cm (8.8-14.5 cm, 2.4 cm mean increase) during erection. No major complications occurred in the series. Minor complications were resolved with conservative treatment within 3 weeks. Sexual activity was resumed from 1 to 2 months after surgery. The psychosexual impact of the operation was beneficial in the majority of cases. Penile girth enlargement with acellular dermal matrix grafts has several advantages over augmentation with autogenous dermis-fat grafts: the elimination of donor site morbidity and a significantly shorter operation time. With this approach, through a short dorsal incision at the base of the penis, the scar is concealed in a crease covered by pubic hair and thus hardly visible. © 2012 International Society for Sexual Medicine.

Use of porcine acellular dermal matrix following early dermabrasion reduces length of stay in extensive deep dermal burns.

PubMed

Guo, Zhi-Qian; Qiu, Le; Gao, You; Li, Jin-Hu; Zhang, Xin-He; Yang, Xin-Lei; Peszel, April; Chen, Xu-Lin

2016-05-01

Extensive deep partial-thickness burns still seriously challenge the surgeon's abilities. This study aimed to assess the impact of early dermabrasion combined with porcine acellular dermal matrix (ADM) in extensive deep dermal burns. From September 2009 to September 2013, a total of 60 adult patients sustained greater than 50% total body surface area (TBSA) burn by hot water or gas explosion were divided into three groups based on dermabrasion: group A (early dermabrasion and porcine ADM), group B (early dermabrasion and nano-silver dressings), and group C (conservative group). The wound healing time and length of hospital stay were analyzed. Scar assessment was performed at 3 and 12 months after the injury with a modified Vancouver Scar Scale linked with TBSA (mVSS-TBSA). No significant difference was found in mean burn size, burn depth, age, male-to-female ratio, or incidence of inhalation injury between the patients in the three groups (p>0.05). Compared with groups B and C, the patients that received early dermabrasion combined with porcine ADM had a shorter wound healing time (p<0.01). The burn patients treated with early dermabrasion and porcine ADM coverage had a mean length of hospital stay of 28.3 days (±7.2), which was significantly shorter than that of groups B and C (p<0.05-0.01). The mVSS-TBSA of patients in group A was significantly improved in comparison with groups B and C at 3 and 12 months after the injury. There was no significant difference in the mortality rate between the three groups (p>0.05). Early dermabrasion combined with porcine ADM coverage facilitates wound healing, reduces the length of hospital stay, and improves esthetic and functional results in extensive deep dermal burns with burn size over 50% TBSA. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Traumatic laryngotracheal stenosis treated by hyoid–sternohyoid osseomuscular flap combined with xenogenic acellular dermal matrix: A case report and literature review

PubMed Central

Yang, Hang; Chen, Zhe; Wang, Qin-Yin; Weng, Li-Xia; Wang, Fang; Wu, Ting-Ting; Zhou, Min-Li; Bao, Yang-Yang

2017-01-01

Objective The treatment of laryngotracheal stenosis is a major therapeutic challenge. Various treatments include observation, medical management, and surgical management. The most effective surgical management is resection and reconstruction. To the authors’ knowledge, no reports have described the use of xenogenic acellular dermal matrix (ADM) for laryngotracheal stenosis. Methods A 27-year-old man presented with hemoptysis of the neck due to a traffic accident. Emergency orotracheal intubation was performed. Tracheostomy was then performed under local anesthesia. Computed tomography revealed fractures of the right thyroid cartilage and posterior arc of the cricoid cartilage and stenosis of the subglottis and first and second tracheal rings. We used a composite hyoid–sternohyoid osseomuscular flap with xenogenic ADM and a straight silicone tube as a lumen stent to reconstruct the laryngotracheal stenosis. Results Surgical recovery was uneventful. The tracheotomy opening was changed to a metal tube 5 days postoperatively. Four months postoperatively, the silicone tube was endoscopically removed under local anesthesia. The patient was decannulated 20 days later. The patient satisfied with his voice, respiration, and deglutition at the 16-month postoperative follow-up. Conclusion The use of ADM for laryngotracheal stenosis may reduce the growth of granulation tissues and promote the repair process. PMID:28480810

Traumatic laryngotracheal stenosis treated by hyoid-sternohyoid osseomuscular flap combined with xenogenic acellular dermal matrix: A case report and literature review.

PubMed

Yang, Hang; Chen, Zhe; Zhou, Shui-Hong; Wang, Qin-Yin; Weng, Li-Xia; Wang, Fang; Wu, Ting-Ting; Zhou, Min-Li; Bao, Yang-Yang

2017-10-01

Objective The treatment of laryngotracheal stenosis is a major therapeutic challenge. Various treatments include observation, medical management, and surgical management. The most effective surgical management is resection and reconstruction. To the authors' knowledge, no reports have described the use of xenogenic acellular dermal matrix (ADM) for laryngotracheal stenosis. Methods A 27-year-old man presented with hemoptysis of the neck due to a traffic accident. Emergency orotracheal intubation was performed. Tracheostomy was then performed under local anesthesia. Computed tomography revealed fractures of the right thyroid cartilage and posterior arc of the cricoid cartilage and stenosis of the subglottis and first and second tracheal rings. We used a composite hyoid-sternohyoid osseomuscular flap with xenogenic ADM and a straight silicone tube as a lumen stent to reconstruct the laryngotracheal stenosis. Results Surgical recovery was uneventful. The tracheotomy opening was changed to a metal tube 5 days postoperatively. Four months postoperatively, the silicone tube was endoscopically removed under local anesthesia. The patient was decannulated 20 days later. The patient satisfied with his voice, respiration, and deglutition at the 16-month postoperative follow-up. Conclusion The use of ADM for laryngotracheal stenosis may reduce the growth of granulation tissues and promote the repair process.

Root coverage of advanced gingival recession: a comparative study between acellular dermal matrix allograft and subepithelial connective tissue grafts.

PubMed

Tal, Haim; Moses, Ofer; Zohar, Ron; Meir, Haya; Nemcovsky, Carlos

2002-12-01

Acellular dermal matrix allograft (ADMA) has successfully been applied as a substitute for free connective tissue grafts (CTG) in various periodontal procedures, including root coverage. The purpose of this study was to clinically compare the efficiency of ADMA and CTG in the treatment of gingival recessions > or = 4 mm. Seven patients with bilateral recession lesions participated. Fourteen teeth presenting gingival recessions > or = 4 mm were randomly treated with ADMA or CTG covered by coronally advanced flaps. Recession, probing depth, and width of keratinized tissue were measured preoperatively and 12 months postoperatively. Changes in these clinical parameters were calculated within and compared between groups and analyzed statistically. Baseline recession, probing depth, and keratinized tissue width were similar for both groups. At 12 months, root coverage gain was 4.57 mm (89.1%) versus 4.29 mm (88.7%) (P = NS), and keratinized tissue gain was 0.86 mm (36%) versus 2.14 mm (107%) (P < 0.05) for ADMA and CTG, respectively. Probing depth remained unchanged (0.22 mm/0 mm), with no difference between the groups. Recession defects may be covered using ADMA or CTG, with no practical difference. However, CTG results in significantly greater gain of keratinized gingiva.

[Comparison of composite grafting of autoskin with acellular dermal matrix from different sources].

PubMed

Chen, Jin-Hui; Qi, Shun-Zhen; Sun, Hui-Chen; He, Zhan-Guo; Li, Hui; Zhu, Yu-Feng; Chen, Xing

2003-10-01

To compare the composite grafts of acellular dermal matrix (ADM) from different sources with autoskin. Six local white mini pigs were employed for the experiment. The pigs were randomly divided into four groups according to different skin grafts, i.e. A (human ADM with razor thin autoskin), B (porcine ADM with razor thin autoskin), C (razor thin autoskin only), and D (split thickness autoskin) as control. The survival rate, the contraction degree of the grafts, and the histological changes in grafting area were observed at 2, 4, 8, 12 and 24 hours after the operation. The grafted area in both A and B groups appeared smooth and elastic with satisfactory graft survival. The in growth of the host reparative cells such as fibroblast and vascular endothelium could be induced by composite grafts of different ADMs with skin grafting. The contraction areas in A and B groups seemed bigger than those in C and D groups. The tissue structure of grafting areas was similar to that of split thickness skin grafting area at 24 post-operation weeks. Combination of the homogenous and heterogeneous ADMs with autografts exhibited similar biological function during the observation period (24 weeks after operation). Xenogenous ADMs might have broader clinical applications.

A two-year prospective study of coronally positioned flap with or without acellular dermal matrix graft.

PubMed

de Queiroz Côrtes, Antonieta; Sallum, Antonio Wilson; Casati, Marcio Z; Nociti, Francisco H; Sallum, Enilson A

2006-09-01

Evaluation of the treatment of gingival recessions with coronally positioned flap with or without acellular dermal matrix allograft (ADM) after a period of 24 months. Thirteen patients with bilateral gingival recessions were included. The defects were randomly assigned to one of the treatments: coronally positioned flap plus ADM or coronally positioned flap alone. The clinical measurements were taken before the surgeries and after 6, 12 and 24 months. At baseline, the mean values for recession height were 3.46 and 3.58 mm for the defects treated with and without the graft, respectively (p>0.05). No significant differences between the groups were observed after 6 and 12 months in this parameter. However, after 24 months, the group treated with coronally positioned flap alone showed a greater recession height when compared with the group treated with ADM (1.62 and 1.15 mm, respectively--p<0.05). A significant increase in the thickness of keratinized tissue was observed in the group treated with ADM as compared with coronally positioned flap alone (p<0.05). ADM may reduce the residual gingival recession observed after 24 months in defects treated with coronally positioned flap. In addition, a greater gingival thickness may be achieved when the graft is used.

Cellular Response to a Novel Fetal Acellular Collagen Matrix: Implications for Tissue Regeneration

PubMed Central

Rennert, Robert C.; Garg, Ravi K.; Gurtner, Geoffrey C.

2013-01-01

Introduction. PriMatrix (TEI Biosciences Inc., Boston, MA, USA) is a novel acellular collagen matrix derived from fetal bovine dermis that is designed for use in partial- and full-thickness wounds. This study analyzes the cellular response to PriMatrix in vivo, as well as the ability of this matrix to facilitate normal tissue regeneration. Methods. Five by five mm squares of rehydrated PriMatrix were implanted in a subcutaneous fashion on the dorsum of wild-type mice. Implant site tissue was harvested for histology, immunohistochemistry (IHC), and flow cytometric analyses at multiple time points until day 28. Results. PriMatrix implants were found to go through a biological progression initiated by a transient infiltrate of inflammatory cells, followed by mesenchymal cell recruitment and vascular development. IHC analysis revealed that the majority of the implanted fetal dermal collagen fibers persisted through day 28 but underwent remodeling and cellular repopulation to form tissue with a density and morphology consistent with healthy dermis. Conclusions. PriMatrix implants undergo progressive in vivo remodeling, facilitating the regeneration of histologically normal tissue through a mild inflammatory and progenitor cell response. Regeneration of normal tissue is especially important in a wound environment, and these findings warrant further investigation of PriMatrix in this setting. PMID:23970899

Cellular response to a novel fetal acellular collagen matrix: implications for tissue regeneration.

PubMed

Rennert, Robert C; Sorkin, Michael; Garg, Ravi K; Januszyk, Michael; Gurtner, Geoffrey C

2013-01-01

Introduction. PriMatrix (TEI Biosciences Inc., Boston, MA, USA) is a novel acellular collagen matrix derived from fetal bovine dermis that is designed for use in partial- and full-thickness wounds. This study analyzes the cellular response to PriMatrix in vivo, as well as the ability of this matrix to facilitate normal tissue regeneration. Methods. Five by five mm squares of rehydrated PriMatrix were implanted in a subcutaneous fashion on the dorsum of wild-type mice. Implant site tissue was harvested for histology, immunohistochemistry (IHC), and flow cytometric analyses at multiple time points until day 28. Results. PriMatrix implants were found to go through a biological progression initiated by a transient infiltrate of inflammatory cells, followed by mesenchymal cell recruitment and vascular development. IHC analysis revealed that the majority of the implanted fetal dermal collagen fibers persisted through day 28 but underwent remodeling and cellular repopulation to form tissue with a density and morphology consistent with healthy dermis. Conclusions. PriMatrix implants undergo progressive in vivo remodeling, facilitating the regeneration of histologically normal tissue through a mild inflammatory and progenitor cell response. Regeneration of normal tissue is especially important in a wound environment, and these findings warrant further investigation of PriMatrix in this setting.

Prospective study of single-stage repair of contaminated hernias using a biologic porcine tissue matrix: the RICH Study.

PubMed

Itani, Kamal M F; Rosen, Michael; Vargo, Daniel; Awad, Samir S; Denoto, George; Butler, Charles E

2012-09-01

In the presence of contamination, the repair of a ventral incisional hernia (VIH) is challenging. The presence of comorbidities poses an additional risk for postoperative wound events and hernia recurrence. To date, very few studies describe the outcomes of VIH repair in this high-risk population. A prospective, multicenter, single-arm, the Repair of Infected or Contaminated Hernias study was performed to study the clinical outcomes of open VIH repair of contaminated abdominal defects with a non-cross-linked, porcine, acellular dermal matrix, Strattice. Of 85 patients who consented to participate, 80 underwent open VIH repair with Strattice. Hernia defects were 'clean-contaminated' (n = 39), 'contaminated' (n = 39), or 'dirty' (n = 2), and the defects were classified as grade 3 (n = 60) or grade 4 (n = 20). The midline was restored, and primary closure was achieved in 64 patients; the defect was bridged in 16 patients. At 24 months, 53 patients (66%) experienced 95 wound events. There were 28 unique, infection-related events in 24 patients. Twenty-two patients experienced seromas, all but 5 of which were transient and required no intervention. No unanticipated adverse events occurred, and no tissue matrix required complete excision. There were 22 hernia (28%) recurrences by month 24. There was no correlation between infection-related events and hernia recurrence. The use of the intact, non-cross-linked, porcine, acellular dermal matrix, Strattice, in the repair of contaminated VIH in high-risk patients allowed for successful, single-stage reconstruction in >70% of patients followed for 24 months after repair. Published by Mosby, Inc.

Acellular dermal matrix in soft tissue reconstruction prior to bone grafting. A case report.

PubMed

Ruiz-Magaz, Vanessa; Hernández-Alfaro, Federico; Díaz-Carandell, Artur; Biosca-Gómez-de-Tejada, María-José

2010-01-01

When hard tissue augmentation is scheduled as a part of an oral rehabilitation, prior to the treatment, it is important to assess if the quality of the underlying gingiva at the recipient site can support the bone grafting procedure. The most frequent complication during autologous onlay grafts are wound dehiscences in the recipient site, so the integrity of soft tissues is a basic aspect of successful reconstructive and plastic surgical procedure. Connective tissue grafts can improve the quality and quantity of soft tissue in oral sites where a hard tissue reconstruction is going to take place. However, particularly when large grafts are harvested, the autogenous donor site can present significant postoperative morbidity, such as necrosis of the palate fibromucosa and bone exposition, pain and bleeding. Another important limitation with the use of autogenous grafts is the limited supply of donor connective tissue. If a large site needs to be grafted, more than one surgical procedure may be required. An Acellular Dermal Matrix (ADM) graft has become increasingly popular as a substitute for donor connective tissue, eliminating the disadvantages described for the autogenous donor graft. The amount of tissue harvested is unlimited, so it gives an option for treating patients that have inadequate harvestable tissue or that present a large defect to be treated. The outcome of using ADM as a matrix for soft tissue reconstruction 12 weeks before bone grafting can reduce the risk of exposure and failure of the bone graft.

Debrided Skin as a Source of Autologous Stem Cells for Wound Repair

DTIC Science & Technology

2011-08-01

dermal tissue shows the presence of hyalinized collagen (bold arrows) with loss of individual collagen bundles and cellular necrosis . The hypodermal...region consisted of intact adipo- cytes separated by intact interlobular septae and thermally collapsed areas with complete necrosis of both fat cells...and no dsASCs showed predom- inantly acellular multifocal amorphous matrix (Supporting In- formation Fig. S3A, S3B) and was avascular (Supporting Infor

Clinical and histological evaluation of an acellular dermal matrix allograft in combination with the coronally advanced flap in the treatment of Miller class I recession defects: an experimental study in the mini-pig.

PubMed

Núñez, Javier; Caffesse, Raul; Vignoletti, Fabio; Guerra, Fernando; San Roman, Fidel; Sanz, Mariano

2009-06-01

To study the wound healing of acellular dermal matrix (ADM) allografts when used together with coronally advanced flaps (CAF) in the treatment of localized gingival recessions in the mini-pig experimental model. Dehiscence defects 4 x 5 mm were surgically created in one buccal root surface in each quadrant of PI, II, or III in three mini-pigs. They were then treated with CAF and the interposition of either a connective tissue graft (CTG) or ADM. As the primary outcome, the histological interface between the ADM and the root surface was studied and was compared with CTG. As secondary outcomes, we assessed the amount and quality of the keratinized tissue and clinical outcomes in terms of root coverage and recession reduction. At 3 months, the CTG group attained a mean 76% root coverage, versus 62% in the ADM group. The histological interface with the root surface was similar in both groups. The apical migration of the epithelium was 1.79+/-0.46 mm for the CTG and 1.21+/-0.35 mm for ADM. Newly formed cementum was observed with both treatments. New bone and a newly formed periodontal ligament were shown in five specimens in the ADM group and in three in the CTG group. Both materials showed similar clinical and histological outcomes.

Acellular dermal matrix and subepithelial connective tissue grafts for root coverage: A systematic review

PubMed Central

Gallagher, Sarah Ivy; Matthews, Debora Candace

2017-01-01

Background: The aim of this systematic review was to evaluate whether patients with gingival recession would benefit from an acellular dermal matrix graft (ADMG) in ways that are comparable to the gold standard of the subepithelial connective tissue graft (SCTG). Materials and Methods: A systematic review and meta-analysis comparing ADMG to SCTG for the treatment of Miller Class I and II recession defects was conducted according to PRISMA guidelines. PubMed, Excerpta Medica Database, and Cochrane Central Register of Controlled Trials databases were searched up to March 2016 for controlled trials with minimum 6 months duration. The primary outcome was root coverage; secondary outcomes included attachment level change, keratinized tissue (KT) change, and patient-based outcomes. Both authors independently assessed the quality of each included trial and extracted the relevant data. Results: From 158 potential titles, 17 controlled trials were included in the meta-analysis. There were no differences between ADMG and SCTG for mean root coverage, percent root coverage, and clinical attachment level gain. ADMG was statistically better than SCTG for gain in width of KT (−0.43 mm; 95% confidence interval: −0.72, −0.15). Only one study compared patient-based outcomes. Conclusion: This review found that an ADMG would be a suitable root coverage substitute for an SCTG when avoidance of the second surgical site is preferred. PMID:29551861

Preparation and characterization of an advanced collagen aggregate from porcine acellular dermal matrix.

PubMed

Liu, Xinhua; Dan, Nianhua; Dan, Weihua

2016-07-01

The objective of this study was to extract and characterize an advanced collagen aggregate (Ag-col) from porcine acellular dermal matrix (pADM). Based on histological examination, scanning electron microscopy (SEM) and atomic force microscope (AFM), Ag-col was composed of the D-periodic cross-striated collagen fibrils and thick collagen fiber bundles with uneven diameters and non-orientated arrangement. Fourier transform infrared (FTIR) spectra of pADM, Ag-col and Col were similar and revealed the presence of the triple helix. Circular dichroism (CD) analysis exhibited a slightly higher content of α-helix but inappreciably less amount of random coil structure in Ag-col compared to Col. Moreover, imino acid contents of pADM, Ag-col and Col were 222.43, 218.30 and 190.01 residues/1000 residues, respectively. From zeta potential analysis, a net charge of zero was found at pH 6.45 and 6.11 for Ag-col and Col, respectively. Differential scanning calorimetry (DSC) study suggested that the Td of Ag-col was 20°C higher than that of Col as expected, and dynamic mechanical analysis (DMA) indicated that Ag-col possessed a higher storage modulus but similar loss factor compared to Col. Therefore, the collagen aggregate from pADM could serve as a better alternative source of collagens for further applications in food and biological industries. Copyright © 2016 Elsevier B.V. All rights reserved.

Treatment of severe burn with DermACELL(®), an acellular dermal matrix.

PubMed

Chen, Shyi-Gen; Tzeng, Yuan-Sheng; Wang, Chih-Hsin

2012-01-01

For treatment of skin burn injuries, there exist several methods of treatment related to tissue regeneration, including the use of autograft skin and cryopreserved skin. However, each method has drawbacks. An alternative method for tissue regeneration is allograft acellular dermal matrix, with potential as a biocompatible scaffold for new tissue growth. One recently produced material of this type is DermACELL(®), which was used in this case presentation for treating a scar resulting from second- and third-degree burns in a 33-year-old female patient. The patient presented with significant hypertrophic scarring from the elbow to the hand and with limited wrist and elbow motion. The scarring was removed, and the patient was treated with a 1:3 mesh of DermACELL. The wound was resurfaced with a split thickness skin graft, and postoperative care included application of pressure garment and silicone sheet, as well as range of motion exercise and massage. At 30 days after DermACELL application, the wound appeared well-healed with little scar formation. At 180 days post-application, the wound continued to appear healed well without significant scar formation. Additionally, the wound was supple, and the patient experienced significant improvement in range of motion. In the case presented, DermACELL appears to have been a successful method of treatment for scarring due to severe burns by preventing further scar formation and improving range of motion.

The Effect of Sterile Acellular Dermal Matrix Use on Complication Rates in Implant-Based Immediate Breast Reconstructions

PubMed Central

Park, Youngsoo; Choi, Kyoung Wook; Chung, Kyu-Jin; Kim, Tae Gon; Kim, Yong-Ha

2016-01-01

Background The use of acellular dermal matrix (ADM) in implant-based immediate breast reconstruction has been increasing. The current ADMs available for breast reconstruction are offered as aseptic or sterile. No published studies have compared aseptic and sterile ADM in implant-based immediate breast reconstruction. The authors performed a retrospective study to evaluate the outcomes of aseptic versus sterile ADM in implant-based immediate breast reconstruction. Methods Implant-based immediate breast reconstructions with ADM conducted between April 2013 and January 2016 were included. The patients were divided into 2 groups: the aseptic ADM (AlloDerm) group and the sterile ADM (MegaDerm) group. Archived records were reviewed for demographic data and postoperative complication types and frequencies. The complications included were infection, flap necrosis, capsular contracture, seroma, hematoma, and explantation for any cause. Results Twenty patients were reconstructed with aseptic ADM, and 68 patients with sterile ADM. Rates of infection (15.0% vs. 10.3%), flap necrosis (5.0% vs. 7.4%), capsular contracture (20.0% vs. 14.7%), seroma (10.0% vs. 14.7%), hematoma (0% vs. 1.5%), and explantation (10.0% vs. 8.8%) were not significantly different in the 2 groups. Conclusions Sterile ADM did not provide better results regarding infectious complications than aseptic ADM in implant-based immediate breast reconstruction. PMID:27896182

A Meta-analysis of Studies Comparing Outcomes of Diverse Acellular Dermal Matrices for Implant-Based Breast Reconstruction.

PubMed

Lee, Kyeong-Tae; Mun, Goo-Hyun

2017-07-01

The current diversity of the available acellular dermal matrix (ADM) materials for implant-based breast reconstruction raises the issue of whether there are any differences in postoperative outcomes according to the kind of ADM used. The present meta-analysis aimed to investigate whether choice of ADM products can affect outcomes. Studies that used multiple kinds of ADM products for implant-based breast reconstruction and compared outcomes between them were searched. Outcomes of interest were rates of postoperative complications: infection, seroma, mastectomy flap necrosis, reconstruction failure, and overall complications. A total of 17 studies met the selection criteria. There was only 1 randomized controlled trial, and the other 16 studies had retrospective designs. Comparison of FlexHD, DermaMatrix, and ready-to-use AlloDerm with freeze-dried AlloDerm was conducted in multiple studies and could be meta-analyzed, in which 12 studies participated. In the meta-analysis comparing FlexHD and freeze-dried AlloDerm, using the results of 6 studies, both products showed similar pooled risks for all kinds of complications. When comparing DermaMatrix and freeze-dried AlloDerm with the results from 4 studies, there were also no differences between the pooled risks of complications of the two. Similarly, the meta-analysis of 4 studies comparing ready-to-use and freeze-dried AlloDerm demonstrated that the pooled risks for the complications did not differ. This meta-analysis demonstrates that the 3 recently invented, human cadaveric skin-based products of FlexHD, DermaMatrix, and ready-to-use AlloDerm have similar risks of complications compared with those of freeze-dried AlloDerm, which has been used for longer. However, as most studies had low levels of evidence, further investigations are needed.

Evaluation of human acellular dermis versus porcine acellular dermis in an in vivo model for incisional hernia repair.

PubMed

Ngo, Manh-Dan; Aberman, Harold M; Hawes, Michael L; Choi, Bryan; Gertzman, Arthur A

2011-05-01

Incisional hernias commonly occur following abdominal wall surgery. Human acellular dermal matrices (HADM) are widely used in abdominal wall defect repair. Xenograft acellular dermal matrices, particularly those made from porcine tissues (PADM), have recently experienced increased usage. The purpose of this study was to compare the effectiveness of HADM and PADM in the repair of incisional abdominal wall hernias in a rabbit model. A review from earlier work of differences between human allograft acellular dermal matrices (HADM) and porcine xenograft acellular dermal matrices (PADM) demonstrated significant differences (P < 0.05) in mechanical properties: Tensile strength 15.7 MPa vs. 7.7 MPa for HADM and PADM, respectively. Cellular (fibroblast) infiltration was significantly greater for HADM vs. PADM (Armour). The HADM exhibited a more natural, less degraded collagen by electrophoresis as compared to PADM. The rabbit model surgically established an incisional hernia, which was repaired with one of the two acellular dermal matrices 3 weeks after the creation of the abdominal hernia. The animals were euthanized at 4 and 20 weeks and the wounds evaluated. Tissue ingrowth into the implant was significantly faster for the HADM as compared to PADM, 54 vs. 16% at 4 weeks, and 58 vs. 20% for HADM and PADM, respectively at 20 weeks. The original, induced hernia defect (6 cm(2)) was healed to a greater extent for HADM vs. PADM: 2.7 cm(2) unremodeled area for PADM vs. 1.0 cm² for HADM at 20 weeks. The inherent uniformity of tissue ingrowth and remodeling over time was very different for the HADM relative to the PADM. No differences were observed at the 4-week end point. However, the 20-week data exhibited a statistically different level of variability in the remodeling rate with the mean standard deviation of 0.96 for HADM as contrasted to a mean standard deviation of 2.69 for PADM. This was significant with P < 0.05 using a one tail F test for the inherent variability of the standard deviation. No significant differences between the PADM and HADM for adhesion, inflammation, fibrous tissue or neovascularization were noted.

The Use of Meshed Dermal Autograft in Breast Reconstruction.

PubMed

Zingaretti, Nicola; Guarneri, Gianni Franco; De Biasio, Fabrizio; Shoeib, Mohamed A; Parodi, Pier Camillo

2018-02-01

The advantages and disadvantages of acellular dermal matrix (ADM) in breast reconstruction have been well documented. ADM is commonly used in breast reconstruction, but it adds cost to the procedure and has been associated with an increased risk of seroma, flap necrosis and infectious complications. A dermal autograft may be a useful alternative to matrices, and it has a lot of advantages: more biocompatible and more likely to be retained as a free graft, low cost, well tolerated, readily available and integrated. This report discusses a new surgical technique that uses an autologous dermis, which was harvested from the controlateral breast in patients having simultaneous breast reduction/mastopexy. Before the insertion, the autologous dermal matrix was meshed at a ratio of 3:1 to increase the graft surface area, to provide additional draining and to improve the engraftment of the autologous dermal matrix. Consequently, the resulting meshed graft allows for the cover of the inferior pole of a larger breast size implant and decreases the complication rate. In our clinic, this method was used on five women; there was one limited necrosis of the mastectomy flaps. The described technique is straightforward and reliable, it adds minimally to the operative time, and it eliminates costs and covers a bigger part of the prosthesis and promises good results. No Level Assigned This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Glycerolized Reticular Dermis as a New Human Acellular Dermal Matrix: An Exploratory Study

PubMed Central

Ferrando, Pietro Maria; Balmativola, Davide; Cambieri, Irene; Scalzo, Maria Stella; Bergallo, Massimiliano; Annaratone, Laura; Casarin, Stefania; Fumagalli, Mara; Stella, Maurizio; Sapino, Anna; Castagnoli, Carlotta

2016-01-01

Human Acellular Dermal Matrices (HADM) are employed in various reconstructive surgery procedures as scaffolds for autologous tissue regeneration. The aim of this project was to develop a new type of HADM for clinical use, composed of glycerolized reticular dermis decellularized through incubation and tilting in Dulbecco’s Modified Eagle’s Medium (DMEM). This manufacturing method was compared with a decellularization procedure already described in the literature, based on the use of sodium hydroxide (NaOH), on samples from 28 donors. Cell viability was assessed using an MTT assay and microbiological monitoring was performed on all samples processed after each step. Two surgeons evaluated the biomechanical characteristics of grafts of increasing thickness. The effects of the different decellularization protocols were assessed by means of histological examination and immunohistochemistry, and residual DNA after decellularization was quantified using a real-time TaqMan MGB probe. Finally, we compared the results of DMEM based decellularization protocol on reticular dermis derived samples with the results of the same protocol applied on papillary dermis derived grafts. Our experimental results indicated that the use of glycerolized reticular dermis after 5 weeks of treatment with DMEM results in an HADM with good handling and biocompatibility properties. PMID:26918526

Histologic evaluation of autogenous connective tissue and acellular dermal matrix grafts in humans.

PubMed

Cummings, Lewis C; Kaldahl, Wayne B; Allen, Edward P

2005-02-01

The clinical success of root coverage with autogenous connective tissue (CT) or acellular dermal matrix (ADM) has been well documented. However, limited histological results of CT grafts have been reported, and a case report of a human block section has been published documenting an ADM graft. The purpose of this study is to document the histological results of CT grafts, ADM grafts, and coronally advanced flaps to cover denuded roots in humans. This study included four patients previously treatment planned for extractions of three or more anterior teeth. Three teeth in each patient were selected and randomly designated to receive either a CT or ADM graft beneath a coronally advanced flap (tests) or coronally advanced flap alone (control). Six months postoperatively block section extractions were performed and the teeth processed for histologic evaluation with hematoxylin-eosin and Verhoeff's stains. Histologically, both the CT and ADM were well incorporated within the recipient tissues. New fibroblasts, vascular elements, and collagen were present throughout the ADM, while retention of the transplanted elastic fibers was apparent. No effect on the keratinization or connective tissue organization of the overlying alveolar mucosa was evident with either graft. For both materials, areas of cemental deposition were present within the root notches, the alveolar bone was essentially unaffected, and the attachments to the root surfaces were similar. Although CT and ADM have a slightly different histological appearance, both can successfully be used to cover denuded roots with similar attachments and no adverse healing.

Cost analysis of postmastectomy reconstruction: A comparison of two staged implant reconstruction using tissue expander and acellular dermal matrix with abdominal-based perforator free flaps.

PubMed

Tran, Bao Ngoc N; Fadayomi, Ayotunde; Lin, Samuel J; Singhal, Dhruv; Lee, Bernard T

2017-09-01

Two staged tissue expander-implant with acellular dermal matrix (TE/I + ADM) and deep inferior epigastric perforator (DIEP) flap are the most common implant and autologous methods of reconstruction in the U.S. Implant-based techniques are disproportionally more popular, partially due to its presumed cost effectiveness. We performed a comprehensive cost analysis to compare TE/I + ADM and DIEP flap. A comparative cost analysis of TE/I + ADM and DIEP flap was performed. Medicare reimbursement costs for each procedure and their associated complications were calculated. Pooled probabilities of complications including cellulitis, seroma, skin necrosis, implant removal, flap loss, partial flap loss, and fat necrosis, were calculated using published studies from 2010 to 2016. Average actual cost for successful TE/I + ADM and DIEP flap were $13 304.55 and $10 237.13, respectively. Incorporating pooled complication data from published literature resulted in an increase in cost to $13 963.46 for TE/I + ADM and $12 624.29 for DIEP flap. The expected costs for successful TE/I + ADM and DIEP flap were $9700.35 and $8644.23, which are lower than the actual costs. DIEP flap breast reconstruction incurs lower costs compared to TE/I + ADM. These costs are lower at baseline and when additional costs from pooled complications are incorporated. © 2017 Wiley Periodicals, Inc.

Pre-hydrated sterile acellular dermal matrix allograft in breast reconstruction: review of a single unit's experience.

PubMed

James, Justin; Corrigan, Brigid; Saunders, Christobel

2018-04-01

The acellular dermal matrix (Flex HD) (FHD) became available for use in Western Australia in 2014 to aid prosthetic breast reconstruction and this descriptive study aims to review and discuss a single institution's experience since its introduction. By retrospective case note, review data were collected for all patients who underwent prosthetic breast reconstruction with the aid of FHD between January 2014 and August 2015 in our institution. Data on basic demographic parameters, risk factors, surgery-related factors, post-operative factors and follow-up information were collected. All complications were recorded and described in detail. FHD was used in 42 breast reconstructions in 26 patients. Procedure-related complications were seen in 26% (n = 11) of cases. A major complication requiring return to theatre was seen in 11% (n = 5) of cases. Cellulitis of the reconstructed breast (red breast syndrome) was seen in 16.67% (n = 7) cases. Overall implant loss was 2.4% (n = 1). Of the six possible risk factors for any complication, only current smoking was found to increase the risk of complications (odds ratio = 9.667, 95% confidence interval = 1.429-65.377). FHD is associated with a relatively high overall complication rate. Use of this optional expensive material has to be carefully selected balancing its perceived advantages against this possible risk. The red breast syndrome merits further studies considering its frequent occurrence with FHD use. © 2017 Royal Australasian College of Surgeons.

Preserving the posttrapeziectomy space with a human acellular dermal matrix spacer: a pilot case series of patients with thumb carpometacarpal joint arthritis.

PubMed

Yao, Caroline A; Ellis, Chandra V; Cohen, Myles J; Kulber, David A

2013-10-01

Advanced thumb carpometacarpal arthritis is widely treated with trapeziectomy and tendon interposition despite donor-site morbidities. Trapeziectomy alone leaves a postresection space, leading to proximal metacarpal migration and scaphoid/trapezoid impingement. Prosthetic implants have been unsuccessful due to particulate debris, silicone synovitis, osteolysis, and migration. Recent studies have shown successful use of allograft for interposition material in the posttrapeziectomy space both in animal and human models. To obviate the need for autologous tissue, maintain thumb length, and reduce the risk of scaphoid impingement, the senior author developed an interposition arthroplasty technique using a spacer constructed from human acellular dermal matrix (HADM). Sixteen patients with Eaton stage III-IV thumb carpometacarpal osteoarthritis received the above procedure from the 2 senior authors. HADM was imbricated to fill the posttrapeziectomy space and secured to the volar capsule and metacarpal base. Pre- and postoperative trapezial space on radiograph, pain scores, and grip strength were recorded. Six months postoperatively, radiographs showed an average joint space loss of 11%. Heights postoperatively were not significantly different from immediate postoperative heights (P ≥ 0.01). At 6 months, patients had improved pain and grip strength (P ≤ 0.01). No infections, foreign body reactions, or other complications occurred. HADM has been used extensively in other forms of reconstruction and has been shown to incorporate into surrounding tissues through neovascularization. Our early results illustrate that HADM can safely fill the dead space left by trapeziectomy.

Dynamic multiphoton imaging of acellular dermal matrix scaffolds seeded with mesenchymal stem cells in diabetic wound healing.

PubMed

Chu, Jing; Shi, Panpan; Deng, Xiaoyuan; Jin, Ying; Liu, Hao; Chen, Maosheng; Han, Xue; Liu, Hanping

2018-03-25

Significantly effective therapies need to be developed for chronic nonhealing diabetic wounds. In this work, the topical transplantation of mesenchymal stem cell (MSC) seeded on an acellular dermal matrix (ADM) scaffold is proposed as a novel therapeutic strategy for diabetic cutaneous wound healing. GFP-labeled MSCs were cocultured with an ADM scaffold that was decellularized from normal mouse skin. These cultures were subsequently transplanted as a whole into the full-thickness cutaneous wound site in streptozotocin-induced diabetic mice. Wounds treated with MSC-ADM demonstrated an increased percentage of wound closure. The treatment of MSC-ADM also greatly increased angiogenesis and rapidly completed the reepithelialization of newly formed skin on diabetic mice. More importantly, multiphoton microscopy was used for the intravital and dynamic monitoring of collagen type I (Col-I) fibers synthesis via second harmonic generation imaging. The synthesis of Col-I fibers during diabetic wound healing is of great significance for revealing wound repair mechanisms. In addition, the activity of GFP-labeled MSCs during wound healing was simultaneously traced via two-photon excitation fluorescence imaging. Our research offers a novel advanced nonlinear optical imaging method for monitoring the diabetic wound healing process while the ADM and MSCs interact in situ. Schematic of dynamic imaging of ADM scaffolds seeded with mesenchymal stem cells in diabetic wound healing using multiphoton microscopy. PMT, photo-multiplier tube. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Outcomes of Acellular Dermal Matrix for Immediate Tissue Expander Reconstruction with Radiotherapy: A Retrospective Cohort Study.

PubMed

Craig, Elizabeth S; Clemens, Mark W; Koshy, John C; Wren, James; Hong, Zhang; Butler, Charles; Garvey, Patrick; Selber, Jesse; Kronowitz, Steven

2018-05-24

Despite increasing literature support for the use of acellular dermal matrix (ADM) in expander-based breast reconstruction, the effect of ADM on clinical outcomes in the presence of post-mastectomy radiation therapy (PMRT) has not been well described. To analyze the impact ADM plays on clinical outcomes on immediate tissue expander (ITE) reconstruction undergoing PMRT. We retrospectively reviewed patients who underwent ITE breast reconstruction from 2004 to 2014 at MD Anderson Cancer Center. Patients were categorized into four cohorts: ADM, ADM with PMRT, non-ADM, and non-ADM with PMRT. Outcomes and complications were compared between cohorts. Over ten years, 957 patients underwent ITE reconstruction (683 non-ADM, 113 non-ADM with PMRT, 486 ADM, and 88 ADM with PMRT) with 1,370 reconstructions. Overall complication rates for the ADM and non-ADM cohorts were 39.0 and 16.7%, respectively (p <0.001). Within both cohorts, mastectomy skin flap necrosis (MSFN) was the most common complication, followed by infection. ADM use was associated with a significantly higher rate of infections and seromas in both radiated and non-radiated groups; however, when comparing radiated cohorts, the incidence of explantation was significantly lower with the use of ADM. The decision to use ADM for expander-based breast reconstruction should be performed with caution, given higher overall rates of complications, including infections and seromas. There may, however, be a role for ADM in cases requiring PMRT, as the overall incidence of implant failure is lower than non-ADM cases.

A patient-centered clinical evaluation of acellular dermal matrix graft in the treatment of gingival recession defects.

PubMed

Mahajan, Ajay; Dixit, Jaya; Verma, Umesh Pratap

2007-12-01

The present randomized controlled trial was conducted to evaluate acellular dermal matrix (ADM) graft in terms of patient satisfaction and its effectiveness and efficiency in the treatment of gingival recession. Fourteen patients (seven males and seven females) with Miller Class I and II recessions > or =3 mm participated in this 6-month clinical study. They were assigned randomly to the ADM group (ADM graft and coronally positioned flap [CPF]) or the CPF group (CPF alone). Results were evaluated based on parameters measuring patient satisfaction and clinical outcomes associated with the two treatment procedures. Significance was set at P <0.05. The mean recession was 4.0 +/- 1.0 mm and 3.7 +/- 0.7 mm for the ADM and CPF groups, respectively. For the ADM group, the defect coverage was 3.85 +/- 0.89 mm or 97.14% compared to the CPF group, in which the defect coverage was 2.85 +/- 0.89 mm or 77.42%. The difference between the two groups was statistically significant (P <0.05). There were no statistically significant differences between the two groups in the remaining clinical parameters and overall patient satisfaction except in criteria related to patient comfort and cost effectiveness, in which CPF alone produced significantly better results (P <0.03). ADM graft is significantly superior with regard to effectiveness and efficiency in the treatment of gingival recession than CPF alone. CPF emerges as a better option than ADM graft in terms of cost effectiveness and patient comfort.

Comparison of two surgical procedures for use of the acellular dermal matrix graft in the treatment of gingival recessions: a randomized controlled clinical study.

PubMed

Felipe, Maria Emília M C; Andrade, Patrícia F; Grisi, Marcio F M; Souza, Sérgio L S; Taba, Mário; Palioto, Daniela B; Novaes, Arthur B

2007-07-01

The aim of this randomized, controlled, clinical investigation was to compare two surgical techniques for root coverage with the acellular dermal matrix graft to evaluate which technique provided better root coverage, a better esthetic result, and less postoperative discomfort. Fifteen patients with bilateral Miller Class I or II gingival recessions were selected. Fifteen pairs of recessions were treated and assigned randomly to the test group, and the contralateral recessions were assigned to the control group. The control group was treated with a broader flap and vertical releasing incisions; the test group was treated with the proposed surgical technique, without vertical releasing incisions. The clinical parameters evaluated were probing depth, relative clinical attachment level, gingival recession (GR), width of keratinized tissue, thickness of keratinized tissue, esthetic result, and pain evaluation. The measurements were taken before the surgeries and after 6 months. At baseline, all parameters were similar for both groups. At 6 months, a statistically significant greater reduction in GR favored the control group. The percentage of root coverage was 68.98% and 84.81% for the test and control groups, respectively. The esthetic result was equivalent between the groups, and all patients tolerated both procedures well. Both techniques provided significant root coverage, good esthetic results, and similar levels of postoperative discomfort. However, the control technique had statistically significantly better results for root coverage of localized gingival recessions.

[Preparation of acellular matrix from antler cartilage and its biological compatibility].

PubMed

Fu, Jing; Zhang, Wei; Zhang, Aiwu; Ma, Lijuan; Chu, Wenhui; Li, Chunyi

2017-06-01

To study the feasibility of acellular matrix materials prepared from deer antler cartilage and its biological compatibility so as to search for a new member of the extracellular matrix family for cartilage regeneration. The deer antler mesenchymal (M) layer tissue was harvested and treated through decellular process to prepare M layer acellular matrix; histologic observation and detection of M layer acellular matrix DNA content were carried out. The antler stem cells [antlerogenic periosteum (AP) cells] at 2nd passage were labelled by fluorescent stains and by PKH26. Subsequently, the M layer acellular matrix and the AP cells at 2nd passage were co-cultured for 7 days; then the samples were transplanted into nude mice to study the tissue compatibility of M layer acellular matrix in the living animals. HE and DAPI staining confirmed that the M layer acellular matrix did not contain nucleus; the DNA content of the M layer acellular matrix was (19.367±5.254) ng/mg, which was significantly lower than that of the normal M layer tissue [(3 805.500±519.119) ng/mg]( t =12.630, P =0.000). In vitro co-culture experiments showed that AP cells could adhere to or even embedded in the M layer acellular matrix. Nude mice transplantation experiments showed that the introduced AP cells could proliferate and induce angiogenesis in the M layer acellular matrix. The deer antler cartilage acellular matrix is successfully prepared. The M layer acellular matrix is suitable for adhesion and proliferation of AP cells in vitro and in vivo , and it has the function of stimulating angiogenesis. This model for deer antler cartilage acellular matrix can be applied in cartilage tissue engineering in the future.

Combined use of fibrin tissue adhesive and acellular dermis in dural repair.

PubMed

Shah, Anil R; Pearlman, Aaron N; O'Grady, Kevin M; Bhattacharyya, Tappan K; Toriumi, Dean M

2007-01-01

The management of cerebrospinal fluid (CSF) leaks can be challenging. Acellular dermal grafts derived from human cadavers can be used as a replacement material when autogenous materials are unavailable. Fibrin tissue adhesive (FTA) is a wound support product that has been used for hemostatic and tissue fixation purposes. The combined use of acellular dermis in conjunction with FTA for dural repair remains a subject of study. The aim of this study was to evaluate wound healing and tissue compatibility characteristics of acellular dermal substitute material when used both with and without FTA, for repair of a dural tear in a chinchilla model. Forty-nine chinchillas were included in this randomized case-control study. The squamous portion of the temporal bone was removed to expose the tegmen. A 2 x 2 mm dural defect was removed to create an iatrogenic CSF leak. Then, animals were randomly assigned to one of three treatment groups: group 1, acellular dermis alone; group 2, acellular dermis with FTA; group 3, fibrinogen, acellular dermis, and FTA. Surgical sites were examined grossly at 1- and 2-week intervals. Temporal bones were examined histologically. Grossly, groups 2 and 3 had significantly less visible CSF leak and brain herniation noted at both 1- and 2-week intervals when compared with group 1. Histological results confirmed the gross results showing the best seal in group 2 and 3. Acellular dermis combined with FTA provided superior support compared with acellular dermis alone in repair of induced dural defects.

Immediate Implant-based Prepectoral Breast Reconstruction Using a Vertical Incision

PubMed Central

Lind, Jeffrey G.; Hopkins, Elizabeth G.

2015-01-01

Background: Ideally, breast reconstruction is performed at the time of mastectomy in a single stage with minimal scarring. However, postoperative complications with direct-to-implant subpectoral reconstruction remain significant. These include asymmetry, flap necrosis, animation deformity, and discomfort. We report on a series of patients who have undergone immediate single-stage prepectoral, implant-based breast reconstruction with a smooth, adjustable saline implant covered with mesh/acellular dermal matrix for support using a vertical mastectomy incision. This technique, when combined with an adjustable implant, addresses the complications related to subpectoral implant placement of traditional expanders. Our follow-up time, 4.6 years (55 months), shows a low risk of implant loss and elimination of animation deformity while also providing patients with a safe and aesthetically pleasing result. Methods: All patients who underwent immediate implant-based prepectoral breast reconstruction using a vertical mastectomy incision as a single-staged procedure were included. Charts were reviewed retrospectively. Adjustable smooth round saline implants and mesh/acellular dermal matrix were used for fixation in all cases. Results: Thirty-one patients (62 breasts) underwent single-staged implant-based prepectoral breast reconstruction using a vertical mastectomy incision. Postoperative complications occurred in 9 patients, 6 of which were resolved with postoperative intervention while only 2 cases resulted in implant loss. Conclusions: There can be significant morbidity associated with traditional subpectoral implant-based breast reconstruction. As an alternative, the results of this study show that an immediate single-stage prepectoral breast reconstruction with a smooth saline adjustable implant, using a vertical incision, in conjunction with mesh/matrix support can be performed with excellent aesthetic outcomes and minimal complications. PMID:26180713

Surgical management of cosmetic mucogingival defects.

PubMed

Dym, Harry; Tagliareni, Jonathan M

2012-01-01

Mucogingival conditions are deviations from the normal anatomic relationship between the gingival margin and the mucogingival junction. Mucogingival surgery is plastic surgery designed to correct defects in the gingiva surrounding the teeth. Common mucogingival conditions are recession, absence, or reduction of keratinized tissue, and probing depths extending beyond the mucogingival junction. Surgical techniques used to augment cosmetic mucogingival defects include the free gingival autograft, the subepithelial connective tissue graft, rotational flaps, lateral sliding flaps, coronally repositioned flaps, and the use of acellular dermal matrix grafts. Copyright © 2012 Elsevier Inc. All rights reserved.

Minimizing shrinkage of interdental papilla height when treating multiple Miller Class III gingival recession defects.

PubMed

Mahn, Douglas H

2015-04-01

Miller Class III and IV gingival recession defects have interdental bone and soft-tissue loss that limit root coverage. Given the importance of the interdental papilla, protecting the integrity of this structure would seem prudent. Tunnel techniques have been successfully used to protect the interdental papilla. This article discusses the results of two cases in which multiple Miller Class III gingival recession defects were treated using tunnel-grafting techniques and an acellular dermal matrix. In both cases, root coverage was achieved while protecting the interdental papilla height.

Preparation of laser micropore porcine acellular dermal matrix for skin graft: an experimental study.

PubMed

Chai, Jia-Ke; Liang, Li-Ming; Yang, Hong-Ming; Feng, Rui; Yin, Hui-Nan; Li, Feng-Yu; Sheng, Zhi-Yong

2007-09-01

In our previous study, we used composite grafts consisting of meshed porcine acellular dermal matrix (PADM) and thin split-thickness autologous epidermis to cover full thickness burn wounds in clinical practice. However, a certain degree of contraction might occur because the distribution of dermal matrix was not uniform in burn wound. In this study, we prepare a composite skin graft consisting of PADM with the aid of laser to improve the quality of healing of burn wound. PADM was prepared by the trypsin/Triton X-100 method. Micropores were produced on the PADM with a laser punch. The distance between micropores varied from 0.8, 1.0, 1.2 to 1.5mm. Full thickness defect wounds were created on the back of 144 SD rats. The rats were randomly divided into six groups: micropore groups I-IV in which the wound were grafted with PADM with micropores, in four different distances, respectively and split-thickness autograft; mesh group rats received meshed PADM graft and split-thickness autograft; control group received simple split-thickness autografting. The status of wound healing was histologically observed at regular time points after surgery. The wound healing rate and contraction rate were calculated. The wound healing rate in micropore groups I and II was not statistically different from that in control group, but was significantly higher than that in mesh group 6 weeks after grafting. The wound healing rate in micropore groups III and IV was lower than that in mesh and control groups 4 and 6 weeks after grafting. The wound contraction rate in micropore groups I and II was remarkably lower than that in control group 4 and 6 weeks after surgery and it was significantly much lower than that in mesh group 6 weeks after surgery. Histological examination revealed good epithelization, regularly arranged collagenous fibers and integral structure of basement membrane. Laser micropore PADM (0.8 or 1.0mm in distance) grafting in combination with split-thickness autografting can improve wound healing. The PADM with laser micropores in 1.0mm distance is the better choice.

Human Keratinocyte Growth and Differentiation on Acellular Porcine Dermal Matrix in relation to Wound Healing Potential

PubMed Central

Zajicek, Robert; Mandys, Vaclav; Mestak, Ondrej; Sevcik, Jan; Königova, Radana; Matouskova, Eva

2012-01-01

A number of implantable biomaterials derived from animal tissues are now used in modern surgery. Xe-Derma is a dry, sterile, acellular porcine dermis. It has a remarkable healing effect on burns and other wounds. Our hypothesis was that the natural biological structure of Xe-Derma plays an important role in keratinocyte proliferation and formation of epidermal architecture in vitro as well as in vivo. The bioactivity of Xe-Derma was studied by a cell culture assay. We analyzed growth and differentiation of human keratinocytes cultured in vitro on Xe-Derma, and we compared the results with formation of neoepidermis in the deep dermal wounds treated with Xe-Derma. Keratinocytes cultured on Xe-Derma submerged in the culture medium achieved confluence in 7–10 days. After lifting the cultures to the air-liquid interface, the keratinocytes were stratified and differentiated within one week, forming an epidermis with basal, spinous, granular, and stratum corneum layers. Immunohistochemical detection of high-molecular weight cytokeratins (HMW CKs), CD29, p63, and involucrin confirmed the similarity of organization and differentiation of the cultured epidermal cells to the normal epidermis. The results suggest that the firm natural structure of Xe-Derma stimulates proliferation and differentiation of human primary keratinocytes and by this way improves wound healing. PMID:22629190

Human keratinocyte growth and differentiation on acellular porcine dermal matrix in relation to wound healing potential.

PubMed

Zajicek, Robert; Mandys, Vaclav; Mestak, Ondrej; Sevcik, Jan; Königova, Radana; Matouskova, Eva

2012-01-01

A number of implantable biomaterials derived from animal tissues are now used in modern surgery. Xe-Derma is a dry, sterile, acellular porcine dermis. It has a remarkable healing effect on burns and other wounds. Our hypothesis was that the natural biological structure of Xe-Derma plays an important role in keratinocyte proliferation and formation of epidermal architecture in vitro as well as in vivo. The bioactivity of Xe-Derma was studied by a cell culture assay. We analyzed growth and differentiation of human keratinocytes cultured in vitro on Xe-Derma, and we compared the results with formation of neoepidermis in the deep dermal wounds treated with Xe-Derma. Keratinocytes cultured on Xe-Derma submerged in the culture medium achieved confluence in 7-10 days. After lifting the cultures to the air-liquid interface, the keratinocytes were stratified and differentiated within one week, forming an epidermis with basal, spinous, granular, and stratum corneum layers. Immunohistochemical detection of high-molecular weight cytokeratins (HMW CKs), CD29, p63, and involucrin confirmed the similarity of organization and differentiation of the cultured epidermal cells to the normal epidermis. The results suggest that the firm natural structure of Xe-Derma stimulates proliferation and differentiation of human primary keratinocytes and by this way improves wound healing.

Acellular dermal matrix seeded with autologous gingival fibroblasts for the treatment of gingival recession: a proof-of-concept study.

PubMed

Jhaveri, Hiral M; Chavan, Mahesh S; Tomar, Geetanjali B; Deshmukh, Vijay L; Wani, Mohan R; Miller, Preston D

2010-04-01

One of the most common esthetic concerns associated with periodontal tissues is gingival recession. There are multiple periodontal plastic surgery approaches documented in the literature for the treatment of such defects. With the tremendous advances being made in periodontal science and technology, tissue engineering could be considered among the latest exciting techniques for recession management. In this split-mouth, controlled, double-masked clinical case series, 20 sites from 10 patients with Miller Class I or II recessions affecting canines or premolars in the maxillary arch were selected. One tooth in each patient was randomized to receive either a subepithelial connective tissue graft (SCTG) (control group) or an acellular dermal matrix allograft (ADMA) seeded with autologous gingival fibroblasts (test group) under a coronally positioned flap. Clinical parameters, including recession depth, probing depth, clinical attachment level, width of keratinized tissue, attached gingiva, and plaque scores, were recorded by a calibrated examiner at baseline and 3 and 6 months. The inflammation of grafted sites was scored, and the healing time was calculated. The final esthetic outcome of treated sites was assessed by the root coverage esthetic score at the end of 6 months. There were no significant differences between test and control sites for all measured clinical parameters. However, the test sites demonstrated less inflammation in the early postoperative period. Within the limits of this case series, the results indicate that an ADMA seeded with autologous gingival fibroblasts by tissue-engineering technology may be explored as a substitute to an SCTG for the treatment of Miller Class I and II recession defects.

Metrics of Cellular and Vascular Infiltration of Human Acellular Dermal Matrix in Ventral Hernia Repairs

PubMed Central

Campbell, Kristin Turza; Burns, Nadja K.; Ensor, Joe; Butler, Charles E.

2012-01-01

Background Human acellular dermal matrix (HADM) is used for ventral hernia repair, as it resists infection and remodels via surrounding tissue. However, the tissue source and impact of basement membrane (BM) on cell and vessel infiltration have not been determined. We hypothesized that musculofascia would be the primary tissue source of cells and vessels infiltrating into HADM and the BM would inhibit infiltration. Methods Fifty-six guinea pigs underwent inlay HADM ventral hernia repair with the BM oriented toward or away from the peritoneum. At postoperative weeks 1, 2, or 4, repair sites were completely excised. Histologic and immunohistochemical analyses were performed to quantify cell and vessel density within repair-site zones, including interface (lateral, beneath musculofascia) and center (beneath subcutaneous fat) zones. Cell and vessel quantities were compared as functions of zone, BM orientation, and time. Results Cellular and vascular infiltration increased over time universally. The interface demonstrated greater mean cell density than the center (weeks 1 and 2, p=0.01, p<0.0001). Cell density was greater with the BM oriented toward the peritoneum at week 4 (p=0.02). The interface zone had greater mean vessel density than the center zone at week 4 (p<0.0001). Orienting the BM toward the peritoneum increased vessel density at week 4 (p=0.0004). Conclusion Cellular and vascular infiltration into HADM for ventral hernia repairs was greater from musculofascia than subcutaneous and the BM inhibited cellular and vascular. HADM should be placed adjacent to the best vascularizing tissue to improve fibrovascular incorporation. PMID:22456361

Comparison of the clinical outcomes of connective tissue and acellular dermal matrix in combination with double papillary flap for root coverage: A 6-month trial

PubMed Central

Gholami, Gholam Ali; Saberi, Arezoo; Kadkhodazadeh, Mahdi; Amid, Reza; Karami, Daryoosh

2013-01-01

Background: Different techniques have been proposed for the treatment of gingival recession. The majority of current procedures use autogenous soft-tissue grafts, which are associated with morbidity at the donor sites. Acellular dermal matrix (ADM) Alloderm is an alternative donor material presented to reduce related morbidity and provide more volume of the donor tissue. This study aimed to evaluate the effectiveness of an ADM allograft for root coverage and to compare it with a connective tissue graft (CTG), when used with a double papillary flap. Materials and Methods: Sixteen patients with bilateral class I or II gingival recessions were selected. A total of 32 recessions were treated and randomly assigned into the test and contralateral recessions into the control group. In the control group, the exposed root surfaces were treated by the placement of a CTG in combination with a double papillary flap; and in the test group, an ADM allograft was used as a substitute for palatal donor tissue. Probing depth, clinical attachment level, width of keratinized tissue (KT), recession height and width were measured before, and after 2 weeks and 6 months of surgery. Results: There were no statistically significant differences between the test and control groups in terms of recession reduction, clinical attachment gain, and reduction in probing depth. The control group had a statistically significant increased area of KT after 6 months compared to the test group. Conclusion: ADM allograft can be considered as a substitute for palatal donor tissue in root coverage procedure. PMID:24130587

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.

A 6-month comparative clinical study of a conventional and a new surgical approach for root coverage with acellular dermal matrix.

PubMed

Barros, Raquel R M; Novaes, Arthur B Júnior; Grisi, Márcio F M; Souza, Sérgio L S; Taba, Mário Júnior; Palioto, Daniela B

2004-10-01

The acellular dermal matrix graft (ADMG) has become widely used in periodontal surgeries as a substitute for the subepithelial connective tissue graft (SCTG). These grafts exhibit different healing processes due to their distinct cellular and vascular structures. Therefore the surgical technique primarily developed for the autograft may not be adequate for the allograft. This study compared the clinical results of two surgical techniques--the "conventional" and a modified procedure--for the treatment of localized gingival recessions with the ADMG. A total of 32 bilateral Miller Class I or II gingival recessions were selected and randomly assigned to test and control groups. The control group received the SCTG and the test group the modified surgical technique. Probing depth (PD), relative clinical attachment level (RCAL), gingival recession (GR), and width of keratinized tissue (KT) were measured 2 weeks prior to surgery and 6 months post-surgery. Both procedures improved all the evaluated parameters after 6 months. Comparisons between the groups by Mann-Whitney rank sum test revealed no statistically significant differences in terms of CAL gain, PD reduction, and increase in KT from baseline to 6-month evaluation. However, there was a statistically significant greater reduction of GR favoring the modified technique (P = 0.002). The percentage of root coverage was 79% for the test group and 63.9% for the control group. We conclude that the modified technique is more suitable for root coverage procedures with the ADMG since it had statistically significant better clinical results compared to the traditional technique.

New surgical approach for root coverage of localized gingival recession with acellular dermal matrix: a 12-month comparative clinical study.

PubMed

Barros, Raquel R M; Novaes, Arthur B; Grisi, Márcio F M; Souza, Sérgio L S; Taba, Mário; Palioto, Daniela B

2005-01-01

Acellular dermal matrix graft (ADMG) has been used as an advantageous substitute for autogenous subepithelial connective tissue graft (SCTG). However, the surgical techniques used were primarily developed for the SCTG, and they may not be adequate for ADMG since it has a different healing process than SCTG owing to its different vascular and cellular structures. This study compared the 1-year clinical outcome of a new surgical approach with the outcome of a conventional procedure for the treatment of localized gingival recessions, both performed using the ADMG. The clinical parameters-probing depth, relative clinical attachment level, gingival recession (GR), and width of keratinized tissue-of 32 bilateral Miller Class I or II gingival recessions were assessed at baseline and 12 months postoperatively. Significant clinical changes for both surgical techniques were achieved after this period, including GR reduction from 3.4 mm presurgery to 1.2 mm at 1 year for the conventional technique and from 3.9 mm presurgery to 0.7 mm at 1 year for the new technique. The percentage of root coverage was 62.3% and 82.5% for the conventional and new techniques, respectively. Comparisons between the groups after this period by Mann-Whitney rank sum test revealed statistically significant greater reduction of GR favoring the new procedure (p = .000). Based on the results of this study, it can be concluded that a new surgical technique using an ADMG is more suitable for root coverage when compared with the conventional technique. The results revealed a statistically significant improvement in clinical performance with the ADMG approach.

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.

Dermal Matrices and Bioengineered Skin Substitutes: A Critical Review of Current Options

PubMed Central

Hamdi, Moustapha; Abberton, Keren; Morrison, Wayne

2015-01-01

Background: Over recent decades, scientists and surgeons have collaborated to develop various bioengineered and synthetic products as an alternative to skin grafts. Despite the numerous articles and reviews written about dermal skin substitutes, there is no general consensus. Methods: This article reviews dermal skin scaffolds used in clinical applications and experimental settings. For scaffold evaluation, we focused on clinical and/or histological results, and conclusions are listed. Explanations for general trends were sought based on existing knowledge about tissue engineering principles and wound healing mechanisms. Results: Decellularized dermis seems to remain the best option with no other acellular scaffold being clinically proven to gain better results yet. In general, chemically cross-linked products were seen to be less effective in skin tissue engineering. Biocompatibility could be enhanced by preseeding substitutes with fibroblasts to allow some natural scaffold remodeling before product application. Conclusions: Skin substitutes are a useful tool in plastic and reconstructive surgery practices as an alternative to skin grafts. In the choice of substitute, the general plastic surgery principle of replacing like tissue with like tissue seems to be still standing, and products most resembling the natural dermal extracellular matrix should be preferred. PMID:25674365

Foreign body reaction to acellular dermal matrix allograft in biologic glenoid resurfacing.

PubMed

Namdari, Surena; Melnic, Christopher; Huffman, G Russell

2013-08-01

Biologic glenoid resurfacing is a treatment option for young patients with glenohumeral arthritis. An optimal synthetic graft for glenoid resurfacing should allow repopulation with host cells, be durable enough to tolerate suture fixation and forces across the joint, and present no host inflammatory response. We report two cases of giant cell reaction to GraftJacket(®) after biologic glenoid resurfacing. Two patients who underwent hemiarthroplasty and biologic glenoid resurfacing using GraftJacket(®) had a foreign body giant cell reaction that required revision surgery. Intraoperatively, both patients were observed to have a well-fixed humeral component and a dense, erythematous, synovitic membrane overlying the glenoid. Pathology specimens showed a benign reactive synovium, chronic inflammation, and foreign body giant cell reaction. After débridement and conversion to total shoulder arthroplasty, both patients continued to be pain-free at greater than 1-year followup. Multinucleated giant cell and mononuclear cell responses have been observed in an animal model after use of GraftJacket(®). Although the use of acellular matrix-based scaffold for biologic glenoid resurfacing is not new, the possibility of foreign body reaction as a source of persistent symptoms has not been described. Given the lack of data to indicate an advantage to biologic resurfacing of the glenoid over hemiarthroplasty alone, resurfacing should not introduce significant additional surgical complications. We suggest foreign body reaction be considered in the differential diagnosis for a persistently painful shoulder after biologic glenoid resurfacing using an acellular allograft patch.

Does the use of an acellular dermal graft in abdominal closure after rectus flap harvest impact the occurrence of post-operative hernia?

PubMed

Saman, Masoud; Kadakia, Sameep; Ducic, Yadranko

2015-12-01

Patients with rectus free flap harvest extending below the arcuate line are predisposed to postoperative hernia formation. As such, many authors have advocated the use of closure adjuncts to increase the integrity of the closure and prevent hernia or abdominal wall bulging. Busy level 1 public trauma center in metropolitan Fort Worth, Texas Following harvest of the rectus free flap, 48 patients underwent primary closure; 24 of these patients had defects extending below the arcuate line. Forty patients were closed with an acellular dermal graft; 22 of these patients had defects extending below the arcuate line. Postoperative hernia formation and local infection rate were examined in a minimum follow-up period of 1 year. Regardless of closure method, no hernias were observed in the postoperative period. Using an unpaired t test and an alpha value of 0.05, there was no statistically significant difference in the infection rate between the two groups. Following rectus abdominis myocutaneous free flap harvest, the use of an acellular dermal graft in abdominal wall closure may not be of any further advantage in the prevention of hernia. Retrospective (Level III).

Histology of the heterostracan dermal skeleton: Insight into the origin of the vertebrate mineralised skeleton.

PubMed

Keating, Joseph N; Marquart, Chloe L; Donoghue, Philip C J

2015-06-01

Living vertebrates are divided into those that possess a fully formed and fully mineralised skeleton (gnathostomes) versus those that possess only unmineralised cartilaginous rudiments (cyclostomes). As such, extinct phylogenetic intermediates of these living lineages afford unique insights into the evolutionary assembly of the vertebrate mineralised skeleton and its canonical tissue types. Extinct jawless and jawed fishes assigned to the gnathostome stem evidence the piecemeal assembly of skeletal systems, revealing that the dermal skeleton is the earliest manifestation of a homologous mineralised skeleton. Yet the nature of the primitive dermal skeleton, itself, is poorly understood. This is principally because previous histological studies of early vertebrates lacked a phylogenetic framework required to derive evolutionary hypotheses. Nowhere is this more apparent than within Heterostraci, a diverse clade of primitive jawless vertebrates. To this end, we surveyed the dermal skeletal histology of heterostracans, inferred the plesiomorphic heterostracan skeleton and, through histological comparison to other skeletonising vertebrate clades, deduced the ancestral nature of the vertebrate dermal skeleton. Heterostracans primitively possess a four-layered skeleton, comprising a superficial layer of odontodes composed of dentine and enameloid; a compact layer of acellular parallel-fibred bone containing a network of vascular canals that supply the pulp canals (L1); a trabecular layer consisting of intersecting radial walls composed of acellular parallel-fibred bone, showing osteon-like development (L2); and a basal layer of isopedin (L3). A three layered skeleton, equivalent to the superficial layer L2 and L3 and composed of enameloid, dentine and acellular bone, is possessed by the ancestor of heterostracans + jawed vertebrates. We conclude that an osteogenic component is plesiomorphic with respect to the vertebrate dermal skeleton. Consequently, we interpret the dermal skeleton of denticles in chondrichthyans and jawless thelodonts as independently and secondarily simplified. J. Morphol. 276:657-680, 2015. © 2015 The Authors Journal of Morphology Published by Wiley Periodicals, Inc. © 2015 The Authors Journal of Morphology Published by Wiley Periodicals, Inc.

Clinical evaluation of alloderm for root coverage and colour match

PubMed Central

Shanmugam, M.; Sivakumar, V.; Anitha, V.; Sivakumar, B.

2012-01-01

Background: Predictable root coverage and good colour match are the major therapeutic end points in the treatment of gingival recession. Alloderm has been used as a substitute to connective tissue graft, but its colour match in populations with a high degree of melanin pigmentation has not been extensively studied. The aim of this study was to evaluate the effectiveness of an Acellular dermal matrix graft for root coverage procedures and to objectively analyze the post-operative esthetics using a Visual Analog Scale (VAS). Materials and Methods: Both male and female patients were selected, aged 20-50 years presenting with aesthetic problems due to the exposure of recession defects when smiling. A total of 14 patients contributed to 15 sites, each site falling into Miller's class I or class II gingival recession. Results: A total of 15 sites were treated and a mean coverage of (85.56±21.70 and 83.33±21.82%) was obtained at the end of 3rd and 12th month respectively. A mean VAS score of 7.93±1.03 and 8.13±0.99 (3rd and 12th month) and 5.73±0.70 and 6.87±0.83 (3rd and 12th month) was obtained when the colour match recorded by the patients and an independent observer, respectively. Conclusion: The study showed that acellular dermal matrix graft (alloderm) may be successfully used to treat gingival recession, as adequate root coverage may be predictably obtained. The grafted areas underwent melanization from the 6th month onwards and complete blending with the adjacent sites was obtained at 1 year. PMID:23055588

Impact of Acellular Dermal Matrix (ADM) Use Under Mastectomy Flap Necrosis on Perioperative Outcomes of Prosthetic Breast Reconstruction.

PubMed

Kim, So Young; Bang, Sa Ik

2017-04-01

There is conflicting data on the potential necrotic complications of acellular dermal matrix (ADM) use in breast reconstruction, and most studies focus on mastectomy flap necrosis as an outcome measure associated with ADM use. The aim of this study was to examine cases with necrotic complications with and without the use of ADM and to investigate whether ADM affected perioperative outcomes in cases with necrotic complications. Patients who experienced mastectomy flap necrosis following mastectomy with tissue expander placement between January 2009 and March 2015 were retrospectively reviewed. The primary outcome was explantation of the expander, and other associated outcomes such as seroma or infection were also recorded. A total of 57 breasts with mastectomy flap necrosis were identified: 32 of which were in the non-ADM group and 25 in the ADM group. The rate of explantation was 28% (7/25) in the ADM group versus 6.3% (2/32) in the non-ADM group, which was significantly different (P = 0.034). The ADM group had a significantly higher rate of "major" infection requiring surgical debridement than the non-ADM group (P = 0.016). Multivariate analysis showed that the use of ADM was trending toward an increasing expander rate with borderline significance (P = 0.05). This study demonstrated that ADM use under mastectomy flap necrosis was a potential risk for explantation of the expander and major infection. Surgeons should be cautious with the use of ADM with devascularized mastectomy skin flaps prone to necrosis. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Dual Coverage of the Inferior Pole with Conjoined Fascial Flap and Acellular Dermal Matrix for Immediate One-Stage Breast Reconstruction with a Prosthetic Implant.

PubMed

Lee, Seo H; Chun, Yong S; Park, Heung K; Kim, Yang W; Cheon, Young W

2018-04-17

Elevation of a conjoined fascial flap composed of the pectoralis major, serratus anterior, and external oblique fascia is a type of surgical technique using autologous tissue to cover the lower pole after immediate one-stage direct-to-implant (DTI) breast reconstruction. However, volumetric breast implants hinder use of this technique alone. For better structural stability and more aesthetically favorable breast contour in large breasts, we have devised a technique involving dual coverage of the lower pole by a conjoined fascial flap and acellular dermal matrix (ADM). Twenty Asian patients underwent DTI breast reconstruction from March 2013 to May 2014. ADM was used to cover the inferomedial quadrant of the breast, and a conjoined fascial flap was elevated to cover the remaining inferolateral quadrant. Both patient- and plastic surgeon-reported outcome measures were assessed using questionnaires. For every domain of the patient- and plastic surgeon-reported questionnaires, the mean scores were between satisfied and very satisfied. Two patients developed a seroma and one patient developed partial skin flap necrosis. Both seromas resolved after a series of aspirations. The necrotic skin flap was revised under local anesthesia 3 weeks after the reconstructive surgery. The use of dual coverage of the inferior pole with a conjoined fascial flap and ADM for immediate DTI among patients with large breasts is supported by high scores in both patient- and plastic surgeon-reported outcome measures, as well as low complication rates. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Acellular dermal matrix allograft versus free gingival graft: a histological evaluation and split-mouth randomized clinical trial.

PubMed

de Resende, Daniel Romeu Benchimol; Greghi, Sebastião Luiz Aguiar; Siqueira, Aline Franco; Benfatti, César Augusto Magalhães; Damante, Carla Andreotti; Ragghianti Zangrando, Mariana Schutzer

2018-04-30

This split-mouth controlled randomized clinical trial evaluated clinical and histological results of acellular dermal matrix allograft (ADM) compared to autogenous free gingival graft (FGG) for keratinized tissue augmentation. Twenty-five patients with the absence or deficiency of keratinized tissue (50 sites) were treated with FGG (control group) and ADM (test group). Clinical parameters included keratinized tissue width (KTW) (primary outcome), soft tissue thickness (TT), recession depth (RD), probing depth (PD), and clinical attachment level (CAL). Esthetic perception was evaluated by patients and by a calibrated periodontist using visual analog scale (VAS). Histological analysis included biopsies of five different patients from both test and control sites for each evaluation period (n = 25). The analysis included percentage of connective tissue components, epithelial luminal to basal surface ratio, tissue maturation, and presence of elastic fibers. Data were evaluated by ANOVA complemented by Tukey's tests (p < 0.05). After 6 months, PD and CAL demonstrated no differences between groups. ADM presented higher RD compared to FGG in all periods. Mean tissue shrinkage for control and test groups was 12.41 versus 55.7%. TT was inferior for ADM group compared to FGG. Esthetics perception by professional evaluation showed superior results for ADM. Histomorphometric analysis demonstrated higher percentage of cellularity, blood vessels, and epithelial luminal to basal surface ratio for FGG group. ADM group presented higher percentage of collagen fibers and inflammatory infiltrate. Both treatments resulted in improvement of clinical parameters, except for RD. ADM group presented more tissue shrinkage and delayed healing, confirmed histologically, but superior professional esthetic perception. This study added important clinical and histological data to contribute in the decision-making process between indication of FGG or ADM.

Short-Term Complications Associated With Acellular Dermal Matrix-Assisted Direct-to-Implant Breast Reconstruction.

PubMed

Hunsicker, Lisa M; Ashikari, Andrew Y; Berry, Colleen; Koch, R Michael; Salzberg, C Andrew

2017-01-01

Although direct-to-implant breast reconstruction is a more concise procedure than 2-stage expander/implant reconstruction, it is less frequently performed. Skeptics of direct-to-implant reconstruction cite risk of postoperative complications as a reason for its rejection. To determine whether these perceptions are valid, we evaluated our 13-year experience of acellular dermal matrix (ADM)-assisted, direct-to-implant breast reconstruction. We report complication and reoperation rates associated with this technique as well as predictors for these outcomes. This retrospective study included all patients who underwent immediate, ADM-assisted, direct-to-implant, breast reconstruction from December 2001 to May 2014 at 2 practices. Postoperative complications, defined as those occurring within the first 12 months after reconstructive surgery, were evaluated. Univariate/multivariate analyses were performed to determine the influence of patient-, breast-, and surgery-related characteristics on the development of complications. A total of 1584 breast reconstructions (721 bilateral, 142 unilateral) in 863 patients were performed; 35% were oncologic, and 65% were prophylactic reconstructions. Complication rate was 8.6% and included skin necrosis (5.9%), infection (3.0%), implant loss (2.9%), seroma (1.1%), and hematoma (0.9%). Reoperative rate in breasts with complications was 3.2%. Age 50 years or older, smoking, nonnipple-sparing mastectomy, and implant size of 600 mL or greater strongly predicted the development of complications (P < 0.001). Our cumulative 13-year experience demonstrates that immediate, ADM-assisted, direct-to-implant breast reconstruction is safe, effective, and reliable. Complication and reoperation rates are less than 10% and are comparable to those reported for 2-stage procedures in the published literature.

Rotator cuff bridging repair using acellular dermal matrix in large to massive rotator cuff tears: histologic and clinical analysis.

PubMed

Kim, Jong Ok; Lee, Jong-Ho; Kim, Kwang-Sup; Ji, Jong-Hun; Koh, Sung-Jun; Lee, Jae-Ho

2017-11-01

This study investigated the efficacy of the bridging repair using an acellular dermal matrix (ADM) and an ADM with stem cells in rabbits. Also investigated were clinical outcomes of ADM bridging repair for large to massive rotator cuff tears. ADM, with and without stem cells, was used to cover a 5- × 5-mm-sized cuff defect in 17 rabbits, and biomechanical, histologic, and immunohistochemical analyses were conducted. Also evaluated were 24 patients with large to massive rotator cuff tears after ADM bridging repair. In the biomechanical test, the normal rotator cuff, cuff with ADM plus stem cells, and cuff with ADM in the rabbit model showed a maximum load (N) of 287.3, 217.5, and 170.3 and ultimate tensile strength (N/mm 2 ) of 11.1, 8.0, and 5.2, respectively. Histologically, the cuff tendons with the ADM or ADM plus stem cells showed characteristically mature tendons as time passed. In the clinical study, the mean American Shoulder and Elbow Surgeons score improved from preoperative 50 to postoperative 83, the University of California Los Angeles Shoulder Rating Scale from 17 to 30, and the Simple Shoulder Test from 4 to 8, respectively. No further fatty deteriorations or muscle atrophy were observed on follow-up magnetic resonance imaging. A retear was found in 5 of 24 patients (21%). Bridging repair with ADM or stem cells in the rabbit model showed cellular infiltration into the graft and some evidence of neotendon formation. Clinically, ADM repair was a safe alternative that did not show any further fatty deterioration nor muscle atrophy in large to massive rotator cuff tears. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Outcomes of arthroscopic revision rotator cuff repair with acellular human dermal matrix allograft augmentation.

PubMed

Hohn, Eric A; Gillette, Blake P; Burns, Joseph P

2018-05-01

The purpose was to assess the minimum 2-year patient-reported outcomes and failure rate of patients who underwent revision arthroscopic rotator cuff repair augmented with acellular human dermal matrix (AHDM) allograft for repairable retears. From 2008-2014, patients who underwent revision rotator cuff repair augmented with AHDM with greater than 2 years' follow-up by a single surgeon were retrospectively reviewed. Data regarding surgical history, demographic characteristics, and medical comorbidities were collected. Outcome data included American Shoulder and Elbow Surgeons (ASES) and Single Assessment Numeric Evaluation (SANE) scores, as well as rotator cuff healing on magnetic resonance imaging or ultrasound. Retears and subsequent surgical procedures were characterized. A total of 28 patients met our inclusion criteria, and 23 (82%) were available for follow-up at 2 years. The mean age was 60.1 ± 9.3 years (range, 43-79 years), with a mean follow-up period of 48 ± 23 months. All patients had at least 1 prior rotator cuff repair. Of the 23 patients, 13 (56%) underwent postoperative imaging, and 4 of these 13 (31%) had a retear. A reoperation was performed in 3 of 23 patients (13%). Among the 6 patients with both preoperative and postoperative outcome scores, we saw improvement in the ASES score from 56 to 85 (P = .03) and in the SANE score from 42 to 76 (P = .03). The full cohort's mean postoperative ASES and SANE scores were 77 and 69, respectively. AHDM allograft augmentation is a safe and effective treatment method for patients with full-thickness rotator cuff retears. Further research is needed with larger studies to confirm these findings from our small cohort of patients. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Reconstruction of cartilage with clonal mesenchymal stem cell-acellular dermal matrix in cartilage defect model in nonhuman primates.

PubMed

Ma, Anlun; Jiang, Li; Song, Lijun; Hu, Yanxin; Dun, Hao; Daloze, Pierre; Yu, Yonglin; Jiang, Jianyuan; Zafarullah, Muhammad; Chen, Huifang

2013-07-01

Articular cartilage defects are commonly associated with trauma, inflammation and osteoarthritis. Mesenchymal stem cell (MSC)-based therapy is a promising novel approach for repairing articular cartilage. Direct intra-articular injection of uncommitted MSCs does not regenerate high-quality cartilage. This study explored utilization of a new three-dimensional, selected chondrogenic clonal MSC-loaded monkey acellular dermal matrix (MSC-ADM) scaffold to repair damaged cartilage in an experimental model of knee joint cartilage defect in Cynomolgus monkeys. MSCs were characterized for cell size, cell yield, phenotypes, proliferation and chondrogenic differentiation capacity. Chondrogenic differentiation assays were performed at different MSC passages by sulfated glycosaminoglycans (sGAG), collagen, and fluorescence activated cell sorter (FACS) analysis. Selected chondrogenic clonal MSCs were seeded onto ADM scaffold with the sandwich model and MSC-loaded ADM grafts were analyzed by confocal microscopy and scanning electron microscopy. Cartilage defects were treated with normal saline, clonal MSCs and clonal MSC-ADM grafts, respectively. The clinical parameters, and histological and immunohistochemical examinations were evaluated at weeks 8, 16, 24 post-treatment, respectively. Polyclonal and clonal MSCs could differentiate into the chondrogenic lineage after stimulation with suitable chondrogenic factors. They expressed mesenchymal markers and were negative for hematopoietic markers. Articular cartilage defects were considerably improved and repaired by selected chondrogenic clonal MSC-based treatment, particularly, in MSC-ADM-treated group. The histological scores in MSC-ADM-treated group were consistently higher than those of other groups. Our results suggest that selected chondrogenic clonal MSC-loaded ADM grafts could improve the cartilage lesions in Cynomolgus monkey model, which may be applicable for repairing similar human cartilage defects. Copyright © 2013 Elsevier B.V. All rights reserved.

ASPS clinical practice guideline summary on breast reconstruction with expanders and implants.

PubMed

Alderman, Amy; Gutowski, Karol; Ahuja, Amy; Gray, Diedra

2014-10-01

After reading this article, participants should be able to: 1. Understand the evidence regarding the timing of expander/implant breast reconstruction in the setting of radiation therapy. 2. Discuss the implications of a patient's risk factors for possible outcomes and complications of expander/implant breast reconstruction. 3. Implement proper prophylactic antibiotic protocols. 4. Use the guidelines to improve their own clinical outcomes and reduce complications. In March of 2013, the Executive Committee of the American Society of Plastic Surgeons approved an evidence-based guideline on breast reconstruction with expanders and implants, as developed by a guideline-specific work group commissioned by the society's Health Policy Committee. The guideline addresses ten clinical questions: patient education, immediate versus delayed reconstruction, risk factors, radiation therapy, chemotherapy, hormonal therapy, antibiotic prophylaxis, acellular dermal matrix, monitoring for cancer recurrence, and oncologic outcomes associated with implant-based reconstruction. The evidence indicates that patients undergoing mastectomy should be offered a preoperative referral to a plastic surgeon. Evidence varies regarding the association between postoperative complications and timing of postmastectomy expander/implant breast reconstruction. Evidence is limited regarding the optimal timing of expand/implant reconstruction in the setting of radiation therapy but suggests that irradiation to the expander or implant is associated with an increased risk of postoperative complications. Evidence also varies regarding the association between acellular dermal matrix and surgical complications in the setting of postmastectomy expander/implant reconstruction. Data support the use of an appropriate preoperative antibiotic, but antibiotics should be discontinued within 24 hours of the procedure, unless a surgical drain is present. Furthermore, postmastectomy expander/implant breast reconstruction does not adversely affect oncologic outcomes.

The clinical effect of acellular dermal matrix on gingival thickness and root coverage compared to coronally positioned flap alone.

PubMed

Woodyard, James G; Greenwell, Henry; Hill, Margaret; Drisko, Connie; Iasella, John M; Scheetz, James

2004-01-01

The primary aim of this randomized, controlled, blinded, clinical investigation was to compare the coronally positioned flap (CPF) plus an acellular dermal matrix (ADM) allograft to CPF alone to determine their effect on gingival thickness and percent root coverage. Twenty-four subjects with one Miller Class I or II buccal recession defect of > or = 3 mm were treated with a CPF plus ADM or a CPF alone. Multiple additional recession sites were treated with the same flap procedure, and all sites were studied for 6 months. Tissue thickness was measured at the sulcus base and at the mucogingival junction of all teeth, with an SDM ultrasonic gingival thickness meter. For the ADM sites, mean initial recession of 3.46 mm was reduced to 0.04 mm for defect coverage of 3.42 mm or 99% (P < 0.05). For the CPF group, mean initial recession of 3.27 mm was reduced to 1.08 mm for defect coverage of 2.19 mm or 67% (P < 0.05). The difference between ADM and CPF groups was statistically significant (P < 0.05). Marginal soft-tissue thickness was increased by 0.40 mm (P < 0.05) for the ADM group, whereas the CPF group remained essentially unchanged. Keratinized tissue was increased for the ADM group by 0.81 mm (P < 0.05), whereas the CPF group increased by 0.33 mm (P > 0.05). No additional root coverage was gained due to creeping attachment between 2 and 6 months for either group. Treatment with a CPF plus an ADM allograft significantly increased gingival thickness when compared with a CPF alone. Recession defect coverage was significantly improved with the use of ADM.

Root coverage using acellular dermal matrix and comparing a coronally positioned tunnel with and without platelet-rich plasma: a pilot study in humans.

PubMed

Shepherd, Neal; Greenwell, Henry; Hill, Margaret; Vidal, Ricardo; Scheetz, James P

2009-03-01

The primary aim of this randomized, controlled, blinded clinical pilot study was to compare the percentage of recession defect coverage obtained with a coronally positioned tunnel (CPT) plus an acellular dermal matrix allograft (ADM) to that of a CPT plus ADM and platelet-rich plasma (CPT/PRP) 4 months post-surgically. Eighteen patients with Miller Class I or II recession >or=3 mm at one site were treated and followed for 4 months. Nine patients received a CPT plus ADM and were considered the positive control group. The test group consisted of nine patients treated with a CPT plus ADM and PRP. Patients were randomly selected by a coin toss to receive the test or positive control treatment. The mean recession at the initial examination for the CPT group was 3.6 +/- 1.0 mm, which was reduced to 1.0 +/- 1.0 mm at the 4-month examination for a gain of 2.6 +/- 1.5 mm or 70% defect coverage (P <0.05). The mean recession at the initial examination for the CPT/PRP group was 3.3 +/- 0.7 mm, which was reduced to 0.4 +/- 0.7 mm at the 4-month examination for a gain of 2.9 +/- 0.5 mm or 90% defect coverage (P <0.05). There were no statistically significant differences between the groups (P >0.05). The CPT plus ADM and PRP produced defect coverage of 90%, whereas the CPT with ADM produced only 70% defect coverage. This difference was not statistically significant, but it may be clinically significant.

Cytocompatibility and biologic characteristics of synthetic scaffold materials of rabbit acellular vascular matrix combining with human-like collagen I.

PubMed

Liu, Xuqian; Wang, Jie; Dong, Fusheng; Song, Peng; Tian, Songbo; Li, Hexiang; Hou, Yali

2017-10-01

Scaffold material provides a three-dimensional growing environment for seed cells in the research field of tissue engineering. In the present study, rabbit arterial blood vessel cells were chemically removed with trypsin and Triton X-100 to prepare rabbit acellular vascular matrix scaffold material. Observation by He&Masson staining revealed that no cellular components or nuclei existed in the vascular intima and media after decellularization. Human-like collagen I was combined with acellular vascular matrix by freeze-drying to prepare an acellular vascular matrix-0.25% human-like collagen I scaffold to compensate for the extracellular matrix loss during the decellularization process. We next performed a series of experiments to test the water absorbing quality, biomechanics, pressure resistance, cytotoxicity, and ultra-micro structure of the acellular vascular matrix composite material and natural rabbit artery and found that the acellular vascular matrix-0.25% human-like collagen I material behaved similarly to natural rabbit artery. In conclusion, the acellular vascular matrix-0.25% human-like collagen I composite material provides a new approach and lays the foundation for novel scaffold material research into tissue engineering of blood vessels.

[The applications of periodontal gingival surgery. Ⅱ: alternative materials].

PubMed

Mao, Er-Jia

2018-04-01

The main purposes of periodontal graft surgery include achieving root coverage, improving the clinical attachment level and keratinized tissue, and advancing the procedure of periodontal plastic surgery. Autogenous graft, such as subepithelial connective tissue graft-based procedure, provide the best outcomes for mean and complete root coverage, as well as increase in keratinized tissue. However, a disadvantage of the procedure is in the location of the operation itself: the additional surgical site (palate). Therefore, clinicians are always looking for graft substitutes. This article will discuss the evidence supporting the use of 1) acellular dermal matrix (ADM); 2) xenogeneic collagen matrix (XCM); 3) recombinant human platelet-derived growth factor (rhPDGF); 4) enamel matrix derivative (EMD); 5) guided tissue regeneration (GTR); 6) living cellular construct (LCC), all of which are used in conjunction with coronally advanced flaps as alternatives to autogenous donor tissue. The decision tree for treatments of Miller recession-type defects are also discussed.

Acellular dermal matrices in breast implant surgery: defining the problem and proof of concept.

PubMed

Baxter, Richard A

2012-04-01

The use of acellular dermal matrices (ADMs) has become a useful adjunct to implant-based breast reconstruction and revision of the augmented breast. In both instances, the goal is replacement or reinforcement of thinned or missing tissues for implant support and control of the implant pocket. This article reviews the factors that contribute to periprosthetic tissue thinning, and the advantages and limitations of the use of ADMs for revision breast surgery and breast reconstruction. Proof of concept for the use of ADMs in the periprosthetic space is detailed from early clinical experience and histologic analysis documenting vascular ingrowth and cellular repopulation. Copyright © 2012 Elsevier Inc. All rights reserved.

Bioprosthetics and repair of complex aerodigestive defects

PubMed Central

Udelsman, Brooks; Mathisen, Douglas J.

2018-01-01

Aerodigestive defects involving the trachea, bronchi and esophagus are a result of prolonged intubation, operative complications, congenital defects, trauma, radiation and neoplastic disease. The vast majority of these defects may be repaired primarily. Rarely, due the size of the defect, underlying complexity, or unfavorable patient characteristics, primary repair is not possible. One alternative to primary repair is bioprosthetic repair. Materials such as acellular dermal matrix and aortic homograft have been used in a variety of applications, including closure of tracheal, bronchial and esophageal defects. Herein, we review the use of bioprosthetics in the repair of aerodigestive defects, along with the unique advantages and disadvantages of these repairs. PMID:29707507

Development of collagen/polydopamine complexed matrix as mechanically enhanced and highly biocompatible semi-natural tissue engineering scaffold.

PubMed

Hu, Yang; Dan, Weihua; Xiong, Shanbai; Kang, Yang; Dhinakar, Arvind; Wu, Jun; Gu, Zhipeng

2017-01-01

To improve the mechanical properties and biocompatibility of collagen I matrix, a novel and facile strategy was developed to modify porcine acellular dermal matrix (PADM) via dopamine self-polymerization followed by collagen immobilization to enhance the biological, mechanical and physicochemical properties of PADM. Mechanism study indicated that the polymerization of dopamine onto PADM surface could be regulated by controlling the amount of hydrogen bonds forming between phenol hydroxyl (COH) and nitrogen atom (NCO) within collagen fibers of PADM. The investigations of surface interactions between PDA and PADM illustrated that PDA-PADM system yielded better mechanical properties, thermal stability, surface hydrophilicity and the structural integrity of PADM was maintained after dopamine coating. Furthermore, collagen (COL) was immobilized onto the fresh PDA-PADM to fabricate the collagen-PDA-PADM (COL-PDA-PADM) complexed scaffold. The MTT assay and CLSM observation showed that COL-PDA-PADM had better biocompatibility and higher cellular attachment than pure PADM and COL-PADM without dopamine coating, thus demonstrating the efficacy of PDA as the intermediate layer. Meanwhile, the expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) of COL-PDA-PADM were investigated by an in vivo study. The results revealed that COL-PDA-PADM could effectively promote bFGF and VEGF expression, possibly leading to enhancing the dura repairing process. Overall, this work contributed a new insight into the development of a semi-natural tissue engineering scaffold with high biocompatibility and good mechanical properties. Obtaining scaffolds with high biocompatibility and good mechanical properties is still one of the most challenging issues in tissue engineering. To have excellent in vitro and in vivo performance, scaffolds are desired to have similar mechanical and biological properties as the natural extracellular matrix, such as collagen based matrix. Utilizing the surface self-crosslinking and coating strategy, we successfully obtained a novel semi-natural platform with excellent biological and mechanical properties from porcine acellular dermal matrix (PADM), polydopamine and collagen. The results confirmed that this scaffold platform has very excellent cellular performance and very little toxicity/side effects in vivo. Therefore, this semi-natural scaffold may be an appropriate platform for tissue engineering and this strategy would further help to develop more robust scaffolds. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Keratinocyte-driven contraction of reconstructed human skin.

PubMed

Chakrabarty, K H; Heaton, M; Dalley, A J; Dawson, R A; Freedlander, E; Khaw, P T; Mac Neil, S

2001-01-01

We have previously reported that reconstructed human skin, using deepidermized acellular sterilized dermis and allogeneic keratinocytes and fibroblasts, significantly contracts in vitro. Contracture of split skin grafts in burns injuries remains a serious problem and this in vitro model provides an opportunity to study keratinocyte/mesenchymal cell interactions and cell interactions with extracted normal human dermis. The aim of this study was to investigate the nature of this in vitro contraction and explore several approaches to prevent or reduce contraction. Three different methodologies for sterilization of the dermal matrix were examined: glycerol, ethylene oxide and a combination of glycerol and ethylene oxide. While the nature of the sterilization technique influenced the extent of contraction and thinner dermal matrices contracted proportionately more than thicker matrices, in all cases contraction was driven by the keratinocytes with relatively little influence from the fibroblasts. The contraction of the underlying dermis did not represent any change in tissue mass but rather a reorganization of the dermis which was rapidly reversed (within minutes) when the epidermal layer was removed. Pharmacological approaches to block contraction showed forskolin and mannose-6-phosphate to be ineffective and ascorbic acid-2-phosphate to exacerbate contraction. However, Galardin, a matrix metalloproteinase inhibitor and keratinocyte conditioned media, both inhibited contraction.

Acellular dermal matrix allograft used alone and in combination with enamel matrix protein in gingival recession: histologic study in dogs.

PubMed

de Oliveira, Cristiane Aparecida; Spolidório, Luís Carlos; Cirelli, Joni Augusto; Marcantonio, Roseemary Adriana Chiérici

2005-12-01

Gingival recession was created in six mongrel dogs. The dogs were divided into two groups based on treatment: group 1--AlloDerm only, group 2--AlloDerm + Emdogain. The histologic results were compared. At the end of the study, the mean values were, for groups 1 and 2, respectively: 0.06 and 0.32 mm for cementum regeneration; -0.75 and -0.86 mm for bone regeneration; -2.15 and -3.11 mm for attachment level; and 4.90 and 5.51 mm for defect extent. The epithelial formation parameter was 2.88 mm in group 1 and 2.15 mm in group 2, which was a statistically significant difference. It could be concluded that Emdogain did not result in beneficial effects when associated with AlloDerm.

[Experimental study on porcine acellular dermal matrix and split-thickness skin grafts to repair full-thickness skin defects].

PubMed

Ma, Shaoying; Li, Baoming; Wang, Xusheng; Li, Youchen; Kang, Yue; Dong, Li; Chen, Xueying; Zhao, Yaping; Li, Baoxing

2010-02-01

To compare the effect of the composite skin graft consisting of split-thickness skin grafts (STSGs) and porcine acellular dermal matrix (PADM) with STSGs only, and to histologically observe the turnover of the PADM in rats. Twenty female Sprague-Dawley rats, weighing 200-225 g, were included. The size of 4.0 cm x 2.5 cm PADM was implanted into hypoderm of the left side of Sprague-Dawley rats' back. After 10-14 days, the size of 4.0 cm x 2.5 cm full-thickness skin defects were made on the left to expose the PADM under the skin and the same size of full-thickness skin defects were made on the right of the rats' back. The excised full-thickness skin was made to STSGs about 0.2 mm by drum dermatome. The defects were grafted with composite skin (STSGs on the PADM, experimental group) and STSGs only (control group). The survival rate, the construction degree of grafts, and the histological change in grafts area were observed at 2, 4, 8, and 20 weeks after operation. At 2 weeks after STSGs (0.2 mm) placed on vascularized PADM, STSGs and PADM adhered together and the composite skin had a good survival. The control group also had a good survival. Histological observations showed that STSGs and PADM grew together, neutrophilic granulocytes and lymphocytes infiltrated in the PADM and some macrophages around the PADM. Fibrous connective tissues were filled under the STSGs in control group. At 4-8 weeks after transplantation, the composite skin had a good survival and the composite skin was thick, soft, and elastic. STSGs survived almost totally in control group, but the grafts were thin. Histological observations showed that inflammatory reactions of PADM faded gradually in experimental group; scar tissues formed under the STSGs in control group. At 20 weeks after transplantation, composite skin was flat, thick, and elastic in experimental group, but the STSGs were thinner and less elastic in control group. Histological observations showed that histological structures of the PADM were similar to the dermal matrix of rats, and the results showed that the collagen matrix of PADM was gradually replaced by the rats' collagen matrix. Scar tissues were filled under the STSGs in control group. Wound healing rates of experimental group were lower than those of control group at 4 and 8 weeks (P < 0.05); wound contraction rates of experimental group had lower tendency than those of control group, but showing no significant differences (P > 0.05). Coverage wound with composite skin which composed of STSGs and PADM could improve wound healing quality; the composite skin is thicker and better elastic than STSGs only. The collagen matrix of PADM is gradually replaced by rats' collagen matrix.

Experimental study on repairing of nude mice skin defects with composite skin consisting of xenogeneic dermis and epidermal stem cells and hair follicle dermal papilla cells.

PubMed

Qi, Shao-Hai; Liu, Po; Xie, Ju-Lin; Shu, Bin; Xu, Ying-Bin; Ke, Chang-Neng; Liu, Xu-Sheng; Li, Tian-Zeng

2008-05-01

To investigate the influence of hair follicle dermal papilla cells (DPCs) on biological features of composite skin. In the test group, xenogeneic acellular dermal matrix was employed as the frame, DPCs were seeded on the subcutaneous side, and epithelial stem cells onto the dermal papilla side of the dermal frame so as to construct a composite skin. In the control group, there was no DPC in the frame. The two kinds of composite skin were employed to cover skin defects on the back of the nude mice. Wound healing was observed 4 weeks after grafting and area was analyzed and contraction rate was calculated. The tissue samples in the grafted area were harvested for HE staining and the state of the composite skin was observed. The stress-strain curve of the sampled skin was measured, so as to calculate the maximal breaking power of the sample. The data were collected and statistically analyzed. HE staining indicated that the epithelial depth was increased (more than 10 layers of cells) in test group, with only 6-7 layers in control group. The skin contraction rate in test group on the 4th week after skin grafting (3.94+/-0.013)% was much lower than that in control group (29.07+/-0.018)% (P<0.05). It was indicated by biomechanical test that the stress-strain curve of the composite skin in the test group was closer to that of normal nude mice skin in comparison to that in control group. The maximal breaking force of the composite skin in test group was (1.835+/-0.035)N (Newton), while that in control group was (1.075+/-0.065)N (P<0.01). Reconstruction of epidermis in composite skin was promoted by dermal DPCs seeded in the dermal matrix frame. As a result, there was less skin contraction in the composite skin with DPCs, so that the biological characteristics of the skin were improved.

A comparison of efficiency of biopolymer and allograft matrix with autogenous gingival graft used in root coverage procedure.

PubMed

Fathima, K Hameed; Harish, V S

2015-08-01

Severe surgical techniques have been introduced to augment gingival tissue dimensions like the free gingival graft, free connective grafts, etc., However, both the techniques are associated with significant patient morbidity due to the secondary surgical site. In order to overcome these postsurgical complications, acellular dermal allografts have been used as a substitute for the palatal donor tissue yielding clinically comparable results. However, the cost and origin of the material raises concern regarding the frequent use of the material. As an improved alternative to above-mentioned graft material, the use of platelet-rich fibrin (PRF) and collagen matrices has been promoted in the recent past. The objective of this illustrative case report is to test the efficacy of collagen matrix, PRF to augment attached gingiva and to assess the esthetic outcome when compared to the standard treatment with free autogenous graft.

A comparison of efficiency of biopolymer and allograft matrix with autogenous gingival graft used in root coverage procedure

PubMed Central

Fathima, K. Hameed; Harish, V. S.

2015-01-01

Severe surgical techniques have been introduced to augment gingival tissue dimensions like the free gingival graft, free connective grafts, etc., However, both the techniques are associated with significant patient morbidity due to the secondary surgical site. In order to overcome these postsurgical complications, acellular dermal allografts have been used as a substitute for the palatal donor tissue yielding clinically comparable results. However, the cost and origin of the material raises concern regarding the frequent use of the material. As an improved alternative to above-mentioned graft material, the use of platelet-rich fibrin (PRF) and collagen matrices has been promoted in the recent past. The objective of this illustrative case report is to test the efficacy of collagen matrix, PRF to augment attached gingiva and to assess the esthetic outcome when compared to the standard treatment with free autogenous graft. PMID:26538946

Long-Term Outcomes after Abdominal Wall Reconstruction with Acellular Dermal Matrix.

PubMed

Garvey, Patrick B; Giordano, Salvatore A; Baumann, Donald P; Liu, Jun; Butler, Charles E

2017-03-01

Long-term outcomes data for hernia recurrence rates after abdominal wall reconstruction (AWR) with acellular dermal matrix (ADM) are lacking. The aim of this study was to assess the long-term durability of AWR using ADM. We studied patients who underwent AWR with ADM at a single center in 2005 to 2015 with a minimum follow-up of 36 months. Hernia recurrence was the primary end point and surgical site occurrence (SSO) was a secondary end point. The recurrence-free survival curves were estimated by Kaplan-Meier product limit method. Univariate and multivariable Cox proportional hazards regression models and logistic regression models were used to evaluate the associations of risk factors at surgery with subsequent risks for hernia recurrence and SSO, respectively. A total of 512 patients underwent AWR with ADM. After excluding those with follow-up less than 36 months, 191 patients were included, with a median follow-up of 52.9 months (range 36 to 104 months). Twenty-six of 191 patients had a hernia recurrence documented in the study. The cumulative recurrence rates were 11.5% at 3 years and 14.6% by 5 years. Factors significantly predictive of hernia recurrence developing included bridged repair, wound skin dehiscence, use of human cadaveric ADM, and coronary disease; component separation was protective. In a subset analysis excluding bridged repairs and human cadaveric ADM patients, cumulative hernia recurrence rates were 6.4% by 3 years and 8.3% by 5 years. The crude rate of SSO was 25.1% (48 of 191). Factors significantly predictive of the incidence of SSO included at least 1 comorbidity, BMI ≥30 kg/m 2 , and defect width >15 cm. Use of ADM for AWR was associated with 11.5% and 14.6% hernia recurrence rates at 3- and 5-years follow-up, respectively. Avoiding bridged repairs and human cadaveric ADM can improve long-term AWR outcomes using ADM. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Outcomes of abdominal wall reconstruction with acellular dermal matrix are not affected by wound contamination.

PubMed

Garvey, Patrick B; Martinez, Roberto A; Baumann, Donald P; Liu, Jun; Butler, Charles E

2014-11-01

The optimal type of mesh for complex abdominal wall reconstruction has not been elucidated. We hypothesized that AWRs using acellular dermal matrix (ADM) experience low rates of surgical site occurrence (SSO) and surgical site infection, despite increasing degrees of wound contamination. We retrospectively reviewed prospectively collected data from consecutive abdominal wall reconstructions with ADM over a 9-year period. Outcomes of abdominal wall reconstructions were compared between patients with different CDC wound classifications. Univariate and multivariate logistic regression and Cox proportional hazard regression analyses identified potential associations and predictive/protective factors. The 359 patients had a mean follow-up of 28.3 ± 19.0 months. Reconstruction of clean wounds (n = 171) required fewer reoperations than that of combined contaminated (n = 188) wounds (2.3% vs 11.2%; p = 0.001) and trended toward experiencing fewer SSOs (19.9% vs 28.7%, p = 0.052). There were no significant differences between clean and combined contaminated cases in 30-day SSI (8.8% vs 8.0%), hernia recurrence (9.9% vs 10.1%), and mesh removal (1.2% vs 1.1%) rates. Independent predictors of SSO included body mass index ≥30 kg/m(2) (odds ratio [OR] 3.6; p < 0.001), 1 or more comorbidities (OR 2.5; p = 0.008), and defect width ≥15 cm (OR 1.8; p = 0.02). Complex abdominal wall reconstructions using ADM demonstrated similar rates of complications between the different CDC wound classifications. This is in contradistinction to published outcomes for abdominal wall reconstruction using synthetic mesh that show progressively higher complication rates with increasing degrees of contamination. These data support the use of ADM rather than synthetic mesh for complex abdominal wall reconstruction in the setting of wound contamination. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

[EFFECTIVENESS OF VAGINOPLASTY WITH ACELLULAR DERMAL MATRIX AND MIXED PARTICLES GRAFT].

PubMed

Zhou, Yu; Li, Qiang; Ll, Senkai; Zhou, Chuande; Li, Fengyong; Cao, Yujiao; Zhang, Siya; Wei, Shuyi; Zhao, Yang

2015-06-01

To evaluate the effectiveness or acellular dermal matrix (ADM) with autologous buccal micro mucosa and micro skin graft in vaginoplasty. A retrospective analysis was made on the clinical data of 67 patients with vaginal agenesis treated between July 2006 and June 2013. ADM and mixed particles were used in 20 cases (ADM group) and mixed particles graft in 47 cases (control group) in vaginoplasty. There was no significant difference in age between 2 groups (t=0.233, P=0.816). The depth, diameter, and volume of neovagina, epithelization time, stent needing time, and female sexual function index (FSFI) score were compared between 2 groups. There was no significant difference in operation time and amount of bleeding between 2 groups (t = -1.922, P = 0.059; t = 0.398, P = 0.692). The patients were followed up 11-38 months (mean, 16.08 months). Fifteen cases in ADM group and 29 cases in control group had sexual life after operation. Bleeding after operation occurred in 6 cases (2 in ADM group and 4 in control group). No stenosis was observed. Difference in epithelization time was not statistically significant (t = -1.938, P = 0.057). However, the stent needing time of ADM group was significantly shorter than that of control group (t = 7.020, P = 0.000). The neovagina was ideal in wetness degree, smoothness, flexibility, and hairlessness during follow-up. The depth, diameter, and volume of vagina had no significant difference between 2 groups (P > 0.05) at last follow-up, which were close to normal vagina. The other patients had normal sexual function except 1 patient whose FSFI score was less than 23; no statistically significant difference was found in FSFI score between 2 groups (P > 0.05). On the basis of mixed particles grafting, the ADM could improve trestle structure for resisting contracture. The effectiveness is better than merely mixed particles graft. The procedure has satisfactory anatomical and functional results.

Direct Hospital Cost of Outcome Pathways in Implant-Based Reconstruction with Acellular Dermal Matrices.

PubMed

Qureshi, Ali A; Broderick, Kristen; Funk, Susan; Reaven, Nancy; Tenenbaum, Marissa M; Myckatyn, Terence M

2016-08-01

Current cost data on tissue expansion followed by exchange for permanent implant (TE/I) reconstruction lack a necessary assessment of the experience of a heterogenous breast cancer patient population and their multiple outcome pathways. We extend our previous analysis to that of direct hospital cost as bundling of payments is likely to follow the changing centralization of cancer care at the hospital level. We performed a retrospective analysis (2003-2009) of TE/I reconstructions with or without an acellular dermal matrix (ADM), namely Alloderm RTM. Postreconstructive events were analyzed and organized into outcome pathways as previously described. Aggregated and normalized inpatient and outpatient hospital direct costs and physician reimbursement were generated for each outcome pathway with or without ADM. Three hundred sixty-seven patients were analyzed. The average 2-year hospital direct cost per TE/I breast reconstruction patient was $11,862 in the +ADM and $12,319 in the -ADM groups (P > 0.05). Initial reconstructions were costlier in the +ADM ($6,868) than in the -ADM ($5,615) group, but the average cost of subsequent postreconstructive events within 2 years was significantly lower in +ADM ($5,176) than -ADM ($6,704) patients (P < 0.05). When a complication occurred, but reconstruction was still completed within 2 years, greater costs were incurred in the -ADM than in the +ADM group for most scenarios, leading to a net equalization of cost between study groups. Although direct hospital cost is an important factor for resource and fund allocation, it should not remain the sole factor when deciding to use ADM in TE/I reconstruction.

Response of human macrophages to wound matrices in vitro.

PubMed

Witherel, Claire E; Graney, Pamela L; Freytes, Donald O; Weingarten, Michael S; Spiller, Kara L

2016-05-01

Chronic wounds remain a major burden to the global healthcare system. Myriad wound matrices are commercially available but their mechanisms of action are poorly understood. Recent studies have shown that macrophages are highly influenced by their microenvironment, but it is not known how different biomaterials affect this interaction. Here, it was hypothesized that human macrophages respond differently to changes in biomaterial properties in vitro with respect to phenotype, including pro-inflammatory M1, anti-inflammatory M2a, known for facilitating extracellular matrix deposition and proliferation, and M2c, which has recently been associated with tissue remodeling. Using multiple donors, it was found that collagen scaffolds cross-linked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide (EDC/NHS) promoted the least inflammatory phenotype in primary human macrophages compared with scaffolds cross-linked with formaldehyde or glutaraldehyde. Importantly, gene expression analysis trends were largely conserved between donors, especially TNFa (M1), CCL22 (M2a), and MRC1 (M2a). Then the response of primary and THP1 monocyte-derived macrophages to four commercially available wound matrices were compared-Integra Dermal Regeneration Template (Integra), PriMatrix Dermal Repair Scaffold (PriMatrix), AlloMend Acellular Dermal Matrix (AlloMend), and Oasis Wound Matrix (Oasis). Gene expression trends were different between primary and THP1 monocyte-derived macrophages for all six genes analyzed in this study. Finally, the behavior of primary macrophages cultured onto the wound matrices over time was analyzed. Integra and Oasis caused down-regulation of M2a markers CCL22 and TIMP3. PriMatrix caused up-regulation of TNFa (M1) and CD163 (M2c) and down-regulation of CCL22 and TIMP3 (both M2a). AlloMend caused up-regulation in CD163 (M2c). Lastly, Oasis promoted the largest increase in the combinatorial M1/M2 score, defined as the sum of M1 genes divided by the sum of M2 genes. This preliminary study suggested that biomaterials influenced the wound microenvironment to affect macrophage phenotype. © 2016 by the Wound Healing Society.

Nonexpansive immediate breast reconstruction using human acellular tissue matrix graft (AlloDerm).

PubMed

Salzberg, C Andrew

2006-07-01

Immediate breast reconstruction has become a standard of care following mastectomy for cancer, largely due to improved esthetic and psychologic outcomes achieved with this technique. However, the current historical standards--transverse rectus abdominis myocutaneous flap reconstruction and expander--implant surgery-still have limitations as regards patient morbidity, short-term body-image improvements, and even cost. To address these shortcomings, we employ a novel concept of human tissue replacement to enhance breast shape and provide total coverage, enabling immediate mound reconstruction without the need for breast expansion prior to permanent implant placement. AlloDerm (human acellular tissue matrix) is a human-derived graft tissue with extensive experience in various settings of skin and soft tissue replacement surgery. This report describes the success using acellular tissue matrix to provide total coverage over the prosthesis in immediate reconstruction, with limited muscle dissection. In this population, 49 patients (76 breasts) successfully underwent the acellular tissue matrix-based immediate reconstruction, resulting in durable breast reconstruction with good symmetry. These findings may predict that acellular tissue matrix-supplemented immediate breast reconstruction will become a new technique for the immediate reconstruction of the postmastectomy breast.

Biologic resurfacing arthroplasty with acellular human dermal allograft and platelet-rich plasma (PRP) in young patients with glenohumeral arthritis-average of 60 months of at mid-term follow-up.

PubMed

Lo, Eddie Y; Flanagin, Brody A; Burkhead, Wayne Z

2016-07-01

The treatment of young patients with glenohumeral arthritis has been challenging. Alternative treatment options include activity modification, arthroscopic débridement, and arthroplasty. Addressing the glenoid during arthroplasty in this population of patients continues to be a significant challenge. In this study, we evaluated the midterm outcomes of hemiarthroplasty with biologic resurfacing of the glenoid with human dermal matrix allograft. Between 2004 and 2011, 55 patients underwent hemiarthroplasty and biologic resurfacing of the glenoid with human dermal matrix allograft. The average age was 50 ± 9 years. Subjective evaluation was performed with the Western Ontario Osteoarthritis of the Shoulder Index, American Shoulder and Elbow Surgeons score, visual analog scale, and Single Assessment Numeric Evaluation. Patients returned to the clinic for clinical examination and radiographic evaluation. The average follow-up was 60 months. The average postoperative American Shoulder and Elbow Surgeons score was 76 ± 22, and the Western Ontario Osteoarthritis of the Shoulder Index score was 76% ± 22%. The visual analog scale score was 2.4 ± 2.6. The average preoperative Single Assessment Numeric Evaluation score was 33% ± 22%, which significantly improved to 72% ± 22% postoperatively. Eighty-one percent of the patients were satisfied (10/47) or highly satisfied (28/47) with their result. With radiographic evaluation, the average joint space was 1 ± 1 mm preoperatively and 2 ± 1 mm postoperatively. A total of 5 cases (9.1%) were revised to anatomic total shoulder arthroplasty with implantation of a glenoid component. Hemiarthroplasty with biologic resurfacing of the glenoid using human dermal matrix allograft can lead to successful midterm outcomes with satisfactory complication and revision rates. Both patient satisfaction and clinical outcome remain high regardless of radiographic outcome. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Comparative evaluation of free gingival graft and AlloDerm® in enhancing the width of attached gingival: A clinical study

PubMed Central

Agarwal, Chitra; Tarun Kumar, A. B.; Mehta, Dhoom Singh

2015-01-01

Background: The presence of an adequate width of keratinized tissue is important to maintain a healthy dentogingival junction. In case of inadequate width of attached gingiva, the gingival augmentation procedure has been performed classically using the patient's own masticatory mucosa and more recently, using an acellular dermal allograft as the donor material. Aims: The aim of the clinical study was to evaluate and compare the effectiveness of free gingival graft (FGG) and acellular dermal matrix (ADM) allograft in the ability to increase the zone of attached gingiva. Materials and Methods: Fifteen patients with 30 sites showing the inadequate width of attached gingiva (≤1 mm) were enrolled for the split-mouth study. The width of keratinized gingiva and other clinical parameters were recorded at baseline and 12th month postoperatively. Statistical Analysis: The difference in clinical parameters within the group was assessed by Wilcoxon signed rank test. However, Mann–Whitney U-test was used to analyze the differences between test and control groups. Results: The width of attached gingiva increased significantly (P < 0.01) following both the treatments but comparatively lesser gain with ADM allograft (2.13 mm vs. 4.8 mm). ADM site had significantly more shrinkage (76.6%) than FGG site (49.7%). Though FGG was found to be more effective, clinicians can prefer ADM allograft because of its certain advantages over the FGG. Conclusion: ADM allograft has resulted in sufficient increase in width of attached gingiva although lesser than FGG. Considering the disadvantages of FGG, it can be concluded that ADM allograft can be used as an alternative to FGG in increasing width of attached gingival in certain clinical situations. PMID:26681852

Isolated mucosal fenestration with localized gingival recession: Closure with an acellular dermal graft. A rare case report with two years' follow-up.

PubMed

Balasubramanian, SaravanaKarthikeyan; Singh, Vishal; Bhat, G Subraya; Acharya, Shashi Rashmi; Nidambur Ballal, Vasudev; Saraswathi, Vidya; Vinayachanan, Divya

2016-01-01

Mucosal fenestrations are rarely encountered in clinical practice, and as such their management is not often reported. Their treatment might be further complicated due to a communication with the oral environment, making them more susceptible to accumulation of debris, plaque, and calculus, thereby reducing the probability of mucosal renewal. The aim of the present case report is to highlight one such rare clinical scenario and its apt and effective management. Surgical management of an uncommon presentation of concomitant gingival recession with an isolated mucosal fenestration in an atypical location, with an allograft matrix is presented here with 2 years' follow-up. A review of the literature reveals no previous application of AlloDerm graft for the management of a similar situation.

Stage-two surgery using collagen soft tissue grafts: clinical cases and ultrastructural analysis.

PubMed

Fischer, Kai R; Fickl, Stefan; Mardas, Nikos; Bozec, Laurent; Donos, Nikolaos

2014-01-01

To present the application of two different soft tissue grafts around dental implants during stage-two surgery. Furthermore, the ultrastructure of these materials is shown and discussed using scanning electron microscopy (SEM). Although soft tissue autografts may be currently regarded as the gold standard, harvesting of these grafts might lead to higher morbidity, longer chair time, and intra-/postoperative complications at the donor site. New developments in collagen scaff olds have provided an alternative to successfully replace autologous grafts in clinical practice. The SEM pictures clearly show the different composition of a bilayer scaff old (collagen matrix, CM) and a porcine acellular dermal matrix (ADM). These distinctive properties lead to different possible indications. Within the presented cases, ADM was used to augment the ridge contour and was placed into a buccal pouch to achieve complete coverage and an uneventful closed healing. On the other side, CM was left exposed to the oral cavity to successfully gain keratinized mucosa around and between two dental implants.

Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound

PubMed Central

Tracy, Lauren E.; Minasian, Raquel A.; Caterson, E.J.

2016-01-01

Significance: Fibroblasts play a critical role in normal wound healing. Various extracellular matrix (ECM) components, including collagens, fibrin, fibronectin, proteoglycans, glycosaminoglycans, and matricellular proteins, can be considered potent protagonists of fibroblast survival, migration, and metabolism. Recent Advances: Advances in tissue culture, tissue engineering, and ex vivo models have made the examination and precise measurements of ECM components in wound healing possible. Likewise, the development of specific transgenic animal models has created the opportunity to characterize the role of various ECM molecules in healing wounds. In addition, the recent characterization of new ECM molecules, including matricellular proteins, dermatopontin, and FACIT collagens (Fibril-Associated Collagens with Interrupted Triple helices), further demonstrates our cursory knowledge of the ECM in coordinated wound healing. Critical Issues: The manipulation and augmentation of ECM components in the healing wound is emerging in patient care, as demonstrated by the use of acellular dermal matrices, tissue scaffolds, and wound dressings or topical products bearing ECM proteins such as collagen, hyaluronan (HA), or elastin. Once thought of as neutral structural proteins, these molecules are now known to directly influence many aspects of cellular wound healing. Future Directions: The role that ECM molecules, such as CCN2, osteopontin, and secreted protein, acidic and rich in cysteine, play in signaling homing of fibroblast progenitor cells to sites of injury invites future research as we continue investigating the heterotopic origin of certain populations of fibroblasts in a healing wound. Likewise, research into differently sized fragments of the same polymeric ECM molecule is warranted as we learn that fragments of molecules such as HA and tenascin-C can have opposing effects on dermal fibroblasts. PMID:26989578

Acellular dermal matrix allograft versus subepithelial connective tissue graft in treatment of gingival recessions: a 5-year randomized clinical study.

PubMed

Moslemi, Neda; Mousavi Jazi, Mahvash; Haghighati, Farideh; Morovati, Seyyedeh Pouya; Jamali, Raika

2011-12-01

The present randomized clinical trial compared the long-term results of subepithelial connective tissue graft (SCTG) versus acellular dermal matrix allograft (ADMA) in treatment of gingival recessions. In 16 patients with bilateral Miller Class I/II gingival recessions, one side was treated with SCTG and the other side with ADMA. Clinical parameters were measured at baseline, 6 months, and at 5 years post-surgery. Fifteen patients completed the study. At 6 months, all parameters showed significant improvement in ADMA and SCTG groups [complete root coverage (CRC): 73.3% versus 26.7%, p = 0.027; reduction of recession depth (RD): 2.6 ± 1.1 mm versus 2.2 ± 1.1 mm, p = 0.376; reduction of recession width (RW): 3.0 ± 1.4 mm versus 2.4 ± 1.4 mm, p = 0.207 respectively]. At 5 years, significant relapses were detected in CRC and reduction of RD and RW in both groups with no statistically significant difference (CRC: 20.0% versus 13.3%, p = 1.00; RD: 1.6 ± 1.2 mm versus 1.5 ± 1.4mm, p = 0.838; RW: 1.8 ± 1.4 mm versus 1.3 ± 1.5mm, p = 0.367). Patients practicing horizontal toothbrushing habit showed more relapse (OR = 11.2; p = 0.01). Compared with baseline, the gingival width (GW) did not increase in ADMA-treated sites (p = 0.903). Five-year results of SCTG and ADMA were similar in terms of CRC and reduction of RD and RW. Both techniques showed a significant relapse associated with returning to horizontal toothbrushing habit. Increase of GW was stable in SCTG-treated sites, but reached to pre-surgical values in ADMA-treated cases. © 2011 John Wiley & Sons A/S.

Mesh choice in ventral hernia repair: so many choices, so little time.

PubMed

Le, Dinh; Deveney, Clifford W; Reaven, Nancy L; Funk, Susan E; McGaughey, Karen J; Martindale, Robert G

2013-05-01

Currently, >200 meshes are commercially available in the United States. To help guide appropriate mesh selection, the investigators examined the postsurgical experiences of all patients undergoing ventral hernia repair at their facility from 2008 to 2011 with ≥12 months of follow-up. A retrospective review of prospectively collected data was conducted. All returns (surgical readmission, office or emergency visit) for complications or recurrences were examined. The impact of demographics (age, gender, and body mass index [BMI]), risk factors (hernia grade, hernia size, concurrent and past bariatric surgery, concurrent and past organ transplantation, any concurrent surgery, and American Society of Anesthesiologists score), and prosthetic type (polypropylene, other synthetic, human acellular dermal matrix, non-cross-linked porcine-derived acellular dermal matrix, other biologic, or none) on the frequency of return was evaluated. A total of 564 patients had 12 months of follow-up, and 417 patients had 18 months of follow-up. In a univariate regression analysis, study arm (biologic, synthetic, or primary repair), hernia grade, hernia size, past bariatric surgery, and American Society of Anesthesiologists score were significant predictors of recurrence (P < .05). Multivariate analysis, stepwise regression, and interaction tests identified three variables with significant predictive power: hernia grade, hernia size, and BMI. The adjusted odds ratios vs hernia grade 2 for surgical readmission were 2.6 (95% confidence interval [CI], 1.3 to 5.1) for grade 3 and 2.6 (95% CI, 1.1 to 6.4) for grade 4 at 12 months and 2.3 (95% CI, 1.1 to 4.6) for grade 3 and 4.2 (95% CI, 1.7 to 10.0) for grade 4 at 18 months. Large hernia size (adjusted odds ratio vs small size, 3.2; 95% CI, 1.6 to 6.2) and higher BMI (adjusted odds ratio for BMI ≥50 vs 30 to 34.99 kg/m(2), 5.7; 95% CI, 1.2 to 26.2) increased the likelihood of surgical readmission within 12 months. The present data support the hypothesis that careful matching of patient characteristics to choice of prosthetic will minimize complications, readmissions, and the number of postoperative office visits. Copyright © 2013 Elsevier Inc. All rights reserved.

Qualitative assessment of connective tissue graft with epithelial component. A microsurgical periodontal plastic surgical technique for soft tissue esthetics.

PubMed

Rossi, Roberto; Pilloni, Andrea; Morales, Regina Santos

2009-01-01

Connective tissue grafts have been used successfully in the treatment of gingival recession. In the mid 80s and late 90s, the periodontal literature presented various techniques such as free gingival grafts, pedicle flaps, subepithelial connective tissue grafts, acellular dermal matrix grafts, and guided tissue regeneration to cover denuded root surfaces. Currently, connective tissue grafting is a reliable treatment for esthetic root coverage. This paper presents a qualitative assessment of a surgical technique that uses a connective tissue graft, including a portion of epithelium in the shape of the defect. This procedure enhances the healing of the covered root surface, increases the thickness of the soft tissue and improves esthetics. The criteria used for evaluation were: color, volume, texture, and blending. This evaluation demonstrated encouraging results from an esthetic viewpoint.

A new material for tissue engineered vagina reconstruction: Acellular porcine vagina matrix.

PubMed

Zhang, Jing-Kun; Du, Run-Xuan; Zhang, Lin; Li, Ya-Nan; Zhang, Ming-Le; Zhao, Shuo; Huang, Xiang-Hua; Xu, Yan-Fang

2017-07-01

Acellular matrix materials have been widely used to repair various tissues and organs. According to the plastic principle, when a part of the body is lost, it should be replaced with a similar material. Therefore, the use of a homologous organ-specific acellular vaginal tissue in vagina reconstruction repair surgery may show good results. However, the acellular vagina matrix (AVM) form large vertebrates is difficult to isolate. In this study, we described a multistep method to prepare porcine AVM and evaluated the efficacy of acellularization. We also investigated the biomechanical properties, biological activity elements, and biocompatibility of the porcine AVM. We then used this material to reconstruct a rat vagina and performed further morphologic and functional analyses. Small intestinal submucosa (SIS), which is a commonly used acellular matrix material, was used in a control group. Histological examination, DNA content analysis, and agarose gel electrophoresis revealed that the decellularization procedure was effective. The AVM had acceptable biomechanical properties and sufficient growth factor production (VEGF, FGF, TGF-β1, and PDGF-BB) compared with that of the SIS. Subcutaneous transplantation in rats showed that the AVM had good biocompatibility. The tissue-engineered vagina using the AVM more resembled normal-appearing tissue than did that using SIS following morphologic and functional analyses. The AVM has great potential for application in vaginal reconstructive surgery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1949-1959, 2017. © 2017 Wiley Periodicals, Inc.

Acellular Mouse Kidney ECM can be Used as a Three-Dimensional Substrate to Test the Differentiation Potential of Embryonic Stem Cell Derived Renal Progenitors.

PubMed

Sambi, Manpreet; Chow, Theresa; Whiteley, Jennifer; Li, Mira; Chua, Shawn; Raileanu, Vanessa; Rogers, Ian M

2017-08-01

The development of strategies for tissue regeneration and bio-artificial organ development is based on our understanding of embryogenesis. Differentiation protocols attempt to recapitulate the signaling modalities of gastrulation and organogenesis, coupled with cell selection regimens to isolate the cells of choice. This strategy is impeded by the lack of optimal in vitro culture systems since traditional culture systems do not allow for the three-dimensional interaction between cells and the extracellular matrix. While artificial three-dimensional scaffolds are available, using the natural extracellular matrix scaffold is advantageous because it has a distinct architecture that is difficult to replicate. The adult extracellular matrix is predicted to mediate signaling related to tissue repair not embryogenesis but existing similarities between the two argues that the extracellular matrix will influence the differentiation of stem and progenitor cells. Previous studies using undifferentiated embryonic stem cells grown directly on acellular kidney ECM demonstrated that the acellular kidney supported cell growth but limited differentiation occurred. Using mouse kidney extracellular matrix and mouse embryonic stem cells we report that the extracellular matrix can support the development of kidney structures if the stem cells are first differentiated to kidney progenitor cells before being applied to the acellular organ.

Development of a pericardial acellular matrix biomaterial: biochemical and mechanical effects of cell extraction.

PubMed

Courtman, D W; Pereira, C A; Kashef, V; McComb, D; Lee, J M; Wilson, G J

1994-06-01

There is evidence to suggest that the cellular components of homografts and bioprosthetic xenografts may contribute to calcification or immunogenic reactions. A four-step detergent and enzymatic extraction process has been developed to remove cellular components from bovine pericardial tissue. The process results in an acellular matrix material consisting primarily of elastin, insoluble collagen, and tightly bound glycosaminoglycans. Light and electron microscopy confirmed that nearly all cellular constituents are removed without ultrastructural evidence of damage to fibrous components. Collagen denaturation temperatures remained unaltered. Biochemical analysis confirmed the retention of collagen and elastin and some differential extraction of glycosaminoglycans. Low strain rate fracture testing and high strain rate viscoelastic characterization showed that, with the exception of slightly increased stress relaxation, the mechanical properties of the fresh tissue were preserved in the pericardial acellular matrix. Crosslinking of the material in glutaraldehyde or poly(glycidyl ether) produced mechanical changes consistent with the same treatments of fresh tissue. The pericardial acellular matrix is a promising approach to the production of biomaterials for heart valve or cardiovascular patching applications.

Comparison of histological structure and biocompatibility between human acellular dermal matrix (ADM) and porcine ADM.

PubMed

Ge, Liangpeng; Zheng, Shuquan; Wei, Hong

2009-02-01

The present study was to compare the difference of histological structure and biocompatibility between human ADM and porcine ADM. The scaffold structure, collagen arrangement and collagen structure of human ADM and those of porcine ADM were very similar except for a slight difference in their black and white bands assessed by both light microscopy and electron microscopy. The positive immunohistochemical staining results of porcine ADM using human antibodies of collagen I, collagen III, collagen IV, fibronectin, laminin and vimentin and the result of SDS-PAGE implied a strong homology between the main proteins of human ADM and porcine ADM. In addition, statistical analysis indicated that there was no significant difference (P<0.05) between the biocompatibility of the two ADMs. Based on these results, we conclude that porcine ADM bears a strong similarity to human ADM, and might be a substitute for human ADM in the future.

Application of an Acellular Dermal Matrix Allograft (CenoDerm) for Treatment of Multiple Gingival Recession Defects: A Case Report with One-year Follow-up

PubMed Central

Moslemi, Neda; Heidari, Mohadeseh; Mousavi Jazi, Mahvash; Daneshmonfared, Mahdieh

2014-01-01

Several techniques and materials have been introduced for the treatment of gingival recession defects. This article reports the case of a 43-year old female patient with chief complaint of esthetic problem, presenting multiple gingival recession defects in anterior maxilla. CenoDerm combined with coronally positioned flap was used for management of six teeth with gingival recession. Complete root coverage was achieved in 66.6% of treated sites in one-year follow-up and the patient was satisfied with the esthetic result. The mean root coverage was 86.0%±22.3. The mean recession depth reduction and clinical attachment gain were 1.8±0.8 mm and 2.5±0.6 mm, respectively. According to the results obtained in this case, CenoDerm can be applied successfully in treatment of multiple gingival recession defects. PMID:25346839

Evaluation of Sidestream Darkfield Microscopy for Real-Time Imaging Acellular Dermal Matrix Revascularization.

PubMed

DeGeorge, Brent R; Olenczak, J Bryce; Cottler, Patrick S; Drake, David B; Lin, Kant Y; Morgan, Raymond F; Campbell, Christopher A

2016-06-01

Acellular dermal matrices (ADMs) serve as a regenerative framework for host cell integration and collagen deposition to augment the soft tissue envelope in ADM-assisted breast reconstruction-a process dependent on vascular ingrowth. To date noninvasive intra-operative imaging techniques have been inadequate to evaluate the revascularization of ADM. We investigated the safety, feasibility, and efficacy of sidestream darkfield (SDF) microscopy to assess the status of ADM microvascular architecture in 8 patients at the time of tissue expander to permanent implant exchange during 2-stage ADM-assisted breast reconstruction. The SDF microscopy is a handheld device, which can be used intraoperatively for the real-time assessment of ADM blood flow, vessel density, vessel size, and branching pattern. The SDF microscopy was used to assess the microvascular architecture in the center and border zone of the ADM and to compare the native, non-ADM-associated capsule in each patient as a within-subject control. No incidences of periprosthetic infection, explantation, or adverse events were reported after SDF image acquisition. Native capsules demonstrate a complex, layered architecture with an average vessel area density of 14.9 mm/mm and total vessel length density of 12.3 mm/mm. In contrast to native periprosthetic capsules, ADM-associated capsules are not uniformly vascularized structures and demonstrate 2 zones of microvascular architecture. The ADM and native capsule border zone demonstrates palisading peripheral vascular arcades with continuous antegrade flow. The central zone of the ADM demonstrates punctate perforating vascular plexi with intermittent, sluggish flow, and intervening 2- to 3-cm watershed zones. Sidestream darkfield microscopy allows for real-time intraoperative assessment of ADM revascularization and serves as a potential methodology to compare revascularization parameters among commercially available ADMs. Thr SDF microscopy demonstrates that the periprosthetic capsule in ADM-assisted implant-based breast reconstruction is not a uniformly vascularized structure.

[NEW PROGRESS OF ACELLULAR FISH SKIN AS NOVEL TISSUE ENGINEERED SCAFFOLD].

PubMed

Wei, Xiaojuan; Wang, Nanping; He, Lan; Guo, Xiuyu; Gu, Qisheng

2016-11-08

To review the recent research progress of acellular fish skin as a tissue engineered scaffold, and to analyze the feasibility and risk management in clinical application. The research and development, application status of acellular fish skin as a tissue engineered scaffold were comprehensively analyzed, and then several key points were put forward. Acellular fish skin has a huge potential in clinical practice as novel acellular extracellular matrix, but there have been no related research reports up to now in China. As an emerging point of translational medicine, investigation of acellular fish skin is mainly focused on artificial skin, surgical patch, and wound dressings. Development of acellular fish skin-based new products is concerned to be clinical feasible and necessary, but a lot of applied basic researches should be carried out.

Comparative clinical evaluation of acellular dermal matrix allograft and connective tissue graft for the treatment of gingival recession.

PubMed

Rahmani, M E; Lades, Mohammad A Rigi

2006-05-01

"Gingival recession is a condition reported to occur due to abnormal periodontal anatomy, poor hygiene, excessive occlusal forces, toothbrush abrasion, and even iatrogenic or factitious causes. Though various surgical techniques are available to treat this problem, the most common is the palatal soft tissue autograft. Recently, an acellular dermal matrix allograft (ADMA) has been available as a substitute for the palatal tissue harvest. The aim of this study is to compare the ADMA with the conventional subepithelial connective tissue graft (SCTG) in the treatment of gingival recession." Fourteen patients with 20 gingival recessions of Miller's grade I and II were selected and randomized in two groups of control (SCTG ) and test (ADMA). In each group ten recession defects were treated. The following parameters were measured at baseline and then at six months post surgery: recession height (RH), recession width (RW), probing depth (PD), attached gingiva (AG), keratinized gingiva (KG), and clinical attachment level (CAL). All parameters were analyzed using the two-sample t-test. Data analysis was performed using SPSS (version 11) software. The following mean changes (mm) occurred in SCTG and ADMA, respectively: 2.60+/-0.97 and 2.90+/-0.81 decrease in RH; 1.70+/-1.01 and 1.65+/-0.67 decrease in RW; 2.50+/-0.97 and 2.95+/-0.69 increase in KG; 2.25+/-0.92 and 2.65+/-0.85 increase in AG; 2.60+/-1.08 and 2.75+/-0.92 decrease in CAL; and finally 0.05+/-0.50 and 0.10+/-0.46 decrease in PD for the SCTG and ADMA groups, respectively. The percentage of root coverage for the two groups was 70.12%+/-22.81% and 72.08%+/-14.12%, respectively. The changes from baseline to the six-month visit were significant for both groups in terms of all parameters but PD. However, the differences in mean changes were not significant between the two groups in any of the parameters. These findings imply the ADMA and SCTG techniques could produce the same results when used for the successful treatment of gingival recessions. In addition the ADMA could be used as an adequate alternative treatment modality for conventional techniques.

Effectiveness of Acellular Dermal Matrix on Autologous Split-Thickness Skin Graft in Treatment of Deep Tissue Defect: Esthetic Subjective and Objective Evaluation.

PubMed

Lee, Yoo Jung; Park, Myong Chul; Park, Dong Ha; Hahn, Hyung Min; Kim, Sue Min; Lee, Il Jae

2017-10-01

A split-thickness skin graft (STSG) is performed to cover a large full-thickness skin defect. Esthetic and functional deficits can result, and many studies have sought to overcome them. This study compared the effectiveness of the acellular dermal matrix (ADM) graft and STSG concerning esthetic and functional effectiveness of ADM on scar quality. Of the patients who underwent anterolateral thigh free flap from 2011 to 2015, patients who received skin graft only (n = 10) or skin graft with ADM (n = 20) for coverage of the donor site were enrolled. In all cases, autologous STSG was performed with 1:1.5 meshed 0.008-0.010-inch-thick skin. In the skin graft with ADM group, 0.008-0.013-inch-thick meshed ADM (CGderm ® ; CGBio, Inc., Seungnam, Korea) was co-grafted. Negative-pressure wound therapy (CuraVAC ® ; CGBio, Inc., Seungnam, Korea) was applied to both groups in continuous mode at -120 mmHg. We investigate early outcomes (skin loss rate, duration of negative-pressure wound therapy, days to removal of stitches, days to achieve complete healing, and complications) and late outcomes in terms of scar quality (vascularity, pigmentation, pliability and height) and graft-related symptoms (itching sensation and pain). Assessments used the Vancouver Scar Scale and the Patient and Observer Scar Assessment Scale. Skin fold was measured to evaluate the elasticity of scar tissue. In the Vancouver Scar Scale, vascularity subscore (p = 0.003) and total score (p = 0.016) were significantly lower in the skin graft with ADM group. In Patient and Observer Scar Assessment Scale, the pain (p = 0.037) and stiffness subscores (p = 0.002), and total score (p = 0.017) were significantly lower in the skin graft with ADM group. Skin graft with ADM results in better scar quality in objective and subjective aspects. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Acellular dermal matrix for mucogingival surgery: a meta-analysis.

PubMed

Gapski, Ricardo; Parks, Christopher Allen; Wang, Hom-Lay

2005-11-01

Many clinical studies revealed the effectiveness of acellular dermal matrix (ADM) in the treatment of mucogingival defects. The purpose of this meta-analysis was to compare the efficacy of ADM-based root coverage (RC) and ADM-based increase in keratinized tissues to other commonly used mucogingival surgeries. Meta-analysis was limited to randomized clinical trials (RCT). Articles from January 1, 1990 to October 2004 related to ADM were searched utilizing the MEDLINE database from the National Library of Medicine, the Cochrane Oral Health Group Specialized Trials Registry, and through hand searches of reviews and recent journals. Relevant studies were identified, ranked independently, and mean data from each were weighted accordingly. Selected outcomes were analyzed using a meta-analysis software program. The significant estimates of the treatment effects from different trials were assessed by means of Cochrane's test of heterogeneity. 1) Few RCT studies were found to compile the data. In summary, selection identified eight RCT that met the inclusion criteria. There were four studies comparing ADM versus a connective tissue graft for root coverage procedures, two studies comparing ADM versus coronally advanced flap (CAF) for root coverage procedures, and two studies comparing ADM to free gingival graft in augmentation of keratinized tissue. 2) There were no statistically significant differences between groups for any of the outcomes measured (recession coverage, keratinized tissue formation, probing depths, and clinical attachment levels). 3) The majority of the analyses demonstrated moderate to high levels of heterogeneity. 4) Considering the heterogeneity values found among the studies, certain trends could be found: a) three out of four studies favored the ADM-RC group for recession coverage; b) a connective tissue graft tended to increase keratinized tissue compared to ADM (0.52-mm difference; P = 0.11); c) there were trends of increased clinical attachment gains comparing ADM to CAF procedures (0.56-mm difference; P = 0.16). Differences in study design and lack of data precluded an adequate and complete pooling of data for a more comprehensive analysis. Therefore, considering the trends presented in this study, there is a need for further randomized clinical studies of ADM procedures in comparison to common mucogingival surgical procedures to confirm our findings. It is difficult to draw anything other than tentative conclusions from this meta-analysis of ADM for mucogingival surgery, primarily because of the weakness in the design and reporting of existing trials.

Reducing postoperative infections and red breast syndrome in patients with acellular dermal matrix-based breast reconstruction: the relative roles of product sterility and lower body mass index.

PubMed

Lewis, Priya; Jewell, James; Mattison, Gennaya; Gupta, Subhas; Kim, Hahns

2015-05-01

The use of human acellular dermal matrices (ADM) has become routinely used in implant-based breast surgery. Notwithstanding the many benefits for tissue support, the morbidity associated with its use includes seroma and infection, among other potential complications. Some patients experience a specific complication called red breast syndrome (RBS), which has been linked to ADM use, but its exact etiology remains elusive. In our institution, AlloDerm aseptic regenerative tissue matrix was recently replaced with a ready-to-use sterile version that undergoes terminal sterilization, eliminating the need for rehydration. We want to determine if this change in processing affected complications, including RBS. We conducted a retrospective chart review analyzing patients from January 1, 2011, to June 1, 2013, who underwent breast surgery with human ADM. Patients with aseptic AlloDerm were compared to patients with sterile AlloDerm. Data were analyzed using the Fisher exact test. A total of 167 reconstructed breasts from 105 patients met inclusion criteria: 56% (n=93) with aseptic ADM, 44% (n=74) with sterile ADM. When comparing the two, patients had a decrease in overall necrosis, infection, seroma, and RBS with sterile ADM. However, the rates did not reach statistical significance. For example, the incidence of RBS decreased from 7.5% to 2.7% (P=0.301) and seroma decreased from 8.6% to 2.7% (P=0.188). The infection rate proved to be equivocal at 11.8% with aseptic ADM to 10.8% with sterile ADM (P=1.000). The only statistically significant change was a decrease in the total complication rate from 41.9% to 27.0% (P=0.046). The absolute risk reduction for total complications was 14.9% with a number-needed-to-treat of 7. According to our study, sterile AlloDerm has a clinically decreased incidence of complications compared to aseptic AlloDerm. Whereas RBS decreased, it was interesting to see that it was not eliminated altogether. This suggests that the etiology may be unrelated to ADM processing and warrants further investigation. Overall, the most notable difference was the statistically significant decrease in the total complication rate. Therefore, the change to sterile AlloDerm seems to be beneficial. Further benefit arises from ease of preparation in the operating room.

Current trends in breast reconstruction: survey of American Society of Plastic Surgeons 2010.

PubMed

Gurunluoglu, Raffi; Gurunluoglu, Aslin; Williams, Susan A; Tebockhorst, Seth

2013-01-01

We conducted a retrospective survey of American Society of Plastic Surgeons to ascertain the current trends in breast reconstruction (BR). Surveys were sent to 2250 active American Society of Plastic Surgeons members by e-mail with a cover letter including the link using Survey Monkey for the year 2010. In all, 489 surveys (a response rate of 21.7%) were returned. Three hundred fifty-eight surveys from respondents performing BR in their practices were included in the study. The survey included questions on surgeon demographics, practice characteristics, BR after mastectomy, number of BR per year, type and timing of BR, use of acellular dermal matrix, reconstructive choices in the setting of previous irradiation and in patients requiring postmastectomy radiation therapy, timing of contralateral breast surgery, fat grafting, techniques used for nipple-areola reconstruction, the complications, and physician satisfaction and physician reported patient satisfaction. Returned responses were tabulated and assessed. After prophylactic mastectomy, 16% of BRs were performed. In all, 81.2% of plastic surgeons predominantly performed immediate BR. In patients requiring postmastectomy radiation therapy, 81% did not perform immediate BR. Regardless of practice setting and laterality of reconstruction, 82.7% of respondents predominantly performed implant-based BR. Half of the plastic surgeons performing prosthetic BR used acellular dermal matrix. Only 14% of plastic surgeons predominantly performed autologous BR. Surgeons in solo, plastic surgery group practices, and multispecialty group practices preferred implant-based BR for both unilateral and bilateral cases more frequently than those in academic practices (P < 0.05). Overall, plastic surgeons in academic settings preferred autologous BR more frequently than those in other practice locations (P < 0.05). Of total respondents, 64.8% did not perform microsurgical BR at all; 28% reported performing deep inferior epigastric perforator flap BR. Pedicled transverse rectus abdominis myocutaneous flap was the most often used option for unilateral autologous reconstruction, whereas deep inferior epigastric perforator flap was the most commonly used technique for bilateral BR. The overall complication rate reported by respondents was 11%. The survey provides an insight to the current trends in BR practice with respect to surgeon and practice setting characteristics. Although not necessarily the correct best practices, the survey does demonstrate a likely portrayal of what is being practiced in the United States in the area of BR.

Long-term Follow-up with AlloDerm in Breast Reconstruction

PubMed Central

2013-01-01

Summary: Little is known about the long-term fate of acellular dermal matrices in breast implant surgery. A 12-year follow-up case with tissue analysis of AlloDerm in revision breast reconstruction reveals retention of graft volume and integration with an organized collagen structure, minimal capsule formation, and little or no indication of inflammation. PMID:25289211

Long-term Follow-up with AlloDerm in Breast Reconstruction.

PubMed

Baxter, Richard A

2013-05-01

Little is known about the long-term fate of acellular dermal matrices in breast implant surgery. A 12-year follow-up case with tissue analysis of AlloDerm in revision breast reconstruction reveals retention of graft volume and integration with an organized collagen structure, minimal capsule formation, and little or no indication of inflammation.

A Novel Biodegradable Polyurethane Matrix for Auricular Cartilage Repair: An In Vitro and In Vivo Study.

PubMed

Iyer, Kartik; Dearman, Bronwyn L; Wagstaff, Marcus J D; Greenwood, John E

2016-01-01

Auricular reconstruction poses a challenge for reconstructive and burns surgeons. Techniques involving cartilage tissue engineering have shown potential in recent years. A biodegradable polyurethane matrix developed for dermal reconstruction offers an alternative to autologous, allogeneic, or xenogeneic biologicals for cartilage reconstruction. This study assesses such a polyurethane matrix for this indication in vivo and in vitro. To evaluate intrinsic cartilage repair, three pigs underwent auricular surgery to create excisional cartilage ± perichondrial defects, measuring 2 × 3 cm in each ear, into which acellular polyurethane matrices were implanted. Biopsies were taken at day 28 for histological assessment. Porcine chondrocytes ± perichondrocytes were cultured and seeded in vitro onto 1 × 1 cm polyurethane scaffolds. The total culture period was 42 days; confocal, histological, and immunohistochemical analyses of scaffold cultures were performed on days 14, 28, and 42. In vivo, the polyurethane matrices integrated with granulation tissue filling all biopsy samples. Minimal neocartilage invasion was observed marginally on some samples. Tissue composition was identical between ears whether perichondrium was left intact, or not. In vitro, the polyurethane matrix was biocompatible with chondrocytes ± perichondrocytes and supported production of extracellular matrix and Type II collagen. No difference was observed between chondrocyte culture alone and chondrocyte/perichondrocyte scaffold coculture. The polyurethane matrix successfully integrated into the auricular defect and was a suitable scaffold in vitro for cartilage tissue engineering, demonstrating its potential application in auricular reconstruction.

Acellular fetal bovine dermal matrix in the treatment of nonhealing wounds in patients with complex comorbidities.

PubMed

Lullove, Eric

2012-01-01

In contrast to the narrow indications for living skin equivalents, extracellular matrix biomaterials are clinically used in a wide range of wound-healing applications. Given the breadth of possible uses, the goal of this study was to retrospectively compile and analyze the clinical application and effectiveness of an extracellular matrix biomaterial derived from fetal bovine dermis (PriMatrix; TEI Biosciences, Boston, Massachusetts) in patients treated by a single physician and monitored postsurgically in an outpatient wound care center. A retrospective medical record review was conducted of consecutive patients treated from January 2007 through January 2009 with meshed PriMatrix after sharp/surgical debridement and coverage with standard moist wound therapy dressings. Twenty-nine patients and 34 wounds were compiled. All of the wounds were unresponsive to conservative treatment owing to complications, including infection, exposed bone or tendon, and other comorbidities known to delay healing. Wounds included 11 diabetic ulcers, 8 venous stasis ulcers, 10 nonhealing traumatic wounds, and 5 other chronic wounds. Thirty of 34 wounds healed, with four patients lost to follow-up. Mean time to healing for diabetic foot ulcers was 105 days with an average of 2.6 PriMatrix applications. Mean time to healing for venous, traumatic, and other chronic wounds was 74 to 82 days with an average of 1.2 to 1.4 PriMatrix applications. In patients with comorbidities known to delay healing, the implantation of PriMatrix promoted the healing and, ultimately, full reepithelialization of otherwise unresponsive wounds of varied etiology, including those with complications of infection or exposed bone or tendon.

Acellular dermal matrix allografts to achieve increased attached gingiva. Part 2. A histological comparative study.

PubMed

Wei, Pein-Chi; Laurell, Lars; Lingen, Mark W; Geivelis, Milton

2002-03-01

In part 1 of this study, we compared the clinical efficacy of freeze-dried acellular dermal matrix (ADM) allograft in 6 patients with autogenous free gingival graft (FGG) in 6 patients for increasing the width of attached gingiva in the mandibular anterior area. The purpose of the present study was to histologically compare the microstructure of ADM and FGG treated sites from the same group. Biopsies were harvested from all 12 patients at 6 months postsurgery. The biopsies included the grafted sites with adjacent alveolar mucosa and gingiva propria and also donor palatal mucosa saved at the time of surgery. The 5 microm thick, neutral buffered formalin fixed, paraffin-embedded tissue sections were stained with hematoxylin and eosin (H&E), Masson's trichrome, and Verhoeff-van Gieson stains in order to investigate the density of collagen and elastic fibers. Additional sections were stained with periodic acid-Schiff (PAS) and Papanicolaou's stain to identify the presence of glycogen granules in the epithelial layer and to highlight the keratin layer respectively. The unique appearance of ADM-derived tissue did not parallel any known oral mucosa. The connective tissue portion contained dense to extremely dense collagen fibers along with scattered elastic fibers. The demarcations between the ADM graft and the coronal gingiva as well as the apical alveolar mucosa were usually not very defined. A moderate to thin epithelial layer, with heterogeneous expression of keratinization and flat epithelium-connective tissue interface, covered the lamina propria. Both the thickness of the epithelium and the degree of keratinization decreased in apical direction, being mostly para- or orthokeratinized in the area close to gingiva and non-keratinized adjacent to the alveolar mucosa. In the FGG-treated sites, the density of collagen fibers was less than in ADM-derived tissue, palatal mucosa, and gingiva. Elastic fibers were very sparse, comparable to gingiva, but much less than in ADM-derived tissue. The epithelium was moderate, somewhat thinner but the shape of the rete ridges resembled that of palatal mucosa. Similar to gingiva epithelium, the epithelium of the FGG-treated area was relatively uniform in both thickness and keratinization, mostly para-keratinized with a well defined border to the non-keratinized alveolar mucosa. Underneath the FGG-alveolar mucosa junction, a scar band composed of extremely dense collagen fibers consistently existed. The results of this 6-month histological evaluation suggest that: 1) the resultant tissue types of ADM grafts were similar to "scar" tissue; 2) the non-vital dermal matrix of ADM allograft lacked the capability of directing cyto-differentiation of the covering epithelium; 3) autogenous FGG-derived tissue was neither identical to donor palatal mucosa nor to adjacent gingiva propria; 4) the connective tissue of donor palatal mucosa only partially contributed to the differentiation of the epithelium covering the FGG-treated area; and 5) the epithelium/connective tissue microenvironment surrounding the recipient site influenced the epithelial differentiation of the graft; this may play a more critical role in ADM grafting than in the grafting of autogenous FGG.

Root coverage with Emdogain/AlloDerm: a new way to treat gingival recessions.

PubMed

Saadoun, André P

2008-01-01

The recession of the gingival margin is becoming a more prominent condition in the oral situation of many patients and should be treated at its earliest detection. The multifactorial etiology, decision modality, and current trends in the treatment of gingival recession are discussed in this article. The surgical technique of choice depends on several factors, but among the different surgical protocols available, the clinician should select one that will minimize surgical trauma and achieve predictable esthetic results. All of the approaches described in this article can effectively treat deep and shallow Class I or II buccal recessions. Recently, as an alternative to autogenous gingival grafts in root coverage procedures, enamel matrix derivative (Emdogain) and acellular dermal matrix allograft (AlloDerm) were utilized to correct these gingival defects, negating the morbidity and the requirement for a second palatal surgical procedure. Emdogain or AlloDerm materials used alone or in combination are a predictable treatment for root coverage, are relatively easy to perform (although they are technique sensitive), present low patient morbidity, offer a significant increase in the percentage of root coverage and amount of keratinized tissue, and should be part of the periodontal plastic surgery armamentarium.

Healing rates for challenging rotator cuff tears utilizing an acellular human dermal reinforcement graft

PubMed Central

Agrawal, Vivek

2012-01-01

Purpose: This study presents a retrospective case series of the clinical and structural outcomes (1.5 T MRI) of arthroscopic rotator cuff repair with acellular human dermal graft reinforcement performed by a single surgeon in patients with large, massive, and previously repaired rotator cuff tears. Materials and Methods: Fourteen patients with mean anterior to posterior tear size 3.87 ± 0.99 cm (median 4 cm, range 2.5–6 cm) were enrolled in the study and were evaluated for structural integrity using a high-field (1.5 T) MRI at an average of 16.8 months after surgery. The Constant-Murley scores, the Flexilevel Scale of Shoulder Function (Flex SF), scapular plane abduction, and strength were analyzed. Results: MRI results showed that the rotator cuff repair was intact in 85.7% (12/14) of the patients studied. Two patients had a Sugaya Type IV recurrent tear (2 of 14; 14.3%), which were both less than 1 cm. The Constant score increased from a preoperative mean of 49.72 (range 13–74) to a postoperative mean of 81.07 (range 45–92) (P value = 0.009). Flexilevel Scale of Shoulder Function (Flex SF) Score normalized to a 100-point scale improved from a preoperative mean of 53.69 to a postoperative mean of 79.71 (P value = 0.003). The Pain Score improved from a preoperative mean of 7.73 to a postoperative mean of 13.57 (P value = 0.008). Scapular plane abduction improved from a preoperative mean of 113.64° to a postoperative mean of 166.43° (P value = 0.010). The strength subset score improved from a preoperative mean of 1.73 kg to a postoperative mean of 7.52 kg (P value = 0.006). Conclusions: This study presents a safe and effective technique that may help improve the healing rates of large, massive, and revision rotator cuff tears with the use of an acellular human dermal allograft. This technique demonstrated favorable structural healing rates and statistically improved functional outcomes in the near term. Level of Evidence: 4. Retrospective case series. PMID:22787332

Efficacy of platelet-rich fibrin matrix on viability of diced cartilage grafts in a rabbit model.

PubMed

Güler, İsmail; Billur, Deniz; Aydin, Sevim; Kocatürk, Sinan

2015-03-01

The objective of this study was to compare the viability of cartilage grafts embedded in platelet-rich fibrin matrix (PRFM) wrapped with no material (bare diced cartilage grafts), oxidized methylcellulose (Surgicel), or acellular dermal tissue (AlloDerm). Experimental study. In this study, six New Zealand rabbits were used. Cartilage grafts including perichondrium were excised from each ear and diced into 2-mm-by 2-mm pieces. There were four comparison groups: 1) group A, diced cartilage (not wrapped with any material); 2) group B, diced cartilage wrapped with AlloDerm; 3) group C, diced cartilage grafts wrapped with Surgicel; and 4) group D, diced cartilage wrapped with PRFM. Four cartilage grafts were implanted under the skin at the back of each rabbit. All rabbits were sacrificed at the end of 10 weeks. The cartilages were stained with hematoxylin-eosin, Masson's Trichrome, and Orcein. After that, they were evaluated for the viability of chondrocytes, collagen content, fibrillar structure of matrix, and changes in peripheral tissues. When the viability of chondrocytes, the content of fiber in matrix, and changes in peripheral tissues were compared, the cartilage embedded in the PRFM group was statistically significantly higher than in the other groups (P < 0.05). We concluded that PRFM has significant advantages in ensuring the chondrocyte viability of diced cartilage grafts. It is also biocompatible, with relatively lesser inflammation and fibrosis. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Esthetic soft tissue management for teeth and implants.

PubMed

Fu, Jia-Hui; Su, Chuan-Yi; Wang, Hom-Lay

2012-09-01

Can newly introduced graft materials be successfully used in soft tissue augmentation around teeth and dental implants? An electronic search on the PubMed database for English articles published before March 31, 2012, was performed using the following key words: "root coverage," "soft tissue graft," "periodontal plastic surgery," "subepithelial connective graft (SCTG)," "acellular dermal matrix (ADM)," "guided tissue regeneration based root coverage (GTRC)," "recession defects," "mucogingival defects," "collagen matrix," "living cellular construct (LCC)," "mucograft," and "biologic agents." Literature featuring new soft tissue graft materials, such as ADM, collagen matrix, GTRC, and biologic agents, were included. Data showed (1) allogeneic grafts were comparable to SCTG in terms of mean complete root coverage (CRC), mean root coverage (RC), and mean amount of keratinized tissue (KT) gain; (2) xenogeneic collagen matrix was as comparable to SCTG in terms of mean amount of KT gain around teeth and dental implants but inferior in achieving RC; (3) GTRC was inferior to SCTG in terms of mean CRC and mean RC; (4) LCC was inferior to free gingival graft in terms of mean amount of KT gain but was superior in esthetics and patient satisfaction; and (5) adjunctive use of biologic agents did not exert a significant effect on mean CRC, mean RC, and mean amount of KT gain. Although these new materials do not surpass the gold standard (SCTG), they do provide improved patient satisfaction and esthetics, are available in abundance, and lead to reduced postoperative discomfort and surgical time. Copyright © 2012 Elsevier Inc. All rights reserved.

Wound healing effects of collagen-laminin dermal matrix impregnated with resveratrol loaded hyaluronic acid-DPPC microparticles in diabetic rats.

PubMed

Gokce, Evren H; Tuncay Tanrıverdi, Sakine; Eroglu, Ipek; Tsapis, Nicolas; Gokce, Goksel; Tekmen, Isıl; Fattal, Elias; Ozer, Ozgen

2017-10-01

An alternative formulation for the treatment of diabetic foot wounds that heal slowly is a requirement in pharmaceutical field. The aim of this study was to develop a dermal matrix consisting of skin proteins and lipids with an antioxidant that will enhance healing and balance the oxidative stress in the diabetic wound area due to the high levels of glucose. Thus a novel three dimensional collagen-laminin porous dermal matrix was developed by lyophilization. Resveratrol-loaded hyaluronic acid and dipalmitoylphosphatidylcholine microparticles were combined with this dermal matrix. Characterization, in vitro release, microbiological and in vivo studies were performed. Spherical microparticles were obtained with a high RSV encapsulation efficacy. The microparticles were well dispersed in the dermal matrix from the surface to deeper layers. Collagenase degraded dermal matrix, however the addition of RSV loaded microparticles delayed the degradation time. The release of RSV was sustained and reached 70% after 6h. Histological changes and antioxidant parameters in different treatment groups were investigated in full-thickness excision diabetic rat model. Collagen fibers were intense and improved by the presence of formulation without any signs of inflammation. The highest healing score was obtained with the dermal matrix impregnated with RSV-microparticles with an increased antioxidant activity. Collagen-laminin dermal matrix with RSV microparticles was synergistically effective due to presence of skin components in the formulation and controlled release achieved. This combination is a safe and promising option for the treatment of diabetic wounds requiring long recovery. Copyright © 2017 Elsevier B.V. All rights reserved.

A Case of “en bloc” Excision of a Chest Wall Leiomyosarcoma and Closure of the Defect with Non-Cross-Linked Collagen Matrix (Egis®)

PubMed Central

Rastrelli, Marco; Tropea, Saveria; Spina, Romina; Costa, Alessandra; Stramare, Roberto; Mocellin, Simone; Bonavina, Maria Giuseppina; Rossi, Carlo Riccardo

2016-01-01

Sarcomas arising from the chest wall account for less than 20% of all soft tissue sarcomas, and at this site, primitive tumors are the most frequent to occur. Leiomyosarcoma is a malignant smooth muscle tumor and the best outcomes are achieved with wide surgical excision. Although advancements have been made in treatment protocols, leiomyosarcoma remains one of the more difficult soft tissue sarcoma to treat. Currently, general local control is obtained with surgical treatment with wide negative margins. We describe the case of a 50-year-old man who underwent a chest wall resection involving a wide portion of the pectoralis major and minor muscle, the serratus and part of the second, third and fourth ribs of the left side. The full-thickness chest wall defect of 10 × 8 cm was closed using a non-cross-linked acellular dermal matrix (Egis®) placed in two layers, beneath the rib plane and over it. A successful repair was achieved with no incisional herniation and with complete tissue regeneration, allowing natural respiratory movements. No complications were observed in the postoperative course. Biological non-cross-linked matrix, derived from porcine dermis, behaves like a scaffold supporting tissue regeneration; it can be successfully used as an alternative to synthetic mesh for chest wall reconstruction. PMID:27920698

Development of a Sterile Amniotic Membrane Tissue Graft Using Supercritical Carbon Dioxide

DTIC Science & Technology

2015-03-04

production of acellular dermal matrices for clinical use . Wound Repair Regen 12, 276, 2004. 40. Movasaghi, Z., Rehman, S., and Rehman, I.U. Fourier...Development of a Sterile Amniotic Membrane Tissue Graft Using Supercritical Carbon Dioxide Jennifer L. Wehmeyer, PhD, Shanmugasundaram Natesan, PhD...and Robert J. Christy, PhD Numerous techniques have been reported for preparing and sterilizing amniotic membrane (AM) for use in clinical

Adipose-Derived Stem-Cell-Seeded Non-Cross-Linked Porcine Acellular Dermal Matrix Increases Cellular Infiltration, Vascular Infiltration, and Mechanical Strength of Ventral Hernia Repairs

PubMed Central

Iyyanki, Tejaswi S.; Dunne, Lina W.; Zhang, Qixu; Hubenak, Justin; Turza, Kristin C.

2015-01-01

Adipose-derived stem cells (ASCs) facilitate wound healing by improving cellular and vascular recruitment to the wound site. Therefore, we investigated whether ASCs would augment a clinically relevant bioprosthetic mesh—non-cross-linked porcine acellular dermal matrix (ncl-PADM)—used for ventral hernia repairs in a syngeneic animal model. ASCs were isolated from the subcutaneous adipose tissue of Brown Norway rats, expanded, and labeled with green fluorescent protein. ASCs were seeded (2.5×104 cells/cm2) onto ncl-PADM for 24 h before surgery. In vitro ASC adhesion to ncl-PADM was assessed at 0.5, 1, and 2 h after seeding, and cell morphology on ncl-PADM was visualized by scanning electron microscopy. Ventral hernia defects (2×4 cm) were created and repaired with ASC-seeded (n=31) and control (n=32) ncl-PADM. Explants were harvested at 1, 2, and 4 weeks after surgery. Explant remodeling outcomes were evaluated using gross evaluation (bowel adhesions, surface area, and grade), histological analysis (hematoxylin and eosin and Masson's trichrome staining), immunohistochemical analysis (von Willebrand factor VIII), fluorescent microscopy, and mechanical strength measurement at the tissue-bioprosthetic mesh interface. Stem cell markers CD29, CD90, CD44, and P4HB were highly expressed in cultured ASCs, whereas endothelial and hematopoietic cell markers, such as CD31, CD90, and CD45 had low expression. Approximately 85% of seeded ASCs adhered to ncl-PADM within 2 h after seeding, which was further confirmed by scanning electron microcopy examination. Gross evaluation of the hernia repairs revealed weak omental adhesion in all groups. Ultimate tensile strength was not significantly different in control and treatment groups. Conversely, elastic modulus was significantly greater at 4 weeks postsurgery in the ASC-seeded group (p<0.001). Cellular infiltration was significantly higher in the ASC-seeded group at all time points (p<0.05). Vascular infiltration was significantly greater at 4 weeks postsurgery in the ASC-seeded group (p<0.001). The presence of ASCs improved remodeling outcomes by yielding an increase in cellular infiltration and vascularization of ncl-PADM and enhanced the elastic modulus at the ncl-PADM-tissue interface. With the ease of harvesting adipose tissues that are rich in ASCs, this strategy may be clinically translatable for improving ncl-PADM ventral hernia repair outcomes. PMID:25156009

Adipose-derived stem-cell-seeded non-cross-linked porcine acellular dermal matrix increases cellular infiltration, vascular infiltration, and mechanical strength of ventral hernia repairs.

PubMed

Iyyanki, Tejaswi S; Dunne, Lina W; Zhang, Qixu; Hubenak, Justin; Turza, Kristin C; Butler, Charles E

2015-02-01

Adipose-derived stem cells (ASCs) facilitate wound healing by improving cellular and vascular recruitment to the wound site. Therefore, we investigated whether ASCs would augment a clinically relevant bioprosthetic mesh-non-cross-linked porcine acellular dermal matrix (ncl-PADM)-used for ventral hernia repairs in a syngeneic animal model. ASCs were isolated from the subcutaneous adipose tissue of Brown Norway rats, expanded, and labeled with green fluorescent protein. ASCs were seeded (2.5×10(4) cells/cm(2)) onto ncl-PADM for 24 h before surgery. In vitro ASC adhesion to ncl-PADM was assessed at 0.5, 1, and 2 h after seeding, and cell morphology on ncl-PADM was visualized by scanning electron microscopy. Ventral hernia defects (2×4 cm) were created and repaired with ASC-seeded (n=31) and control (n=32) ncl-PADM. Explants were harvested at 1, 2, and 4 weeks after surgery. Explant remodeling outcomes were evaluated using gross evaluation (bowel adhesions, surface area, and grade), histological analysis (hematoxylin and eosin and Masson's trichrome staining), immunohistochemical analysis (von Willebrand factor VIII), fluorescent microscopy, and mechanical strength measurement at the tissue-bioprosthetic mesh interface. Stem cell markers CD29, CD90, CD44, and P4HB were highly expressed in cultured ASCs, whereas endothelial and hematopoietic cell markers, such as CD31, CD90, and CD45 had low expression. Approximately 85% of seeded ASCs adhered to ncl-PADM within 2 h after seeding, which was further confirmed by scanning electron microcopy examination. Gross evaluation of the hernia repairs revealed weak omental adhesion in all groups. Ultimate tensile strength was not significantly different in control and treatment groups. Conversely, elastic modulus was significantly greater at 4 weeks postsurgery in the ASC-seeded group (p<0.001). Cellular infiltration was significantly higher in the ASC-seeded group at all time points (p<0.05). Vascular infiltration was significantly greater at 4 weeks postsurgery in the ASC-seeded group (p<0.001). The presence of ASCs improved remodeling outcomes by yielding an increase in cellular infiltration and vascularization of ncl-PADM and enhanced the elastic modulus at the ncl-PADM-tissue interface. With the ease of harvesting adipose tissues that are rich in ASCs, this strategy may be clinically translatable for improving ncl-PADM ventral hernia repair outcomes.

Clinical outcome and patient satisfaction with the use of bovine-derived acellular dermal matrix (SurgiMend™) in implant based immediate reconstruction following skin sparing mastectomy: A prospective observational study in a single centre.

PubMed

Headon, Hannah; Kasem, Abdul; Manson, Aisling; Choy, Christina; Carmichael, Amtul R; Mokbel, Kefah

2016-06-01

The advent of acellular dermal matrix devices (ADMs) has enhanced both the scope of implant-based immediate breast reconstruction (IBR) following skin sparing mastectomy (SSM) for the treatment or risk reduction of breast cancer. Currently, there are a wide range of options available for the use of ADMs. This is a prospective observational single institution study of 118 consecutive patients undergoing a total of 164 SSM and IBR procedures either for treatment for breast cancer or for risk reduction, between 2012 and 2014. IBR was performed using an implant and bovine-derived ADM (SurgiMend™). Nipple sparing mastectomy (NSM) accounted for 103 procedures. IBR was performed as a single stage procedure in 23% of patients. The primary endpoint of this prospective study was the explantation rate and secondary endpoints included quality of life, patient satisfaction, aesthetic outcome assessed objectively, surgical complications, overall and disease free survival. Forty-six patients (39%) had a bilateral and 72 underwent a unilateral SSM. Of those who underwent a unilateral SSM, 25 had a contralateral adjustment procedure. Out of 164 procedures, 117 (71%) were for the treatment of breast cancer. Sixty-one patients received chemotherapy (52%) and 32 (27%) had radiotherapy. In this study 27 patients underwent post-mastectomy radiotherapy. At a mean follow of 21 months, the explantation rate was 1.2%, 4% (6 patients) developed wound complications. The patient satisfaction with the procedure was found to be very high. The mean Breast Q Score was 85 and the mean overall patient satisfaction rating was 9 out of a possible 10. The mean objective assessment score was 8.9 out of a possible 10 and the mean subjective capsular contracture severity score was 2.9 out of 10. There were two cases of local recurrence (1.7%), one distant recurrence (0.8%) and one patient died of metastatic breast cancer (0.8%). Overall survival was 99.2% and locoregional disease free survival (LRFS) was 98.3%. One patient (0.8%) developed a mild inflammatory reaction secondary to the underlying mesh. SurgiMend™ is an effective adjunct to implant based IBR following SSM. It is associated with a very low rate of implant loss and a high level of patient satisfaction and is associated with a very low incidence of inflammatory reaction. Neither prior radiotherapy nor post-mastectomy radiotherapy (PMRT) represents a contraindication to its use. Copyright © 2016 Elsevier Ltd. All rights reserved.

Augmentation of Distal Biceps Repair With an Acellular Dermal Graft Restores Native Biomechanical Properties in a Tendon-Deficient Model.

PubMed

Conroy, Christine; Sethi, Paul; Macken, Craig; Wei, David; Kowalsky, Marc; Mirzayan, Raffy; Pauzenberger, Leo; Dyrna, Felix; Obopilwe, Elifho; Mazzocca, Augustus D

2017-07-01

The majority of distal biceps tendon injuries can be repaired in a single procedure. In contrast, complete chronic tears with severe tendon substance deficiency and retraction often require tendon graft augmentation. In cases with extensive partial tears of the distal biceps, a human dermal allograft may be used as an alternative to restore tendon thickness and biomechanical integrity. Dermal graft augmentation will improve load to failure compared with nonaugmented repair in a tendon-deficient model. Controlled laboratory study. Thirty-six matched specimens were organized into 1 of 4 groups: native tendon, native tendon with dermal graft augmentation, tendon with an attritional defect, and tendon with an attritional defect repaired with a graft. To mimic a chronic attritional biceps lesion, a defect was created by a complete tear, leaving 30% of the tendon's width intact. The repair technique in all groups consisted of cortical button and interference screw fixation. All specimens underwent cyclical loading for 3000 cycles and were then tested to failure; gap formation and peak load at failure were documented. The mean (±SD) load to failure (320.9 ± 49.1 N vs 348.8 ± 77.6 N, respectively; P = .38) and gap formation (displacement) (1.8 ± 1.4 mm vs 1.6 ± 1.1 mm, respectively; P = .38) did not differ between the native tendon groups with and without graft augmentation. In the tendon-deficient model, the mean load to failure was significantly improved with graft augmentation compared with no graft augmentation (282.1 ± 83.8 N vs 199.7 ± 45.5 N, respectively; P = .04), while the mean gap formation was significantly reduced (1.2 ± 1.0 mm vs 2.7 ± 1.4 mm, respectively; P = .04). The mean load to failure of the deficient tendon with graft augmentation (282.1 N) compared with the native tendon (348.8 N) was not significantly different ( P = .12). This indicates that the native tendon did not perform differently from the grafted deficient tendon. In a tendon-deficient, complete distal biceps rupture model, acellular dermal allograft augmentation restored the native tendon's biomechanical properties at time zero. The grafted tissue-deficient model demonstrated no significant differences in the load to failure and gap formation compared with the native tendon. As expected, dermal augmentation of attritional tendon repair increased the load to failure and stiffness as well as decreased displacement compared with the ungrafted tissue-deficient model. Tendons with their native width showed no statistical difference or negative biomechanical consequences of dermal augmentation. Dermal augmentation of the distal biceps is a biomechanically feasible option for patients with an attritionally thinned-out tendon.

Treatment of gingival recession with coronally advanced flap procedures: a systematic review.

PubMed

Cairo, Francesco; Pagliaro, Umberto; Nieri, Michele

2008-09-01

The treatment of buccal gingival recessions is a common requirement due to aesthetic concern or root sensitivity. The aim of this manuscript was to systematically review the literature on coronally advanced flap (CAF) alone or in combination with tissue grafts, barrier membranes (BM), enamel matrix derivative (EMD) or other material for treating gingival recession. Randomized clinical trials on treatment of Miller Class I and II gingival recessions with at least 6 months of follow-up were identified. Data sources included electronic databases and hand-searched journals. The primary outcome variable was complete root coverage (CRC). The secondary outcome variables were recession reduction, clinical attachment gain, keratinized tissue gain, aesthetic satisfaction, root sensitivity, post-operative patient pain and complications. A total of 794 Miller Class I and II gingival recessions in 530 patients from 25 RCTs were evaluated in this systematic review. CAF was associated with mean recession reduction and CRC. The addition of connective tissue graft (CTG) or EMD enhanced the clinical outcomes of CAF in terms of CRC, while BM did not. The results with respect to the adjunctive use of acellular dermal matrix were controversial. CTG or EMD in conjunction with CAF enhances the probability of obtaining CRC in Miller Class I and II single gingival recessions.

Applications of biomaterials in plastic surgery.

PubMed

Kim, Jeff J; Evans, Gregory R D

2012-10-01

The expansion of the application of biomaterials in plastic surgery has led to the increased availability of commercial products in recent years. This overview discusses soft tissue fillers, bioengineered skins, acellular dermal matrices, biomaterials for craniofacial surgery, and peripheral nerve repair. We summarize indications, properties, uses, types, advantages and disadvantages of some of the currently available products from each category. Finally, the current state of development in drug delivery system is also briefly summarized. Published by Elsevier Inc.

Alternatives to connective tissue graft in the treatment of localized gingival recessions: A systematic review.

PubMed

Amine, K; El Amrani, Y; Chemlali, S; Kissa, J

2018-02-01

The aim of this Systematic Review (SR) was to assess the clinical efficacy of alternatives procedures; Acellular Dermal Matrix (ADM), Xenogeneic Collagen Matrix (XCM), Enamel Matrix Derivative (EMD) and Platelet Rich Fibrin (PRF), compared to conventional procedures in the treatment of localized gingival recessions. Electronic searches were performed to identify randomized clinical trials (RCTs) on treatment of single gingival recession with at least 6 months of follow-up. Applying guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses statement (PRISMA). The risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool. Eighteen randomized controlled trials (RCTs) with a total of 390 treated patients (606 recessions) were included. This systematic review showed that: Coronally Advanced Flap (CAF) in conjunction with ADM was significantly better than CAF alone, while the comparison between CAF+ADM and CTG was affected by large uncertainty. The CAF+EMD was significantly better than CAF alone, whereas the comparison between CAF+EMD and CTG was affected by large uncertainty. No significant difference was recorded when comparing CAF+XCM with CAF alone, and the comparison between CAF+XCM and CTG was affected by large uncertainty. The comparison between PRF and others technique was affected by large uncertainty. ADM, XCM and EMD assisted to CAF might be considered alternatives of CTG in the treatment of Miller class I and II gingival recession. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The effect of porcine ADM to improve the burn wound healing

PubMed Central

Chen, Xiaodong; Shi, Yan; Shu, Bin; Xie, Xiaoxia; Yang, Ronghua; Zhang, Lijun; Ruan, Shubin; Lin, Yan; Lin, Zepeng; Shen, Rui; Zhang, Fenggang; Feng, Xiangsheng; Xie, Julin

2013-01-01

To study the effect of porcine acellular dermal matrix (ADM) on the burn wound healing. Seventy healthy Wistar rats were inflicted with 2 cm second degree burn and divided into 2 groups; one group was treated with porcine ADM and the other with Povidone Iodine Cream. Biopsies were taken on day 1, 3, 5, 7, 10, 14, 21 for histopathological and biochemical analysis to test PCNA, K19, Integrin-β1, PDGF, EGF and FGF. The results revealed relatively better and faster regeneration after treatment of porcine ADM, along with greatly increased synthesis in collagen in the experimental group. PCNA, K19, Integrin-β1 had an increase and then tapered down, and were stronger in the experimental group than in the contrast group during 21 days after burns. PDGF, EGF and FGF levels increased on day 3, peaked on day 5 and then started to decrease, while significantly enhanced expression of relevant growth factors were observed in the experimental group. Porcine ADM stimulate collagen synthesis, stem cells proliferation and differentiation, and the expression of relevant growth factors and ultimately improve the burn wound healing. PMID:24228089

Reducing infection risk in implant-based breast-reconstruction surgery: challenges and solutions

PubMed Central

Ooi, Adrian SH; Song, David H

2016-01-01

Implant-based procedures are the most commonly performed method for postmastectomy breast reconstruction. While donor-site morbidity is low, these procedures are associated with a higher risk of reconstructive loss. Many of these are related to infection of the implant, which can lead to prolonged antibiotic treatment, undesired additional surgical procedures, and unsatisfactory results. This review combines a summary of the recent literature regarding implant-related breast-reconstruction infections and combines this with a practical approach to the patient and surgery aimed at reducing this risk. Prevention of infection begins with appropriate reconstructive choice based on an assessment and optimization of risk factors. These include patient and disease characteristics, such as smoking, obesity, large breast size, and immediate reconstructive procedures, as well as adjuvant therapy, such as radiotherapy and chemotherapy. For implant-based breast reconstruction, preoperative planning and organization is key to reducing infection. A logical and consistent intraoperative and postoperative surgical protocol, including appropriate antibiotic choice, mastectomy-pocket creation, implant handling, and considered acellular dermal matrix use contribute toward the reduction of breast-implant infections. PMID:27621667

Hydrocortisone and triiodothyronine regulate hyaluronate synthesis in a tissue-engineered human dermal equivalent through independent pathways.

PubMed

Deshpande, Madhura; Papp, Suzanne; Schaffer, Lana; Pouyani, Tara

2015-02-01

Hydrocortisone (HC) and triiodothyronine (T3) have both been shown to be capable of independently inhibiting hyaluronate (HA, hyaluronic acid) synthesis in a self-assembled human dermal equivalent (human dermal matrix). We sought to investigate the action of these two hormones in concert on extracellular matrix formation and HA inhibition in the tissue engineered human dermal matrix. To this end, neonatal human dermal fibroblasts were cultured in defined serum-free medium for 21 days in the presence of each hormone alone, or in combination, in varying concentrations. Through a process of self-assembly, a substantial dermal extracellular matrix formed that was characterized. The results of these studies demonstrate that combinations of the hormones T3 and hydrocortisone showed significantly higher levels of hyaluronate inhibition as compared to each hormone alone in the human dermal matrix. In order to gain preliminary insight into the genes regulating HA synthesis in this system, a differential gene array analysis was conducted in which the construct prepared in the presence of 200 μg/mL HC and 0.2 nM T3 was compared to the normal construct (0.4 μg/mL HC and 20 pM T3). Using a GLYCOv4 gene chip containing approximately 1260 human genes, we observed differential expression of 131 genes. These data suggest that when these two hormones are used in concert a different mechanism of inhibition prevails and a combination of degradation and inhibition of HA synthesis may be responsible for HA regulation in the human dermal matrix. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Angiogenic response induced by acellular femoral matrix in vivo

PubMed Central

Conconi, Maria Teresa; Nico, Beatrice; Rebuffat, Piera; Crivellato, Enrico; Parnigotto, Pier Paolo; Nussdorfer, Gastone G; Ribatti, Domenico

2005-01-01

We investigated the angiogenic response induced by acellular femoral matrices implanted in vivo on to the chick embryo chorioallantoic membrane (CAM), a useful model for such investigation. The results showed that acellular matrices were able to induce a strong angiogenic response, comparable with that of fibroblast growth factor-2 (FGF-2), a well-known angiogenic cytokine. The angiogenic response was further increased when exogenous FGF-2 or transforming growth factor beta-1 (TGF-β1) was added to the matrices and inhibited by the addition of anti-FGF-2 or anti-TGF-β1 antibodies. The response may be considered to be dependent on a direct angiogenic effect exerted by the matrices, and also in part by the presence of FGF-2 and TGF-β1 in the acellular matrices. PMID:16011546

The true incidence of near-term postoperative complications in prosthetic breast reconstruction utilizing human acellular dermal matrices: a meta-analysis.

PubMed

Newman, Martin I; Swartz, Kimberly A; Samson, Michel C; Mahoney, Chris Brown; Diab, Khaled

2011-02-01

The use of human acellular dermal matrix (HADM) materials in prosthetic-based breast reconstruction has gained popularity in recent years. Questions remain, however, regarding the nature and incidence of postoperative complications associated with this technique. The results reported in the available literature vary widely. This meta-analysis examines this question further with a broad review of the available literature in an effort to better define the true nature and incidence of near-term complications associated with the use of HADM in prosthetic-based breast reconstruction. It does not aim to compare this method of reconstruction to others. A review of the available literature was performed in July 2009. The goal was to identify all previous works describing the placement of HADM at prosthetic-based breast reconstruction. Included were studies that documented the use of HADM for coverage of tissue expanders or permanent implants following therapeutic or prophylactic mastectomy. Excluded were studies that reported on the use of HADM in cosmetic breast surgery or studies that included the use of xenografts. Data collected included demographics as well as the nature and incidence of complications, with separate categories assigned for seroma, infection, flap necrosis, and "other." Data were analyzed using Comprehensive Meta-Analysis(®) software (Biostat, Englewood, NJ). Raw proportions, fixed-effect models, and random-effect models were used to assess the complication rates across studies. Eleven published articles and one abstract that was later published as an article were identified. Within these 12 studies, a total of 789 breasts were identified that had undergone reconstruction with HADM. The mean follow-up was 13.7 months. Under the random-effects model, the total complication rate was 12.0%. The most common complications were flap necrosis (3.3%), seroma (3.3%), and infection (5.6%). All complications not included in these categories were set apart in a separate category, "Other," and totaled 3.0% The true incidence of postoperative complications in the near term utilizing HADM in prosthetic-based breast reconstruction appears to be approximately 12%. The incidence of long-term complications such as capsular contracture remains unknown. However, as surgical experience with HADM grows, operative techniques designed at reducing risks will mature, strategies for managing complications will advance, and more advanced products designed to reduce the incidence of complications are likely to become available.

Skin derived precursor Schwann cell-generated acellular matrix modified chitosan/silk scaffolds for bridging rat sciatic nerve gap.

PubMed

Zhu, Changlai; Huang, Jing; Xue, Chengbin; Wang, Yaxian; Wang, Shengran; Bao, Shuangxi; Chen, Ruyue; Li, Yuan; Gu, Yun

2017-12-27

Extracellular/acellular matrix has been attracted much research interests for its unique biological characteristics, and ACM modified neural scaffolds shows the remarkable role of promoting peripheral nerve regeneration. In this study, skin-derived precursors pre-differentiated into Schwann cells (SKP-SCs) were used as parent cells to generate acellular(ACM) for constructing a ACM-modified neural scaffold. SKP-SCs were co-cultured with chitosan nerve guidance conduits (NGC) and silk fibroin filamentous fillers, followed by decellularization to stimulate ACM deposition. This NGC-based, SKP-SC-derived ACM-modified neural scaffold was used for bridging a 10 mm long rat sciatic nerve gap. Histological and functional evaluation after grafting demonstrated that regenerative outcomes achieved by this engineered neural scaffold were better than those achieved by a plain chitosan-silk fibroin scaffold, and suggested the benefits of SKP-SC-derived ACM for peripheral nerve repair. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Structural and biomechanical characterizations of porcine myocardial extracellular matrix

PubMed Central

Wang, Bo; Tedder, Mary E.; Perez, Clara E.; Wang, Guangjun; de Jongh Curry, Amy L.; To, Filip; Elder, Steven H.; Williams, Lakiesha N.; Simionescu, Dan T.; Liao, Jun

2012-01-01

Extracellular matrix (ECM) of myocardium plays an important role to maintain a multilayered helical architecture of cardiomyocytes. In this study, we have characterized the structural and biomechanical properties of porcine myocardial ECM. Fresh myocardium were decellularized in a rotating bioreactor using 0.1 % sodium dodecyl sulfate solution. Masson’s trichrome staining and SEM demonstrated the removal of cells and preservation of the interconnected 3D cardiomyocyte lacunae. Movat’s pentachrome staining showed the preservation of cardiac elastin ultrastructure and vascular elastin distribution/alignment. DNA assay result confirmed a 98.59 % reduction in DNA content; the acellular myocardial scaffolds were found completely lack of staining for the porcine α-Gal antigen; and the accelerating enzymatic degradation assessment showed a constant degradation rate. Tensile and shear properties of the acellular myocardial scaffolds were also evaluated. Our observations showed that the acellular myocardial ECM possessed important traits of biodegradable scaffolds, indicating the potentials in cardiac regeneration and whole heart tissue engineering. PMID:22584822

The Use of Fetal Bovine Dermal Scaffold (PriMatrix) in the Management of Full-Thickness Hand Burns.

PubMed

Parcells, Alexis Lanteri; Karcich, Jenika; Granick, Mark S; Marano, Michael A

2014-01-01

Management of full-thickness burn wounds represents a challenge when reconstructive options are not applicable. Fetal bovine dermal matrix is a bioactive collagen scaffold that assimilates into wounds and stimulates vascularization and dermal regeneration. We present the use of fetal bovine dermal scaffold PriMatrix in the treatment of a patient who sustained scald-immersion full-thickness burns of her bilateral hands that failed conventional wound therapy. A 71-year-old woman with advanced Parkinson's disease sustained self-induced 5% mixed second- and third-degree scald-immersion burns of her bilateral hands and fingers. The patient underwent extensive debridement that resulted in partially avascular wounds measuring 66 cm(2) and 72 cm(2) with exposed extensor tendons and no evidence of bleeding. Meshed homograft was applied, but her hands remained partly avascular. PriMatrix fetal bovine dermal scaffold was applied to provide tissue remodeling over the bones, which allowed successful skin grafting and complete wound healing. Our experience shows fetal bovine dermal scaffold to be an effective method in management of complicated burn wounds in selected cases. Further studies need to be implemented to confer this conclusion.

The Use of Fetal Bovine Dermal Scaffold (PriMatrix) in the Management of Full-Thickness Hand Burns

PubMed Central

Karcich, Jenika; Granick, Mark S.; Marano, Michael A.

2014-01-01

Objective: Management of full-thickness burn wounds represents a challenge when reconstructive options are not applicable. Fetal bovine dermal matrix is a bioactive collagen scaffold that assimilates into wounds and stimulates vascularization and dermal regeneration. Methods: We present the use of fetal bovine dermal scaffold PriMatrix in the treatment of a patient who sustained scald-immersion full-thickness burns of her bilateral hands that failed conventional wound therapy. Results: A 71-year-old woman with advanced Parkinson's disease sustained self-induced 5% mixed second- and third-degree scald-immersion burns of her bilateral hands and fingers. The patient underwent extensive debridement that resulted in partially avascular wounds measuring 66 cm2 and 72 cm2 with exposed extensor tendons and no evidence of bleeding. Meshed homograft was applied, but her hands remained partly avascular. PriMatrix fetal bovine dermal scaffold was applied to provide tissue remodeling over the bones, which allowed successful skin grafting and complete wound healing. Conclusions: Our experience shows fetal bovine dermal scaffold to be an effective method in management of complicated burn wounds in selected cases. Further studies need to be implemented to confer this conclusion. PMID:25328569

Cyclosporin A reduces matrix metalloproteinases and collagen expression in dermal fibroblasts from regenerative FOXN1 deficient (nude) mice

PubMed Central

2013-01-01

Background Cyclosporin A (CsA), an immunosuppressive agent modifies the wound healing process through an influence on extracellular matrix metabolism. We have compared the effects of CsA on dermal fibroblasts from nude (FOXN1 deficient) mice, a genetic model of skin scarless healing, and from control (C57BL/6 J (B6) mice to evaluate metabolic pathways that appear to have important roles in the process of scarless healing/regeneration. Results High levels of matrix metalloproteinases (MMPs) and collagen III expression in dermal fibroblasts from nude (regenerative) mice were down-regulated by CsA treatment to the levels observed in dermal fibroblasts from B6 (non-regenerative) mice. In contrast, dermal fibroblasts from control mice respond to CsA treatment with a minor reduction of Mmps mRNA and 2.5-fold increase expression of collagen I mRNA. An in vitro migratory assay revealed that CsA treatment profoundly delayed the migratory behavior of dermal fibroblasts from both nude and control mice. Conclusion The data suggest that by alternation of the accumulation of extracellular matrix components CsA treatment stimulates the transition from a scarless to a scar healing. PMID:23547542

Cell recruitment by amnion chorion grafts promotes neovascularization.

PubMed

Maan, Zeshaan N; Rennert, Robert C; Koob, Thomas J; Januszyk, Michael; Li, William W; Gurtner, Geoffrey C

2015-02-01

Nonhealing wounds are a significant health burden. Stem and progenitor cells can accelerate wound repair and regeneration. Human amniotic membrane has demonstrated efficacy in promoting wound healing, though the underlying mechanisms remain unknown. A dehydrated human amnion chorion membrane (dHACM) was tested for its ability to recruit hematopoietic progenitor cells to a surgically implanted graft in a murine model of cutaneous ischemia. dHACM was subcutaneously implanted under elevated skin (ischemic stimulus) in either wild-type mice or mice surgically parabiosed to green fluorescent protein (GFP) + reporter mice. A control acellular dermal matrix, elevated skin without an implant, and normal unwounded skin were used as controls. Wound tissue was harvested and processed for histology and flow cytometric analysis. Implanted dHACMs recruited significantly more progenitor cells compared with controls (*P < 0.05) and displayed in vivo SDF-1 expression with incorporation of CD34 + progenitor cells within the matrix. Parabiosis modeling confirmed the circulatory origin of recruited cells, which coexpressed progenitor cell markers and were localized to foci of neovascularization within implanted matrices. In summary, dHACM effectively recruits circulating progenitor cells, likely because of stromal derived factor 1 (SDF-1) expression. The recruited cells express markers of "stemness" and localize to sites of neovascularization, providing a partial mechanism for the clinical efficacy of human amniotic membrane in the treatment of chronic wounds. Copyright © 2015 Elsevier Inc. All rights reserved.

Cell recruitment by amnion chorion grafts promotes neovascularization

PubMed Central

Koob, Thomas J.; Januszyk, Michael; Li, William W.; Gurtner, Geoffrey C.

2015-01-01

Background Nonhealing wounds are a significant health burden. Stem and progenitor cells can accelerate wound repair and regeneration. Human amniotic membrane has demonstrated efficacy in promoting wound healing, though the underlying mechanisms remain unknown. A dehydrated human amnion chorion membrane (dHACM) was tested for its ability to recruit hematopoietic progenitor cells to a surgically implanted graft in a murine model of cutaneous ischemia. Methods dHACM was subcutaneously implanted under elevated skin (ischemic stimulus) in either wild-type mice or mice surgically parabiosed to green fluorescent protein (GFP) + reporter mice. A control acellular dermal matrix, elevated skin without an implant, and normal unwounded skin were used as controls. Wound tissue was harvested and processed for histology and flow cytometric analysis. Results Implanted dHACMs recruited significantly more progenitor cells compared with controls (*P < 0.05) and displayed in vivo SDF-1 expression with incorporation of CD34 + progenitor cells within the matrix. Parabiosis modeling confirmed the circulatory origin of recruited cells, which coexpressed progenitor cell markers and were localized to foci of neovascularization within implanted matrices. Conclusions In summary, dHACM effectively recruits circulating progenitor cells, likely because of stromal derived factor 1 (SDF-1) expression. The recruited cells express markers of “stemness” and localize to sites of neovascularization, providing a partial mechanism for the clinical efficacy of human amniotic membrane in the treatment of chronic wounds. PMID:25266600

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.

Implantation of In Vitro Tissue Engineered Muscle Repair Constructs and Bladder Acellular Matrices Partially Restore In Vivo Skeletal Muscle Function in a Rat Model of Volumetric Muscle Loss Injury

DTIC Science & Technology

2014-01-01

thickness abdominal wall defects. Tissue Eng 12, 1929, 2006. 7. Gamba, P.G., Conconi, M.T., Lo Piccolo, R., Zara , G., Spi nazzi, R., and Parnigotto... Zara , G., Sabatti, M., Marzaro, M., et al. Homologous muscle acellular matrix seeded with autologous myoblasts as a tissue engineering approach to

Xenogeneic Acellular Conjunctiva Matrix as a Scaffold of Tissue-Engineered Corneal Epithelium

PubMed Central

Zhao, Haifeng; Qu, Mingli; Wang, Yao; Wang, Zhenyu; Shi, Weiyun

2014-01-01

Amniotic membrane-based tissue-engineered corneal epithelium has been widely used in the reconstruction of the ocular surface. However, it often degrades too early to ensure the success of the transplanted corneal epithelium when treating patients with severe ocular surface disorders. In the present study, we investigated the preparation of xenogeneic acellular conjunctiva matrix (aCM) and evaluated its efficacy and safety as a scaffold of tissue-engineered corneal epithelium. Native porcine conjunctiva was decellularized with 0.1% sodium dodecyl sulfate (SDS) for 12 h at 37°C and sterilized via γ-irradiation. Compared with native conjunctiva, more than 92% of the DNA was removed, and more than 90% of the extracellular matrix components (glycosaminoglycan and collagen) remained after the decellularization treatment. Compared with denuded amniotic membrane (dAM), the aCM possessed favorable optical transmittance, tensile strength, stability and biocompatibility as well as stronger resistance to degradation both in vitro and in vivo. The corneal epithelial cells seeded on aCM formed a multilayered epithelial structure and endured longer than did those on dAM. The aCM-based tissue-engineered corneal epithelium was more effective in the reconstruction of the ocular surface in rabbits with limbal stem cell deficiency. These findings support the application of xenogeneic acellular conjunctiva matrix as a scaffold for reconstructing the ocular surface. PMID:25375996

Complete horizontal skin cell resurfacing and delayed vertical cell infiltration into porcine reconstructive tissue matrix compared to bovine collagen matrix and human dermis.

PubMed

Mirastschijski, Ursula; Kerzel, Corinna; Schnabel, Reinhild; Strauss, Sarah; Breuing, Karl-Heinz

2013-10-01

Xenogenous dermal matrices are used for hernia repair and breast reconstruction. Full-thickness skin replacement is needed after burn or degloving injuries with exposure of tendons or bones. The authors used a human skin organ culture model to study whether porcine reconstructive tissue matrix (Strattice) is effective as a dermal tissue replacement. Skin cells or split-thickness skin grafts were seeded onto human deepidermized dermis, Strattice, and Matriderm. Cellular resurfacing and matrix infiltration were monitored by live fluorescence imaging, histology, and electron microscopy. Proliferation, apoptosis, cell differentiation, and adhesion were analyzed by immunohistochemistry. Epithelial resurfacing and vertical proliferation were reduced and delayed with both bioartificial matrices compared with deepidermized dermis; however, no differences in apoptosis, cell differentiation, or basement membrane formation were found. Vertical penetration was greatest on Matriderm, whereas no matrix infiltration was found on Strattice in the first 12 days. Uncompromised horizontal resurfacing was greatest with Strattice but was absent with Matriderm. Strattice showed no stimulatory effect on cellular inflammation. Matrix texture and surface properties governed cellular performance on tissues. Although dense dermal compaction delayed vertical cellular ingrowth for Strattice, it allowed uncompromised horizontal resurfacing. Dense dermal compaction may slow matrix decomposition and result in prolonged biomechanical stability of the graft. Reconstructive surgeons should choose the adequate matrix substitute depending on biomechanical requirements at the recipient site. Strattice may be suitable as a dermal replacement at recipient sites with high mechanical load requirements.

Dermal Filler Injection: A Novel Approach for Limiting Infarct Expansion

PubMed Central

Ryan, Liam P.; Matsuzaki, Kanji; Noma, Mio; Jackson, Benjamin M.; Eperjesi, Thomas J.; Plappert, Theodore J.; St. John-Sutton, Martin G.; Gorman, Joseph H.; Gorman, Robert C.

2011-01-01

Background Early infarct expansion after coronary occlusion compromises contractile function in perfused myocardial regions and promotes adverse long-term left ventricular (LV) remodeling. We hypothesized that injection of a tissue-expanding dermal filler material into a myocardial infarction (MI) would attenuate infarct expansion and limit LV remodeling. Methods Fifteen sheep were subjected to an anteroapical MI involving approximately 20% of the LV followed by the injection of 1.3 mL of a calcium hydroxyapatite–based dermal filler into the infarct. Real-time three-dimensional echocardiography was performed at baseline, 30 minutes after MI, and 15 minutes after injection to assess infarct expansion. Sixteen additional sheep were subjected to the same infarction and followed echocardiographically and hemodynamically for 4 weeks after MI to assess chronic remodeling. Eight animals had injection with dermal filler as described above immediately after MI, and 8 animals were injected with an equal amount of saline solution. Results All animals exhibited infarct expansion soon after coronary occlusion. The regional ejection fraction of the apex became negative after infarction, consistent with systolic dyskinesia. Injection of the dermal filler converted the apical wall motion from dyskinetic to akinetic and resulted immediately in significant decreases in global, regional, and segmental LV volumes. Chronically, relative to saline control, dermal filler injection significantly reduced LV end-systolic volume (62.2 ± 3.6 mL versus 44.5 ± 3.9 mL; p < 0.05) and improved global ejection fraction (0.295 ± 0.016 versus 0.373 ± 0.017; p < 0.05) at 4 weeks after infarction. Conclusions Injection of an acellular dermal filler into an MI immediately after coronary occlusion reduces early infarct expansion and limits chronic LV remodeling. PMID:19101288

Optimization of human tendon tissue engineering: peracetic acid oxidation for enhanced reseeding of acellularized intrasynovial tendon.

PubMed

Woon, Colin Y L; Pridgen, Brian C; Kraus, Armin; Bari, Sina; Pham, Hung; Chang, James

2011-03-01

Tissue engineering of human flexor tendons combines tendon scaffolds with recipient cells to create complete cell-tendon constructs. Allogenic acellularized human flexor tendon has been shown to be a useful natural scaffold. However, there is difficulty repopulating acellularized tendon with recipient cells, as cell penetration is restricted by a tightly woven tendon matrix. The authors evaluated peracetic acid treatment in optimizing intratendinous cell penetration. Cadaveric human flexor tendons were harvested, acellularized, and divided into experimental groups. These groups were treated with peracetic acid in varying concentrations (2%, 5%, and 10%) and for varying time periods (4 and 20 hours) to determine the optimal treatment protocol. Experimental tendons were analyzed for differences in tendon microarchitecture. Additional specimens were reseeded by incubation in a fibroblast cell suspension at 1 × 10(6) cells/ml. This group was then analyzed for reseeding efficacy. A final group underwent biomechanical studies for strength. The optimal treatment protocol comprising peracetic acid at 5% concentration for 4 hours produced increased scaffold porosity, improving cell penetration and migration. Treated scaffolds did not show reduced collagen or glycosaminoglycan content compared with controls (p = 0.37 and p = 0.65, respectively). Treated scaffolds were cytotoxic to neither attached cells nor the surrounding cell suspension. Treated scaffolds also did not show inferior ultimate tensile stress or elastic modulus compared with controls (p = 0.26 and p = 0.28, respectively). Peracetic acid treatment of acellularized tendon scaffolds increases matrix porosity, leading to greater reseeding. It may prove to be an important step in tissue engineering of human flexor tendon using natural scaffolds.

Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix

NASA Astrophysics Data System (ADS)

Geng, Hongquan; Song, Hua; Qi, Jun; Cui, Daxiang

2011-12-01

We fabricated a novel vascular endothelial growth factor (VEGF)-loaded poly(lactic- co-glycolic acid) (PLGA)-nanoparticles (NPs)-embedded thermo-sensitive hydrogel in porcine bladder acellular matrix allograft (BAMA) system, which is designed for achieving a sustained release of VEGF protein, and embedding the protein carrier into the BAMA. We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic®) F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system. Then the thermal behavior of the system was proven by in vitro and in vivo study, and the kinetic-sustained release profile of the system embedded in porcine bladder acellular matrix was investigated. Results indicated that the bioactivity of the encapsulated VEGF released from the NPs was reserved, and the VEGF-NPs thermo-sensitive gel system can achieve sol-gel transmission successfully at appropriate temperature. Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach. In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy.

[Tissue engineering of urinary bladder using acellular matrix].

PubMed

Glybochko, P V; Olefir, Yu V; Alyaev, Yu G; Butnaru, D V; Bezrukov, E A; Chaplenko, A A; Zharikova, T M

2017-04-01

Tissue engineering has become a new promising strategy for repairing damaged organs of the urinary system, including the bladder. The basic idea of tissue engineering is to integrate cellular technology and advanced bio-compatible materials to replace or repair tissues and organs. of the study is the objective reflection of the current trends and advances in tissue engineering of the bladder using acellular matrix through a systematic search of preclinical and clinical studies of interest. Relevant studies, including those on methods of tissue engineering of urinary bladder, was retrieved from multiple databases, including Scopus, Web of Science, PubMed, Embase. The reference lists of the retrieved review articles were analyzed for the presence of the missing relevant publications. In addition, a manual search for registered clinical trials was conducted in clinicaltrials.gov. Following the above search strategy, a total of 77 eligible studies were selected for further analysis. Studies differed in the types of animal models, supporting structures, cells and growth factors. Among those, studies using cell-free matrix were selected for a more detailed analysis. Partial restoration of urothelium layer was observed in most studies where acellular grafts were used for cystoplasty, but no the growth of the muscle layer was observed. This is the main reason why cellular structures are more commonly used in clinical practice.

Creation of an acellular vaginal matrix for potential vaginal augmentation and cloacal repair.

PubMed

Greco, K V; Jones, L G; Obiri-Yeboa, I; Ansari, T

2018-05-21

our aim was to use porcine vagina to create a vaginal matrix and test its cellular biocompatibility. vagina was harvested from pigs and de-cellularised (DC) using a combination of detergents (Triton x-100 and sodium deoxycholate) and enzymes (DNAse/RNAse). the presence of cellular material, collagen structural integrity and basement membrane proteins were assessed histologically. To address cytocompatibility, porcine adipose derived-mesenchymal stem cells (AD-MSC) were harvested from abdominal fat together with vaginal epithelial cells (VEC) and seeded onto the mucosal aspect of the vaginal scaffold. Both cells populations were seeded individually and assessed histologically at days 3 and 10. MAIN OUTCOMES/RESULTS: the combination of enzymes and detergents resulted in a totally acellular matrix with very low DNA amount (control= 97.5ng/μl ± 10.8 vs DC= 40.1 ng/μl ±0.33 p=0.02). The extra cellular matrix (ECM) showed retention of collagen fibres and elastin and a 50% retention in glycosaminoglycan content; (control= 1.18μg/mg ± 0.28 DC = 1.35μg/mg ± 0.1 p=0.03) and an intact basement membrane (positive for both laminin and collagen IV). Seeded scaffolds showed cell attachment with both AD-MSC and VEC at days 3 and 10. it is possible to generate an acellular porcine vaginal matrix capable of supporting cells to reconstruct the vagina for future pre-clinical testing, and holds promise for creating clinically relevant sized tissue for human application. Copyright © 2018. Published by Elsevier Inc.

A novel animal model for skin flap prelamination with biomaterials

NASA Astrophysics Data System (ADS)

Zhou, Xianyu; Luo, Xusong; Liu, Fei; Gu, Chuan; Wang, Xi; Yang, Qun; Qian, Yunliang; Yang, Jun

2016-09-01

Several animal models of skin flap construction were reported using biomaterials in a way similar to prefabrication. However, there are few animal model using biomaterials similar to prelamination, another main way of clinical skin flap construction that has been proved to be reliable. Can biomaterials be added in skin flap prelamination to reduce the use of autogenous tissues? Beside individual clinical attempts, animal model is needed for randomized controlled trial to objectively evaluate the feasibility and further investigation. Combining human Acellular Dermal Matrix (hADM) and autologous skin graft, we prelaminated flaps based on inguinal fascia. One, two, three and four weeks later, hADM exhibited a sound revascularization and host cell infiltration. Prelaminated skin flaps were then raised and microsurgically transplanted back to groin region. Except for flaps after one week of prelamination, flaps from other subgroups successfully reconstructed defects. After six to sixteen weeks of transplantation, hADM was proved to being able to maintain its original structure, having a wealth of host tissue cells and achieving full revascularization.To our knowledge, this is the first animal model of prelaminating skin flap with biomaterials. Success of this animal model indicates that novel flap prelamination with biomaterials is feasible.

Technical advances for abdominal wall closure after intestinal and multivisceral transplantation.

PubMed

Gerlach, Undine A; Pascher, Andreas

2012-06-01

Abdominal wall closure after intestinal transplantation (ITX) or multivisceral transplantation (MVTX) is challenging because of the loss of abdominal domain and wall elasticity as a result of previous operations and donor-to-recipient weight and height mismatch. We report on abdominal wall closure management in 30 ITX and MVTX recipients. In 60% of patients (n = 18), a primary abdominal closure (PAC) was achieved, in 40% (n = 12) a staged closure (SAC) was necessary. Patients with PAC had undergone less pretransplant operations and required less posttransplant relaparotomies. They were mainly ITX recipients or more abdominal domain because of a longer intestinal remnant. A literature review revealed different strategies to overcome a failed primary closure. They focus on graft reduction or an enlargement of the abdominal domain. The latter includes temporary coverage with prosthetic materials for SAC. Definite abdominal closure is achieved by skin only closure, or by using acellular dermal matrix, rotational flaps, rectus muscle fascia or abdominal wall grafts. Abdominal wall reconstruction after ITX/MVTX is commonly demanded and can be conducted by different strategies. The technique should be easy to use in a timely manner and should prevent abdominal infections, intestinal fistulation, incisional hernias, and wound dehiscence.

A Giant Lumbar Pseudomeningocele in a Patient with Neurofibromatosis Type 1: A Case Report.

PubMed

Dobran, Mauro; Iacoangeli, Maurizio; Ruscelli, Paolo; Della Costanza, Martina; Nasi, Davide; Scerrati, Massimo

2017-01-01

This is a rare case of giant lumbar pseudomeningocele with intra-abdominal extension in patient with neurofibromatosis type 1 (NF1). The patient's clinical course is retrospectively reviewed. A 34-year-old female affected by NF1 was referred to our institution for persistent low back pain and MRI diagnosis of pseudomeningocele located at L3 level with paravertebral extension. From the first surgical procedure by a posterior approach until the relapse of the pseudomeningocele documented by MRI, the patient underwent two subsequent posterior surgical procedures to repair the dural sac defect with fat graft and fibrin glue. One month after the third operation, the abdominal MRI showed a giant intra-abdominal pseudomeningocele causing compression of visceral structures. The patient was asymptomatic. The pseudomeningocele was treated with an anterior abdominal approach and the use of the acellular dermal matrix (ADM) sutured directly on the dural defect on the anterolateral wall of the spinal canal. After six months of follow-up the MRI showed no relapse of the pseudomeningocele. Our case highlights the possible use of ADM as an effective and safe alternative to the traditional fat graft to repair challenging and large dural defects.

Hydrocortisone effect on hyaluronate synthesis in a self-assembled human dermal equivalent.

PubMed

Deshpande, Madhura; Papp, Suzanne; Schaffer, Lana; Pouyani, Tara

2016-10-01

Human dermal matrix is a 'self-assembled' dermal equivalent containing large amounts of the glycosaminoglycan hyaluronic acid (hyaluronate, hyaluronan, HA). We sought to investigate the actions of the hormone hydrocortisone on hyaluronate synthesis in the human dermal matrix. To this end, human dermal fibroblasts were cultured under serum-free conditions, and in the absence of a three-dimensional matrix, in the presence of varying amounts of hydrocortisone. The resultant human dermal matrices were characterized. We report that low concentrations of hydrocortisone enhance hyaluronate synthesis in the human dermal equivalent and higher concentrations cause inhibition of hyaluronate synthesis. Other glycosaminoglycan (chondroitin sulphate) synthesis is not affected by changing hydrocortisone concentrations up to 500× (200 µg/ml) of the base value. In order to gain preliminary insight into the molecular mechanism of hyaluronate inhibition, a differential gene array analysis was conducted of human dermal matrix grown in the presence of 200 µg/ml hydrocortisone and in a physiological concentration (0.4 µg/ml, normal conditions). The results of these experiments demonstrate the differential expression of 43 genes in the 500× (200 µg/ml) hydrocortisone construct as compared to the construct grown under normal conditions (0.4 µg/ml hydrocortisone). These preliminary experiments suggest that hydrocortisone at higher concentrations may exert its inhibitory effect on hyaluronate synthesis early in the glycolytic pathway, leading to HA biosynthesis by downregulation of phosphoglucomutase and glucose phosphate isomerase, possibly leading to depletion of the cellular pool of UDP-sugar precursors necessary for HA synthesis. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

Histology and affinity of anaspids, and the early evolution of the vertebrate dermal skeleton

PubMed Central

Keating, Joseph N.; Donoghue, Philip C. J.

2016-01-01

The assembly of the gnathostome bodyplan constitutes a formative episode in vertebrate evolutionary history, an interval in which the mineralized skeleton and its canonical suite of cell and tissue types originated. Fossil jawless fishes, assigned to the gnathostome stem-lineage, provide an unparalleled insight into the origin and evolution of the skeleton, hindered only by uncertainty over the phylogenetic position and evolutionary significance of key clades. Chief among these are the jawless anaspids, whose skeletal composition, a rich source of phylogenetic information, is poorly characterized. Here we survey the histology of representatives spanning anaspid diversity and infer their generalized skeletal architecture. The anaspid dermal skeleton is composed of odontodes comprising spheritic dentine and enameloid, overlying a basal layer of acellular parallel fibre bone containing an extensive shallow canal network. A recoded and revised phylogenetic analysis using equal and implied weights parsimony resolves anaspids as monophyletic, nested among stem-gnathostomes. Our results suggest the anaspid dermal skeleton is a degenerate derivative of a histologically more complex ancestral vertebrate skeleton, rather than reflecting primitive simplicity. Hypotheses that anaspids are ancestral skeletonizing lampreys, or a derived lineage of jawless vertebrates with paired fins, are rejected. PMID:26962140

Using Acellular Bioactive Extracellular Matrix Scaffolds to Enhance Endogenous Cardiac Repair

PubMed Central

Svystonyuk, Daniyil A.; Mewhort, Holly E. M.; Fedak, Paul W. M.

2018-01-01

An inability to recover lost cardiac muscle following acute ischemic injury remains the biggest shortcoming of current therapies to prevent heart failure. As compared to standard medical and surgical treatments, tissue engineering strategies offer the promise of improved heart function by inducing regeneration of functional heart muscle. Tissue engineering approaches that use stem cells and genetic manipulation have shown promise in preclinical studies but have also been challenged by numerous critical barriers preventing effective clinical translational. We believe that surgical intervention using acellular bioactive ECM scaffolds may yield similar therapeutic benefits with minimal translational hurdles. In this review, we outline the limitations of cellular-based tissue engineering strategies and the advantages of using acellular biomaterials with bioinductive properties. We highlight key anatomic targets enriched with cellular niches that can be uniquely activated using bioactive scaffold therapy. Finally, we review the evolving cardiovascular tissue engineering landscape and provide critical insights into the potential therapeutic benefits of acellular scaffold therapy. PMID:29696148

Influence of extracellular matrix proteins on human keratinocyte attachment, proliferation and transfer to a dermal wound model.

PubMed

Dawson, R A; Goberdhan, N J; Freedlander, E; MacNeil, S

1996-03-01

The aim of this study was to investigate whether prior culture of cells on ECM proteins might positively influence the performance of keratinocytes when cells are transferred to a dermal in vitro wound bed model. Keratinocytes were cultured using a method for producing cultured epithelial autografts for severely burned patients (essentially using Green's medium, a mitogen-rich medium containing fetal calf serum, cholera toxin, EGF, insulin, transferrin and triiodothyronine). Cells were cultured either on irradiated 3T3 fibroblasts (as in the standard Rheinwald and Green technique) or, alternatively, on collagen I, collagen IV, matrigel, RGD, vitronectin or fibronectin. Under these conditions matrigel, collagen I and IV enhanced initial attachment, RGD, vitronectin, fibronectin and irradiated 3T3 fibroblasts did not. Proliferation of cells was positively influenced by matrigel, collagen I and IV and irradiated 3T3 fibroblasts; of these, however, only matrigel and 3T3 fibroblasts had sustained significant effects on keratinocyte proliferation over 4 days. Cells on fibronectin showed significantly reduced proliferation. An acellular non-viable dermis was then used to mimic the homograft allodermis onto which cultured epithelial autograft sheets are grafted clinically and cells cultured on the various ECM proteins for 96 h were transferred to this in vitro wound model. None of the substrates enhanced keratinocyte performance on this model. It was concluded that under these conditions some ECM proteins can significantly affect keratinocyte attachment and, to a lesser extent, proliferation but that the culture of keratinocytes on these ECM proteins does not appear to confer any lasting benefit to the attachment of these keratinocytes to an in vitro wound-bed model.

Development and functional evaluation of biomimetic silicone surfaces with hierarchical micro/nano-topographical features demonstrates favourable in vitro foreign body response of breast-derived fibroblasts.

PubMed

Kyle, Daniel J T; Oikonomou, Antonios; Hill, Ernie; Bayat, Ardeshir

2015-06-01

Reproducing extracellular matrix topographical cues, such as those present within acellular dermal matrix (ADM), in synthetic implant surfaces, may augment cellular responses, independent of surface chemistry. This could lead to enhanced implant integration and performance while reducing complications. In this work, the hierarchical micro and nanoscale features of ADM were accurately and reproducibly replicated in polydimethylsiloxane (PDMS), using an innovative maskless 3D grayscale fabrication process not previously reported. Human breast derived fibroblasts (n=5) were cultured on PDMS surfaces and compared to commercially available smooth and textured silicone implant surfaces, for up to one week. Cell attachment, proliferation and cytotoxicity, in addition to immunofluorescence staining, SEM imaging, qRT-PCR and cytokine array were performed. ADM PDMS surfaces promoted cell adhesion, proliferation and survival (p=<0.05), in addition to increased focal contact formation and spread fibroblast morphology when compared to commercially available implant surfaces. PCNA, vinculin and collagen 1 were up-regulated in fibroblasts on biomimetic surfaces while IL8, TNFα, TGFβ1 and HSP60 were down-regulated (p=<0.05). A reduced inflammatory cytokine response was also observed (p=<0.05). This study represents a novel approach to the development of functionalised biomimetic prosthetic implant surfaces which were demonstrated to significantly attenuate the acute in vitro foreign body reaction to silicone. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chondrogenic potential of physically treated bovine cartilage matrix derived porous scaffolds on human dermal fibroblast cells.

PubMed

Moradi, Ali; Ataollahi, Forough; Sayar, Katayoun; Pramanik, Sumit; Chong, Pan-Pan; Khalil, Alizan Abdul; Kamarul, Tunku; Pingguan-Murphy, Belinda

2016-01-01

Extracellular matrices have drawn attention in tissue engineering as potential biomaterials for scaffold fabrication because of their bioactive components. Noninvasive techniques of scaffold fabrication and cross-linking treatments are believed to maintain the integrity of bioactive molecules while providing proper architectural and mechanical properties. Cartilage matrix derived scaffolds are designed to support the maintenance of chondrocytes and provide proper signals for differentiation of chondroinducible cells. Chondroinductive potential of bovine articular cartilage matrix derived porous scaffolds on human dermal fibroblasts and the effect of scaffold shrinkage on chondrogenesis were investigated. An increase in sulfated glycosaminoglycans production along with upregulation of chondrogenic genes confirmed that physically treated cartilage matrix derived scaffolds have chondrogenic potential on human dermal fibroblasts. © 2015 Wiley Periodicals, Inc.

Development and Characterization of Acellular Extracellular Matrix Scaffolds from Porcine Menisci for Use in Cartilage Tissue Engineering

PubMed Central

Chen, Ying-Chen; Chen, Ray-Neng; Jhan, Hua-Jing; Liu, Der-Zen; Ho, Hsiu-O; Mao, Yong; Kohn, Joachim

2015-01-01

Given the growing number of arthritis patients and the limitations of current treatments, there is great urgency to explore cartilage substitutes by tissue engineering. In this study, we developed a novel decellularization method for menisci to prepare acellular extracellular matrix (ECM) scaffolds with minimal adverse effects on the ECM. Among all the acid treatments, formic acid treatment removed most of the cellular contents and preserved the highest ECM contents in the decellularized porcine menisci. Compared with fresh porcine menisci, the content of DNA decreased to 4.10%±0.03%, and there was no significant damage to glycosaminoglycan (GAG) or collagen. Histological staining also confirmed the presence of ECM and the absence of cellularity. In addition, a highly hydrophilic scaffold with three-dimensional interconnected porous structure was fabricated from decellularized menisci tissue. Human chondrocytes showed enhanced cell proliferation and synthesis of chondrocyte ECM including type II collagen and GAG when cultured in this acellular scaffold. Moreover, the scaffold effectively supported chondrogenesis of human bone marrow-derived mesenchymal stem cells. Finally, in vivo implantation was conducted in rats to assess the biocompatibility of the scaffolds. No significant inflammatory response was observed. The acellular ECM scaffold provided a native environment for cells with diverse physiological functions to promote cell proliferation and new tissue formation. This study reported a novel way to prepare decellularized meniscus tissue and demonstrated the potential as scaffolds to support cartilage repair. PMID:25919905

Regeneration of the oesophageal muscle layer from oesophagus acellular matrix scaffold using adipose-derived stem cells.

PubMed

Wang, Fang; Maeda, Yasuko; Zachar, Vladimir; Ansari, Tahera; Emmersen, Jeppe

2018-06-14

This study explored the feasibility of constructing a tissue engineered muscle layer in the oesophagus using oesophageal acellular matrix (OAM) scaffolds and human aortic smooth muscle cells (hASMCs) or human adipose-derived stem cells (hASCs). The second objective was to investigate the effect of hypoxic preconditioning of seeding cells on cell viability and migration depth. Our results demonstrated that hASMCs and hASCs could attach and adhere to the decellularized OAM scaffold and survive and proliferate for at least 7 days depending on the growth conditions. This indicates adipose-derived stem cells (ASCs) have the potential to substitute for smooth muscle cells (SMCs) in the construction of tissue engineered oesophageal muscle layers. Copyright © 2018 Elsevier Inc. All rights reserved.

Acellularization-Induced Changes in Tensile Properties Are Organ Specific - An In-Vitro Mechanical and Structural Analysis of Porcine Soft Tissues

PubMed Central

Aust, Gabriela; Boldt, Andreas; Fritsch, Sebastian; Keil, Isabel; Koch, Holger; Möbius, Robert; Scheidt, Holger A.; Wagner, Martin F. X.; Hammer, Niels

2016-01-01

Introduction Though xenogeneic acellular scaffolds are frequently used for surgical reconstruction, knowledge of their mechanical properties is lacking. This study compared the mechanical, histological and ultrastructural properties of various native and acellular specimens. Materials and Methods Porcine esophagi, ureters and skin were tested mechanically in a native or acellular condition, focusing on the elastic modulus, ultimate tensile stress and maximum strain. The testing protocol for soft tissues was standardized, including the adaption of the tissue’s water content and partial plastination to minimize material slippage as well as templates for normed sample dimensions and precise cross-section measurements. The native and acellular tissues were compared at the microscopic and ultrastructural level with a focus on type I collagens. Results Increased elastic modulus and ultimate tensile stress values were quantified in acellular esophagi and ureters compared to the native condition. In contrast, these values were strongly decreased in the skin after acellularization. Acellularization-related decreases in maximum strain were found in all tissues. Type I collagens were well-preserved in these samples; however, clotting and a loss of cross-linking type I collagens was observed ultrastructurally. Elastins and fibronectins were preserved in the esophagi and ureters. A loss of the epidermal layer and decreased fibronectin content was present in the skin. Discussion Acellularization induces changes in the tensile properties of soft tissues. Some of these changes appear to be organ specific. Loss of cross-linking type I collagen may indicate increased mechanical strength due to decreasing transverse forces acting upon the scaffolds, whereas fibronectin loss may be related to decreased load-bearing capacity. Potentially, the alterations in tissue mechanics are linked to organ function and to the interplay of cells and the extracellular matrix, which is different in hollow organs when compared to skin. PMID:26960134

The acellular matrix (ACM) for bladder tissue engineering: A quantitative magnetic resonance imaging study.

PubMed

Cheng, Hai-Ling Margaret; Loai, Yasir; Beaumont, Marine; Farhat, Walid A

2010-08-01

Bladder acellular matrices (ACMs) derived from natural tissue are gaining increasing attention for their role in tissue engineering and regeneration. Unlike conventional scaffolds based on biodegradable polymers or gels, ACMs possess native biomechanical and many acquired biologic properties. Efforts to optimize ACM-based scaffolds are ongoing and would be greatly assisted by a noninvasive means to characterize scaffold properties and monitor interaction with cells. MRI is well suited to this role, but research with MRI for scaffold characterization has been limited. This study presents initial results from quantitative MRI measurements for bladder ACM characterization and investigates the effects of incorporating hyaluronic acid, a natural biomaterial useful in tissue-engineering and regeneration. Measured MR relaxation times (T(1), T(2)) and diffusion coefficient were consistent with increased water uptake and glycosaminoglycan content observed on biochemistry in hyaluronic acid ACMs. Multicomponent MRI provided greater specificity, with diffusion data showing an acellular environment and T(2) components distinguishing the separate effects of increased glycosaminoglycans and hydration. These results suggest that quantitative MRI may provide useful information on matrix composition and structure, which is valuable in guiding further development using bladder ACMs for organ regeneration and in strategies involving the use of hyaluronic acid.

Validation of in vitro assays in three-dimensional human dermal constructs.

PubMed

Idrees, Ayesha; Chiono, Valeria; Ciardelli, Gianluca; Shah, Siegfried; Viebahn, Richard; Zhang, Xiang; Salber, Jochen

2018-05-01

Three-dimensional cell culture systems are urgently needed for cytocompatibility testing of biomaterials. This work aimed at the development of three-dimensional in vitro dermal skin models and their optimization for cytocompatibility evaluation. Initially "murine in vitro dermal construct" based on L929 cells was generated, leading to the development of "human in vitro dermal construct" consisting of normal human dermal fibroblasts in rat tail tendon collagen type I. To assess the viability of the cells, different assays CellTiter-Blue ® , RealTime-Glo ™ MT, and CellTiter-Glo ® (Promega) were evaluated to optimize the best-suited assay to the respective cell type and three-dimensional system. Z-stack imaging (Live/Dead and Phalloidin/DAPI-Promokine) was performed to visualize normal human dermal fibroblasts inside matrix revealing filopodia-like morphology and a uniform distribution of normal human dermal fibroblasts in matrix. CellTiter-Glo was found to be the optimal cell viability assay among those analyzed. CellTiter-Blue reagent affected the cell morphology of normal human dermal fibroblasts (unlike L929), suggesting an interference with cell biological activity, resulting in less reliable viability data. On the other hand, RealTime-Glo provided a linear signal only with a very low cell density, which made this assay unsuitable for this system. CellTiter-Glo adapted to three-dimensional dermal construct by optimizing the "shaking time" to enhance the reagent penetration and maximum adenosine triphosphate release, indicating 2.4 times higher viability value by shaking for 60 min than for 5 min. In addition, viability results showed that cells were viable inside the matrix. This model would be further advanced with more layers of skin to make a full thickness model.

One-stage Reconstruction of Soft Tissue Defects with the Sandwich Technique: Collagen-elastin Dermal Template and Skin Grafts

PubMed Central

Wollina, Uwe

2011-01-01

Background: A full-thickness soft tissue defect closure often needs complex procedures. The use of dermal templates can be helpful in improving the outcome. Objective: The objective was to evaluate a sandwich technique combining the dermal collagen–elastin matrix with skin grafts in a one-stage procedure. Materials and Methods: Twenty-three patients with 27 wounds were enrolled in this prospective single-centre observational study. The mean age was 74.8 ± 17.2 years. Included were full-thickness defects with exposed bone, cartilage and/ or tendons. The dermal collagen–elastin matrix was applied onto the wound bed accomplished by skin transplants, i.e. ‘sandwich’ transplantation. In six wounds, the transplants were treated with intermittent negative pressure therapy. Results: The size of defects was ≤875 cm2. The use of the dermal template resulted in a complete and stable granulation in 100% of wounds. Seventeen defects showed a complete closure and 19 achieved a complete granulation with an incomplete closure. There was a marked pain relief. No adverse events were noted due to the dermal template usage. Conclusions: Sandwich transplantation with the collagen–elastin matrix is a useful tool when dealing with full-thickness soft tissue defects with exposed bone, cartilage or tendons. PMID:22279382

A single-arm trial indirect comparison investigation: a proof-of-concept method to predict venous leg ulcer healing time for a new acellular synthetic matrix matched to standard care control.

PubMed

Shannon, Ronald; Nelson, Andrea

2017-08-01

To compare data on time to healing from two separate cohorts: one treated with a new acellular synthetic matrix plus standard care (SC) and one matched from four large UK pragmatic, randomised controlled trials [venous leg ulcer (VLU) evidence network]. We introduce a new proof-of-concept strategy to a VLU clinical evidence network, propensity score matching and sensitivity analysis to predict the feasibility of the new acellular synthetic matrix plus SC for success in future randomised, controlled clinical trials. Prospective data on chronic VLUs from a safety and effectiveness study on an acellular synthetic matrix conducted in one wound centre in the UK (17 patients) and three wound centres in Australia (36 patients) were compared retrospectively to propensity score-matched data from patients with comparable leg ulcer disease aetiology, age, baseline ulcer area, ulcer duration, multi-layer compression bandaging and majority of care completed in specialist wound centres (average of 1 visit per week), with the outcome measures at comparable follow-up periods from patients enrolled in four prospective, multicentre, pragmatic, randomised studies of venous ulcers in the UK (the comparison group; VLU evidence network). Analysis using Kaplan-Meier survival curves showed a mean healing time of 73·1 days for ASM plus SC (ASM) treated ulcers in comparison with 83·5 days for comparison group ulcers treated with SC alone (Log rank test, χ 2 5·779, P = 0·016) within 12 weeks. Sensitivity analysis indicates that an unobserved covariate would have to change the odds of healing for SC by a factor of 1·1 to impact the baseline results. Results from this study predict a significant effect on healing time when using a new ASM as an adjunct to SC in the treatment of non-healing venous ulcers in the UK, but results are sensitive to unobserved covariates that may be important in healing time comparison. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

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

Tashiro, Kanae; Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka; Shishido, Mayumi

2014-01-03

Highlights: •Autophagosomes accumulate in aged dermal fibroblasts. •Autophagic degradation is impaired in aged dermal fibroblasts. •Autophagy disruption affects extracellular matrix components in dermal fibroblasts. -- Abstract: Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Westernmore » blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5—genes essential for autophagosome formation—was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.« less

Red light accelerates the formation of a human dermal equivalent.

PubMed

Oliveira, Anna Cb; Morais, Thayz Fl; Bernal, Claudia; Martins, Virginia Ca; Plepis, Ana Mg; Menezes, Priscila Fc; Perussi, Janice R

2018-04-01

Development of biomaterials' substitutes and/or equivalents to mimic normal tissue is a current challenge in tissue engineering. Thus, three-dimensional cell culture using type I collagen as a polymeric matrix cell support designed to promote cell proliferation and differentiation was employed to create a dermal equivalent in vitro, as well to evaluate the photobiomodulation using red light. Polymeric matrix cell support was prepared from porcine serous collagen (1.1%) hydrolyzed for 96 h. The biomaterial exhibited porosity of 95%, a median pore of 44 µm and channels with an average distance between the walls of 78 ± 14 µm. The absorption of culture medium was 95%, and the sponge showed no cytotoxicity to Vero cells, a non-tumor cell line. Additionally, it was observed that irradiation with light at 630 nm (fluency 30 J cm -2 ) leads to the cellular photobiomodulation in both monolayer and human dermal equivalent (three-dimensional cell culture system). It was also verified that the cells cultured in the presence of the polymeric matrix cell support, allows differentiation and extracellular matrix secretion. Therefore, the results showed that the collagen sponge used as polymeric matrix cell support and the photobiomodulation at 630 nm are efficient for the production of a reconstructed human dermal equivalent in vitro.

A novel model of acellular dermal matrix plug for anal fistula treatment. Report of a case and surgical consideration based on first utility in Poland.

PubMed

Bobkiewicz, Adam; Krokowicz, Łukasz; Borejsza-Wysocki, Maciej; Banasiewicz, Tomasz

2017-08-31

Anal fistula (AF) is a pathological connection between anus and skin in its surroundings. The main reason for the formation of anal fistula is a bacterial infection of the glands within the anal crypts. One of the modern techniques for the treatment of fistulas that do not interfere with the sphincters consists in implantation of a plug made from collagen material. We are presenting the first Polish experience with a new model of biomaterial plug for the treatment of anal fistula. We also point out key elements of the procedure (both preoperative and intraoperative) associated with this method. In the authors' opinion, the method is simple, safe and reproducible. Innovative shape of the plug minimizes the risk of its migration and rotation. It also perfectly blends with and adapts to the course and shape of the fistula canal, allowing it to become incorporated and overgrown with tissue in the fistula canal. The relatively short operation time, minor postoperative pain and faster convalescence are with no doubt additional advantages of the method. Long-term observation involving more patients is essential for evaluation of the efficacy of the treatment of fistulas with the new type of plug.

An acellular dermal matrix allograft (Alloderm®) for increasing keratinized attached gingiva: A case series

PubMed Central

Agarwal, Chitra; Kumar, Baron Tarun; Mehta, Dhoom Singh

2015-01-01

Context: Adequate amount of keratinized gingiva is necessary to keep gingiva healthy and free of inflammation. Autografts have been used for years with great success to increase the width of attached gingiva. Autografts, however, have the disadvantage of increasing postoperative morbidity and improper color match with the adjacent tissues. Alloderm® allograft has been introduced as an alternative to autografts to overcome these disadvantages. Aim: In this study, the efficacy of alloderm® in increasing the width of attached gingiva and the stability of gained attached gingiva was evaluated clinically. Materials and Methods: Five patients with sites showing inadequate width of attached gingiva (≤1 mm) were enrolled for the study. The width of keratinized gingiva and other clinical parameters were recorded at baseline and 9th month postoperatively. Result: In all cases, there is the average increase of about 2.5 mm of attached gingiva and was maintained for 9-month. Percentage shrinkage of the graft is about 75% at the end of 3rd month in all cases. Excellent colors match with adjacent tissue has been obtained. Conclusion: The study signifies that Alloderm® results in an adequate increase in the amount of attached gingiva and therefore can be used successfully in place of autografts. PMID:26015676

Coverage of Deep Cutaneous Wounds Using Dermal Template in Combination with Negative-pressure Therapy and Subsequent Skin Graft

PubMed Central

Chang, Alexandre A.; Lobato, Rodolfo C.; Nakamoto, Hugo A.; Tuma, Paulo; Ferreira, Marcus C.

2014-01-01

Background: We consider the use of dermal matrix associated with a skin graft to cover deep wounds in the extremities when tendon and bone are exposed. The objective of this article was to evaluate the efficacy of covering acute deep wounds through the use of a dermal regeneration template (Integra) associated with vacuum therapy and subsequent skin grafting. Methods: Twenty patients were evaluated prospectively. All of them had acute (up to 3 weeks) deep wounds in the limbs. We consider a deep wound to be that with exposure of bone, tendon, or joint. Results: The average area of integration of the dermal regeneration template was 86.5%. There was complete integration of the skin graft over the dermal matrix in 14 patients (70%), partial integration in 5 patients (25%), and total loss in 1 case (5%). The wound has completely closed in 95% of patients. Conclusions: The use of Integra dermal template associated with negative-pressure therapy and skin grafting showed an adequate rate of resolution of deep wounds with low morbidity. PMID:25289363

Effect of gel re-organization and tensional forces on alpha2beta1 integrin levels in dermal fibroblasts.

PubMed

Jenkins, G; Redwood, K L; Meadows, L; Green, M R

1999-07-01

Mechanical forces are known to play an important role in regulating cell function in a wide range of biological systems. This is of particular relevance to dermal fibroblast function, given that the skin is known to be held under an intrinsic natural tension. To understand more about the generation of force by dermal fibroblasts and their ability to respond to changes in it, we have studied the role of the beta1 integrin receptors expressed by dermal fibroblasts in their ability to generate tensional forces within a collagen type I matrix and the effect of altered tensional force on integrin expression by dermal fibroblasts. Using a purpose-built culture force monitor, function-blocking antibodies directed towards the beta1 receptors dramatically reduced the tensional forces generated by dermal fibroblasts in a 3D collagen I matrix. However, the specific involvement of alpha1 or alpha2 subunits could not be demonstrated. Analysis of cellular response demonstrated that cells isolated from contracting collagen gels expressed fourfold higher levels of alpha2 mRNA than cells isolated from fully restrained gels. The levels of beta1 messenger RNA were relatively unaffected by reductions in force. Cells exposed to single reductions in force, however, did not exhibit alterations in either alpha1 or beta1 mRNA levels. We propose, therefore that alpha2beta1 integrin receptor levels in dermal fibroblasts are not altered in response to single reductions of gel tension, but do change following a continual change in force and associated matrix re-organization

Evaluation of the efficacy of keratinized mucosa augmentation techniques around dental implants: a systematic review.

PubMed

Wu, Qingqing; Qu, Yili; Gong, Ping; Wang, Tianlu; Gong, Ting; Man, Yi

2015-05-01

The absence of periimplant keratinized mucosa is considered risky in patients with a predisposition to periodontitis or recession. Although various soft tissue augmentation techniques exist, dentists are seeking for more efficient approaches to augment periimplant keratinized mucosa. The purpose of this systematic review was to evaluate the efficacy of the various techniques and biomaterials adopted in periimplant keratinized mucosa augmentation and whether one technique or biomaterial is superior. A search in Medline-PubMed and the Cochrane Central Register of controlled trials was conducted. Randomized clinical trials, prospective cohort studies, clinical control studies, and case series from January 1, 1980, to December 31, 2013, with a follow-up of at least 6 months reporting changes on keratinized mucosa width were included. Several journals were hand-searched for related articles. The bibliographies of all publications selected for inclusion were also scanned. The screening of titles and abstracts resulted in 60 relevant publications. Six of them were finally included. Free gingival graft, connective tissue graft, acellular dermal matrix, and collagen matrix were used for keratinized mucosa augmentation. Because of heterogeneity of the studies, only descriptive analysis was performed. Improvements in keratinized mucosa width were reported in all studies. A definitive conclusion could not be achieved owing to the lack of well-designed studies and appropriate methods of studying soft tissue. The establishment of universal surgical guidelines and measurement systems is imperative in the future. Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Clinical applications of decellularized extracellular matrices for tissue engineering and regenerative medicine.

PubMed

Parmaksiz, Mahmut; Dogan, Arin; Odabas, Sedat; Elçin, A Eser; Elçin, Y Murat

2016-03-17

Decellularization is the process of removing the cellular components from tissues or organs. It is a promising technology for obtaining a biomaterial with a highly preserved extracellular matrix (ECM), which may also act as a biological scaffold for tissue engineering and regenerative therapies. Decellularized products are gaining clinical importance and market space due to their ease of standardized production, constant availability for grafting and mechanical or biochemical superiority against competing clinical options, yielding clinical results ahead of the ones with autografts in some applications. Current drawbacks and limitations of traditional treatments and clinical applications can be overcome by using decellularized or acellular matrices. Several companies are leading the market with versatile acellular products designed for diverse use in the reconstruction of tissues and organs. This review describes ECM-based decellularized and acellular products that are currently in use for different branches of clinic.

Gene Expression Profiling of the Intact Dermal Sheath Cup of Human Hair Follicles.

PubMed

Niiyama, Shiro; Ishimatsu-Tsuji, Yumiko; Nakazawa, Yosuke; Yoshida, Yuzo; Soma, Tsutomu; Ideta, Ritsuro; Mukai, Hideki; Kishimoto, Jiro

2018-04-24

Cells that constitute the dermal papillae of hair follicles might be derived from the dermal sheath, the peribulbar component of which is the dermal sheath cup. The dermal sheath cup is thought to include the progenitor cells of the dermal papillae and possesses hair inductive potential; however, it has not yet been well characterized. This study investigated the gene expression profile of the intact dermal sheath cup, and identified dermal sheath cup signature genes, including extracellular matrix components and BMP-binding molecules, as well as TGF-b1 as an upstream regulator. Among these, GREM2, a member of the BMP antagonists, was found by in situ hybridization to be highly specific to the dermal sheath cup, implying that GREM2 is a key molecule contributing to maintenance of the properties of the dermal sheath cup.

Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart.

PubMed

Ott, Harald C; Matthiesen, Thomas S; Goh, Saik-Kia; Black, Lauren D; Kren, Stefan M; Netoff, Theoden I; Taylor, Doris A

2008-02-01

About 3,000 individuals in the United States are awaiting a donor heart; worldwide, 22 million individuals are living with heart failure. A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Generating a bioartificial heart requires engineering of cardiac architecture, appropriate cellular constituents and pump function. We decellularized hearts by coronary perfusion with detergents, preserved the underlying extracellular matrix, and produced an acellular, perfusable vascular architecture, competent acellular valves and intact chamber geometry. To mimic cardiac cell composition, we reseeded these constructs with cardiac or endothelial cells. To establish function, we maintained eight constructs for up to 28 d by coronary perfusion in a bioreactor that simulated cardiac physiology. By day 4, we observed macroscopic contractions. By day 8, under physiological load and electrical stimulation, constructs could generate pump function (equivalent to about 2% of adult or 25% of 16-week fetal heart function) in a modified working heart preparation.

Matrix-directed differentiation of human adipose-derived mesenchymal stem cells to dermal-like fibroblasts that produce extracellular matrix.

PubMed

Sivan, Unnikrishnan; Jayakumar, K; Krishnan, Lissy K

2016-10-01

Commercially available skin substitutes lack essential non-immune cells for adequate tissue regeneration of non-healing wounds. A tissue-engineered, patient-specific, dermal substitute could be an attractive option for regenerating chronic wounds, for which adipose-derived mesenchymal stem cells (ADMSCs) could become an autologous source. However, ADMSCs are multipotent in nature and may differentiate into adipocytes, osteocytes and chondrocytes in vitro, and may develop into undesirable tissues upon transplantation. Therefore, ADMSCs committed to the fibroblast lineage could be a better option for in vitro or in vivo skin tissue engineering. The objective of this study was to standardize in vitro culture conditions for ADMSCs differentiation into dermal-like fibroblasts which can synthesize extracellular matrix (ECM) proteins. Biomimetic matrix composite, deposited on tissue culture polystyrene (TCPS), and differentiation medium (DM), supplemented with fibroblast-conditioned medium and growth factors, were used as a fibroblast-specific niche (FSN) for cell culture. For controls, ADMSCs were cultured on bare TCPS with either DM or basal medium (BM). Culture of ADMSCs on FSN upregulated the expression of differentiation markers such as fibroblast-specific protein-1 (FSP-1) and a panel of ECM molecules specific to the dermis, such as fibrillin-1, collagen I, collagen IV and elastin. Immunostaining showed the deposition of dermal-specific ECM, which was significantly higher in FSN compared to control. Fibroblasts derived from ADMSCs can synthesize elastin, which is an added advantage for successful skin tissue engineering as compared to fibroblasts from skin biopsy. To obtain rapid differentiation of ADMSCs to dermal-like fibroblasts for regenerative medicine, a matrix-directed differentiation strategy may be employed. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Porosity of porcine bladder acellular matrix: impact of ACM thickness.

PubMed

Farhat, Walid; Chen, Jun; Erdeljan, Petar; Shemtov, Oren; Courtman, David; Khoury, Antoine; Yeger, Herman

2003-12-01

The objectives of this study are to examine the porosity of bladder acellular matrix (ACM) using deionized (DI) water as the model fluid and dextran as the indicator macromolecule, and to correlate the porosity to the ACM thickness. Porcine urinary bladders from pigs weighing 20-50 kg were sequentially extracted in detergent containing solutions, and to modify the ACM thickness, stretched bladders were acellularized in the same manner. Luminal and abluminal ACM specimens were subjected to fixed static DI water pressure (10 cm); and water passing through the specimens was collected at specific time interval. While for the macromolecule porosity testing, the diffusion rate and direction of 10,000 MW fluoroescein-labeled dextrans across the ACM specimens mounted in Ussing's chambers were measured. Both experiments were repeated on the thin stretched ACM. In both ACM types, the fluid porosity in both directions did not decrease with increased test duration (3 h); in addition, the abluminal surface was more porous to fluid than the luminal surface. On the other hand, when comparing thin to thick ACM, the porosity in either direction was higher in the thick ACM. Macromolecule porosity, as measured by absorbance, was higher for the abluminal thick ACM than the luminal side, but this characteristic was reversed in the thin ACM. Comparing thin to thick ACM, the luminal side in the thin ACM was more porous to dextran than in the thick ACM, but this characteristic was reversed for the abluminal side. The porcine bladder ACM possesses directional porosity and acellularizing stretched urinary bladders may increase structural density and alter fluid and macromolecule porosity. Copyright 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 970-974, 2003

Decellularized Diaphragmatic Muscle Drives a Constructive Angiogenic Response In Vivo.

PubMed

Alvarèz Fallas, Mario Enrique; Piccoli, Martina; Franzin, Chiara; Sgrò, Alberto; Dedja, Arben; Urbani, Luca; Bertin, Enrica; Trevisan, Caterina; Gamba, Piergiorgio; Burns, Alan J; De Coppi, Paolo; Pozzobon, Michela

2018-04-28

Skeletal muscle tissue engineering (TE) aims to efficiently repair large congenital and acquired defects. Biological acellular scaffolds are considered a good tool for TE, as decellularization allows structural preservation of tissue extracellular matrix (ECM) and conservation of its unique cytokine reservoir and the ability to support angiogenesis, cell viability, and proliferation. This represents a major advantage compared to synthetic scaffolds, which can acquire these features only after modification and show limited biocompatibility. In this work, we describe the ability of a skeletal muscle acellular scaffold to promote vascularization both ex vivo and in vivo. Specifically, chicken chorioallantoic membrane assay and protein array confirmed the presence of pro-angiogenic molecules in the decellularized tissue such as HGF, VEGF, and SDF-1α. The acellular muscle was implanted in BL6/J mice both subcutaneously and ortotopically. In the first condition, the ECM-derived scaffold appeared vascularized 7 days post-implantation. When the decellularized diaphragm was ortotopically applied, newly formed blood vessels containing CD31⁺, αSMA⁺, and vWF⁺ cells were visible inside the scaffold. Systemic injection of Evans Blue proved function and perfusion of the new vessels, underlying a tissue-regenerative activation. On the contrary, the implantation of a synthetic matrix made of polytetrafluoroethylene used as control was only surrounded by vWF⁺ cells, with no cell migration inside the scaffold and clear foreign body reaction (giant cells were visible). The molecular profile and the analysis of macrophages confirmed the tendency of the synthetic scaffold to enhance inflammation instead of regeneration. In conclusion, we identified the angiogenic potential of a skeletal muscle-derived acellular scaffold and the pro-regenerative environment activated in vivo, showing clear evidence that the decellularized diaphragm is a suitable candidate for skeletal muscle tissue engineering and regeneration.

Enhanced secretion of TIMP-1 by human hypertrophic scar keratinocytes could contribute to fibrosis.

PubMed

Simon, Franck; Bergeron, Daniele; Larochelle, Sébastien; Lopez-Vallé, Carlos A; Genest, Hervé; Armour, Alexis; Moulin, Véronique J

2012-05-01

Hypertrophic scars are a pathological process characterized by an excessive deposition of extracellular matrix components. Using a tissue-engineered reconstructed human skin (RHS) method, we previously reported that pathological keratinocytes induce formation of a fibrotic dermal matrix. We further investigated keratinocyte action using conditioned media. Results showed that conditioned media induce a similar action on dermal thickness similar to when an epidermis is present. Using a two-dimensional electrophoresis technique, we then compared conditioned media from normal or hypertrophic scar keratinocytes and determined that TIMP-1 was increased in conditioned media from hypertrophic scar keratinocytes. This differential profile was confirmed using ELISA, assaying TIMP-1 presence on media from monolayer cultured keratinocytes and from RHS. The dermal matrix of these RHS was recreated using mesenchymal cells from three different origins (skin, wound and hypertrophic scar). The effect of increased TIMP-1 levels on dermal fibrosis was also validated independently from the mesenchymal cell origin. Immunodetection of TIMP-1 showed that this protein was increased in the epidermis of hypertrophic scar biopsies. The findings of this study represent an important advance in understanding the role of keratinocytes as a direct potent modulator for matrix degradation and scar tissue remodeling, possibly through inactivation of MMPs. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

Decellularised skeletal muscles allow functional muscle regeneration by promoting host cell migration.

PubMed

Urciuolo, Anna; Urbani, Luca; Perin, Silvia; Maghsoudlou, Panagiotis; Scottoni, Federico; Gjinovci, Asllan; Collins-Hooper, Henry; Loukogeorgakis, Stavros; Tyraskis, Athanasios; Torelli, Silvia; Germinario, Elena; Fallas, Mario Enrique Alvarez; Julia-Vilella, Carla; Eaton, Simon; Blaauw, Bert; Patel, Ketan; De Coppi, Paolo

2018-05-30

Pathological conditions affecting skeletal muscle function may lead to irreversible volumetric muscle loss (VML). Therapeutic approaches involving acellular matrices represent an emerging and promising strategy to promote regeneration of skeletal muscle following injury. Here we investigated the ability of three different decellularised skeletal muscle scaffolds to support muscle regeneration in a xenogeneic immune-competent model of VML, in which the EDL muscle was surgically resected. All implanted acellular matrices, used to replace the resected muscles, were able to generate functional artificial muscles by promoting host myogenic cell migration and differentiation, as well as nervous fibres, vascular networks, and satellite cell (SC) homing. However, acellular tissue mainly composed of extracellular matrix (ECM) allowed better myofibre three-dimensional (3D) organization and the restoration of SC pool, when compared to scaffolds which also preserved muscular cytoskeletal structures. Finally, we showed that fibroblasts are indispensable to promote efficient migration and myogenesis by muscle stem cells across the scaffolds in vitro. This data strongly support the use of xenogeneic acellular muscles as device to treat VML conditions in absence of donor cell implementation, as well as in vitro model for studying cell interplay during myogenesis.

Endothelial network formed with human dermal microvascular endothelial cells in autologous multicellular skin substitutes.

PubMed

Ponec, Maria; El Ghalbzouri, Abdoelwaheb; Dijkman, Remco; Kempenaar, Johanna; van der Pluijm, Gabri; Koolwijk, Pieter

2004-01-01

A human skin equivalent from a single skin biopsy harboring keratinocytes and melanocytes in the epidermal compartment, and fibroblasts and microvascular dermal endothelial cells in the dermal compartment was developed. The results of the study revealed that the nature of the extracellular matrix of the dermal compartments plays an important role in establishment of endothelial network in vitro. With rat-tail type I collagen matrices only lateral but not vertical expansion of endothelial networks was observed. In contrast, the presence of extracellular matrix of entirely human origin facilitated proper spatial organization of the endothelial network. Namely, when human dermal fibroblasts and microvascular endothelial cells were seeded on the bottom of an inert filter and subsequently epidermal cells were seeded on top of it, fibroblasts produced extracellular matrix throughout which numerous branched tubes were spreading three-dimensionally. Fibroblasts also facilitated the formation of basement membrane at the epidermal/matrix interface. Under all culture conditions, fully differentiated epidermis was formed with numerous melanocytes present in the basal epidermal cell layer. The results of the competitive RT-PCR revealed that both keratinocytes and fibroblasts expressed VEGF-A, -B, -C, aFGF and bFGF mRNA, whereas fibroblasts also expressed VEGF-D mRNA. At protein level, keratinocytes produced 10 times higher amounts of VEGF-A than fibroblasts did. The generation of multicellular skin equivalent from a single human skin biopsy will stimulate further developments for its application in the treatment of full-thickness skin defects. The potential development of biodegradable, biocompatible material suitable for these purposes is a great challenge for future research.

Synthesis and characterization of injectable, thermosensitive, and biocompatible acellular bone matrix/poly(ethylene glycol)-poly (ε-caprolactone)-poly(ethylene glycol) hydrogel composite.

PubMed

Ni, Pei-Yan; Fan, Min; Qian, Zhi-Yong; Luo, Jing-Cong; Gong, Chang-Yang; Fu, Shao-Zhi; Shi, Shuai; Luo, Feng; Yang, Zhi-Ming

2012-01-01

In orthopedic tissue engineering, the extensively applied acellular bone matrix (ABM) can seldom be prefabricated just right to mold the cavity of the diverse defects, might induce severe inflammation on account of the migration of small granules and usually bring the patients great pain in the treatment. In this study, a new injectable thermosensitive ABM/PECE composite with good biocompatibility was designed and prepared by adding the ABM granules into the triblock copolymer poly(ethylene eglycol)-poly(ε-caprolactone)-poly(ethylene eglycol) (PEG-PCL-PEG, PECE). The PECE was synthesized by ring-opening copolymerization and characterized by ¹H NMR. The ABM was prepared by acellular treatment of natural bone and ground to fine granules. The obtained ABM/PECE composite showed the most important absorption bands of ABM and PECE copolymer in FT-IR spectroscopy and underwent sol-gel phage transition from solution to nonflowing hydrogel at 37°C. SEM results indicated that the ABM/PECE composite with different ABM contents all presented similar porous 3D structure. ABM/PECE composite presented mild cytotoxicity to rat MSCs in vitro and good biocompatibility in the BALB/c mice subcutis up to 4 weeks. In conclusion, all the results confirmed that the injectable thermosensitive ABM/PECE composite was a promising candidate for orthopedic tissue engineering in a minimally-invasive way. Copyright © 2011 Wiley Periodicals, Inc.

Microencapsulated VEGF gene-modified umbilical cord mesenchymal stromal cells promote the vascularization of tissue-engineered dermis: an experimental study.

PubMed

Han, Yanfu; Tao, Ran; Han, Yanqing; Sun, Tianjun; Chai, Jiake; Xu, Guang; Liu, Jing

2014-02-01

Tissue-engineered dermis (TED) is thought to be the best treatment for skin defect wounds; however, lack of vascular structures in these products can cause slow vascularization or even transplant failure. We assessed the therapeutic potential of microencapsulated human umbilical cord mesenchymal stromal cells (hUCMSCs) expressing vascular endothelial growth factor (VEGF) in vascularization of TED. hUCMSCs were isolated by means of enzymatic digestion and identified by means of testing biological characteristics. hUCMSCs were induced to differentiate into dermal fibroblasts in conditioned induction media. Collagen-chitosan laser drilling acellular dermal matrix (ADM) composite scaffold was prepared by means of the freeze dehydration and dehydrothermal cross-linking method. hUCMSC-derived fibroblasts were implanted on composite scaffolds to construct TED. TED with microencapsulated VEGF gene-modified hUCMSCs was then transplanted into skin defect wounds in pigs. The angiogenesis of TED at 1 week and status of wound healing at 3 weeks were observed. The collagen-chitosan laser ADM composite has a uniform microporous structure. This composite has been used to grow hUCMSC-derived fibroblasts in vitro and to successfully construct stem cell-derived TED. Microencapsulated VEGF gene-modified hUCMSCs were prepared with the use of a sodium alginate-barium chloride one-step encapsulation technology. Seven days after the transplantation of the stem cell-derived TED and microencapsulated VEGF gene-modified hUCMSCs into the skin defect wounds on the backs of miniature pigs, the VEGF expression increased and the TED had a higher degree of vascularization. Re-epithelialization of the wound was completed after 3 weeks. Microencapsulated VEGF gene-modified hUCMSCs can effectively improve the vascularization of TED and consequently the quality of wound healing. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Role of acellular collagen matrix surgisis in the endoscopic management of ureteropelvic junction obstruction.

PubMed

Yohannes, Paulos; Rotariu, Paul; Liatsikos, Evangelos; Malik, Aftab; Alexianu, Mihai; Pinkasov, David; Morgenstern, Nora; Lee, Benjamin R; Smith, Arthur D

2002-10-01

To investigate the role of acellular collagen matrix (Surgisis during endopyelotomy. Nine female pigs (25-35 kg) were enrolled in our protocol. The pigs were categorized as follows. Group I (N = 3) had endopyelotomy + insertion of SIS, Group II (N = 3) creation of UPJ stricture + endopyelotomy + insertion of SIS, and Group III (N = 3) Davis intubated ureterotomy using SIS. The contralateral side served as a control for each group (one pig in each group). In three pigs (two in Group III and one in Group II), Surgisis was treated with India ink prior to insertion at the endopyelotomy site. An endopyelotomy stent (14/8 F x 24 cm) was used to stent the ureteropelvic junction (UPJ) for 4 weeks. Four weeks after the stent was removed, laparoscopic nephroureterectomy was performed, and the animals were euthanized. Histopathologic analysis of the Surgisis-regenerated segment of the UPJ was performed using hematoxylin and eosin, reticular (collagen), smooth muscle actin, and S-100 (nerve) stains. All animals tolerated the procedure. The mean operative time was 162 minutes. One pig (Group II) developed pyonephrosis; one pig (Group III) developed significant ascites and was sacrificed 2 week before the end of the experiment. Histopathologic analysis showed complete epithelializaton at 8 weeks. Reticular stain demonstrated abundant collagen matrix in the submucosa. Smooth muscle staining revealed myofibroblastic proliferation within the SIS-regenerated tissue adjacent to disorganized smooth muscle cells. India ink-stained SIS-regenerated tissue did not show smooth muscle cells. The S-100 stain did not demonstrate neurons at 8 weeks; however, in three pigs, peristaltic activity was noted across the UPJ. The use of acellular collagen matrix in the endoscopic management of UPJ obstruction is a promising technique. The abundance of myofibroblasts and absence of abundant smooth muscle regeneration indicates a need to investigate the role of growth factors in SIS regeneration of host tissue.

Human dermal and gingival fibroblasts in a three-dimensional culture: a comparative study on matrix remodeling.

PubMed

Chaussain Miller, C; Septier, D; Bonnefoix, M; Lecolle, S; Lebreton-Decoster, C; Coulomb, B; Pellat, B; Godeau, G

2002-03-01

Free-floating collagen lattice is considered a useful tool for assessing wound healing in vitro. This work compared extracellular matrix remodeling in collagen lattices populated by gingival or dermal fibroblasts. For 21 days we followed gel contraction and changes in cell number of collagen lattices seeded with l.5 x 10(5) fibroblasts of each tissue. We also used indirect immunodetection to study extracellular matrix components, metalloproteinases (MMPs), and their tissues inhibitors (TIMPs). In addition, the presence of MMPs and TIMPs in the culture media was analyzed by zymography and western blotting. No significant difference was found concerning gel contraction and changes in cell number. We observed the early expression of fibrillin I and collagen type III, apparently codistributed and at the end of the gel contraction their disappearance. Concomitantly we demonstrated the expression of MMPs and TIMPs, initially localized in cellular cytoplasm, then spreading in the extracellular compartment, and even found in the culture medium. This remodeling was more rapid and intense with gingival fibroblasts than dermal fibroblasts. In conclusion, gingival fibroblasts seem more efficient at remodeling the connective tissue than dermal fibroblasts and could lead to the better wound healing observed in vivo.

Three-Dimensional In Vitro Skin and Skin Cancer Models Based on Human Fibroblast-Derived Matrix.

PubMed

Berning, Manuel; Prätzel-Wunder, Silke; Bickenbach, Jackie R; Boukamp, Petra

2015-09-01

Three-dimensional in vitro skin and skin cancer models help to dissect epidermal-dermal and tumor-stroma interactions. In the model presented here, normal human dermal fibroblasts isolated from adult skin self-assembled into dermal equivalents with their specific fibroblast-derived matrix (fdmDE) over 4 weeks. The fdmDE represented a complex human extracellular matrix that was stabilized by its own heterogeneous collagen fiber meshwork, largely resembling a human dermal in vivo architecture. Complemented with normal human epidermal keratinocytes, the skin equivalent (fdmSE) thereof favored the establishment of a well-stratified and differentiated epidermis and importantly allowed epidermal regeneration in vitro for at least 24 weeks. Moreover, the fdmDE could be used to study the features of cutaneous skin cancer. Complementing fdmDE with HaCaT cells in different stages of malignancy or tumor-derived cutaneous squamous cell carcinoma cell lines, the resulting skin cancer equivalents (fdmSCEs) recapitulated the respective degree of tumorigenicity. In addition, the fdmSCE invasion phenotypes correlated with their individual degree of tissue organization, disturbance in basement membrane organization, and presence of matrix metalloproteinases. Together, fdmDE-based models are well suited for long-term regeneration of normal human epidermis and, as they recapitulate tumor-specific growth, differentiation, and invasion profiles of cutaneous skin cancer cells, also provide an excellent human in vitro skin cancer model.

Oral Supplementation with Cocoa Extract Reduces UVB-Induced Wrinkles in Hairless Mouse Skin.

PubMed

Kim, Jong-Eun; Song, Dasom; Kim, Junil; Choi, Jina; Kim, Jong Rhan; Yoon, Hyun-Sun; Bae, Jung-Soo; Han, Mira; Lee, Sein; Hong, Ji Sun; Song, Dayoung; Kim, Seong-Jin; Son, Myoung-Jin; Choi, Sang-Woon; Chung, Jin Ho; Kim, Tae-Aug; Lee, Ki Won

2016-05-01

Cacao beans contain various bioactive phytochemicals that could modify the pathogeneses of certain diseases. Here, we report that oral administration of cacao powder (CP) attenuates UVB-induced skin wrinkling by the regulation of genes involved in dermal matrix production and maintenance. Transcriptome analysis revealed that 788 genes are down- or upregulated in the CP supplemented group, compared with the UVB-irradiated mouse skin controls. Among the differentially expressed genes, cathepsin G and serpin B6c play important roles in UVB-induced skin wrinkle formation. Gene regulatory network analysis also identified several candidate regulators responsible for the protective effects of CP supplementation against UVB-induced skin damage. CP also elicited antiwrinkle effects via inhibition of UVB-induced matrix metalloproteinases-1 expression in both the human skin equivalent model and human dermal fibroblasts. Inhibition of UVB-induced activator protein-1 via CP supplementation is likely to affect the expression of matrix metalloproteinases-1. CP supplementation also downregulates the expression of cathepsin G in human dermal fibroblasts. 5-(3',4'-Dihydroxyphenyl)-γ-valerolactone, a major in vivo metabolite of CP, showed effects similar to CP supplementation. These results suggest that cacao extract may offer a protective effect against photoaging by inhibiting the breakdown of dermal matrix, which leads to an overall reduction in wrinkle formation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.

PubMed

Wang, Z J; An, R Z; Zhao, J Y; Zhang, Q; Yang, J; Wang, J B; Wen, G Y; Yuan, X H; Qi, X W; Li, S J; Ye, X C

2014-06-18

After injury, inflammation, or degeneration, articular cartilage has limited self-repair ability. We aimed to explore the feasibility of repair of articular cartilage defects with tissue-engineered cartilage constructed by acellular cartilage matrices (ACMs) seeded with adipose-derived stem cells (ADSCs). The ADSCs were isolated from 3-month-old New Zealand albino rabbit by using collagenase and cultured and amplified in vitro. Fresh cartilage isolated from adult New Zealand albino rabbit were freeze-dried for 12 h and treated with Triton X-100, DNase, and RNase to obtain ACMs. ADSCs were seeded in the acellular cartilaginous matrix at 2x10(7)/mL, and cultured in chondrogenic differentiation medium for 2 weeks to construct tissue-engineered cartilage. Twenty-four New Zealand white rabbits were randomly divided into A, B, and C groups. Engineered cartilage was transplanted into cartilage defect position of rabbits in group A, group B obtained ACMs, and group C did not receive any transplants. The rabbits were sacrificed in week 12. The restored tissue was evaluated using macroscopy, histology, immunohistochemistry, and transmission electron microscopy (TEM). In the tissue-engineered cartilage group (group A), articular cartilage defects of the rabbits were filled with chondrocyte-like tissue with smooth surface. Immunohistochemistry showed type II-collagen expression and Alcian blue staining was positive. TEM showed chondrocytes in the recesses, with plenty of secretary matrix particles. In the scaffold group (group B), the defect was filled with fibrous tissue. No repaired tissue was found in the blank group (group C). Tissue-engineered cartilage using ACM seeded with ADSCs can help repair articular cartilage defects in rabbits.

Acellular organ scaffolds for tumor tissue engineering

NASA Astrophysics Data System (ADS)

Guller, Anna; Trusova, Inna; Petersen, Elena; Shekhter, Anatoly; Kurkov, Alexander; Qian, Yi; Zvyagin, Andrei

2015-12-01

Rationale: Tissue engineering (TE) is an emerging alternative approach to create models of human malignant tumors for experimental oncology, personalized medicine and drug discovery studies. Being the bottom-up strategy, TE provides an opportunity to control and explore the role of every component of the model system, including cellular populations, supportive scaffolds and signalling molecules. Objectives: As an initial step to create a new ex vivo TE model of cancer, we optimized protocols to obtain organ-specific acellular matrices and evaluated their potential as TE scaffolds for culture of normal and tumor cells. Methods and results: Effective decellularization of animals' kidneys, ureter, lungs, heart, and liver has been achieved by detergent-based processing. The obtained scaffolds demonstrated biocompatibility and growthsupporting potential in combination with normal (Vero, MDCK) and tumor cell lines (C26, B16). Acellular scaffolds and TE constructs have been characterized and compared with morphological methods. Conclusions: The proposed methodology allows creation of sustainable 3D tumor TE constructs to explore the role of organ-specific cell-matrix interaction in tumorigenesis.

Hybrid Carbon-Based Scaffolds for Applications in Soft Tissue Reconstruction

PubMed Central

Lafdi, Khalid; Joseph, Robert M.; Tsonis, Panagiotis A.

2012-01-01

Current biomedical scaffolds utilized in surgery to repair soft tissues commonly fail to meet the optimal combination of biomechanical and tissue regenerative properties. Carbon is a scaffold alternative that potentially optimizes the balance between mechanical strength, durability, and function as a cell and biologics delivery vehicle that is necessary to restore tissue function while promoting tissue repair. The goals of this study were to investigate the feasibility of fabricating hybrid fibrous carbon scaffolds modified with biopolymer, polycaprolactone and to analyze their mechanical properties and ability to support cell growth and proliferation. Environmental scanning electron microscopy, micro-computed tomography, and cell adhesion and cell proliferation studies were utilized to test scaffold suitability as a cell delivery vehicle. Mechanical properties were tested to examine load failure and elastic modulus. Results were compared to an acellular dermal matrix scaffold control (GraftJacket® [GJ] Matrix), selected for its common use in surgery for the repair of soft tissues. Results indicated that carbon scaffolds exhibited similar mechanical maximums and capacity to support fibroblast adhesion and proliferation in comparison with GJ. Fibroblast adhesion and proliferation was collinear with carbon fiber orientation in regions of sparsely distributed fibers and occurred in clusters in regions of higher fiber density and low porosity. Overall, fibroblast adhesion and proliferation was greatest in lower porosity carbon scaffolds with highly aligned fibers. Stepwise multivariate regression showed that the variability in maximum load of carbon scaffolds and controls were dependent on unique and separate sets of parameters. These finding suggested that there were significant differences in the functional implications of scaffold design and material properties between carbon and dermis derived scaffolds that affect scaffold utility as a tissue replacement construct. PMID:22092333

[Hair growth effect of minoxidil].

PubMed

Otomo, Susumu

2002-03-01

The length and size of hair are depend on the anagen term in its hair cycle. It has been reported that the some cell growth factors, such as VEGF, FGF-5S, IGF-1 and KGF, induce the proliferation of cells in the matrix, dermal papilla and dermal papillary vascular system and increase the amount of extra cellular matrix in dermal papilla and then maintain follicles in the anagen phase. On the other hand, negative factors, like FGF-5, thrombospondin, or still unknown ones, terminate the anagen phase. If the negative factors become dominant against cell proliferation factors according to fulfilling some time set by the biological clock for hair follicles, TGF beta induced in the matrix tissues evokes apoptosis of matrix cells and shifts the follicles from anagen to catagen. Androgenetic alopecia is caused by miniaturizing of hair follicles located in the frontal or crown part of scalp and are hereditarily more sensitive to androgen. In their hair cycles, the androgen shortens the anagen phase of follicles and shifts them to the catagen phase earlier than usual. The mode of action of hair growth effect of minoxidil is not completely elucidated, but the most plausible explanation proposed here is that minoxidil works as a sulfonylurea receptor (SUR) activator and prolongs the anagen phase of hair follicles in the following manner: minoxidil (1) induces cell growth factors such as VEGF, HGF, IGF-1 and potentiates HGF and IGF-1 actions by the activation of uncoupled SUR on the plasma membrane of dermal papilla cells, (2) inhibits of TGF beta induced apoptosis of hair matrix cells by opening the Kir 6.0 channel pore coupled with SUR on the mitochondrial inner membrane, and (3) dilates hair follicle arteries and increases blood flow in dermal papilla by opening the Kir 6.0 channel pore coupled with SUR on the plasma membrane of vascular smooth muscle cells.

The Application of Sheet Technology in Cartilage Tissue Engineering.

PubMed

Ge, Yang; Gong, Yi Yi; Xu, Zhiwei; Lu, Yanan; Fu, Wei

2016-04-01

Cartilage tissue engineering started to act as a promising, even essential alternative method in the process of cartilage repair and regeneration, considering adult avascular structure has very limited self-renewal capacity of cartilage tissue in adults and a bottle-neck existed in conventional surgical treatment methods. Recent progressions in tissue engineering realized the development of more feasible strategies to treat cartilage disorders. Of these strategies, cell sheet technology has shown great clinical potentials in the regenerative areas such as cornea and esophagus and is increasingly considered as a potential way to reconstruct cartilage tissues for its non-use of scaffolds and no destruction of matrix secreted by cultured cells. Acellular matrix sheet technologies utilized in cartilage tissue engineering, with a sandwich model, can ingeniously overcome the drawbacks that occurred in a conventional acellular block, where cells are often blocked from migrating because of the non-nanoporous structure. Electrospun-based sheets with nanostructures that mimic the natural cartilage matrix offer a level of control as well as manipulation and make them appealing and widely used in cartilage tissue engineering. In this review, we focus on the utilization of these novel and promising sheet technologies to construct cartilage tissues with practical and beneficial functions.

Tissue expansion for breast reconstruction: Methods and techniques.

PubMed

Bertozzi, Nicolò; Pesce, Marianna; Santi, PierLuigi; Raposio, Edoardo

2017-09-01

In this work, the authors review recent data on the different methods and techniques of TE/implant-based reconstruction to determine the complication profiles and the advantages and disadvantages of the different techniques. This information will be valuable for surgeons performing breast reconstructions. A thorough literature review was conducted by the authors concerning the current strategy of tissue expander (TE)/implant-based breast reconstruction following breast cancer surgery. Loss of the breast can strongly affect a woman's personal and social life while breast reconstruction reduces the sense of mutilation felt by women after a mastectomy, and provides psychosocial as well as aesthetic benefits. TE/implant-based reconstruction is the most common breast reconstructive strategy, constituting almost 65% of all breast reconstructions in the US. Although numerous studies have been published on various aspects of alloplastic breast reconstructions, most studies are single-center observations. No evidence-based guidelines are available as yet. Conventional TE/implant-based reconstruction can be performed as a two-stage procedure either in the immediate or delayed setting. Moreover, the adjunctive use of acellular dermal matrix further broadened the alloplastic breast reconstruction indication and also enhanced aesthetic outcomes. TE/implant-based reconstruction has proved to be a safe, cost-effective, and reliable technique that can be performed in women with various comorbidities. Short operative time, fast recovery, and absence of donor site morbidity are other advantages over autologous breast reconstruction.

Expansion and delivery of adipose-derived mesenchymal stem cells on three microcarriers for soft tissue regeneration.

PubMed

Zhou, Yalei; Yan, Zhiwei; Zhang, Hongmei; Lu, Wei; Liu, Shiyu; Huang, Xinhui; Luo, Hailang; Jin, Yan

2011-12-01

Cell/microcarrier combinations can be injected to repair tissue defects, but whether currently available microcarriers can be utilized to repair different tissue defects remains unknown. Here, we compared the suitability of fabricated micronized acellular dermal matrix (MADM), micronized small intestinal submucosa (MSIS), and gelatin microspheres as expansion and delivery scaffolds for adipose-derived mesenchymal stem cells (ADSCs). The results of MTS assay, scanning electron microscopy (SEM), and flow cytometry suggested that the three microcarriers all have good biocompatibility. Quantitative polymerase chain reaction revealed enhanced epidermal growth factor, vascular endothelial growth factor, basal fibroblast growth factor, and transforming growth factor-β expression levels after ADSCs had been cultured on MADM or MSIS for 5 days. After culturing ADSCs on microcarriers in osteogenic medium for 7 days, the expression levels of bone formation-related genes were enhanced. ADSC/microcarrier treatment accelerated wound closure. The ADSC/MADM and ADSC/MSIS combinations retained more of the original implant volume at 1 month postimplantation than ADSC/gelatin microspheres combination in soft-tissue augmentation studies. All implants displayed fibroblast and capillary vessel infiltrations; but ectopic bone formation did not occur, and the calvarial defect repair results were unfavorable. Our study demonstrates the potential utility of these microcarriers not only as a cell-culture substrate but also as a cell-transplantation vehicle for skin regeneration and soft-tissue reconstruction.

Clinical study of cultured epithelial autografts in liquid suspension in severe burn patients.

PubMed

Yim, Haejun; Yang, Hyeong Tae; Cho, Yong Suk; Seo, Cheong Hoon; Lee, Boung Chul; Ko, Jang Hyu; Kwak, In Suk; Kim, Dohern; Hur, Jun; Kim, Jong Hyun; Chun, Wook

2011-09-01

We address the clinical application of the suspension type cultured epithelial autografts (CEAs), Keraheal™ (MCTT, Seoul, Korea), along with the effects, application method, merits and demerits thereof. From February 2007 to June 2010, 29 burn patients with extensive burns, participated in the suspension type of CEA clinical test. A widely meshed autograft (1:4-6 ratio) was applied to the wound bed and the suspension type CEA was sprayed with a Tissomat cell sprayer, followed by a Tissucol spray, a fibrin sealant. The patients' (men/women=26/3) median (interquartile ranges) age was 42 (30-49) years old, the burned TBSA was 55 (44-60) %, and the full thickness burn area was 40 (30-46.5) %. The area of Keraheal™ applied was 800 (400-1200) cm(2). The take rate was 96 (90.5-99) % and 100 (98.5-100) % at 2 and 4 weeks after treatment with Keraheal™, respectively. The Vancouver burn scar scale was 5 (4-6.5), 4 (3-6), and 3 (2-4) at 8, 12 and 24 weeks after the Keraheal™ application. Widely meshed autograft must be applied in massive burns but it's take rate is greatly reduced. The CEAs enhance the take rate of a wide meshed autograft in massive burns and allow for grafting wide meshed autograft together with acellular dermal matrix in some cases. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

PEGylated graphene oxide-mediated quercetin-modified collagen hybrid scaffold for enhancement of MSCs differentiation potential and diabetic wound healing.

PubMed

Chu, Jing; Shi, Panpan; Yan, Wenxia; Fu, Jinping; Yang, Zhi; He, Chengmin; Deng, Xiaoyuan; Liu, Hanping

2018-05-24

Nanoscale delivery based on polyethylene glycol (PEG)ylated graphene oxide (GO-PEG) merits attention for biomedical applications owing to its functional surface modification, superior solubility/biocompatibility and controllable drug release capability. However, impaired skin regeneration in applications of these fascinating nanomaterials in diabetes is still limited, and critical issues need to be addressed regarding insufficient collagen hyperplasia and inadequate blood supply. Therefore, a high-performance tissue engineering scaffold with biocompatible and biodegradable properties is essential for diabetic wound healing. Natural and artificial acellular dermal matrix (ADM) scaffolds with spatially organized collagen fibers can provide a suitable architecture and environment for cell attachment and proliferation. Here, a novel collagen-nanomaterial-drug hybrid scaffold was constructed from GO-PEG-mediated quercetin (GO-PEG/Que)-modified ADM (ADM-GO-PEG/Que). The resulting unique and versatile hybrid scaffold exhibited multiple advantages, including the following: a biocompatible, cell-adhesive surface for accelerating mesenchymal stem cell (MSC) attachment and proliferation; superior stability and adjustability of the conduction potential of quercetin for inducing the differentiation of MSCs into adipocytes and osteoblasts; and a biodegradable nanofiber interface for promoting collagen deposition and angiogenesis in diabetic wound repair. This study provides new prospects for the design of innovative GO-PEG-based collagen hybrid scaffolds for application in efficient therapeutic drug delivery, stem cell-based therapies, tissue engineering and regenerative medicine.

Attachment, proliferation and collagen type I mRNA expression of human gingival fibroblasts on different biodegradable membranes.

PubMed

Hakki, Sema S; Korkusuz, Petek; Purali, Nuhan; Bozkurt, Buket; Kus, Mahmut; Duran, Ismet

2013-01-01

The purpose of this study was to investigate adhesion, proliferation and type I collagen (COL I) mRNA expression of gingival fibroblasts on different membranes used in periodontal applications. Collagen (C), acellular dermal matrix (ADM) and polylactic acid; polyglycolic acid; lactide/glycolide copolymer (PLGA) biodegradable membranes were combined with gingival fibroblasts in culture and incubated for 48 h. Cell adhesion was examined with scanning electron and confocal microscopy. MTT assay was used to measure proliferation. COL I mRNA expression was assessed using quantitative-polymerase chain reaction (QPCR). The PLGA group exhibited the lowest cell survival on day 5 and 10, and lowest cell proliferation on days 5, 10 and 14. While cell proliferation was similar in C and ADM groups, the C membrane showed a slightly greater increase in viable cells to day 10. Confocal and scanning electron microscopy confirmed the results of proliferation and MTT assays. The highest COL I mRNA expression was noted in the PLGA membrane group when compared to the C (p < 0.01) and ADM (p < 0.05) membrane groups. These data revealed that adherence and proliferation of primary gingival fibroblasts on collagen-based C and ADM membranes is better than that seen with PLGA membranes, and thus may be preferable in the treatment of gingival recession defects.

Functional characterization of optimized acellular peripheral nerve graft in a rat sciatic nerve injury model.

PubMed

Nagao, Ryan J; Lundy, Scott; Khaing, Zin Z; Schmidt, Christine E

2011-07-01

Acellular grafts are a viable option for use in nerve reconstruction surgeries. Recently, our lab created a novel optimized decellularization procedure that removes immunological material while leaving the majority of the extracellular matrix structure intact. The optimized acellular (OA) graft has been shown to elicit an immune response equal to or less than that elicited by the isograft, the analog of the autograft in the rat model. We investigated the performance of the OA graft to provide functional recovery in a long-term study. We performed a long-term functional regeneration evaluation study using the sciatic functional index to quantify recovery of Lewis rats at regular time intervals for up to 52 weeks after graft implantation following 1 cm sciatic nerve resection. OA grafts were compared against other decellularized methods (Sondell treatment and thermal decellularization), as well as the isograft and primary neurorrhaphy. The OA graft supported comparable functional recovery to the isograft and superior regeneration to thermal and Sondell decellularization methods. Furthermore, the OA graft promoted early recovery to a greater degree compared to acellular grafts obtained using either the thermal or the Sondell methods. Equivalent functional recovery to the isograft suggests that the OA nerve graft may be a future clinical alternative to the current autologous tissue graft.

Doxycycline alters collagen composition following ventral hernia repair.

PubMed

Tharappel, Job C; Harris, Jennifer W; Totten, Crystal; Zwischenberger, Brittany A; Roth, John S

2017-04-01

Doxycycline, a nonspecific metalloproteinase (MMP) inhibitor, has been demonstrated to impact the strength of the polypropylene (PP) mesh-repaired hernia with an increase in the deposition of collagen type 1. The impact of doxycycline with porcine acellular dermal matrices (PADM) is unknown; therefore, we evaluated the impact of doxycycline administration upon hernia repair with PP and PADM mesh. Sprague-Dawley rats weighing ~400 g underwent laparotomy with creation of a midline ventral hernia. After a 27-day recovery, animals were randomly assigned to four groups of eight and underwent intraperitoneal underlay hernia repair with either PP or PADM. Groups were assigned to daily normal saline (S) or daily doxycycline in normal saline 10 mg/kg (D) via oral gavage for 8 weeks beginning 24 h preoperatively. Animals were euthanized at 8 weeks and underwent tensiometric testing of the abdominal wall and western blot analyses for collagen subtypes and MMPs. Thirty-two animals underwent successful hernia creation and repair with either PADM or PP. At 8 weeks, 15 of 16 PP-implanted animals survived with only 12 of 16 PADM-implanted animals surviving. There were no differences in the mesh to fascial interface tensiometric strength between groups. Densitometric counts in the PADM-D group demonstrated increased collagen type 1 compared to PP-S (PADM-D [1286.5], PADM-S [906.9], PP-S [700.4], p = 0.037) and decreased collagen type 3 compared to PP-S (PADM-D [7446.9], PADM-S [8507.6], PP-S [11,297.1], p = 0.01). MMP-9 levels were increased in PADM-D (PP-S vs. PADM-D, p = 0.04), while MMP-2 levels were similar between PADM-D and PADM-S, respectively. Collagen type 1 deposition at the mesh to fascial interface is enhanced following administration of doxycycline in ventral hernia repairs with porcine acellular dermal matrices. Doxycycline administration may have implications for enhancing hernia repair outcomes using biologic mesh.

Multilayer cell-seeded polymer nanofiber constructs for soft-tissue reconstruction.

PubMed

Barker, Daniel A; Bowers, Daniel T; Hughley, Brian; Chance, Elizabeth W; Klembczyk, Kevin J; Brayman, Kenneth L; Park, Stephen S; Botchwey, Edward A

2013-09-01

Cell seeding throughout the thickness of a nanofiber construct allows for patient-specific implant alternatives with long-lasting effects, earlier integration, and reduced inflammation when compared with traditional implants. Cell seeding may improve implant integration with host tissue; however, the effect of cell seeding on thick nanofiber constructs has not been studied. To use a novel cell-preseeded nanofiber tissue engineering technique to create a 3-dimensional biocompatible implant alternative to decellularized extracellular matrix. Animal study with mammalian cell culture to study tissue engineered scaffolds. Academic research laboratory. Thirty-six Sprague-Dawley rats. The rats each received 4 implant types. The grafts included rat primary (enhanced green fluorescent protein-positive [eGFP+]) fibroblast-seeded polycaprolactone (PCL)/collagen nanofiber scaffold, PCL/collagen cell-free nanofiber scaffold, acellular human cadaveric dermis (AlloDerm), and acellular porcine dermis (ENDURAGen). Rats were monitored postoperatively and received enrofloxacin in the drinking water for 4 days prophylactically and buprenorphine (0.2-0.5 mg/kg administered subcutaneously twice a day postoperatively for pain for 48 hours). The viability of NIH/3T3 fibroblasts cultured on PCL electrospun nanofibers was evaluated using fluorescence microscopy. Soft-tissue remodeling was examined histologically and with novel ex vivo volume determinations of implants using micro-computed tomography of cell-seeded implants relative to nanofibers without cells and commonly used dermal grafts of porcine and human origin (ENDURAGen and AlloDerm, respectively). The fate and distribution of eGFP+ seeded donor fibroblasts were assessed using immunohistochemistry. Fibroblasts migrated across nanofiber layers within 12 hours and remained viable on a single layer for up to 14 days. Scanning electron microscopy confirmed a nanoscale structure with a mean (SD) diameter of 158 (72) nm. Low extrusion rates demonstrated the excellent biocompatibility in vivo. Histological examination of the scaffolds demonstrated minimal inflammation. Cell seeding encouraged rapid vascularization of the nanofiber implants. Cells of donor origin (eGFP+) declined with the duration of implantation. Implant volume was not significantly affected for up to 8 weeks by the preseeding of cells (P > .05). Polymer nanofiber-based scaffolds mimic natural extracellular matrix. Preseeding the nanofiber construct with cells improved vascularization without notable effects on volume. An effect of cell preseeding on scaffold vascularization was evident beyond the presence of preseeded cells. This 3-dimensional, multilayer method of cell seeding throughout a 1-mm-thick construct is simple and feasible for clinical application. Further development of this technique may affect the clinical practice of facial plastic and reconstructive surgeons.

A blanching technique for intradermal injection of the hyaluronic acid Belotero.

PubMed

Micheels, Patrick; Sarazin, Didier; Besse, Stéphanie; Sundaram, Hema; Flynn, Timothy C

2013-10-01

With the proliferation of dermal fillers in the aesthetic workplace have come instructions from various manufacturers regarding dermal placement. Determination of injection needle location in the dermis has in large part been based on physician expertise, product and needle familiarity, and patient-specific skin characteristics. An understanding of the precise depth of dermal structures may help practitioners improve injection specificity. Unlike other dermal fillers that suggest intradermal and deep dermal injection planes, a new hyaluronic acid with a cohesive polydensified matrix may be more appropriate for the superficial dermis because of its structure and its high degree of integration into the dermis. To that end, the authors designed a small study to quantify the depth of the superficial dermis by means of ultrasound and histology. Using ultrasound resources, the authors determined the depths of the epidermis, the dermis, and the reticular dermis in the buttocks of six patients; the authors then extrapolated the depth of the superficial reticular dermis. Histologic studies of two of the patients showed full integration of the product in the reticular dermis. Following determination of injection depths and filler integration, the authors describe a technique ("blanching") for injection of the cohesive polydensified matrix hyaluronic acid into the superficial dermis. At this time, blanching is appropriate only for injection of the cohesive polydensified matrix hyaluronic acid known as Belotero Balance in the United States, although it may have applications for other hyaluronic acid products outside of the United States.

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.

Sterilization of Lung Matrices by Supercritical Carbon Dioxide

PubMed Central

Balestrini, Jenna L.; Liu, Angela; Gard, Ashley L.; Huie, Janet; Blatt, Kelly M.S.; Schwan, Jonas; Zhao, Liping; Broekelmann, Tom J.; Mecham, Robert P.; Wilcox, Elise C.

2016-01-01

Lung engineering is a potential alternative to transplantation for patients with end-stage pulmonary failure. Two challenges critical to the successful development of an engineered lung developed from a decellularized scaffold include (i) the suppression of resident infectious bioburden in the lung matrix, and (ii) the ability to sterilize decellularized tissues while preserving the essential biological and mechanical features intact. To date, the majority of lungs are sterilized using high concentrations of peracetic acid (PAA) resulting in extracellular matrix (ECM) depletion. These mechanically altered tissues have little to no storage potential. In this study, we report a sterilizing technique using supercritical carbon dioxide (ScCO2) that can achieve a sterility assurance level 10−6 in decellularized lung matrix. The effects of ScCO2 treatment on the histological, mechanical, and biochemical properties of the sterile decellularized lung were evaluated and compared with those of freshly decellularized lung matrix and with PAA-treated acellular lung. Exposure of the decellularized tissue to ScCO2 did not significantly alter tissue architecture, ECM content or organization (glycosaminoglycans, elastin, collagen, and laminin), observations of cell engraftment, or mechanical integrity of the tissue. Furthermore, these attributes of lung matrix did not change after 6 months in sterile buffer following sterilization with ScCO2, indicating that ScCO2 produces a matrix that is stable during storage. The current study's results indicate that ScCO2 can be used to sterilize acellular lung tissue while simultaneously preserving key biological components required for the function of the scaffold for regenerative medicine purposes. PMID:26697757

Measuring optical properties of a blood vessel model using optical coherence tomography

NASA Astrophysics Data System (ADS)

Levitz, David; Hinds, Monica T.; Tran, Noi; Vartanian, Keri; Hanson, Stephen R.; Jacques, Steven L.

2006-02-01

In this paper we develop the concept of a tissue-engineered optical phantom that uses engineered tissue as a phantom for calibration and optimization of biomedical optics instrumentation. With this method, the effects of biological processes on measured signals can be studied in a well controlled manner. To demonstrate this concept, we attempted to investigate how the cellular remodeling of a collagen matrix affected the optical properties extracted from optical coherence tomography (OCT) images of the samples. Tissue-engineered optical phantoms of the vascular system were created by seeding smooth muscle cells in a collagen matrix. Four different optical properties were evaluated by fitting the OCT signal to 2 different models: the sample reflectivity ρ and attenuation parameter μ were extracted from the single scattering model, and the scattering coefficient μ s and root-mean-square scattering angle θ rms were extracted from the extended Huygens-Fresnel model. We found that while contraction of the smooth muscle cells was clearly evident macroscopically, on the microscopic scale very few cells were actually embedded in the collagen. Consequently, no significant difference between the cellular and acellular samples in either set of measured optical properties was observed. We believe that further optimization of our tissue-engineering methods is needed in order to make the histology and biochemistry of the cellular samples sufficiently different from the acellular samples on the microscopic level. Once these methods are optimized, we can better verify whether the optical properties of the cellular and acellular collagen samples differ.

A dynamic distention protocol for whole-organ bladder decellularization: histological and biomechanical characterization of the acellular matrix.

PubMed

Consolo, F; Brizzola, S; Tremolada, G; Grieco, V; Riva, F; Acocella, F; Fiore, G B; Soncini, M

2016-02-01

A combined physical-chemical protocol for whole full-thickness bladder decellularization is proposed, based on organ cyclic distention through repeated infusion/withdrawal of the decellularization agents through the urethra. The dynamic decellularization was intended to enhance cell removal efficiency, facilitating the delivery of detergents within the inner layers of the tissue and the removal of cell debris. The use of mild chemical detergents (hypotonic solution and non-ionic detergent) was employed to limit adverse effects upon matrix 3D ultrastructure. Inspection of the presence of residual DNA and RNA was carried out on decellularized matrices to verify effective cell removal. Histological investigation was focused on assessing the retention of adequate structural and functional components that regulate the biomechanical behaviour of the acellular tissue. Biomechanical properties were evaluated through uniaxial tensile loading tests of tissue strips and through ex vivo filling cystometry to evaluate the whole-organ mechanical response to a physiological-like loading state. According to our results, a dynamic decellularization protocol of 17 h duration with a 5 ml/min detergent infusion flow rate revealed higher DNA removal efficiency than standard static decellularization, resulting in residual DNA content < 50 ng/mg dry tissue weight. Furthermore, the collagen network and elastic fibres distribution were preserved in the acellular ECM, which exhibited suitable biomechanical properties in the perspective of its future use as an implant for bladder augmentation. Copyright © 2013 John Wiley & Sons, Ltd.

Detergent-enzymatic decellularization of swine blood vessels: insight on mechanical properties for vascular tissue engineering.

PubMed

Pellegata, Alessandro F; Asnaghi, M Adelaide; Stefani, Ilaria; Maestroni, Anna; Maestroni, Silvia; Dominioni, Tommaso; Zonta, Sandro; Zerbini, Gianpaolo; Mantero, Sara

2013-01-01

Small caliber vessels substitutes still remain an unmet clinical need; few autologous substitutes are available, while synthetic grafts show insufficient patency in the long term. Decellularization is the complete removal of all cellular and nuclear matters from a tissue while leaving a preserved extracellular matrix representing a promising tool for the generation of acellular scaffolds for tissue engineering, already used for various tissues with positive outcomes. The aim of this work is to investigate the effect of a detergent-enzymatic decellularization protocol on swine arteries in terms of cell removal, extracellular matrix preservation, and mechanical properties. Furthermore, the effect of storage at -80°C on the mechanical properties of the tissue is evaluated. Swine arteries were harvested, frozen, and decellularized; histological analysis revealed complete cell removal and preserved extracellular matrix. Furthermore, the residual DNA content in decellularized tissues was far low compared to native one. Mechanical testings were performed on native, defrozen, and decellularized tissues; no statistically significant differences were reported for Young's modulus, ultimate stress, compliance, burst pressure, and suture retention strength, while ultimate strain and stress relaxation of decellularized vessels were significantly different from the native ones. Considering the overall results, the process was confirmed to be suitable for the generation of acellular scaffolds for vascular tissue engineering.

Acellular Flowable Matrix in the Treatment of Tunneled or Cavity Ulcers in Diabetic Feet: A Preliminary Report.

PubMed

Campitiello, Ferdinando; Mancone, Manfredi; Della Corte, Angela; Guerniero, Raffaella; Canonico, Silvestro

2018-06-01

The authors aimed to explore the feasibility and safety of an advanced, acellular, flowable wound matrix (FWM) in patients with diabetes-related cavity or tunnel lesions involving deep structures. Patients with diabetic foot ulcers were hospitalized at the General and Geriatric Surgery Unit of the University of Campania in Naples, Italy, between March 2015 and December 2015. Twenty-three patients with tunneled or cavity ulcers were treated. The lesions were filled with the FWM. Surgical wound edges were either approximated with stitches or left to heal by secondary intention. After 6 weeks, 78.26% of patients completely healed after a single application of the FWM. The healing time for all healed wounds was 30.85 ± 12.62 days, or 26.11 ± 5.43 days in patients for whom wound edges were approximated by stitches, and 57.66 ± 3.05 days in the patients who healed by secondary intention (P = .01). Permanent tissue regeneration was observed in a high percentage of patients, and shorter healing time was achieved. Study authors observed a low rate of complications such as major amputation and increased hospitalization. The FWM seems ideal for tunneled and cavity ulcers with irregular geometry. This new porous matrix allows closure of the lesion while reducing healing time and demolition surgery.

Human acellular cartilage matrix powders as a biological scaffold for cartilage tissue engineering with synovium-derived mesenchymal stem cells.

PubMed

Chang, Chih-Hung; Chen, Chia-Chun; Liao, Cheng-Hao; Lin, Feng-Huei; Hsu, Yuan-Ming; Fang, Hsu-Wei

2014-07-01

In our previous study, we found that cartilage fragments from osteoarthritic knee promoted chondrogenesis of mesenchymal stem cells. In this study, we further transformed the cartilage tissues into acellular cartilage matrix (ACM) and explored the feasibility of using ACM as a biological scaffold. Nonworn parts of cartilage tissues were obtained during total knee arthroplasty (TKA) surgery and were successfully fabricated into ACM powders. The ACM powders and human synovium-derived mesenchymal stem cells (SMSCs) were mixed into collagen gel for in vitro culture. Histological results showed a synergistic effect of ACM powders and chondrogenic growth factors in the formation of engineered cartilage. The findings of real-time polymerase chain reaction (PCR) suggested that ACM powders had the potential of promoting type II collagen gene expression in the growth factors-absent environment. Moreover, with growth factors induction, the ACM powders could reduce the hypertrophy in chondrogenesis of SMSCs. In summary, ACM powders could serve as a functional scaffold that benefited the chondrogenesis of SMSCs for cartilage tissue engineering. © 2013 Wiley Periodicals, Inc.

INFLUENCE OF MATRIX FORMULATION ON DERMAL PERCUTANEOUS ABSORPTION OF TRIAZOLE FUNGICIDES USING QSAR AND PBPK / PD MODELS

EPA Science Inventory

The objective of this work is to use the Exposure Related Dose Estimating Model (ERDEM) and quantitative structure-activity relationship (QSAR) models to develop an assessment tool for human exposure assessment to triazole fungicides. A dermal exposure route is used for the physi...

Cavernous nerve repair with allogenic adipose matrix and autologous adipose-derived stem cells.

PubMed

Lin, Guiting; Albersen, Maarten; Harraz, Ahmed M; Fandel, Thomas M; Garcia, Maurice; McGrath, Mary H; Konety, Badrinath R; Lue, Tom F; Lin, Ching-Shwun

2011-06-01

To investigate whether adipose-derived matrix seeded with adipose-derived stem cells (ADSC) can facilitate the repair of injured cavernous nerves (CNs). Human and rat adipose tissues were decellularized and fabricated into various forms, including adipose tissue-derived acellular matrix thread (ADMT). ADMT seeded with ADSC were transplanted into subcutaneous space and examined for signs of inflammation. ADSC-seeded ADMTs were then used to repair CN injury in rats, followed by assessment of histology and erectile function. Adipose tissue can be fabricated into acellular matrices of various shapes and sizes, including threads and sheets. Seeding of ADMT occurred rapidly: within 24 hours, 55% of the surface was covered with ADSC and within 1 week, 90% was covered. Transplantation of the seeded ADMT into the subcutaneous space of an allogenic host showed no signs of inflammatory reaction. At 3 months after grafting into CN injury rats, approximately twice as many cells were found on seeded ADMT as on unseeded ADMT. The seeded ADMT also had various degrees of S100 and neuronal nitric oxide synthase expression, suggesting CN axonal ingrowth. Rats grafted with seeded ADMT overall had the best erectile function recovery when compared with those grafted with unseeded ADMT and those ungrafted. However, as a result of large variations, the differences did not reach statistic significance (P = .07). Grafting of ADSC-seeded matrix resulted in a substantial recovery of erectile function and improvement of histology. However, further refinement of the matrix architecture is needed to improve the success rate. Copyright © 2011 Elsevier Inc. All rights reserved.

Fibroblast extracellular matrix gene expression in response to keratinocyte-releasable stratifin.

PubMed

Ghaffari, Abdi; Li, Yunyaun; Karami, Ali; Ghaffari, Mazyar; Tredget, Edward E; Ghahary, Aziz

2006-05-15

Termination of wound-healing process requires a fine balance between connective tissue deposition and its hydrolysis. Previously, we have demonstrated that keratinocyte-releasable stratifin, also known as 14-3-3 sigma protein, stimulates collagenase (MMP-1) expression in dermal fibroblasts. However, role of extracellular stratifin in regulation of extracellular matrix (ECM) factors and other matrix metalloproteinases (MMPs) in dermal fibroblast remains unexplored. To address this question, large-scale ECM gene expression profile were analyzed in human dermal fibroblasts co-cultured with keratinocytes or treated with recombinant stratifin. Superarray pathway-specific microarrays were utilized to identify upregulation or downregulation of 96 human ECM and adhesion molecule genes. RT-PCR and Western blot were used to validate microarray expression profiles of selected genes. Comparison of gene profiles with the appropriate controls showed a significant (more than twofold) increase in expression of collagenase-1, stromelysin-1 and -2, neutrophil collagenase, and membrane type 5 MMP in dermal fibroblasts treated with stratifin or co-cultured with keratinocytes. Expression of type I collagen and fibronectin genes decreased in the same fibroblasts. The results of a dose-response experiment showed that stratifin stimulates the expression of stromelysin-1 (MMP-3) mRNA by dermal fibroblasts in a concentration-dependent fashion. Furthermore, Western blot analysis of fibroblast-conditioned medium showed a peak in MMP-3 protein levels 48 h following treatment with recombinant stratifin. In a lasting-effect study, MMP-3 protein was detected in fibroblast-condition medium for up to 72 h post removal of stratifin. In conclusion, our results suggest that keratinocyte-releasable stratifin plays a major role in induction of ECM degradation by dermal fibroblasts through stimulation of key MMPs, such as MMP-1 and MMP-3. Therefore, stratifin protein may prove to be a useful target for clinical intervention in controlling excessive wound healing in fibrotic conditions. Copyright 2006 Wiley-Liss, Inc.

Effectiveness and properties of the biological prosthesis Permacol™ in pediatric surgery: A large single center experience.

PubMed

Filisetti, Claudia; Costanzo, Sara; Marinoni, Federica; Vella, Claudio; Klercy, Catherine; Riccipetitoni, Giovanna

2016-05-01

The use of prosthetic patches of non-absorbable materials represents a valid tool in the treatment of abdominal wall and diaphragmatic defects in pediatric age. In recent years research has developed biological dermal scaffolds made from a sheet of acellular matrix that can provide the desired support and reduce the occurrence of complications from non-absorbable implant. We present our experience and a systematic review to evaluate the use of biologic prosthesis for abdominal wall closure in pediatric patients. The study from January 2009 to January 2015 involved 20 patients treated with Permacol™ implant. We observed postoperative complications only in patients treated for abdominal wall closure, which is the major indication for the use of Permacol™. We conducted a systematic review and meta-analysis (according to PRISMA) on PubMed/Medline, Scopus and EMBASE regarding the use of biological prosthesis in pediatric population considering the incidence of complications as the primary outcome. 3/20 patients experienced complications: 2 patients with skin necrosis healed conservatively and 1 of them developed laparocele. Thus only 1 patient with incisional hernia had significant surgery complication. In patients who were permanently implanted with Permacol™ it has not determined adverse reactions with optimal functional outcome. In accordance with the few data (case reports and case series) reported in literature about pediatric patients, our experience in different pathologies and applications has shown the effectiveness of Permacol™, in particular for the non-occurrence of infections, that often affect the use of prosthesis.

Immediate direct-to-implant breast reconstruction using anatomical implants.

PubMed

Kim, Sung-Eun; Jung, Dong-Woo; Chung, Kyu-Jin; Lee, Jun Ho; Kim, Tae Gon; Kim, Yong-Ha; Lee, Soo Jung; Kang, Su Hwan; Choi, Jung Eun

2014-09-01

In 2012, a new anatomic breast implant of form-stable silicone gel was introduced onto the Korean market. The intended use of this implant is in the area of aesthetic breast surgery, and many reports are promising. Thus far, however, there have been no reports on the use of this implant for breast reconstruction in Korea. We used this breast implant in breast reconstruction surgery and report our early experience. From November 2012 to April 2013, the Natrelle Style 410 form-stable anatomically shaped cohesive silicone gel-filled breast implant was used in 31 breasts of 30 patients for implant breast reconstruction with an acellular dermal matrix. Patients were treated with skin-sparing mastectomies followed by immediate breast reconstruction. The mean breast resection volume was 240 mL (range, 83-540 mL). The mean size of the breast implants was 217 mL (range, 125-395 mL). Breast shape outcomes were considered acceptable. Infection and skin thinning occurred in one patient each, and hematoma and seroma did not occur. Three cases of wound dehiscence occurred, one requiring surgical intervention, while the others healed with conservative treatment in one month. Rippling did not occur. So far, complications such as capsular contracture and malrotation of breast implant have not yet arisen. By using anatomic breast implants in breast reconstruction, we achieved satisfactory results with aesthetics better than those obtained with round breast implants. Therefore, we concluded that the anatomical implant is suitable for breast reconstruction.

Three types of dermal grafts in rats: the importance of mechanical property and structural design.

PubMed

You, Chuangang; Wang, Xingang; Zheng, Yurong; Han, Chunmao

2013-12-04

To determine how the mechanical property and micro structure affect tissue regeneration and angiogenesis, three types of scaffolds were studied. Acellular dermal matrices (ADM), produced from human skin by removing the epidermis and cells, has been widely used in wound healing because of its high mechanical strength. Collagen scaffolds (CS) incorporated with poly(glycolide-co-L-lactide) (PLGA) mesh forms a well-supported hybrid dermal equivalent poly(glycolide-co-L-lactide) mesh/collagen scaffolds (PMCS). We designed this scaffold to enhance the CS mechanical property. These three different dermal substitutes-ADM, CS and PMCSs are different in the tensile properties and microstructure. Several basic physical characteristics of dermal substitutes were investigated in vitro. To characterize the angiogenesis and tissue regeneration, the materials were embedded subcutaneously in Sprague-Dawley (SD) rats. At weeks 1, 2, 4 and 8 post-surgery, the tissue specimens were harvested for histology, immunohistochemistry and real-time quantitative PCR (RT-qPCR). In vitro studies demonstrated ADM had a higher Young's modulus (6.94 MPa) rather than CS (0.19 MPa) and PMCS (3.33 MPa) groups in the wet state. Compared with ADMs and CSs, PMCSs with three-dimensional porous structures resembling skin and moderate mechanical properties can promote tissue ingrowth more quickly after implantation. In addition, the vascularization of the PMCS group is more obvious than that of the other two groups. The incorporation of a PLGA knitted mesh in CSs can improve the mechanical properties with little influence on the three-dimensional porous microstructure. After implantation, PMCSs can resist the contraction and promote cell infiltration, neotissue formation and blood vessel ingrowth, especially from the mesh side. Although ADM has high mechanical strength, its vascularization is poor because the pore size is too small. In conclusion, the mechanical properties of scaffolds are important for maintaining the three-dimensional microarchitecture of constructs used to induce tissue regeneration and vascularization. The results illustrated that tissue regeneration requires the proper pore size and an appropriate mechanical property like PMCS which could satisfy these conditions to sustain growth.

Three types of dermal grafts in rats: the importance of mechanical property and structural design

PubMed Central

2013-01-01

Background To determine how the mechanical property and micro structure affect tissue regeneration and angiogenesis, three types of scaffolds were studied. Acellular dermal matrices (ADM), produced from human skin by removing the epidermis and cells, has been widely used in wound healing because of its high mechanical strength. Collagen scaffolds (CS) incorporated with poly(glycolide-co-L-lactide) (PLGA) mesh forms a well-supported hybrid dermal equivalent poly(glycolide-co-L-lactide) mesh/collagen scaffolds (PMCS). We designed this scaffold to enhance the CS mechanical property. These three different dermal substitutes—ADM, CS and PMCSs are different in the tensile properties and microstructure. Methods Several basic physical characteristics of dermal substitutes were investigated in vitro. To characterize the angiogenesis and tissue regeneration, the materials were embedded subcutaneously in Sprague–Dawley (SD) rats. At weeks 1, 2, 4 and 8 post-surgery, the tissue specimens were harvested for histology, immunohistochemistry and real-time quantitative PCR (RT-qPCR). Results In vitro studies demonstrated ADM had a higher Young’s modulus (6.94 MPa) rather than CS (0.19 MPa) and PMCS (3.33 MPa) groups in the wet state. Compared with ADMs and CSs, PMCSs with three-dimensional porous structures resembling skin and moderate mechanical properties can promote tissue ingrowth more quickly after implantation. In addition, the vascularization of the PMCS group is more obvious than that of the other two groups. The incorporation of a PLGA knitted mesh in CSs can improve the mechanical properties with little influence on the three-dimensional porous microstructure. After implantation, PMCSs can resist the contraction and promote cell infiltration, neotissue formation and blood vessel ingrowth, especially from the mesh side. Although ADM has high mechanical strength, its vascularization is poor because the pore size is too small. In conclusion, the mechanical properties of scaffolds are important for maintaining the three-dimensional microarchitecture of constructs used to induce tissue regeneration and vascularization. Conclusion The results illustrated that tissue regeneration requires the proper pore size and an appropriate mechanical property like PMCS which could satisfy these conditions to sustain growth. PMID:24304500

Accelerated expansion of epidermal keratinocyte and improved dermal reconstruction achieved by engineered amniotic membrane.

PubMed

Huang, Guofeng; Ji, Shizhao; Luo, Pengfei; Liu, Houqi; Zhu, Shihui; Wang, Guangyi; Zhou, Panyu; Xiao, Shichu; Xia, Zhaofan

2013-01-01

In this study, we used human amniotic membrane (AM) to prepare a dermal scaffold with intact basement membrane (BM) and good biostability for quick expansion and transplantation of epidermal keratinocytes (EKs). Fresh AM was treated by repeated freeze-thaw cycles and DNase digestion. This new method was able to cleanse the cell components effectively and retain the BM structure with continuous distributions of laminin, collagen IV, VI, and VII. Subsequently, the acellular amniotic membrane (AAM) was cross-linked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) for 5 min, 30 min, and 6 h. With the time of cross-linking prolonging, the mechanical strength and biostability of AAM increased gradually, while its cytotoxicity to EKs also increased. The 5-min cross-linked AAM (5min-AAM) had no significant cytotoxicity with good histocompatibility. The relative cell viability of EKs seeded on the 5min-AAM surface was 367 ± 33% and 631 ± 43% at 7 and 14 days of culture, respectively, both higher than 294 ± 30% and 503 ± 41% of the conventional cell culture dish (CCD) group, and the proportion of P63-positive cells was significantly higher than that of the CCD group on day 7 (54.32 ± 4.27% vs. 33.32 ± 3.18%, p < 0.05). When the 5min-AAM loaded with EKs (EK-AAM) was grafted onto full-thickness skin defects in nude mice, the cells survived well and formed an epidermis similar to normal skin. The new epidermis was thicker, and reconstruction of the dermal structure was good with an intact BM. Four weeks after transplantation, the wound contraction rate in the EK-AAM group was 43.09 ± 7.05%, significantly lower than that in the EK sheet group (57.49 ± 5.93%) and control group (69.94 ± 9.47%) (p < 0.05). In conclusion, repeated freeze-thaw treatment with appropriate EDC cross-linking offers AAM an intact BM structure with good operability and biostability. It may prove to be an ideal dermal scaffold to promote expansion of EKs in vitro and be transplanted for reconstruction of the dermal structure.

Acellular porcine intestinal submucosa as fascial graft in an animal model: applications for revision tympanoplasty.

PubMed

Ort, Stuart A; Ehrlich, H Paul; Isaacson, Jon E

2010-09-01

To demonstrate regeneration of muscle fascia appropriate for future harvest with the use of acellular porcine intestinal submucosa in a rat model. Animal cohort study. Tertiary care academic medical center. Sixteen male Sprague-Dawley rats underwent excision of rectus abdominis muscle fascia. A sheet of acellular porcine intestinal submucosa was placed in the fascia harvest defect. Graft and underlying muscle were harvested at three-, six-, and nine-week intervals. Histologic examination, including immunohistology for anti-von Willebrand factor, was performed at each timepoint. Additional selected specimens were subjected to latex vascular perfusion casts to examine vessel growth patterns within the graft. Gross examination revealed a new tissue plane, indistinguishable from surrounding native fascia. Histology revealed an initial inflammatory response within the graft. Progressive influx of native tissue was noted over successive timepoints. Via collagen-specific staining, we noted progressive reorganization and maturation of the graft collagen matrix. At the final nine-week time point, a new loose connective tissue plane was reestablished between the graft and underlying muscle. Immunohistochemistry and latex perfusion both demonstrate an initial development of small capillaries that progresses over time to greater organization and arteriole formation. Fascia regeneration may be possible with use of an acellular porcine intestinal submucosa graft in an animal model. Future studies may prove beneficial in restoring fascia in humans. Implications for potential advantages in tympanoplasty are discussed. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

Effects of freezing-induced cell-fluid-matrix interactions on the cells and extracellular matrix of engineered tissues.

PubMed

Teo, Ka Yaw; DeHoyos, Tenok O; Dutton, J Craig; Grinnell, Frederick; Han, Bumsoo

2011-08-01

The two most significant challenges for successful cryopreservation of engineered tissues (ETs) are preserving tissue functionality and controlling highly tissue-type dependent preservation outcomes. In order to address these challenges, freezing-induced cell-fluid-matrix interactions should be understood, which determine the post-thaw cell viability and extracellular matrix (ECM) microstructure. However, the current understanding of this tissue-level biophysical interaction is still limited. In this study, freezing-induced cell-fluid-matrix interactions and their impact on the cells and ECM microstructure of ETs were investigated using dermal equivalents as a model ET. The dermal equivalents were constructed by seeding human dermal fibroblasts in type I collagen matrices with varying cell seeding density and collagen concentration. While these dermal equivalents underwent an identical freeze/thaw condition, their spatiotemporal deformation during freezing, post-thaw ECM microstructure, and cellular level cryoresponse were characterized. The results showed that the extent and characteristics of freezing-induced deformation were significantly different among the experimental groups, and the ETs with denser ECM microstructure experienced a larger deformation. The magnitude of the deformation was well correlated to the post-thaw ECM structure, suggesting that the freezing-induced deformation is a good indicator of post-thaw ECM structure. A significant difference in the extent of cellular injury was also noted among the experimental groups, and it depended on the extent of freezing-induced deformation of the ETs and the initial cytoskeleton organization. These results suggest that the cells have been subjected to mechanical insult due to the freezing-induced deformation as well as thermal insult. These findings provide insight on tissue-type dependent cryopreservation outcomes, and can help to design and modify cryopreservation protocols for new types of tissues from a pre-developed cryopreservation protocol. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bryostatin and its synthetic analog, picolog rescue dermal fibroblasts from prolonged stress and contribute to survival and rejuvenation of human skin equivalents.

PubMed

Khan, Tapan K; Wender, Paul A; Alkon, Daniel L

2018-02-01

Skin health is associated with the day-to-day activity of fibroblasts. The primary function of fibroblasts is to synthesize structural proteins, such as collagen, extracellular matrix proteins, and other proteins that support the structural integrity of the skin and are associated with younger, firmer, and more elastic skin that is better able to resist and recover from injury. At sub-nanomolar concentrations (0.03-0.3 nM), bryostatin-1 and its synthetic analog, picolog (0.1-10 nM) sustained the survival and activation of human dermal fibroblasts cultured under the stressful condition of prolonged serum deprivation. Bryostatin-1 treatment stabilized human skin equivalents (HSEs), a bioengineered combination of primary human skin cells (keratinocytes and dermal fibroblasts) on an extracellular matrix composed of mainly collagen. Fibroblasts activated by bryostatin-1 protected the structural integrity of HSEs. Bryostatin-1 and picolog prolonged activation of Erk in fibroblasts to promote cell survival. Chronic stress promotes the progression of apoptosis. Dermal fibroblasts constitutively express all components of Fas associated apoptosis, including caspase-8, an initiator enzyme of apoptosis. Prolong bryostatin-1 treatment reduced apoptosis by decreasing caspase-8 and protected dermal fibroblasts. Our data suggest that bryostatin-1 and picolog could be useful in anti-aging skincare, and could have applications in tissue engineering and regenerative medicine. © 2017 Wiley Periodicals, Inc.

Quantitative proteomics reveals altered expression of extracellular matrix related proteins of human primary dermal fibroblasts in response to sulfated hyaluronan and collagen applied as artificial extracellular matrix.

PubMed

Müller, Stephan A; van der Smissen, Anja; von Feilitzsch, Margarete; Anderegg, Ulf; Kalkhof, Stefan; von Bergen, Martin

2012-12-01

Fibroblasts are the main matrix producing cells of the dermis and are also strongly regulated by their matrix environment which can be used to improve and guide skin wound healing processes. Here, we systematically investigated the molecular effects on primary dermal fibroblasts in response to high-sulfated hyaluronan [HA] (hsHA) by quantitative proteomics. The comparison of non- and high-sulfated HA revealed regulation of 84 of more than 1,200 quantified proteins. Based on gene enrichment we found that sulfation of HA alters extracellular matrix remodeling. The collagen degrading enzymes cathepsin K, matrix metalloproteinases-2 and -14 were found to be down-regulated on hsHA. Additionally protein expression of thrombospondin-1, decorin, collagen types I and XII were reduced, whereas the expression of trophoblast glycoprotein and collagen type VI were slightly increased. This study demonstrates that global proteomics provides a valuable tool for revealing proteins involved in molecular effects of growth substrates for further material optimization.

Age-related morphological changes of the dermal matrix in human skin documented in vivo by multiphoton microscopy

NASA Astrophysics Data System (ADS)

Wang, Hequn; Shyr, Thomas; Fevola, Michael J.; Cula, Gabriela Oana; Stamatas, Georgios N.

2018-03-01

Two-photon fluorescence (TPF) and second harmonic generation (SHG) microscopy provide direct visualization of the skin dermal fibers in vivo. A typical method for analyzing TPF/SHG images involves averaging the image intensity and therefore disregarding the spatial distribution information. The goal of this study is to develop an algorithm to document age-related effects of the dermal matrix. TPF and SHG images were acquired from the upper inner arm, volar forearm, and cheek of female volunteers of two age groups: 20 to 30 and 60 to 80 years of age. The acquired images were analyzed for parameters relating to collagen and elastin fiber features, such as orientation and density. Both collagen and elastin fibers showed higher anisotropy in fiber orientation for the older group. The greatest difference in elastin fiber anisotropy between the two groups was found for the upper inner arm site. Elastin fiber density increased with age, whereas collagen fiber density decreased with age. The proposed analysis considers the spatial information inherent to the TPF and SHG images and provides additional insights into how the dermal fiber structure is affected by the aging process.

Protective effect of crocin on ultraviolet B‑induced dermal fibroblast photoaging.

PubMed

Deng, Mingwu; Li, Dong; Zhang, Yichen; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Wenjie

2018-06-11

Ultraviolet B (UVB) radiation induces the production of reactive oxygen species (ROS), resulting in the aging of dermal fibroblasts. Crocin, a bioactive constituent of Crocus sativus, possesses anti‑oxidation effects. The purpose of the present study was to evaluate the protective effect of crocin on UVB‑induced dermal fibroblast photoaging. Human dermal fibroblasts were isolated and cultured with different concentrations of crocin prior to and following exposure to UVB irradiation. The senescent phenotypes of cells were evaluated, including cell proliferation, cell cycle, senescence‑associated β‑galactosidase (SA‑β‑gal) expression, intracellular ROS, expression of antioxidant protein glutathione peroxidase 1 (GPX‑1) and extracellular matrix protein collagen type 1 (Col‑1). Crocin rescued the cell proliferation inhibited by UVB irradiation, prevented cell cycle arrest and markedly decreased the number of SA‑β‑gal‑positive cells. In addition, crocin reduced UVB‑induced ROS by increasing GPX‑1 expression and other direct neutralization effects. Furthermore, crocin promoted the expression of the extracellular matrix protein Col‑1. Crocin could effectively prevent UVB‑induced cell damage via the reduction of intracellular ROS; thus, it could potentially be used in the prevention of skin photoaging.

Ex-vivo transduced autologous skin fibroblasts expressing human Lim Mineralization Protein-3 efficiently form new bone in animal models

PubMed Central

Lattanzi, Wanda; Parrilla, Claudio; Fetoni, Annarita; Logroscino, Giandomenico; Straface, Giuseppe; Pecorini, Giovanni; Stigliano, Egidio; Tampieri, Anna; Bedini, Rossella; Pecci, Raffaella; Michetti, Fabrizio; Gambotto, Andrea; Robbins, Paul D.; Pola, Enrico

2012-01-01

Local gene transfer of the human LIM Mineralization Protein (LMP), a novel intracellular positive regulator of the osteoblast differentiation program, can induce efficient bone formation in rodents. In order to develop a clinically relevant gene therapy approach to facilitate bone healing, we have used primary dermal fibroblasts transduced ex vivo with Ad.LMP3 and seeded on an hydroxyapatite/collagen matrix prior to autologous implantation. Here we demonstrate that genetically modified autologous dermal fibroblasts expressing Ad.LMP-3 are able to induce ectopic bone formation following implantation of the matrix into the mouse triceps and paravertebral muscles. Moreover, implantation of the Ad.LMP-3-modified dermal fibroblasts into a rat mandibular bone critical size defect model results in efficient healing as determined by X-ray, histology and three dimensional micro computed tomography (3DμCT). These results demonstrate the effectiveness of the non-secreted intracellular osteogenic factor LMP-3, in inducing bone formation in vivo. Moreover, the utilization of autologous dermal fibroblasts implanted on a biomaterial represents a promising approach for possible future clinical applications aimed at inducing new bone formation. PMID:18633445

Repeated folding stress-induced morphological changes in the dermal equivalent.

PubMed

Arai, Koji Y; Sugimoto, Mami; Ito, Kanako; Ogura, Yuki; Akutsu, Nobuko; Amano, Satoshi; Adachi, Eijiro; Nishiyama, Toshio

2014-11-01

Repeated mechanical stresses applied to the same region of the skin are thought to induce morphological changes known as wrinkle. However, the underlying mechanisms are not fully understood. To study the mechanisms, we examined effects of repeated mechanical stress on the dermal equivalent. We developed a novel device to apply repeated folding stress to the dermal equivalent. After applying the mechanical stress, morphological changes of the dermal equivalent and expression of several genes related to extracellular matrix turn over and cell contraction were examined. The repeated folding stress induced a noticeable decrease in the width of the dermal equivalent. The mechanical stress altered orientations of collagen fibrils. Hydroxyproline contents, dry weights and cell viability of the dermal equivalents were not affected by the mechanical stress. On the other hand, Rho-associated coiled-coil-containing kinase (ROCK) specific inhibitor Y27632 completely suppressed the decrease in the width of the dermal equivalent. The present results revealed that either degradation of collagen or changes in the number of cells were not responsible for the decrease in the width of the dermal equivalent and indicate that the repeated mechanical stress induces unidirectional contraction in the dermal equivalent through the RhoA-ROCK signaling pathway. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Exploratory study on the micro-remodeling of dermal tissue].

PubMed

Jiang, Yu-zhi; Ding, Gui-fu; Lu, Shu-liang

2009-10-01

To explore the effect of three-dimensional structure of dermal matrix on biological behavior of fibroblasts (Fb) in the microcosmic perspective. The three-dimensional structure of dermal tissue was analyzed by plane geometric and trigonometric function. Microdots structure array with cell adhesion effect was designed by computer-assisted design software according to the adhesive and non-adhesive components of dermal tissue. Four sizes (8 microm x 3 microm, space 6 microm; 16 microm x 3 microm, space 6 microm; 16 microm x 5 microm, space 8 microm; 20 microm x 3 microm, space 2 microm) of micropier grid used for cell culture (MPGCC) with cell-adhesive microdots, built up with micro-pattern printing and molecule self-assembly method were used to culture dermal Fb. Fb cultured with cell culture matrix without micropier grid was set up as control. The expression of skeleton protein (alpha-SMA) of Fb, cell viability and cell secretion were detected with immunohistochemistry, fluorescent immunohistochemistry, MTT test and the hydroxyproline content assay. The three-dimensional structure of dermal tissue could be simulated by MPGCC as shown in arithmetic analysis. Compared with those of control group [(12 +/- 3)% and (0.53 +/- 0.03) microg/mg, (0.35 +/- 0.04)], the expression of alpha-SMA [(49 +/- 3)%, (61 +/- 3)%, (47 +/- 4)%, (51 +/- 3)%] and the content of hydroxyproline [(0.95 +/- 0.04), (0.87 +/- 0.03), (0.81 +/- 0.03), (0.77 +/- 0.03) microg/mg] were increased significantly (P < 0.05), the cell viability of Fb (0.12 +/- 0.03, 0.13 +/- 0.04, 0.14 +/- 0.03, 0.19 +/- 0.03) cultured in MPGCC was decreased significantly (P < 0.05). When the parameters of micropier grid were changed, the expression of alpha-SMA, the cell viability and the content of hydroxyproline of Fb cultured in four sizes of MPGCC were also significantly changed as compared with one another (P < 0.05). MPGCC may be the basic functional unit of dermal template, or unit of dermal template to call. Different three-dimensional circumstances for dermal tissue can result in different template effect and wound healing condition.

Efficacy of periodontal plastic surgery procedures in the treatment of localized facial gingival recessions. A systematic review.

PubMed

Cairo, Francesco; Nieri, Michele; Pagliaro, Umberto

2014-04-01

The aim of this Systematic Review (SR) was to assess the clinical efficacy of periodontal plastic surgery procedures in the treatment of localized gingival recessions (Rec) with or without inter-dental clinical attachment loss (iCAL). Electronic and hand searches were performed to identify randomized clinical trials (RCTs) on treatment of single gingival recessions with at least 6 months of follow-up. Primary outcome variable was complete root coverage (CRC). Secondary outcome variables were recession reduction (RecRed) and keratinized tissue (KT) gain. To evaluate treatment effect, Odds Ratios were combined for dichotomous data and mean differences in continuous data using a random-effect model. Fifty-one RCTs (53 articles) with a total of 1574 treated patients (1744 recessions) were included in this SR. Finally, 30 groups of comparisons were identified and a total of 80 meta-analyses were performed. Coronally Advanced Flap (CAF) was associated with higher probability of CRC and higher amount of RecRed than Semilunar Coronal Positioned Flap (SCPF). The combination CAF plus Connective Tissue Graft (CAF+CTG) or CAF plus Enamel Matrix Derivative (CAF+EMD) was more effective than CAF alone in terms of CRC and RecRed. The combination CAF plus Collagen Matrix (CAF+CM) achieved higher RecRed than CAF alone. In addition, CAF+CTG achieved CRC more frequently than CAF+EMD, SCPF, Free Gingival Graft (FGG) and Laterally Positioned Flap (LPS). CAF+CTG was also associated with higher RecRed than Barrier Membranes (CAF+GTR), CAF+EMD and CAF+CM. GTR was not able to improve the clinical efficacy of CAF. Studies adding Acellular Dermal Matrix (ADM) under CAF showed a large heterogeneity and not significant benefits compared with CAF alone. Multiple combinations, using more than a single graft/biomaterial under the flap, usually provide similar or less benefits than simpler, control procedures in term of root coverage outcomes. CAF procedures alone or with CTG, EMD are supported by large evidence in modern periodontal plastic surgery. CAF+CTG achieved the best clinical outcomes in single gingival recessions with or without iCAL. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Preservation of micro-architecture and angiogenic potential in a pulmonary acellular matrix obtained using intermittent intra-tracheal flow of detergent enzymatic treatment.

PubMed

Maghsoudlou, Panagiotis; Georgiades, Fanourios; Tyraskis, Athanasios; Totonelli, Giorgia; Loukogeorgakis, Stavros P; Orlando, Giuseppe; Shangaris, Panicos; Lange, Peggy; Delalande, Jean-Marie; Burns, Alan J; Cenedese, Angelo; Sebire, Neil J; Turmaine, Mark; Guest, Brogan N; Alcorn, John F; Atala, Anthony; Birchall, Martin A; Elliott, Martin J; Eaton, Simon; Pierro, Agostino; Gilbert, Thomas W; De Coppi, Paolo

2013-09-01

Tissue engineering of autologous lung tissue aims to become a therapeutic alternative to transplantation. Efforts published so far in creating scaffolds have used harsh decellularization techniques that damage the extracellular matrix (ECM), deplete its components and take up to 5 weeks to perform. The aim of this study was to create a lung natural acellular scaffold using a method that will reduce the time of production and better preserve scaffold architecture and ECM components. Decellularization of rat lungs via the intratracheal route removed most of the nuclear material when compared to the other entry points. An intermittent inflation approach that mimics lung respiration yielded an acellular scaffold in a shorter time with an improved preservation of pulmonary micro-architecture. Electron microscopy demonstrated the maintenance of an intact alveolar network, with no evidence of collapse or tearing. Pulsatile dye injection via the vasculature indicated an intact capillary network in the scaffold. Morphometry analysis demonstrated a significant increase in alveolar fractional volume, with alveolar size analysis confirming that alveolar dimensions were maintained. Biomechanical testing of the scaffolds indicated an increase in resistance and elastance when compared to fresh lungs. Staining and quantification for ECM components showed a presence of collagen, elastin, GAG and laminin. The intratracheal intermittent decellularization methodology could be translated to sheep lungs, demonstrating a preservation of ECM components, alveolar and vascular architecture. Decellularization treatment and methodology preserves lung architecture and ECM whilst reducing the production time to 3 h. Cell seeding and in vivo experiments are necessary to proceed towards clinical translation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Endoscopic treatment of Roux-en-Y gastric bypass-related gastrocutaneous fistulas using a novel biomaterial.

PubMed

Maluf-Filho, Fauze; Hondo, Fabio; Halwan, Bhawna; de Lima, Marcelo Simas; Giordano-Nappi, José Humberto; Sakai, Paulo

2009-07-01

Roux-en-Y gastric bypass (RYGB) is amongst the commonest surgical intervention for weight loss in obese patients. Gastrocutaneous fistula, which usually occurs along the vertical staple line of the pouch, is amongst its most alarming complications. Medical management comprised of wound drainage, nutritional support, acid suppression, and antibiotics may be ineffective in as many as a third of patients with this complication. We present outcomes after endoscopic application of SurgiSIS, which is a novel biomaterial for the treatment of this complication. A case series of 25 patients. Twenty-five patients who had failed conservative medical management of gastrocutaneous fistula after RYGB underwent endoscopic application of SurgiSIS--an acellular fibrogenic matrix biomaterial to help fistula healing. Fistula closure as assessed by upper gastrointestinal imaging and endoscopic examination. In patients who had failed medical management lasting 4-25 (median, 7) weeks, closure of the fistulous tract was successful after one application in six patients (30%), two applications in 11 patients (55%), and three applications in three patients (15%). There were no procedure-related complications. Endoscopic application of SurgiSIS-an acellular fibrogenic matrix--is safe and effective for the treatment of gastrocutaneous fistula after RYGB.

Blood Vessel-Derived Acellular Matrix for Vascular Graft Application

PubMed Central

Dall'Olmo, Luigi; Zanusso, Ilenia; Di Liddo, Rosa; Chioato, Tatiana; Bertalot, Thomas; Conconi, Maria Teresa

2014-01-01

To overcome the issues connected to the use of autologous vascular grafts and artificial materials for reconstruction of small diameter (<6 mm) blood vessels, this study aimed to develop acellular matrix- (AM-) based vascular grafts. Rat iliac arteries were decellularized by a detergent-enzymatic treatment, whereas endothelial cells (ECs) were obtained through enzymatic digestion of rat skin followed by immunomagnetic separation of CD31-positive cells. Sixteen female Lewis rats (8 weeks old) received only AM or previously in vitro reendothelialized AM as abdominal aorta interposition grafts (about 1 cm). The detergent-enzymatic treatment completely removed the cellular part of vessels and both MHC class I and class II antigens. One month after surgery, the luminal surface of implanted AMs was partially covered by ECs and several platelets adhered in the areas lacking cell coverage. Intimal hyperplasia, already detected after 1 month, increased at 3 months. On the contrary, all grafts composed by AM and ECs were completely covered at 1 month and their structure was similar to that of native vessels at 3 months. Taken together, our findings show that prostheses composed of AM preseeded with ECs could be a promising approach for the replacement of blood vessels. PMID:25136610

The impact of high-dose narrowband ultraviolet A1 on dermal thickness, collagen and matrix-metalloproteinases in animal model of scleroderma.

PubMed

Karpec, Diana; Rudys, Romualdas; Leonaviciene, Laima; Mackiewicz, Zygmunt; Bradunaite, Ruta; Kirdaite, Gailute; Venalis, Algirdas

2017-08-01

The main purpose of the present study was to define the impact of high-dose of 365±5nm ultraviolet A1 (UVA1) on dermal fibrosis in the pre-established, bleomycin-induced mouse model of scleroderma. DBA/2 strain mice with the pre-established, bleomycin-induced scleroderma were irradiated with cumulative UVA1 dose of 1200J/cm 2 and in parallel were challenged with prolonged administration of bleomycin. Non-treated groups served as the control. Light source emitting a narrow band UVA1 light of 365±5nm and 21mW/cm 2 power density was used in the study. Histological analysis was performed for the evaluation of dermal thickness. The expressions of matrix-metalloproteinase-1 (MMP-1), matrix-metalloproteinase-3 (MMP-3), collagen types I and III were evaluated by immunohistochemical analyses. The Mann - Whitney U test was used for statistical analysis. Dermal thickness in mice injected with bleomycin during all the experiment (8weeks) and irradiated with UVA1 for the last 5weeks was significantly lower than that in mice challenged only with bleomycin for 8weeks (253.96±31.83μm and 497.43±57.83μm, respectively; P=0.002). The dermal thickness after phototherapy was lower as compared with the pre-existing fibrotic changes observed after 3weeks of bleomycin injections (253.96±31.83μm and 443.87±41.76μm, respectively; P=0.002). High-dose of UVA1 induced the 5.8- and 5.2-fold increase in MMP-1 and MMP-3 expressions, respectively, and the 1.2- and 1.4-fold decrease in collagen type I and collagen type III expressions in the pre-established, bleomycin-induced scleroderma model as compared to that in the control non-irradiated mice (P=0.002). Our study has demonstrated that a cumulative 365±5nm UVA1 radiation dosage of 1200J/cm 2 not only prevents the progression of dermal fibrosis, but also induces a regression of pre-existing fibrotic changes. Copyright © 2017 Elsevier B.V. All rights reserved.

Periodontal soft tissue root coverage procedures: a consensus report from the AAP Regeneration Workshop.

PubMed

Tatakis, Dimitris N; Chambrone, Leandro; Allen, Edward P; Langer, Burton; McGuire, Michael K; Richardson, Christopher R; Zabalegui, Ion; Zadeh, Homayoun H

2015-02-01

Management of gingival recession defects, a common periodontal condition, using root coverage procedures is an important aspect of periodontal regenerative therapy. The goal of the periodontal soft tissue root coverage procedures group was to develop a consensus report based on the accompanying systematic review of root coverage procedures, including priorities for future research and identification of the best evidence available to manage different clinical scenarios. The group reviewed and discussed the accompanying systematic review, which covered treatment of single-tooth recession defects, multiple-tooth recession defects, and additional focused questions on relevant clinical topics. The consensus group members submitted additional material for consideration by the group in advance and at the time of the meeting. The group also identified priorities for future research. All reviewed root coverage procedures provide significant reduction in recession depth, especially for Miller Class I and II recession defects. Subepithelial connective tissue graft (SCTG) procedures provide the best root coverage outcomes. Acellular dermal matrix graft (ADMG) or enamel matrix derivative (EMD) in conjunction with a coronally advanced flap (CAF) can serve as alternatives to autogenous donor tissue. Additional research is needed to do the following: 1) assess the treatment outcomes for multiple-tooth recession defects, oral sites other than maxillary canine and premolar teeth, and Miller Class III and IV defects; 2) assess the role of patient- and site-specific factors on procedure outcomes; and 3) obtain evidence on patient-reported outcomes. Predictable root coverage is possible for single-tooth and multiple-tooth recession defects, with SCTG procedures providing the best root coverage outcomes. Alternatives to SCTG are supported by evidence of varying strength. Additional research is needed on treatment outcomes for specific oral sites. Clinical Recommendation: For Miller Class I and II single-tooth recession defects, SCTG procedures provide the best outcomes, whereas ADMG or EMD in conjunction with CAF may be used as an alternative.

Clinical Outcomes of Comparing Soft Tissue Alternatives to Free Gingival Graft: A Systematic Review and Meta-Analysis
.

PubMed

Dragan, Irina F; Hotlzman, Lucrezia Paterno; Karimbux, Nadeem Y; Morin, Rebecca A; Bassir, Seyed Hossein

2017-12-01

This systematic review and meta-analysis aimed to compare clinical outcomes and width of keratinized tissue (KT) around teeth, following the soft tissue alter- natives and free gingival graft (FGG) procedures. The specific graft materials that were explored were extracellular matrix membrane, bilayer collagen membrane, living cellular construct, and acellular dermal matrix. Four different databases were queried to identify human controlled clinical trials and randomized controlled clinical trials that fulfilled the eligibility criteria. Relevant studies were identified by 3 independent reviewers, compiling the results of the electronic and handsearches. Studies identified through electronic and handsearches were reviewed by title, abstract, and full text using Covidence Software. Primary outcome in the present study was change in the width of KT. Results of the included studies were pooled to estimate the effect size, expressed as weighted mean differences and 95% confidence interval. A random-effects model was used to perform the meta-analyses. Six hundred thirty-eight articles were screened by title, 55 articles were screened by abstracts, and 34 full-text articles were reviewed. Data on quantitative changes in width of KT were provided in 7 studies. Quantitative analyses revealed a significant difference in changes in width of KT between patients treated with soft tissue alternatives and patients treated with FGGs (P < .001). The weighted mean difference of changes in the width of KT was 21.39 (95% confidence interval: 21.82 to 20.96; heterogeneity I 5 70.89%), indicating patients who were treated with soft tissue alternatives gained 1.39 mm less KT width compared with the patients who received free gingival graft. Based on the clinical outcomes, the results of this systematic review and meta-analysis showed that soft tissue alternatives result in an increased width of KT. Patients in the soft tissue alternatives group obtained 1.39 mm less KT compared with those in the FGGs group. Copyright © 2017 Elsevier Inc. All rights reserved.

Bladder tissue regeneration using acellular bi-layer silk scaffolds in a large animal model of augmentation cystoplasty.

PubMed

Tu, Duong D; Chung, Yeun Goo; Gil, Eun Seok; Seth, Abhishek; Franck, Debra; Cristofaro, Vivian; Sullivan, Maryrose P; Di Vizio, Dolores; Gomez, Pablo; Adam, Rosalyn M; Kaplan, David L; Estrada, Carlos R; Mauney, Joshua R

2013-11-01

Acellular scaffolds derived from Bombyx mori silk fibroin were investigated for their ability to support functional tissue regeneration in a porcine model of augmentation cystoplasty. Two bi-layer matrix configurations were fabricated by solvent-casting/salt leaching either alone (Group 1) or in combination with silk film casting (Group 2) to yield porous foams buttressed by heterogeneous surface pore occlusions or homogenous silk films, respectively. Bladder augmentation was performed with each scaffold group (6 × 6 cm(2)) in juvenile Yorkshire swine for 3 m of implantation. Augmented animals exhibited high rates of survival (Group 1: 5/6, 83%; Group 2: 4/4, 100%) and voluntary voiding over the course of the study period. Urodynamic evaluations demonstrated mean increases in bladder capacity over pre-operative levels (Group 1: 277%; Group 2: 153%) which exceeded nonsurgical control gains (144%) encountered due to animal growth.In addition, animals augmented with both matrix configurations displayed increases in bladder compliance over pre-operative levels(Group 1: 357%; Group 2: 338%) similar to growth-related elevations observed in non-surgical controls (354%) [corrected]. Gross tissue evaluations revealed that both matrix configurations supported extensive de novo tissue formation throughout the entire original implantation site which exhibited ultimate tensile strength similar to nonsurgical counterparts. Histological and immunohistochemical analyses showed that both implant groups promoted comparable extents of smooth muscle regeneration and contractile protein (α-smooth muscle actin and SM22α) expression within defect sites similar to controls. Parallel evaluations demonstrated the formation of a transitional, multi-layered urothelium with prominent cytokeratin, uroplakin, and p63 protein expression in both matrix groups. De novo innervation and vascularization processes were evident in all regenerated tissues indicated by synaptophysin-positive neuronal cells and vessels lined with CD31 expressing endothelial cells. Ex vivo organ bath studies demonstrated that regenerated tissues supported by both silk matrices displayed contractile responses to carbachol, α,β-methylene-ATP, KCl, and electrical field stimulation similar to controls. Our data detail the ability of acellular silk scaffolds to support regeneration of innervated, vascularized smooth muscle and urothelial tissues within 3 m with structural, mechanical, and functional properties comparable to native tissue in a porcine model of bladder repair. © 2013 Elsevier Ltd. All rights reserved.

Use of human and porcine dermal-derived bioprostheses in complex abdominal wall reconstructions: a literature review and case report.

PubMed

Baillie, Daniel R; Stawicki, S Peter; Eustance, Nicole; Warsaw, David; Desai, Darius

2007-05-01

The goal of abdominal wall reconstruction is to restore and maintain abdominal domain. A PubMed(R) review of the literature (including "old" MEDLINE through February 2007) suggests that bioprosthetic materials are increasingly used to facilitate complex abdominal wall reconstruction. Reported results (eight case reports/series involving 137 patients) are encouraging. The most commonly reported complications are wound seroma (18 patients, 13%), skin dehiscence with graft exposure without herniation (six, 4.4%), superficial and deep wound infections (five, 3.6%), hernia recurrence (four, 2.9%), graft failure with dehiscence (two), hematoma (two), enterocutaneous fistula (one), and flap necrosis (one). Two recent cases are reported herein. In one, a 46-year-old woman required open abdominal management after gastric remnant perforation following a Roux-en-Y gastric bypass procedure. Porcine dermal collagen combined with cutaneous flaps was used for definitive abdominal wall reconstruction. The patient's condition improved postoperatively and she was well 5 months after discharge from the hospital. In the second, a 54-year-old woman underwent repair of an abdominal wall defect following resection of a large leiomyosarcoma. Human acellular dermis combined with myocutaneous flaps was used to reconstruct the abdominal wall defect. The patient's recovery was uncomplicated and 20 weeks following surgery she was doing well with no evidence of recurrence or hernia. The results reported to date and the outcomes presented here suggest that bioprosthetic materials are safe and effective for repair of large abdominal wall defects. Prospective, randomized, controlled studies are needed to compare the safety and efficacy of other reconstructive techniques as well as human and porcine dermal-derived bioprostheses.

Characterization of dermal plates from armored catfish Pterygoplichthys pardalis reveals sandwich-like nanocomposite structure.

PubMed

Ebenstein, Donna; Calderon, Carlos; Troncoso, Omar P; Torres, Fernando G

2015-05-01

Dermal plates from armored catfish are bony structures that cover their body. In this paper we characterized structural, chemical, and nanomechanical properties of the dermal plates from the Amazonian fish Pterygoplichthys pardalis. Analysis of the morphology of the plates using scanning electron microscopy (SEM) revealed that the dermal plates have a sandwich-like structure composed of an inner porous matrix surrounded by two external dense layers. This is different from the plywood-like laminated structure of elasmoid fish scales but similar to the structure of osteoderms found in the dermal armour of some reptiles and mammals. Chemical analysis performed using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results revealed similarities between the composition of P. pardalis plates and the elasmoid fish scales of Arapaima gigas. Reduced moduli of P. pardalis plates measured using nanoindentation were also consistent with reported values for A. gigas scales, but further revealed that the dermal plate is an anisotropic and heterogeneous material, similar to many other fish scales and osteoderms. It is postulated that the sandwich-like structure of the dermal plates provides a lightweight and tough protective layer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chronic UVB-irradiation actuates perpetuated dermal matrix remodeling in female mice: Protective role of estrogen

PubMed Central

Röck, Katharina; Joosse, Simon Andreas; Müller, Julia; Heinisch, Nina; Fuchs, Nicola; Meusch, Michael; Zipper, Petra; Reifenberger, Julia; Pantel, Klaus; Fischer, Jens Walter

2016-01-01

Chronic UVB-exposure and declined estradiol production after menopause represent important factors leading to extrinsic and intrinsic aging, respectively. Remodeling of the extracellular matrix (ECM) plays a crucial role in both responses. Whether the dermal ECM is able to recover after cessation of UVB-irradiation in dependence of estradiol is not known, however of relevance when regarding possible treatment options. Therefore, the endogenous sex hormone production was depleted by ovariectomy in female mice. Half of the mice received estradiol substitution. Mice were UVB-irradiated for 20 weeks and afterwards kept for 10 weeks without irradiation. The collagen-, hyaluronan- and proteoglycan- (versican, biglycan, lumican) matrix, collagen cleavage products and functional skin parameters were analyzed. The intrinsic aging process was characterized by increased collagen fragmentation and accumulation of biglycan. Chronic UVB-irradiation additionally augmented the lumican, versican and hyaluronan content of the dermis. In the absence of further UVB-irradiation the degradation of collagen and accumulation of biglycan in the extrinsically aged group was perpetuated in an excessive matter. Whereas estradiol increased the proteoglycan content, it reversed the effects of the perpetuated extrinsic response on collagen degradation. Suspension of the intrinsic pathway might therefore be sufficient to antagonize UVB-evoked long-term damage to the dermal ECM. PMID:27460287

Mycobacterium fortuitum Infection following Reconstructive Breast Surgery: Differentiation from Classically Described Red Breast Syndrome.

PubMed

Cicilioni, Orlando J; Foles, Van Brandon; Sieger, Barry; Musselman, Kelly

2013-10-01

Red breast syndrome (RBS) has been described as an erythema that may be associated with 2-stage prosthetic reconstructive breast surgery using biologic mesh. RBS is differentiated from infectious cellulitis through absence of fever and laboratory abnormalities and usually has a self-limiting course. There have been no clinical reports on etiology, risk factors, or management of RBS. This report describes patient data that raise the need to rule out mycobacterial infection when RBS is being considered as a diagnosis. We present 6 cases of Mycobacterium fortuitum infection occurring after prosthetic breast reconstruction performed with a human-derived acellular dermal matrix, including the timing and course of erythema, laboratory results, treatments used, and long-term outcomes. We also describe the differential diagnoses of RBS in the context of these cases, including emergence of acid-fast bacilli and diagnostic and treatment considerations. Exact two-tailed 95% confidence intervals based on the F-distribution are provided with estimates of the incidence rates of infection. The 6 cases presented here do not fit the typical description of RBS and were caused by mycobacterium infection. Statistical evaluation of the estimated incidence rate of M. fortuitum infection in a patient thought to have RBS, which occurred 100% of the time in this series, revealed a 95% confidence interval of 54.1-100%. When presented with possible RBS, surgeons must rule out cellulitis, culture for acid-fast bacilli such as mycobacterium species, and then determine the best course of treatment. Patient counseling regarding potential household sources of infection is warranted to minimize postoperative infection risk.

Porcine bladder acellular matrix (ACM): protein expression, mechanical properties.

PubMed

Farhat, Walid A; Chen, Jun; Haig, Jennifer; Antoon, Roula; Litman, Jessica; Sherman, Christopher; Derwin, Kathleen; Yeger, Herman

2008-06-01

Experimentally, porcine bladder acellular matrix (ACM) that mimics extracellular matrix has excellent potential as a bladder substitute. Herein we investigated the spatial localization and expression of different key cellular and extracellular proteins in the ACM; furthermore, we evaluated the inherent mechanical properties of the resultant ACM prior to implantation. Using a proprietary decellularization method, the DNA contents in both ACM and normal bladder were measured; in addition we used immunohistochemistry and western blots to quantify and localize the different cellular and extracellular components, and finally the mechanical testing was performed using a uniaxial mechanical testing machine. The mean DNA content in the ACM was significantly lower in the ACM compared to the bladder. Furthermore, the immunohistochemical and western blot analyses showed that collagen I and IV were preserved in the ACM, but possibly denatured collagen III in the ACM. Furthermore, elastin, laminin and fibronectin were mildly reduced in the ACM. Although the ACM did not exhibit nucleated cells, residual cellular components (actin, myosin, vimentin and others) were still present. There was, on the other hand, no significant difference in the mean stiffness between the ACM and the bladder. Although our decellularization method is effective in removing nuclear material from the bladder while maintaining its inherent mechanical properties, further work is mandatory to determine whether these residual DNA and cellular remnants would lead to any immune reaction, or if the mechanical properties of the ACM are preserved upon implantation and cellularization.

Early biocompatibility of crosslinked and non-crosslinked biologic meshes in a porcine model of ventral hernia repair.

PubMed

Melman, L; Jenkins, E D; Hamilton, N A; Bender, L C; Brodt, M D; Deeken, C R; Greco, S C; Frisella, M M; Matthews, B D

2011-04-01

Biologic meshes have unique physical properties as a result of manufacturing techniques such as decellularization, crosslinking, and sterilization. The purpose of this study is to directly compare the biocompatibility profiles of five different biologic meshes, AlloDerm(®) (non-crosslinked human dermal matrix), PeriGuard(®) (crosslinked bovine pericardium), Permacol(®) (crosslinked porcine dermal matrix), Strattice(®) (non-crosslinked porcine dermal matrix), and Veritas(®) (non-crosslinked bovine pericardium), using a porcine model of ventral hernia repair. Full-thickness fascial defects were created in 20 Yucatan minipigs and repaired with the retromuscular placement of biologic mesh 3 weeks later. Animals were euthanized at 1 month and the repair sites were subjected to tensile testing and histologic analysis. Samples of unimplanted (de novo) meshes and native porcine abdominal wall were also analyzed for their mechanical properties. There were no significant differences in the biomechanical characteristics between any of the mesh-repaired sites at 1 month postimplantation or between the native porcine abdominal wall without implanted mesh and the mesh-repaired sites (P > 0.05 for all comparisons). Histologically, non-crosslinked materials exhibited greater cellular infiltration, extracellular matrix (ECM) deposition, and neovascularization compared to crosslinked meshes. While crosslinking differentiates biologic meshes with regard to cellular infiltration, ECM deposition, scaffold degradation, and neovascularization, the integrity and strength of the repair site at 1 month is not significantly impacted by crosslinking or by the de novo strength/stiffness of the mesh.

Efficient dermal delivery of retinyl palmitate: Progressive polarimetry and Raman spectroscopy to evaluate the structure and efficacy.

PubMed

Lee, Jun Bae; Lee, Dong Ryeol; Choi, Nak Cho; Jang, Jihui; Park, Chun Ho; Yoon, Moung Seok; Lee, Miyoung; Won, Kyoungae; Hwang, Jae Sung; Kim, B Moon

2015-10-12

Over the past decades, there has been a growing interest in dermal drug delivery. Although various novel delivery devices and methods have been developed, dermal delivery is still challenging because of problems such as poor drug permeation, instability of vesicles and drug leakage from vesicles induced by fusion of vesicles. To solve the vesicle instability problems in current dermal delivery systems, we developed materials comprised of liquid crystals as a new delivery vehicle of retinyl palmitate and report the characterization of the liquid crystals using a Mueller matrix polarimetry. The stability of the liquid-crystal materials was evaluated using the polarimeter as a novel evaluation tool along with other conventional methods. The dermal delivery of retinyl palmitate was investigated through the use of confocal Raman spectroscopy. The results indicate that the permeation of retinyl palmitate was enhanced by up to 106% compared to that using an ordinary emulsion with retinyl palmitate. Copyright © 2015 Elsevier B.V. All rights reserved.

Outcomes with porcine acellular dermal matrix versus synthetic mesh and suture in complicated open ventral hernia repair.

PubMed

Liang, Mike K; Berger, Rachel L; Nguyen, Mylan Thi; Hicks, Stephanie C; Li, Linda T; Leong, Mimi

2014-10-01

Mesh reinforcement as part of open ventral hernia repair (OVHR) has become the standard of care. However, there is no consensus on the ideal type of mesh to use. In many clinical situations, surgeons are reluctant to use synthetic mesh. Options in these complicated OVHRs include suture repair or the use of biologic mesh such as porcine acellular dermal matrix (PADM). There has been a paucity of controlled studies reporting long-term outcomes with biologic meshes. We hypothesized that compared with synthetic mesh in OVHR, PADM is associated with fewer surgical site infections (SSI) but more seromas and recurrences. Additionally, compared with suture repair, we hypothesized that PADM is associated with fewer recurrences but more SSIs and seromas. A retrospective study was performed of all complicated OVHRs performed at a single institution from 2000-2011. All data were captured from the electronic medical records of the service network. Data were compared in two ways. First, patients who had OVHR with PADM were case-matched with patients having synthetic mesh repairs on the basis of incision class, Ventral Hernia Working Group (VHWG) grade, hernia size, American Society of Anesthesiologists (ASA) class, and emergency status. The PADM cases were also matched with suture repairs on the basis of incision class, hernia grade, duration of the operation, ASA class, and emergency status. Second, we developed a propensity score-adjusted multi-variable logistic regression model utilizing internal resampling to identify predictors of primary outcomes of the overall cohort. The U.S. Centers for Disease Control and Prevention (CDC) definition of SSI was utilized; seromas and recurrences were defined and tracked similarly for all patients. Data were analyzed using the McNemar, X(2), paired two-tailed Student t, or Mann-Whitney U test as appropriate. A total of 449 complicated OVHR cases were reviewed for a median follow up of 61 mos (range 1-143 mos): 94 patients had PADM repairs, whereas 154 patients underwent synthetic mesh repairs, and 201 had suture repairs. The 40 PADM repairs were matched to synthetic repairs and 59 were matched to suture repairs. The PADM repairs that could not be well matched (n=54 unmatched for synthetic repairs, 35 unmatched for suture repairs) were characterized generally by larger hernias, VHWG grades of 3 or 4, and incision class 3 or 4 with longer operative durations and more ASA class 4 cases. The patients were well matched. Comparing PADM with synthetic mesh, there was no difference in SSI (20% vs. 35%; p=0.29), seromas (32.5% vs. 15%; p=0.17), mesh explantations (5% vs. 15%, p=0.28), readmissions within 90 d (37.5% vs. 45%; p=1.00), or recurrence (8.5% vs. 22.5%; p=0.15). Compared with suture repair, patients with PADM had fewer recurrences (11.9% vs. 33.9%; p<0.01) and more seromas (32.2% vs. 10.2%; p=0.02), but a similar number of SSIs (23.7% vs. 39.0%; p=0.19) and 90-d readmissions (35.6% vs. 39.0%; p=0.88). Propensity score-adjusted multi-variable logistic regression of the entire cohort corroborated the results of the case-matched patients. The PADM repair of complicated OVHR resulted in fewer recurrences, more seromas, and no difference in SSI compared with suture repair. Although no reduction in SSI was identified with the use of PADM rather than synthetic mesh or suture for OVHR, the meaning of this finding is unclear, as this case-controlled study was underpowered and limited by selection bias. According to our data, 280 patients would have been needed to identify a clinically significant difference in the primary outcome of SSI as well as secondary outcomes of mesh explantation and recurrence (α=0.05; β=0.20). A randomized trial is warranted to compare PADM with synthetic mesh in complicated OVHR.

Construction of a 3D rGO-collagen hybrid scaffold for enhancement of the neural differentiation of mesenchymal stem cells

NASA Astrophysics Data System (ADS)

Guo, Weibo; Wang, Shu; Yu, Xin; Qiu, Jichuan; Li, Jianhua; Tang, Wei; Li, Zhou; Mou, Xiaoning; Liu, Hong; Wang, Zhonglin

2016-01-01

The cell-material interface is one of the most important considerations in designing a high-performance tissue engineering scaffold because the surface of the scaffold can determine the fate of stem cells. A conductive surface is required for a scaffold to direct stem cells toward neural differentiation. However, most conductive polymers are toxic and not amenable to biological degradation, which restricts the design of neural tissue engineering scaffolds. In this study, we used a bioactive three-dimensional (3D) porcine acellular dermal matrix (PADM), which is mainly composed of type I collagen, as a basic material and successfully assembled a layer of reduced graphene oxide (rGO) nanosheets on the surface of the PADM channels to obtain a porous 3D, biodegradable, conductive and biocompatible PADM-rGO hybrid neural tissue engineering scaffold. Compared with the PADM scaffold, assembling the rGO into the scaffold did not induce a significant change in the microstructure but endowed the PADM-rGO hybrid scaffold with good conductivity. A comparison of the neural differentiation of rat bone-marrow-derived mesenchymal stem cells (MSCs) was performed by culturing the MSCs on PADM and PADM-rGO scaffolds in neuronal culture medium, followed by the determination of gene expression and immunofluorescence staining. The results of both the gene expression and protein level assessments suggest that the rGO-assembled PADM scaffold may promote the differentiation of MSCs into neuronal cells with higher protein and gene expression levels after 7 days under neural differentiation conditions. This study demonstrated that the PADM-rGO hybrid scaffold is a promising scaffold for neural tissue engineering; this scaffold can not only support the growth of MSCs at a high proliferation rate but also enhance the differentiation of MSCs into neural cells.The cell-material interface is one of the most important considerations in designing a high-performance tissue engineering scaffold because the surface of the scaffold can determine the fate of stem cells. A conductive surface is required for a scaffold to direct stem cells toward neural differentiation. However, most conductive polymers are toxic and not amenable to biological degradation, which restricts the design of neural tissue engineering scaffolds. In this study, we used a bioactive three-dimensional (3D) porcine acellular dermal matrix (PADM), which is mainly composed of type I collagen, as a basic material and successfully assembled a layer of reduced graphene oxide (rGO) nanosheets on the surface of the PADM channels to obtain a porous 3D, biodegradable, conductive and biocompatible PADM-rGO hybrid neural tissue engineering scaffold. Compared with the PADM scaffold, assembling the rGO into the scaffold did not induce a significant change in the microstructure but endowed the PADM-rGO hybrid scaffold with good conductivity. A comparison of the neural differentiation of rat bone-marrow-derived mesenchymal stem cells (MSCs) was performed by culturing the MSCs on PADM and PADM-rGO scaffolds in neuronal culture medium, followed by the determination of gene expression and immunofluorescence staining. The results of both the gene expression and protein level assessments suggest that the rGO-assembled PADM scaffold may promote the differentiation of MSCs into neuronal cells with higher protein and gene expression levels after 7 days under neural differentiation conditions. This study demonstrated that the PADM-rGO hybrid scaffold is a promising scaffold for neural tissue engineering; this scaffold can not only support the growth of MSCs at a high proliferation rate but also enhance the differentiation of MSCs into neural cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06602f

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

Fan, Rong-hui, E-mail: fan_ronghuixa@163.com; Zhu, Xiu-mei; Sun, Yao-wen

Skin fibrosis is characterized by excessive proliferation of fibroblasts and overproduction of extracellular matrix (ECM). C1q/tumor necrosis factor-related protein 6 (CTRP6), a member of CTRPs, has been involved in the development of cardiac fibrosis. However, the function and detailed regulatory mechanism of CTRP6 in skin fibrosis remain unclear. The aim of this study was to investigate the effect of CTRP6 on the activation of human dermal fibroblasts. Our results showed that CTRP6 was lowly expressed in scar tissues and transforming growth factor-β1 (TGF-β1)-treated dermal fibroblasts. CTRP6 overexpression significantly inhibited the proliferation of dermal fibroblasts, as well as suppressed the expressionmore » of ECM in TGF-β1-treated dermal fibroblasts. Furthermore, CTRP6 overexpression markedly inhibited TGF-β1-induced phosphorylation of Smad3 in dermal fibroblasts. In conclusion, the data reported here demonstrate that CTRP6 is able to inhibit the proliferation and ECM expression in human dermal fibroblasts through suppressing the TGF-β1/Smad3 signaling pathway. These findings suggest that CTRP6 may be a potential therapeutic target for the prevention of skin fibrosis. -- Highlights: •CTRP6 expression was decreased in scar tissues and TGF-β1-treated dermal fibroblasts. •CTRP6 inhibits TGF-β1-induced the proliferation of dermal fibroblasts. •CTRP6 inhibits expression of collagen type I and α-SMA. •CTRP6 inhibits the activation of TGF-β1/Smad3 signaling pathway in dermal fibroblasts.« less

Perilla frutescens leaves extract ameliorates ultraviolet radiation-induced extracellular matrix damage in human dermal fibroblasts and hairless mice skin.

PubMed

Bae, Jung-Soo; Han, Mira; Shin, Hee Soon; Kim, Min-Kyoung; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

2017-01-04

Perilla frutescens (L.) Britt. (Lamiaceae) is a traditional herb that is consumed in East Asian countries as a traditional medicine. This traditional herb has been documented for centuries to treat various diseases such as depression, allergies, inflammation and asthma. However, the effect of Perilla frutescens on skin has not been characterized well. The present study aimed to investigate the effect of Perilla frutescens leaves extract (PLE) on ultraviolet radiation-induced extracellular matrix damage in human dermal fibroblasts and hairless mice skin. Human dermal fibroblasts and Skh-1 hairless mice were irradiated with UV and treated with PLE. Protein and mRNA levels of various target molecules were analyzed by western blotting and quantitative RT-PCR, respectively. Histological changes of mouse skin were analyzed by H&E staining. To elucidate underlying mechanism of PLE, activator protein-1 (AP-1) DNA binding assay and the measurement of reactive oxygen species (ROS) were performed. PLE significantly inhibited basal and UV-induced MMP-1 and MMP-3 expression dose-dependently, and also decreased UV-induced phosphorylation of extracellular signal-regulated kinases and c-Jun N-terminal kinases. This inhibitory effects of PLE on MMP-1 and MMP-3 were mediated by reduction of ROS generation and AP-1 DNA binding activity induced by UV. Furthermore, PLE promoted type I procollagen production irrespective of UV irradiation. In the UV-irradiated animal model, PLE significantly reduced epidermal skin thickness and MMP-13 expression induced by UV. Our results demonstrate that PLE has the protective effect against UV-induced dermal matrix damage. Therefore, we suggest that PLE can be a potential agent for prevention of skin aging. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Organic composite-mediated surface coating of human acellular bone matrix with strontium.

PubMed

Huang, Yi-Zhou; Wang, Jing-Jing; Huang, Yong-Can; Wu, Cheng-Guang; Zhang, Yi; Zhang, Chao-Liang; Bai, Lin; Xie, Hui-Qi; Li, Zhao-Yang; Deng, Li

2018-03-01

Acellular bone matrix (ACBM) provides an osteoconductive scaffold for bone repair, but its osteoinductivity is poor. Strontium (Sr) improves the osteoinductivity of bone implants. In this study, we developed an organic composite-mediated strontium coating strategy for ACBM scaffolds by using the ion chelating ability of carboxymethyl cellulose (CMC) and the surface adhesion ability of dopamine (DOPA). The organic coating composite, termed the CMC-DOPA-Sr composite, was synthesized under a mild condition, and its chemical structure and strontium ion chelating ability were then determined. After surface decoration, the physicochemical properties of the strontium-coated ACBM (ACBM-Sr) scaffolds were characterized, and their biocompatibility and osteoinductivity were determined in vitro and in vivo. The results showed that the CMC-DOPA-Sr composite facilitated strontium coating on the surface of ACBM scaffolds. The ACBM-Sr scaffolds possessed a sustained strontium ion release profile, exhibited good cytocompatibility, and enhanced the osteogenic differentiation of mesenchymal stem cells in vitro. Furthermore, the ACBM-Sr scaffolds showed good histocompatibility after subcutaneous implantation in nude mice. Taken together, this study provided a simple and mild strategy to realize strontium coating for ACBM scaffolds, which resulted in good biocompatibility and improved osteoinductivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Recellularization of Rat Liver Scaffolds by Human Liver Stem Cells

PubMed Central

Navarro-Tableros, Victor; Herrera Sanchez, Maria Beatriz; Figliolini, Federico; Romagnoli, Renato; Tetta, Ciro

2015-01-01

In the present study, rat liver acellular scaffolds were used as biological support to guide the differentiation of human liver stem-like cells (HLSC) to hepatocytes. Once recellularized, the scaffolds were maintained for 21 days in different culture conditions to evaluate hepatocyte differentiation. HLSC lost the embryonic markers (alpha-fetoprotein, nestin, nanog, sox2, Musashi1, Oct 3/4, and pax2), increased the expression of albumin, and acquired the expression of lactate dehydrogenase and three subtypes of cytochrome P450. The presence of urea nitrogen in the culture medium confirmed their metabolic activity. In addition, cells attached to tubular remnant matrix structures expressed cytokeratin 19, CD31, and vimentin. The rat extracellular matrix (ECM) provides not only a favorable environment for differentiation of HLSC in functional hepatocytes (hepatocyte like) but also promoted the generation of some epithelial-like and endothelial-like cells. When fibroblast growth factor–epidermal growth factor or HLSC-derived conditioned medium was added to the perfusate, an improvement of survival rate was observed. The conditioned medium from HLSC potentiated also the metabolic activity of hepatocyte-like cells repopulating the acellular liver. In conclusion, HLSC have the potential, in association with the natural ECM, to generate in vitro a functional “humanized liver-like tissue.” PMID:25794768

Biophysical properties of dermal building-blocks affects extra cellular matrix assembly in 3D endogenous macrotissue.

PubMed

Urciuolo, F; Garziano, A; Imparato, G; Panzetta, V; Fusco, S; Casale, C; Netti, P A

2016-01-29

The fabrication of functional tissue units is one of the major challenges in tissue engineering due to their in vitro use in tissue-on-chip systems, as well as in modular tissue engineering for the construction of macrotissue analogs. In this work, we aim to engineer dermal tissue micromodules obtained by culturing human dermal fibroblasts into porous gelatine microscaffold. We proved that such stromal cells coupled with gelatine microscaffolds are able to synthesize and to assemble an endogenous extracellular matrix (ECM) resulting in tissue micromodules, which evolve their biophysical features over the time. In particular, we found a time-dependent variation of oxygen consumption kinetic parameters, of newly formed ECM stiffness and of micromodules self-aggregation properties. As consequence when used as building blocks to fabricate larger tissues, the initial tissue micromodules state strongly affects the ECM organization and maturation in the final macrotissue. Such results highlight the role of the micromodules properties in controlling the formation of three-dimensional macrotissue in vitro, defining an innovative design criterion for selecting tissue-building blocks for modular tissue engineering.

Design of a Novel Two-Component Hybrid Dermal Scaffold for the Treatment of Pressure Sores.

PubMed

Sharma, Vaibhav; Kohli, Nupur; Moulding, Dale; Afolabi, Halimat; Hook, Lilian; Mason, Chris; García-Gareta, Elena

2017-11-01

The aim of this study is to design a novel two-component hybrid scaffold using the fibrin/alginate porous hydrogel Smart Matrix combined to a backing layer of plasma polymerized polydimethylsiloxane (Sil) membrane to make the fibrin-based dermal scaffold more robust for the treatment of the clinically challenging pressure sores. A design criteria are established, according to which the Sil membranes are punched to avoid collection of fluid underneath. Manual peel test shows that native silicone does not attach to the fibrin/alginate component while the plasma polymerized silicone membranes are firmly bound to fibrin/alginate. Structural characterization shows that the fibrin/alginate matrix is intact after the addition of the Sil membrane. By adding a Sil membrane to the original fibrin/alginate scaffold, the resulting two-component scaffolds have a significantly higher shear or storage modulus G'. In vitro cell studies show that dermal fibroblasts remain viable, proliferate, and infiltrate the two-component hybrid scaffolds during the culture period. These results show that the design of a novel two-component hybrid dermal scaffold is successful according to the proposed design criteria. To the best of the authors' knowledge, this is the first study that reports the combination of a fibrin-based scaffold with a plasma-polymerized silicone membrane. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of cultured human dermal- and dermo-epidermal substitutes focusing on extracellular matrix components: Comparison of protein and RNA analysis.

PubMed

Oostendorp, Corien; Meyer, Sarah; Sobrio, Monia; van Arendonk, Joyce; Reichmann, Ernst; Daamen, Willeke F; van Kuppevelt, Toin H

2017-05-01

Treatment of full-thickness skin defects with split-thickness skin grafts is generally associated with contraction and scar formation and cellular skin substitutes have been developed to improve skin regeneration. The evaluation of cultured skin substitutes is generally based on qualitative parameters focusing on histology. In this study we focused on quantitative evaluation to provide a template for comparison of human bio-engineered skin substitutes between clinical and/or research centers, and to supplement histological data. We focused on extracellular matrix proteins since these components play an important role in skin regeneration. As a model we analyzed the human dermal substitute denovoDerm and the dermo-epidermal skin substitute denovoSkin. The quantification of the extracellular matrix proteins type III collagen and laminin 5 in tissue homogenates using western blotting analysis and ELISA was not successful. The same was true for assaying lysyl oxidase, an enzyme involved in crosslinking of matrix molecules. As an alternative, gene expression levels were measured using qPCR. Various RNA isolation procedures were probed. The gene expression profile for specific dermal and epidermal genes could be measured reliably and reproducibly. Differences caused by changes in the cell culture conditions could easily be detected. The number of cells in the skin substitutes was measured using the PicoGreen dsDNA assay, which was found highly quantitative and reproducible. The (dis) advantages of assays used for quantitative evaluation of skin substitutes are discussed. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Photobiomodulation of a flowable matrix in a human skin ex vivo model demonstrates energy-based enhancement of engraftment integration and remodeling.

PubMed

Neves, Lia M G; Parizotto, Nivaldo A; Cominetti, Marcia R; Bayat, Ardeshir

2018-04-24

The use of dermal substitutes to treat skin defects such as ulcers has shown promising results, suggesting a potential role for skin substitutes for treating acute and chronic wounds. One of the main drawbacks with the use of dermal substitutes is the length of time from engraftment to graft take, plus the risk of contamination and failure due to this prolonged integration. Therefore, the use of adjuvant energy-based therapeutic modalities to augment and accelerate the rate of biointegration by dermal substitute engraftments is a desirable outcome. The photobiomodulation (PBM) therapy modulates the repair process, by stimulating cellular proliferation and angiogenesis. Here, we evaluated the effect of PBM on a collagen-glycosaminoglycan flowable wound matrix (FWM) in an ex vivo human skin wound model. PBM resulted in accelerated rate of re-epithelialization and organization of matrix as seen by structural arrangement of collagen fibers, and a subsequent increased expression of alpha-smooth muscle actin (α-SMA) and vascular endothelial growth factor A (VEGF-A) leading to an overall improved healing process. The use of PBM promoted a beneficial effect on the rate of integration and healing of FWM. We therefore propose that the adjuvant use of PBM may have utility in enhancing engraftment and tissue repair and be of value in clinical practice. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chronic exposure of interleukin-13 suppress the induction of matrix metalloproteinase-1 by tumour necrosis factor α in normal and scleroderma dermal fibroblasts through protein kinase B/Akt.

PubMed

Brown Lobbins, M L; Shivakumar, B R; Postlethwaite, A E; Hasty, K A

2018-01-01

Peripheral blood mononuclear cells taken from patients with scleroderma express increased levels of interleukin (IL)-13. Moreover, the expression of matrix metalloproteinase-1 (MMP-1) from involved scleroderma skin fibroblasts is refractory to stimulation by tumour necrosis factor (TNF)-α. To elucidate the mechanism(s) involved, we examined the effect of IL-13 on TNF-α-induced MMP-1 expression in normal and scleroderma human dermal fibroblast lines and studied the involvement of serine/threonine kinase B/protein kinase B (Akt) in this response. Dermal fibroblast lines were stimulated with TNF-α in the presence of varying concentrations of IL-13. Total Akt and pAkt were quantitated using Western blot analyses. Fibroblasts were treated with or without Akt inhibitor VIII in the presence of IL-13 followed by TNF-α stimulation. MMP-1 expression was analysed by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using analysis of variance (anova) or Student's t-test. Upon TNF-α stimulation, normal dermal fibroblasts secrete more MMP-1 than systemic sclerosis (SSc) fibroblasts. This increase in MMP-1 is lost when fibroblasts are co-incubated with IL-13 and TNF-α. IL-13 induced a significant increase in levels of pAkt in dermal fibroblasts, while Akt inhibitor VIII reversed the suppressive effects of IL-13 on the response of cultured fibroblasts to TNF-α, increasing their expression of MMP-1. We show that IL-13 suppresses MMP-1 in TNF-α-stimulated normal and scleroderma dermal fibroblast. Akt inhibitor VIII is able to reverse the suppressive effect of IL-13 on MMP-1 expression and protein synthesis. Our data suggest that IL-13 regulates MMP-1 expression in response to TNF-α through an Akt-mediated pathway and may play a role in fibrotic diseases such as scleroderma. © 2017 British Society for Immunology.

Reduction of facial wrinkles by hydrolyzed water-soluble egg membrane associated with reduction of free radical stress and support of matrix production by dermal fibroblasts

PubMed Central

Jensen, Gitte S; Shah, Bijal; Holtz, Robert; Patel, Ashok; Lo, Donald C

2016-01-01

Objective The aim of this study was to evaluate the effects of water-soluble egg membrane (WSEM) on wrinkle reduction in a clinical pilot study and to elucidate specific mechanisms of action using primary human immune and dermal cell-based bioassays. Methods To evaluate the effects of topical application of WSEM (8%) on human skin, an open-label 8-week study was performed involving 20 healthy females between the age of 45 years and 65 years. High-resolution photography and digital analysis were used to evaluate the wrinkle depth in the facial skin areas beside the eye (crow’s feet). WSEM was tested for total antioxidant capacity and effects on the formation of reactive oxygen species by human polymorphonuclear cells. Human keratinocytes (HaCaT cells) were used for quantitative polymerase chain reaction analysis of the antioxidant response element genes Nqo1, Gclm, Gclc, and Hmox1. Evaluation of effects on human primary dermal fibroblasts in vitro included cellular viability and production of the matrix components collagen and elastin. Results Topical use of a WSEM-containing facial cream for 8 weeks resulted in a significant reduction of wrinkle depth (P<0.05). WSEM contained antioxidants and reduced the formation of reactive oxygen species by inflammatory cells in vitro. Despite lack of a quantifiable effect on Nrf2, WSEM induced the gene expression of downstream Nqo1, Gclm, Gclc, and Hmox1 in human keratinocytes. Human dermal fibroblasts treated with WSEM produced more collagen and elastin than untreated cells or cells treated with dbcAMP control. The increase in collagen production was statistically significant (P<0.05). Conclusion The topical use of WSEM on facial skin significantly reduced the wrinkle depth. The underlying mechanisms of this effect may be related to protection from free radical damage at the cellular level and induction of several antioxidant response elements, combined with stimulation of human dermal fibroblasts to secrete high levels of matrix components. PMID:27789968

Rheological and mechanical properties of acellular and cell-laden methacrylated gellan gum hydrogels.

PubMed

Silva-Correia, Joana; Gloria, Antonio; Oliveira, Mariana B; Mano, João F; Oliveira, Joaquim M; Ambrosio, Luigi; Reis, Rui L

2013-12-01

Tissue engineered hydrogels hold great potential as nucleus pulposus substitutes (NP), as they promote intervertebral disc (IVD) regeneration and re-establish its original function. But, the key to their success in future clinical applications greatly depends on its ability to replicate the native 3D micro-environment and circumvent their limitation in terms of mechanical performance. In the present study, we investigated the rheological/mechanical properties of both ionic- (iGG-MA) and photo-crosslinked methacrylated gellan gum (phGG-MA) hydrogels. Steady shear analysis, injectability and confined compression stress-relaxation tests were carried out. The injectability of the reactive solutions employed for the preparation of iGG-MA and phGG-MA hydrogels was first studied, then the zero-strain compressive modulus and permeability of the acellular hydrogels were evaluated. In addition, human intervertebral disc (hIVD) cells encapsulated in both iGG-MA and phGG-MA hydrogels were cultured in vitro, and its mechanical properties also investigated under dynamic mechanical analysis at 37°C and pH 7.4. After 21 days of culturing, hIVD cells were alive (Calcein AM) and the E' of ionic-crosslinked hydrogels and photo-crosslinked was higher than that observed for acellular hydrogels. Our study suggests that methacrylated gellan gum hydrogels present promising mechanical and biological performance as hIVD cells were producing extracellular matrix. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Microvascular Targets for Anti-Fibrotic Therapeutics

PubMed Central

Pu, Kai-Ming T.; Sava, Parid; Gonzalez, Anjelica L.

2013-01-01

Fibrosis is characterized by excessive extracellular matrix deposition and is the pathological outcome of repetitive tissue injury in many disorders. The accumulation of matrix disrupts the structure and function of the native tissue and can affect multiple organs including the lungs, heart, liver, and skin. Unfortunately, current therapies against the deadliest and most common fibrosis are ineffective. The pathogenesis of fibrosis is the result of aberrant wound healing, therefore, the microvasculature plays an important role, contributing through regulation of leukocyte recruitment, inflammation, and angiogenesis. Further exacerbating the condition, microvascular endothelial cells and pericytes can transdifferentiate into matrix depositing myofibroblasts. The contribution of the microvasculature to fibrotic progression makes its cellular components and acellular products attractive therapeutic targets. In this review, we examine many of the cytokine, matrix, and cellular microvascular components involved in fibrosis and discuss their potential as targets for fibrotic therapies with a particular focus on developing nanotechnologies. PMID:24348218

Dermal bioavailability of benzo[a]pyrene on lampblack: implications for risk assessment.

PubMed

Stroo, Hans F; Roy, Timothy A; Liban, Cris B; Kreitinger, Joseph P

2005-06-01

Lampblack is the principal source of contamination in soils at manufactured gas plant (MGP) sites where oil was used as the feedstock. Risks and cleanup criteria at these sites are determined primarily by the total carcinogenic polynuclear aromatic hydrocarbon (PAH) content, particularly the concentration of benzo[a]pyrene (BaP). Dermal contact with soils at oil-gas MGP sites is a significant component of the overall risks. Seven samples were collected from oil-gas MGP sites and the steady-state dermal fluxes were measured over 96 h in vitro. The standard dermal bioassay technique (in which 3H-BaP is added to the soil matrix) was modified to allow direct measurement of the dermal absorption of the native BaP in the samples. The experimentally derived dermal absorption factors for BaP were 14 to 107 times lower than the default assumption of 15% over 24 h (55-fold lower on average). The dermal fluxes were correlated positively to the total BaP and total carbon concentrations. The measured dermal absorption factors were compared to the default risk-assessment calculations for all seven samples. The calculated excess cancer risk was reduced as a result of using the measured absorption factors by 97% on average (with reductions ranging from 93 to 99%). This work indicates the risks at oil-gas MGP sites currently are overestimated by one to two orders of magnitude, and provides a protocol for the testing and data analysis needed to generate site-specific cleanup levels.

Estradiol Protects Dermal Hyaluronan/Versican Matrix during Photoaging by Release of Epidermal Growth Factor from Keratinocytes*

PubMed Central

Röck, Katharina; Meusch, Michael; Fuchs, Nikola; Tigges, Julia; Zipper, Petra; Fritsche, Ellen; Krutmann, Jean; Homey, Bernhard; Reifenberger, Julia; Fischer, Jens W.

2012-01-01

Hyaluronan (HA) and versican are key components of the dermis and are responsive to ultraviolet (UV)B-induced remodeling. The aim of this study was to explore the molecular mechanisms mediating the effects of estrogen (E2) on HA-rich extracellular matrix during photoaging. Hairless skh-1 mice were irradiated with UVB (three times, 1 minimal erythema dose (80 mJ/cm2), weekly) for 10 weeks, and endogenous sex hormone production was abrogated by ovariectomy. Subcutaneous substitution of E2 by means of controlled-release pellets caused a strong increase in the dermal HA content in both irradiated and nonirradiated skin. The increase in dermal HA correlated with induction of HA synthase HAS3 by E2. Expression of splice variant 2 of the HA-binding proteoglycan versican was also increased by E2. In search of candidate mediators of these effects, it was found that E2 strongly induced the expression of epidermal growth factor (EGF) in UVB-irradiated epidermis in vivo and in keratinocytes in vitro. EGF in turn up-regulated the expression of HAS3 and versican V2 in dermal fibroblasts. HAS3 knockdown by shRNA caused inhibition of fibroblast proliferation. Furthermore, HAS3 and versican V2 induction by E2 correlated positively with proliferation in vivo. In addition, the accumulation of inflammatory macrophages, expression of inducible cyclooxygenase 2, as well as proinflammatory monocyte chemotactic protein 1 were decreased in response to E2 in the dermis. Collectively, these data suggest that E2 treatment increases the amount of dermal HA and versican V2 via paracrine release of EGF, which may be implicated in the pro-proliferative and anti-inflammatory effects of E2 during photoaging. PMID:22493503

Dextran-shelled oxygen-loaded nanodroplets reestablish a normoxia-like pro-angiogenic phenotype and behavior in hypoxic human dermal microvascular endothelium

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

Basilico, Nicoletta, E-mail: nicoletta.basilico@unimi.it; Magnetto, Chiara, E-mail: c.magnetto@inrim.it; D'Alessandro, Sarah, E-mail: sarah.dalessandro@unimi.it

In chronic wounds, hypoxia seriously undermines tissue repair processes by altering the balances between pro-angiogenic proteolytic enzymes (matrix metalloproteinases, MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) released from surrounding cells. Recently, we have shown that in human monocytes hypoxia reduces MMP-9 and increases TIMP-1 without affecting TIMP-2 secretion, whereas in human keratinocytes it reduces MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. Provided that the phenotype of the cellular environment is better understood, chronic wounds might be targeted by new oxygenating compounds such as chitosan- or dextran-shelled and 2H,3H-decafluoropentane-cored oxygen-loaded nanodroplets (OLNs). Here, we investigated the effects ofmore » hypoxia and dextran-shelled OLNs on the pro-angiogenic phenotype and behavior of human dermal microvascular endothelium (HMEC-1 cell line), another cell population playing key roles during wound healing. Normoxic HMEC-1 constitutively released MMP-2, TIMP-1 and TIMP-2 proteins, but not MMP-9. Hypoxia enhanced MMP-2 and reduced TIMP-1 secretion, without affecting TIMP-2 levels, and compromised cell ability to migrate and invade the extracellular matrix. When taken up by HMEC-1, nontoxic OLNs abrogated the effects of hypoxia, restoring normoxic MMP/TIMP levels and promoting cell migration, matrix invasion, and formation of microvessels. These effects were specifically dependent on time-sustained oxygen diffusion from OLN core, since they were not achieved by oxygen-free nanodroplets or oxygen-saturated solution. Collectively, these data provide new information on the effects of hypoxia on dermal endothelium and support the hypothesis that OLNs might be used as effective adjuvant tools to promote chronic wound healing processes. - Highlights: • Hypoxia enhances MMP-2 and reduces TIMP-1 secretion by dermal HMEC-1 cell line. • Hypoxia compromises migration and matrix invasion abilities of HMEC-1. • Nontoxic dextran-shelled oxygen-loaded nanodroplets (OLNs) are uptaken by HMEC-1. • Dextran-shelled OLNs abrogate hypoxia effects on HMEC-1 pro-angiogenic phenotype. • Dextran-shelled OLNs abrogate hypoxia effects on HMEC-1 pro-angiogenic behavior.« less

Intraoral Grafting of Tissue-Engineered Human Oral Mucosa

PubMed Central

Izumi, Kenji; Neiva, Rodrigo F.; Feinberg, Stephen E.

2014-01-01

Purpose The primary objective of this study was to evaluate the safety of a tissue-engineered human ex vivo–produced oral mucosa equivalent (EVPOME) in intraoral grafting procedures. The secondary objective was to assess the efficacy of the grafted EVPOME in producing a keratinized mucosal surface epithelium. Materials and Methods Five patients who met the inclusion criteria of having one mucogingival defect or a lack of keratinized gingiva on a nonmolar tooth, along with radiographic evidence of sufficient interdental bone height, were recruited as subjects to increase the width of keratinized gingiva at the defect site. A punch biopsy specimen of the hard palate was taken to acquire oral keratinocytes, which were expanded, seeded, and cultured on an acellular dermal matrix for fabrication of an EVPOME. EVPOME grafts were applied directly over an intact periosteal bed and secured in place. At baseline (biopsy specimen retrieval) and at 7, 14, 30, 90, and 180 days postsurgery, Plaque Index and Gingival Index were recorded for each subject. In addition, probing depths, keratinized gingival width, and keratinized gingival thickness were recorded at baseline, 30, 90, and 180 days. Results No complications or adverse reactions to EVPOME were observed in any subjects during the study. The mean gain in keratinized gingival width was 3 mm (range, 3 to 4 mm). The mean gain in keratinized gingival thickness was 1 mm (range, 1 to 2 mm). No significant changes in probing depths were observed. Conclusion Based on these findings, it can be concluded that EVPOME is safe for intraoral use and has the ability to augment keratinized tissue around teeth. Future clinical trials are needed to further explore this potential. PMID:24066347

Prior Radiotherapy Does Not Affect Abdominal Wall Reconstruction Outcomes: Evidence from Propensity Score Analysis.

PubMed

Giordano, Salvatore; Garvey, Patrick B; Baumann, Donald P; Liu, Jun; Butler, Charles E

2017-03-01

Prior abdominal wall radiotherapy (XRT) adversely affects wound healing, but data are limited on how prior XRT may affect abdominal wall reconstruction (AWR) outcomes. The purpose of this study was to determine whether prior abdominal wall radiotherapy is associated with a higher incidence of complications following AWR for a hernia or oncologic resection defect. We performed a retrospective study of consecutive patients who underwent complex AWR using acellular dermal matrix (ADM) at a single center. We compared outcomes between patients who underwent prior XRT that directly involved the abdominal wall and those who did not receive XRT. Propensity score match-paired and multivariate analyses were performed. A total of 511 patients (130 [25.4 %] with prior XRT; 381 [74.6 %] without prior XRT) underwent AWR with ADM for repair of a complex hernia or oncologic resection defect. Mean follow-up was 31.4 months, mean XRT dose was 48.9 Gy, and mean time between XRT and reconstruction was 19.2 months. XRT AWR patients underwent more flap reconstructions (14.6 vs. 5.0 %, P < 0.001) but fewer component separations (61.5 vs. 71.4 %; P = 0.036) than non-XRT AWR patients. The two groups had similar rates of hernia recurrence (8.5 vs. 9.4 %; P = 0.737) and surgical site occurrence (25.4 vs. 23.4 %; P = 0.640). In the propensity score-matched subgroups, there were no differences in hernia recurrence, surgical site occurrence, and wound healing complication rates. Prior XRT does not adversely affect outcomes in AWR. However, surgeons should be aware of the higher likelihood of needing a soft tissue flap reconstruction for soft tissue replacement when performing AWR after XRT.

Can subepithelial connective tissue grafts be considered the gold standard procedure in the treatment of Miller Class I and II recession-type defects?

PubMed

Chambrone, Leandro; Chambrone, Daniela; Pustiglioni, Francisco E; Chambrone, Luiz A; Lima, Luiz A

2008-09-01

The objective of this systematic review was to answer the following question: 'Can subepithelial connective tissue grafts (SCTG) be considered the gold standard procedure in the treatment of recession-type defects?' DATA AND SOURCE: An electronic search (MEDLIINE, EMBASE and CENTRAL) for randomized controlled clinical trials with at least 6 months' follow-up comparing SCTG with other procedures for the treatment of gingival recession was performed up to December 2007. To be eligible to this review patients had to present a diagnosis of gingival recession with the following characteristics: (a) recession areas selected for treatment classified as Miller [Miller Jr PD. A classification of marginal tissue recession. International Journal of Periodontics & Restorative Dentistry 1985;5:8-13.] Class I or Class II of at least 2mm; (b) recession areas containing teeth with no caries or restorations; and (c) at least 10 participants per group at final examination. From a total of 568 references, 23 studies were considered relevant. The results indicated a statistically significant greater reduction in gingival recession for SCTG, when compared to acellular dermal matrix grafts and guided tissue regeneration with resorbable membranes (GTR rm). For clinical attachment level changes, differences between all groups were not significant. For changes in the keratinized tissue (KT), the results showed a statistically significant gain in the width of KT for SCTG when compared to GTR rm. The results of this review show that subepithelial connective tissue grafts provided significant root coverage, clinical attachment and keratinized tissue gain. Overall comparisons allow us to consider it as the 'gold standard' procedure in the treatment of recession-type defects.

The use of a biostatic fascia lata thigh allograft as a scaffold for autologous human culture of fibroblasts--An in vitro study.

PubMed

Żurek, Jarek; Dominiak, Marzena; Botzenhart, Ute; Bednarz, Wojciech

2015-05-01

The method for covering gingival recession defects and augmenting keratinized gingiva involves the use of autogenuous connective tissue grafts obtained from palatal mucosa in combination with various techniques of flap repositioning or tunnel techniques. In the case of multiple gingival recession defects the amount of connective tissue available for grafting is insufficient. Therefore, the use of substitutes is necessary. The most widely used material in recent years has been the acellular dermal matrix allograft. The disadvantage of its application lies in the absence of cells and blood vessels, which increases incorporation time. Primary cultured human autologic fibroblasts are commonly used to optimize the healing process. The aim of this study was to examine the in vitro biocompatibility of human fascia lata allograft as a new scaffold for primary cultured human autologic fibroblasts. For that, a fibroblast culture obtained from a fragment of gingival tissue taken from the hard palate mucosa of a subject was used. After 14 days the colony cells were inoculated on a fragment of human fascia lata allograft. After a further 7 days of incubation the material was frozen, cut and prepared for histochemical examination. After two weeks of incubation, and 7 days after inoculation on a fragment of fascia lata allograft numerous accumulations of the cultured fibroblast were found that had a typical structure and produced collagen fibres. A human fascia lata allograft can be used as a scaffold for primary cultured human autologic fibroblasts. Further studies should confirm the clinical efficacy of this solution. Copyright © 2014 Elsevier GmbH. All rights reserved.

In vitro study of the impact of mechanical tension on the dermal fibroblast phenotype in the context of skin wound healing.

PubMed

Rolin, Gwenae L; Binda, Delphine; Tissot, Marion; Viennet, Céline; Saas, Philippe; Muret, Patrice; Humbert, Philippe

2014-11-07

Skin wound healing is finely regulated by both matrix synthesis and degradation which are governed by dermal fibroblast activity. Actually, fibroblasts synthesize numerous extracellular matrix proteins (i.e., collagens), remodeling enzymes and their inhibitors. Moreover, they differentiate into myofibroblasts and are able to develop endogenous forces at the wound site. Such forces are crucial during skin wound healing and have been widely investigated. However, few studies have focused on the effect of exogenous mechanical tension on the dermal fibroblast phenotype, which is the objective of the present paper. To this end, an exogenous, defined, cyclic and uniaxial mechanical strain was applied to fibroblasts cultured as scratch-wounded monolayers. Results showed that fibroblasts' response was characterized by both an increase in procollagen type-I and TIMP-1 synthesis, and a decrease in MMP-1 synthesis. The monitoring of scratch-wounded monolayers did not show any decrease in kinetics of the filling up when mechanical tension was applied. Additional results obtained with proliferating fibroblasts and confluent monolayer indicated that mechanical tension-induced response of fibroblasts depends on their culture conditions. In conclusion, mechanical tension leads to the differentiation of dermal fibroblasts and may increase their wound-healing capacities. So, the exogenous uniaxial and cyclic mechanical tension reported in the present study may be considered in order to improve skin wound healing. Copyright © 2014 Elsevier Ltd. All rights reserved.

YAG laser treatment causes rapid degeneration and regeneration of collagen fibres in pig skin and facilitates fibroblast growth.

PubMed

Kono, Ayuko; Oguri, Akiko; Yokoo, Kazuhisa; Watanabe, Hideto

2012-10-01

The non-ablative laser therapies have been speculated to cause microinjury in the dermal collagen fibres and increase collagen synthesis in the fibroblasts, leading to remodelling of the extracellular matrix. This study investigated the effects of neodymium YAG laser treatment on pig skin, especially focusing on its extracellular matrix molecules. The dorsal areas of a minipig were subjected to laser treatment, and samples were obtained by punch biopsies, and histological, immunohistochemical, and biochemical analyses were performed. The laser treatment caused degeneration of collagen fibres and fibrils, which were reconstituted within 24 hours, whereas there was no inflammation and no apparent damage on elastic fibres. Small blood vessels disappeared by the laser treatment, which re-appeared in 3 days. Biochemically, the amounts of collagen decreased up to day 3 after the treatment and then increased at day 7. When fibroblasts in dermal tissue at day 28 were counted, more fibroblasts in the treated tissue were observed than non-treated control. These results suggest that, although the laser treatment transiently degenerates collagen fibres and fibrils, it restores and increases them, mainly by an increase in dermal fibroblasts, assuring its minimal complication of skin.

Oxygen diffusion and consumption in extracellular matrix gels: implications for designing three-dimensional cultures.

PubMed

Colom, Adai; Galgoczy, Roland; Almendros, Isaac; Xaubet, Antonio; Farré, Ramon; Alcaraz, Jordi

2014-08-01

Three-dimensional (3D) cultures are increasingly used as tissue surrogates to study many physiopathological processes. However, to what extent current 3D culture protocols provide physiologic oxygen tension conditions remains ill defined. To address this limitation, oxygen tension was measured in a panel of acellular or cellularized extracellular matrix (ECM) gels with A549 cells, and analyzed in terms of oxygen diffusion and consumption. Gels included reconstituted basement membrane, fibrin and collagen. Oxygen diffusivity in acellular gels was up to 40% smaller than that of water, and the lower values were observed in the denser gels. In 3D cultures, physiologic oxygen tension was achieved after 2 days in dense (≥3 mg/mL) but not sparse gels, revealing that the latter gels are not suitable tissue surrogates in terms of oxygen distribution. In dense gels, we observed a dominant effect of ECM composition over density in oxygen consumption. All diffusion and consumption data were used in a simple model to estimate ranges for gel thickness, seeding density and time-window that may support physiologic oxygen tension. Thus, we identified critical variables for oxygen tension in ECM gels, and introduced a model to assess initial values of these variables, which may short-cut the optimization step of 3D culture studies. © 2013 Wiley Periodicals, Inc.

Anti-endotoxic and antibacterial effects of a dermal substitute coated with host defense peptides.

PubMed

Kasetty, Gopinath; Kalle, Martina; Mörgelin, Matthias; Brune, Jan C; Schmidtchen, Artur

2015-01-01

Biomaterials used during surgery and wound treatment are of increasing importance in modern medical care. In the present study we set out to evaluate the addition of thrombin-derived host defense peptides to human acellular dermis (hAD, i.e. epiflex(®)). Antimicrobial activity of the functionalized hAD was demonstrated using radial diffusion and viable count assays against Gram-negative Escherichia coli, Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus bacteria. Electron microscopy analyses showed that peptide-mediated bacterial killing led to reduced hAD degradation. Furthermore, peptide-functionalized hAD displayed endotoxin-binding activity in vitro, as evidenced by inhibition of NF-κB activation in human monocytic cells (THP-1 cells) and a reduction of pro-inflammatory cytokine production in whole blood in response to lipopolysaccharide stimulation. The dermal substitute retained its anti-endotoxic activity after washing, compatible with results showing that the hAD bound a significant amount of peptide. Furthermore, bacteria-induced contact activation was inhibited by peptide addition to the hAD. E. coli infected hAD, alone, or after treatment with the antiseptic substance polyhexamethylenebiguanide (PHMB), yielded NF-κB activation in THP-1 cells. The activation was abrogated by peptide addition. Thus, thrombin-derived HDPs should be of interest in the further development of new biomaterials with combined antimicrobial and anti-endotoxic functions for use in surgery and wound treatment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

TCDD induces dermal accumulation of keratinocyte-derived matrix metalloproteinase-10 in an organotypic model of human skin

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

De Abrew, K. Nadira; Thomas-Virnig, Christina L.; Rasmussen, Cathy A.

2014-05-01

The epidermis of skin is the first line of defense against the environment. A three dimensional model of human skin was used to investigate tissue-specific phenotypes induced by the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Continuous treatment of organotypic cultures of human keratinocytes with TCDD resulted in intracellular spaces between keratinocytes of the basal and immediately suprabasal layers as well as thinning of the basement membrane, in addition to the previously reported hyperkeratinization. These tissue remodeling events were preceded temporally by changes in expression of the extracellular matrix degrading enzyme, matrix metalloproteinase-10 (MMP-10). In organotypic cultures MMP-10 mRNA and protein were highlymore » induced following TCDD treatment. Q-PCR and immunoblot results from TCDD-treated monolayer cultures, as well as indirect immunofluorescence and immunoblot analysis of TCDD-treated organotypic cultures, showed that MMP-10 was specifically contributed by the epidermal keratinocytes but not the dermal fibroblasts. Keratinocyte-derived MMP-10 protein accumulated over time in the dermal compartment of organotypic cultures. TCDD-induced epidermal phenotypes in organotypic cultures were attenuated by the keratinocyte-specific expression of tissue inhibitor of metalloproteinase-1, a known inhibitor of MMP-10. These studies suggest that MMP-10 and possibly other MMP-10-activated MMPs are responsible for the phenotypes exhibited in the basement membrane, the basal keratinocyte layer, and the cornified layer of TCDD-treated organotypic cultures. Our studies reveal a novel mechanism by which the epithelial–stromal microenvironment is altered in a tissue-specific manner thereby inducing structural and functional pathology in the interfollicular epidermis of human skin. - Highlights: • TCDD causes hyperkeratosis and basement membrane changes in a model of human skin. • TCDD induces MMP-10 expression in organotypic cultures of human keratinocytes. • Keratinocyte-expressed MMP-10 accumulates in the dermal compartment. • Keratinocyte K14 promoter-driven TIMP-1 expression ablates TCDD-induced phenotypes.« less

Striae and Their Relation to Topical Steroid Therapy

PubMed Central

Adam, J. E.; Craig, Gibson

1965-01-01

Atrophic striae have been reported to occur normally in 35% of adolescents and abnormally in a variety of medical conditions. Recently, the occurrence of striae has been observed in adults after the use of potent topical steroids with occlusion. Pre-existing striae have been found to enlarge after topical steroid therapy, even without occlusion. The mechanism of striae formation appears to be due to the action of the steroids on the dermal connective tissue and/or dermal matrix rather than to mechanical tension. ImagesFig. 1Fig. 2 PMID:14270214

Increasing number of small hole diameter microfracture compared with traditional microfracture in same size cartilage defects and effect of HA based aselluler scaffold. An animal study

PubMed Central

Uzer, Gökçer; Elmadağ, Nuh Mehmet; Yıldız, Fatih; Güzel, Yunus; Tok, Olgu Enis

2017-01-01

Purpose: The purpose of this study is small hole microfracure method comparing with traditional microfracture method and investigation of effect of HA based acellular matrix scaffold on microfracture area. Materials-Methods: 21 Twenty-one New Zealand white rabbits were used for the in vitro portion of this study, bilateral knee joint from the same rabbit were same technic. An articular cartilage defect was established in the femoral trochlear groove about 5 mm. Control group was established alone microfracture (MF). 6 groups were formed in this study and each group has 3 rabbits and their six knees. In 3 groups were applied different number of small diameter hole microfracture (4,5,6 small holes microfracture respectively)and the other 3 groups were applied different number of small diameter hole microfracture (4,5,6 small holes micro fracture respectively added HA based acellular matrix scaffold in the same size ostechondral lesion. The regenerated tissues were harvested for gross morphology, histology at 12 weeks postoperatively. Results: Cartilage were regenerated, maintaining a constant thickness of cartilage. MF group has worse Wakitani scores than 6 small diameter holes mıcrofracture groups(group 6 and group 7) in either parameter of the score. (p=0,043, p=0,016) Matrix addition did not contribute to healing. (p=1,000) Conclusions: Increasing number of the small diameter holes microfracture (minimum %15 of defect size) improves cartilage repair compared with traditional MF in the same size ostechondral lesion. Also small diameter holes microfracture combined with HA-based AM implantation didn’t result in improved quality of the regenerated cartilage tissue.

TGF-beta antisense oligonucleotides reduce mRNA expression of matrix metalloproteinases in cultured wound-healing-related cells.

PubMed

Philipp, Katrin; Riedel, Frank; Germann, Günter; Hörmann, Karl; Sauerbier, Michael

2005-02-01

The pathology of chronic dermal ulcers is characterized by excessive proteolytic activity which degrades extracellular matrix. The transforming growth factor-beta (TGF-beta) has been identified as an important component of wound healing. Recent developments in molecular therapy offer exciting prospects for the modulation of wound healing, specifically those targeting TGF-beta. We investigated the effect of TGF-beta antisense oligonucleotides on the mRNA expression of matrix metalloproteinases in cultured human keratinocytes, fibroblasts and endothelial cells using multiplex RT-PCR. The treatment of keratinocytes and fibroblasts with TGF-beta antisense oligonucleotides resulted in a significant decrease of expression of mRNA of MMP-1 and MMP-9 compared to controls. Accordingly, a decreased expression of MMP-1 mRNA in endothelial cells was detectable. Other MMPs were not affected. Affecting all dermal wound-healing-related cell types, TGF-beta antisense oligonucleotide technology may be a potential therapeutic option for the inhibition of proteolytic tissue destruction in chronic wounds. Pharmaceutical intervention in this area ultimately may help clinicians to proactively intervene in an effort to prevent normal wounds from becoming chronic.

Multidisciplinary care in severe pediatric electrical oral burn.

PubMed

Pontini, A; Reho, F; Giatsidis, G; Bacci, C; Azzena, B; Tiengo, C

2015-05-01

Oral burns in pediatric patient are commonly due to electrical injuries, representing an important reconstructive issue even for functional than esthetic reason. Different classification, surgical management and even oral device were described to allow the best long-term result. In most case a multidisciplinary approach is necessary to achieve a satisfactory outcome. A severe case of pediatric oral burn with germinative teeth damage is presented, describing a multispecialist team approach that guarantee a satisfactory outcome by reconstructive surgery, careful progressive evaluation of dental and soft tissue healing and speech recovery. The use of acellular dermal substitute template within traditional reconstructive surgery had provided a good functional and esthetic result joint to valid preservation of germinative dental element as shown at long-term X-ray evaluation. Intensive rehabilitation speech program has also avoided phonetic impairment in an important speech develop period. It was so evident that the necessity of a multispecialist care in such difficult injury to achieve the best long-term result. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Alteration of Skin Properties with Autologous Dermal Fibroblasts

PubMed Central

Thangapazham, Rajesh L.; Darling, Thomas N.; Meyerle, Jon

2014-01-01

Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA) while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices. PMID:24828202

Use of versican variant V3 and versican antisense expression to engineer cultured human skin containing increased content of insoluble elastin.

PubMed

Merrilees, Mervyn J; Falk, Ben A; Zuo, Ning; Dickinson, Michelle E; May, Barnaby C H; Wight, Thomas N

2017-01-01

Skin substitutes for repair of dermal wounds are deficient in functional elastic fibres. We report that the content of insoluble elastin in the dermis of cultured human skin can be increased though the use of two approaches that enhance elastogenesis by dermal fibroblasts, forced expression of versican variant V3, which lacks glycosaminoglycan (GAG) chains, and forced expression of versican antisense to decrease levels of versican variant V1 with GAG chains. Human dermal fibroblasts transduced with V3 or anti-versican were cultured under standard conditions over a period of 4 weeks to produce dermal sheets, with growth enhanced though multiple seedings for the first 3 weeks. Human keratinocytes, cultured in supplemented media, were added to the 4-week dermal sheets and the skin layer cultured for a further week. At 5 weeks, keratinocytes were multilayered and differentiated, with desmosome junctions thoughout and keratin deposits in the upper squamous layers. The dermal layer was composed of layered fibroblasts surrounded by extracellular matrix of collagen bundles and, in control cultures, small scattered elastin deposits. Forced expression of V3 and versican antisense slowed growth, decreased versican V1 expression, increased tropoelastin expression and/or the deposition of large aggregates of insoluble elastin in the dermal layer, and increased tissue stiffness, as measured by nano-indentation. Skin sheets were also cultured on Endoform Dermal Template™, the biodegradable wound dressing made from the lamina propria of sheep foregut. Skin structure and the enhanced deposition of elastin by forced expression of V3 and anti-versican were preserved on this supportive substrate. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Deficiency of CRTAP in non-lethal recessive osteogenesis imperfecta reduces collagen deposition into matrix.

PubMed

Valli, M; Barnes, A M; Gallanti, A; Cabral, W A; Viglio, S; Weis, M A; Makareeva, E; Eyre, D; Leikin, S; Antoniazzi, F; Marini, J C; Mottes, M

2012-11-01

Deficiency of any component of the ER-resident collagen prolyl 3-hydroxylation complex causes recessive osteogenesis imperfecta (OI). The complex modifies the α1(I)Pro986 residue and contains cartilage-associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1) and cyclophilin B (CyPB). Fibroblasts normally secrete about 10% of CRTAP. Most CRTAP mutations cause a null allele and lethal type VII OI. We identified a 7-year-old Egyptian boy with non-lethal type VII OI and investigated the effects of his null CRTAP mutation on collagen biochemistry, the prolyl 3-hydroxylation complex, and collagen in extracellular matrix. The proband is homozygous for an insertion/deletion in CRTAP (c.118_133del16insTACCC). His dermal fibroblasts synthesize fully overmodified type I collagen, and 3-hydroxylate only 5% of α1(I)Pro986. CRTAP transcripts are 10% of control. CRTAP protein is absent from proband cells, with residual P3H1 and normal CyPB levels. Dermal collagen fibril diameters are significantly increased. By immunofluorescence of long-term cultures, we identified a severe deficiency (10-15% of control) of collagen deposited in extracellular matrix, with disorganization of the minimal fibrillar network. Quantitative pulse-chase experiments corroborate deficiency of matrix deposition, rather than increased matrix turnover. We conclude that defects of extracellular matrix, as well as intracellular defects in collagen modification, contribute to the pathology of type VII OI. © 2011 John Wiley & Sons A/S.

Expression of matrix metalloproteinase-2 and metalloproteinase-9 in the skin of dogs with visceral leishmaniasis.

PubMed

Jacintho, Ana Paula Prudente; Melo, Guilherme D; Machado, Gisele F; Bertolo, Paulo Henrique Leal; Moreira, Pamela Rodrigues Reina; Momo, Claudia; Souza, Thiago A; Vasconcelos, Rosemeri de Oliveira

2018-06-01

The skin is the first organ to be infected by the parasite in canine visceral leishmaniasis. The enzyme matrix metalloproteinase (MMP) acts towards degradation of the extracellular matrix (ECM) and modulation of the inflammatory response against many kinds of injuries. The aims of this study were to evaluate the expression of MMP-2 and MMP-9 through immunohistochemistry and zymography on the skin (muzzle, ears, and abdomen) of dogs that were naturally infected by Leishmania spp. and to compare these results with immunodetection of the parasite and with alterations to the dermal ECM. Picrosirius red staining was used to differentiate collagen types I and III in three regions of the skin. The parasite load, intensity of inflammation, and production of MMP-2 (latent) and MMP-9 (active and latent) were higher in the ear and muzzle regions. MMP-9 (active) predominated in the infected group of dogs and its production was significantly different to that of the control group. Macrophages, lymphocytes, and plasma cells predominated in the dermal inflammation and formed granulomas in association with degradation of mature collagen (type I) and with discrete deposition of young collagen (type III). This dermal change was more pronounced in dogs with high parasite load in the skin. Therefore, it was concluded that the greater parasite load and intensity of inflammation in the skin led consequently to increased degradation of mature collagen, caused by increased production of MMPs, particularly active MMP-9, in dogs with visceral leishmaniasis. This host response profile possibly favors systemic dissemination of the parasite.

Skin aging by glycation: lessons from the reconstructed skin model.

PubMed

Pageon, Hervé; Zucchi, Hélène; Rousset, Françoise; Monnier, Vincent M; Asselineau, Daniel

2014-01-01

Aging is the result of several mechanisms which operate simultaneously. Among them, glycation is of particular interest because it is a reaction which affects slowly renewing tissues and macromolecules with elevated half-life, like the dermis, a skin compartment highly affected by aging. Glycation produces crosslinks between macromolecules thereby providing an explanation for the increased age-related stiffness of the skin. Glycation products, also called AGEs (advanced glycation end products), accumulate primarily in extracellular matrix molecules like collagen or elastin. In order to reproduce this phenomenon in vitro we have created a model of reconstructed skin modified by glycation of the collagen used to fabricate the dermal compartment. This system allowed us to uncover biological modifications of dermal markers, and more surprisingly epidermal markers, as well as an increase of metalloproteinases responsible for degradation of the dermal matrix. Consequently, the imbalance between synthesis and degradation that results from glycation, may contribute to skin aging, as shown in this model. Moreover these modifications were shown to be prevented by the addition of aminoguanidine, a well-known inhibitor of glycation. Using this experimental approach our results taken together stress the importance and possibly central role of glycation in skin aging and the usefulness of the reconstructed skin as a model of physiological aging.

Critical involvement of ZEB2 in collagen fibrillogenesis: the molecular similarity between Mowat-Wilson syndrome and Ehlers-Danlos syndrome.

PubMed

Teraishi, Mika; Takaishi, Mikiro; Nakajima, Kimiko; Ikeda, Mitsunori; Higashi, Yujiro; Shimoda, Shinji; Asada, Yoshinobu; Hijikata, Atsushi; Ohara, Osamu; Hiraki, Yoko; Mizuno, Seiji; Fukada, Toshiyuki; Furukawa, Takahisa; Wakamatsu, Nobuaki; Sano, Shigetoshi

2017-04-19

Mowat-Wilson syndrome (MOWS) is a congenital disease caused by de novo heterozygous loss of function mutations or deletions of the ZEB2 gene. MOWS patients show multiple anomalies including intellectual disability, a distinctive facial appearance, microcephaly, congenital heart defects and Hirschsprung disease. However, the skin manifestation(s) of patients with MOWS has not been documented in detail. Here, we recognized that MOWS patients exhibit many Ehlers-Danlos syndrome (EDS)-like symptoms, such as skin hyperextensibility, atrophic scars and joint hypermobility. MOWS patients showed a thinner dermal thickness and electron microscopy revealed miniaturized collagen fibrils. Notably, mice with a mesoderm-specific deletion of the Zeb2 gene (Zeb2-cKO) demonstrated redundant skin, dermal hypoplasia and miniaturized collagen fibrils similar to those of MOWS patients. Dermal fibroblasts derived from Zeb2-cKO mice showed a decreased expression of extracellular matrix (ECM) molecules, such as collagens, whereas molecules involved in degradation of the ECM, such as matrix metalloproteinases (MMPs), were up-regulated. Furthermore, bleomycin-induced skin fibrosis was attenuated in Zeb2-cKO mice. We conclude that MOWS patients exhibit an EDS-like skin phenotype through alterations of collagen fibrillogenesis due to ZEB2 mutations or deletions.

Cell surface engineering using glycosylphosphatidylinositol anchored tissue inhibitor of matrix metalloproteinase-1 stimulates cutaneous wound healing.

PubMed

Djafarzadeh, Roghieh; Conrad, Claudius; Notohamiprodjo, Susan; Hipp, Stephanie; Niess, Hanno; Bruns, Christiane J; Nelson, Peter J

2014-01-01

The balance between matrix metalloproteinases and their endogenous tissue inhibitors (TIMPs) is an important component in effective wound healing. The biologic action of these proteins is linked in part to the stoichiometry of TIMP/matrix metalloproteinases/surface protein interactions. We recently described the effect of a glycosylphosphatidylinositol (GPI) anchored version of TIMP-1 on dermal fibroblast biology. Here, cell proliferation assays, in vitro wound healing, electrical wound, and impedance measurements were used to characterize effects of TIMP-1-GPI treatment on primary human epidermal keratinocytes. TIMP-1-GPI stimulated keratinocyte proliferation, as well as mobilization and migration. In parallel, it suppressed the migration and matrix secretion of dermal myofibroblasts, and reduced their secretion of active TGF-β1. Topical application of TIMP-1-GPI in an in vivo excisional wound model increased the rate of wound healing. The agent positively influenced different aspects of wound healing depending on the cell type studied. TIMP-1-GPI counters potential negative effects of overactive myofibroblasts and enhances the mobilization and proliferation of keratinocytes essential for effective wound healing. The application of TIMP-1-GPI represents a novel and practical clinical solution for facilitating healing of difficult wounds. © 2014 by the Wound Healing Society.

Evaluation of dermal-epidermal skin equivalents ('composite-skin') of human keratinocytes in a collagen-glycosaminoglycan matrix(Integra artificial skin).

PubMed

Kremer, M; Lang, E; Berger, A C

2000-09-01

Integra artificial skin (Integra LifeSciences Corp., Plainsboro, NJ, USA) is a dermal template consisting of bovine collagen, chondroitin-6-sulphate and a silastic membrane manufactured as Integra. This product has gained widespread use in the clinical treatment of third degree burn wounds and full thickness skin defects of different aetiologies. The product was designed to significantly reduce the time needed to achieve final wound closure in the treatment of major burn wounds, to optimise the sparse autologous donor skin resources and to improve the durable mechanical quality of the skin substitute. The clinical procedure requires two stages. The first step creates a self neodermis, the second creates a self epidermis on the neodermis. However, it is desirable to cover major burn wounds early in a single step by a skin substitute consisting of a dermal equivalent seeded in vitro with autologous keratinocytes ('composite-skin') out of which a full thickness skin develops in vivo.The goal of this experimental study was to develop a method to integrate human keratinocytes in homogeneous distribution and depth into Integra Artificial Skin. The seeded cell-matrix composites were grafted onto athymic mice in order to evaluate their potential to reconstitute a human epidermis in vivo. We were able to demonstrate that the inoculated human keratinocytes reproducibly displayed a homogeneous pattern of distribution, adherence, proliferation and confluence. The cell-matrix composites grafted in this model exhibited good wound adherence, complete healing, minor wound contraction and had the potential to reconstitute an elastic, functional and durable human skin. Histologically we were able to show that the inoculated human keratinocytes in vivo colonised the matrix in a histomorphologically characteristic epidermal pattern (keratomorula, keratinocyte bubbling) and developed a persisting, stratified, keratinising epidermis which immunohistologically proved to be of human origin. These experimental results demonstrate the establishment of an effective cell cultivation process which may be suitable for scale-up production of the epidermal component as large-scale composite-skin grafts. When seeded into Integratrade mark and grafted onto the nude mouse a replacement skin with normal functioning dermal-epidermal components was developed. These results encourage the design of a clinical trial to assess the function of this composite graft in man.

Chitosan/silk fibroin-based, Schwann cell-derived extracellular matrix-modified scaffolds for bridging rat sciatic nerve gaps.

PubMed

Gu, Yun; Zhu, Jianbin; Xue, Chengbin; Li, Zhenmeiyu; Ding, Fei; Yang, Yumin; Gu, Xiaosong

2014-02-01

Extracellular matrix (ECM) plays a prominent role in establishing and maintaining an ideal microenvironment for tissue regeneration, and ECM scaffolds are used as a feasible alternative to cellular and molecular therapy in the fields of tissue engineering. Because of their advantages over tissue-derived ECM scaffolds, cultured cell-derived ECM scaffolds are beginning to attract attention, but they have been scarcely studied for peripheral nerve repair. Here we aimed to develop a tissue engineered nerve scaffold by reconstituting nerve cell-derived ECM with natural biomaterials. A protocol was adopted to prepare and characterize the cultured Schwann cell (SC)-derived ECM. A chitosan conduit and silk fibroin (SF) fibers were prepared, cultured with SCs for ECM deposition, and subjected to decellularization, followed by assembly into a chitosan/SF-based, SC-derived ECM-modified scaffold, which was used to bridge a 10 mm rat sciatic nerve gap. The results from morphological analysis as well as electrophysiological examination indicated that regenerative outcomes achieved by our developed scaffold were similar to those by an acellular nerve graft (namely a nerve tissue-derived ECM scaffold), but superior to those by a plain chitosan/SF scaffold. Moreover, blood and histopathological parameters confirmed the safety of scaffold modification by SC-derived ECM. Therefore, a hybrid scaffold based on joint use of acellular and classical biomaterials represents a promising approach to nerve tissue engineering. Copyright © 2013 Elsevier Ltd. All rights reserved.

Decellularized Rat Lung Scaffolds Using Sodium Lauryl Ether Sulfate for Tissue Engineering.

PubMed

Ma, Jinhui; Ju, Zhihai; Yu, Jie; Qiao, Yeru; Hou, Chenwei; Wang, Chen; Hei, Feilong

Perfusion decellularization with detergents is effective to maintain the architecture and proteins of extracellular matrix (ECM) for use in the field of lung tissue engineering (LTE). However, it is unclear which detergent is ideal to produce an acellular lung scaffold. In this study, we obtained two decellularized rat lung scaffolds using a novel detergent sodium lauryl ether sulfate (SLES) and a conventional detergent sodium dodecyl sulfate (SDS). Both decellularized lung scaffolds were assessed by histology, immunohistochemistry, scanning electron microscopy, DNA quantification, sulfated glycosaminoglycans (GAGs) quantification and western blot. Subsequently, the scaffolds were implanted subcutaneously in rats for 6 weeks and were evaluated via hematoxylin and eosin staining and Masson staining. Results indicated that SLES was effective to remove cells; moreover, lungs decellularized with SLES showed better preservation of sulfated GAGs, lung architecture, and ECM proteins than SDS. After 6 weeks, SLES scaffolds demonstrated a significantly greater potential for cell infiltration and blood vessel formation compared with SDS scaffolds. Taken together, we conclude that SLES is a promising detergent to produce an acellular scaffold using LTE for eventual transplantation.

Cold-perfusion decellularization of whole-organ porcine pancreas supports human fetal pancreatic cell attachment and expression of endocrine and exocrine markers

PubMed Central

Elebring, Erik; Kuna, Vijay K; Kvarnström, Niclas; Sumitran-Holgersson, Suchitra

2017-01-01

Despite progress in the field of decellularization and recellularization, the outcome for pancreas has not been adequate. This might be due to the challenging dual nature of pancreas with both endocrine and exocrine tissues. We aimed to develop a novel and efficient cold-perfusion method for decellularization of porcine pancreas and recellularize acellular scaffolds with human fetal pancreatic stem cells. Decellularization of whole porcine pancreas at 4°C with sodium deoxycholate, Triton X-100 and DNase efficiently removed cellular material, while preserving the extracellular matrix structure. Furthermore, recellularization of acellular pieces with human fetal pancreatic stem cells for 14 days showed attached and proliferating cells. Both endocrine (C-peptide and PDX1) and exocrine (glucagon and α-amylase) markers were expressed in recellularized tissues. Thus, cold-perfusion can successfully decellularize porcine pancreas, which when recellularized with human fetal pancreatic stem cells shows relevant endocrine and exocrine phenotypes. Decellularized pancreas is a promising biomaterial and might translate to clinical relevance for treatment of diabetes. PMID:29118967

Tissue engineering and regenerative medicine approaches to enhance the functional response to skeletal muscle injury.

PubMed

Sicari, Brian M; Dearth, Christopher L; Badylak, Stephen F

2014-01-01

The well-recognized ability of skeletal muscle for functional and structural regeneration following injury is severely compromised in degenerative diseases and in volumetric muscle loss. Tissue engineering and regenerative medicine strategies to support muscle reconstruction have typically been cell-centric with approaches that involve the exogenous delivery of cells with myogenic potential. These strategies have been limited by poor cell viability and engraftment into host tissue. Alternative approaches have involved the use of biomaterial scaffolds as substrates or delivery vehicles for exogenous myogenic progenitor cells. Acellular biomaterial scaffolds composed of mammalian extracellular matrix (ECM) have also been used as an inductive niche to promote the recruitment and differentiation of endogenous myogenic progenitor cells. An acellular approach, which activates or utilizes endogenous cell sources, obviates the need for exogenous cell administration and provides an advantage for clinical translation. The present review examines the state of tissue engineering and regenerative medicine therapies directed at augmenting the skeletal muscle response to injury and presents the pros and cons of each with respect to clinical translation. Copyright © 2013 Wiley Periodicals, Inc.

Engineered Tissue–Stent Biocomposites as Tracheal Replacements

PubMed Central

Zhao, Liping; Sundaram, Sumati; Le, Andrew V.; Huang, Angela H.; Zhang, Jiasheng; Hatachi, Go; Beloiartsev, Arkadi; Caty, Michael G.; Yi, Tai; Leiby, Katherine; Gard, Ashley; Kural, Mehmet H.; Gui, Liqiong; Rocco, Kevin A.; Sivarapatna, Amogh; Calle, Elizabeth; Greaney, Allison; Urbani, Luca; Maghsoudlou, Panagiotis; Burns, Alan; DeCoppi, Paolo

2016-01-01

Here we report the creation of a novel tracheal construct in the form of an engineered, acellular tissue–stent biocomposite trachea (TSBT). Allogeneic or xenogeneic smooth muscle cells are cultured on polyglycolic acid polymer–metal stent scaffold leading to the formation of a tissue comprising cells, their deposited collagenous matrix, and the stent material. Thorough decellularization then produces a final acellular tubular construct. Engineered TSBTs were tested as end-to-end tracheal replacements in 11 rats and 3 nonhuman primates. Over a period of 8 weeks, no instances of airway perforation, infection, stent migration, or erosion were observed. Histological analyses reveal that the patent implants remodel adaptively with native host cells, including formation of connective tissue in the tracheal wall and formation of a confluent, columnar epithelium in the graft lumen, although some instances of airway stenosis were observed. Overall, TSBTs resisted collapse and compression that often limit the function of other decellularized tracheal replacements, and additionally do not require any cells from the intended recipient. Such engineered TSBTs represent a model for future efforts in tracheal regeneration. PMID:27520928

Esophageal tissue engineering: Current status and perspectives.

PubMed

Poghosyan, T; Catry, J; Luong-Nguyen, M; Bruneval, P; Domet, T; Arakelian, L; Sfeir, R; Michaud, L; Vanneaux, V; Gottrand, F; Larghero, J; Cattan, P

2016-02-01

Tissue engineering, which consists of the combination and in vivo implantation of elements required for tissue remodeling toward a specific organ phenotype, could be an alternative for classical techniques of esophageal replacement. The current hybrid approach entails creation of an esophageal substitute composed of an acellular matrix and autologous epithelial and muscle cells provides the most successful results. Current research is based on the use of mesenchymal stem cells, whose potential for differentiation and proangioogenic, immune-modulator and anti-inflammatory properties are important assets. In the near future, esophageal substitutes could be constructed from acellular "intelligent matrices" that contain the molecules necessary for tissue regeneration; this should allow circumvention of the implantation step and still obtain standardized in vivo biological responses. At present, tissue engineering applications to esophageal replacement are limited to enlargement plasties with absorbable, non-cellular matrices. Nevertheless, the application of existing clinical techniques for replacement of other organs by tissue engineering in combination with a multiplication of translational research protocols for esophageal replacement in large animals should soon pave the way for health agencies to authorize clinical trials. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Protective effect of chromene isolated from Sargassum horneri against UV-A-induced damage in skin dermal fibroblasts.

PubMed

Kim, Jung-Ae; Ahn, Byul-Nim; Kong, Chang-Suk; Kim, Se-Kwon

2012-08-01

Skin homoeostasis is interrupted during UV-A irradiation. How the UV-A-altered skin components influences photoageing of skin should be investigated using human in vitro models that are important for understanding skin ageing. In this study, chromene compound, sargachromenol, was isolated from Sargassum horneri, and its potency on inhibition of photoageing was investigated in UV-A-irradiated dermal fibroblasts. Effects of sargachromenol on the prevention of photoageing were evaluated by measuring ROS production, membrane protein oxidation, lipid peroxidation and ageing-related gene expression in UV-A-irradiated human skin dermal fibroblasts. The results indicated that treatment with sargachromenol suppressed the collagenase matrix metalloproteinases (MMPs), MMP-1, MMP-2 and MMP-9 expression without any cytotoxicity and phototoxicity. It was further found that these inhibitions were because of increase in the expression of TIMP-1 and TIMP-2 genes. Furthermore, we confirmed that the UV-A-induced transcriptions of AP-1 signalling pathway were regulated by sargachromenol treatment in UV-A-irradiated dermal fibroblasts. © 2012 John Wiley & Sons A/S.

Hydrogels in acellular and cellular strategies for intervertebral disc regeneration.

PubMed

Pereira, D R; Silva-Correia, J; Oliveira, J M; Reis, R L

2013-02-01

Low back pain is an extremely common illness syndrome that causes patient suffering and disability and requires urgent solutions to improve the quality of life of these patients. Treatment options aimed to regenerate the intervertebral disc (IVD) are still under development. The cellular complexity of IVD, and consequently its fine regulatory system, makes it a challenge to the scientific community. Biomaterials-based therapies are the most interesting solutions to date, whereby tissue engineering and regenerative medicine (TE&RM) strategies are included. By using such strategies, i.e., combining biomaterials, cells, and biomolecules, the ultimate goal of reaching a complete integration between native and neo-tissue can be achieved. Hydrogels are promising materials for restoring IVD, mainly nucleus pulposus (NP). This study presents an overview of the use of hydrogels in acellular and cellular strategies for intervertebral disc regeneration. To better understand IVD and its functioning, this study will focus on several aspects: anatomy, pathophysiology, cellular and biomolecular performance, intrinsic healing processes, and current therapies. In addition, the application of hydrogels as NP substitutes will be addressed due to their similarities to NP mechanical properties and extracellular matrix. These hydrogels can be used in cellular strategies when combined with cells from different sources, or in acellular strategies by performing the functionalization of the hydrogels with biomolecules. In addition, a brief summary of therapies based on simple injection for primary biological repair will be examined. Finally, special emphasis will focus on reviewing original studies reporting on the use of autologous cells and biomolecules such as platelet-rich plasma and their potential clinical applications. Copyright © 2011 John Wiley & Sons, Ltd.

Effect of Adipose-Derived Stromal Cells and BMP12 on Intrasynovial Tendon Repair: A Biomechanical, Biochemical, and Proteomics Study

PubMed Central

Gelberman, Richard H.; Shen, Hua; Kormpakis, Ioannis; Rothrauff, Benjamin; Yang, Guang; Tuan, Rocky S.; Xia, Younan; Sakiyama-Elbert, Shelly; Silva, Matthew J.; Thomopoulos, Stavros

2016-01-01

The outcomes of flexor tendon repair are highly variable. As recent efforts to improve healing have demonstrated promise for growth factor- and cell-based therapies, the objective of the current study was to enhance repair via application of autologous adipose derived stromal cells (ASCs) and the tenogenic growth factor bone morphogenetic protein (BMP) 12. Controlled delivery of cells and growth factor was achieved in a clinically relevant canine model using a nanofiber/fibrin-based scaffold. Control groups consisted of repair-only (no scaffold) and acellular scaffold. Repairs were evaluated after 28 days of healing using biomechanical, biochemical, and proteomics analyses. Range of motion was reduced in the groups that received scaffolds compared to normal. There was no effect of ASC+BMP12 treatment for range of motion or tensile properties outcomes versus repair-only. Biochemical assays demonstrated increased DNA, glycosaminoglycans, and crosslink concentration in all repair groups compared to normal, but no effect of ASC+BMP12. Total collagen was significantly decreased in the acellular scaffold group compared to normal and significantly increased in the ASC+BMP12 group compared to the acellular scaffold group. Proteomics analysis comparing healing tendons to uninjured tendons revealed significant increases in proteins associated with inflammation, stress response, and matrix degradation. Treatment with ASC+BMP12 amplified these unfavorable changes. In summary, the treatment approach used in this study induced a negative inflammatory reaction at the repair site leading to poor healing. Future approaches should consider cell and growth factor delivery methods that do not incite negative local reactions. PMID:26445383

Conodont affinity and chordate phylogeny.

PubMed

Donoghue, P C; Forey, P L; Aldridge, R J

2000-05-01

Current information on the conodonts Clydagnathus windsorensis (Globensky) and Promissum pulchrum Kovács-Endrödy, together with the latest interpretations of conodont hard tissues, are reviewed and it is concluded that sufficient evidence exists to justify interpretation of the conodonts on a chordate model. A new phylogenetic analysis is undertaken, consisting of 17 chordate taxa and 103 morphological, physiological and biochemical characters; conodonts are included as a primary taxon. Various experiments with character coding, taxon deletion and the use of constraint trees are carried out. We conclude that conodonts are cladistically more derived than either hagfishes or lampreys because they possess a mineralised dermal skeleton and that they are the most plesiomorphic member of the total group Gnathostomata. We discuss the evolution of the nervous and sensory systems and the skeleton in the context of our optimal phylogenetic tree. There appears to be no simple evolution of free to canal-enclosed neuromasts; organised neuromasts within canals appear to have arisen at least three times from free neuromasts or neuromasts arranged within grooves. The mineralised vertebrate skeleton first appeared as odontodes of dentine or dentine plus enamel in the paraconodont/euconodont feeding apparatus. Bone appeared later, co-ordinate with the development of a dermal skeleton, and it appears to have been primitively acellular. Atubular dentine is more primitive than tubular dentine. However, the subsequent distribution of the different types of dentine (e.g. mesodentine, orthodentine), suggests that these tissue types are homoplastic. The topology of relationships and known stratigraphic ranges of taxa in our phylogeny predict the existence of myxinoids and petromyzontids in the Cambrian.

Retrospective comparison of diabetic foot ulcer and venous stasis ulcer healing outcome between a dermal repair scaffold (PriMatrix) and a bilayered living cell therapy (Apligraf).

PubMed

Karr, Jeffrey C

2011-03-01

The goal of this study was to review clinical experience in treating diabetic and venous stasis wounds with Apligraf or PriMatrix. A total of 40 diabetic foot ulcers and 28 venous stasis ulcers were treated with either PriMatrix or Apligraf for number of days open and for number of days for complete healing between the 2 treatments. Although both treatments were highly effective, the study results of 68 ulcers in 48 patients demonstrated that patients treated with PriMatrix healed faster than patients treated with Apligraf despite larger wound sizes.

Myricetin, a potent natural agent for treatment of diabetic skin damage by modulating TIMP/MMPs balance and oxidative stress

PubMed Central

2016-01-01

Foot ulceration is a major cause of morbidity in patients with diabetes, and abnormal peripheral neuropathy often results in hospitalization. Up-regulation of matrix metalloproteinases and down-regulation of tissue inhibitor of metalloproteinase 1 are noted to be distinctive biological functions of diabetic dermal fibroblasts. The aim of this study was to evaluate the biological effects of modified retinoids on diabetic fibroblasts. Myricetin, a natural compound, balances the TIMP1/MMP ratio and oxidative stress in diabetic fibroblasts. Our results indicate that myricetin significantly ameliorates the effects of diabetes on dermal fibroblasts. In addition, we found that the oxidative stress imbalance induced by a high glucose concentration plays an important role in the changes to dermal fibroblasts that occur in diabetes. Our findings support the hypothesis that myricetin has the potential to repair faulty skin function arising from diabetes. PMID:27765936

23-Hydroxytormentic acid protects human dermal fibroblasts by attenuating UVA-induced oxidative stress.

PubMed

Youn, Hae Jeong; Kim, Ki Bbeum; Han, Hyo-Sun; An, In-Sook; Ahn, Kyu Joong

2017-03-01

Ultraviolet A (UVA), one of the major components of sunlight, can penetrate the dermal layer of the skin and generate reactive oxygen species (ROS). It causes alterations in the dermal connective tissue and gene expression, inflammation, photoaging, and DNA damage. Therefore, the harmful effects of UVA and strategies to reduce it have been consistently investigated. 23-Hydroxytormentic acid (23-HTA) has been demonstrated to improve drug-induced nephrotoxicity and exhibit several free radical scavenging effects with other molecules. Therefore, the aim of this study was to investigate the anti-inflammatory effects and extracellular matrix (ECM) reconstructive activity of 23-HTA in UVA-irradiated normal human dermal fibroblasts (NHDFs). The antioxidant capacity of 23-HTA was determined by examining its scavenging activities against hydrogen peroxide, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and diphenylpicrylhydrazyl in vitro. Its effect on cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tertazolium bromide, and 2,7-dichlorofluorescin diacetate was used to investigate intracellular ROS scavenging activity. The mRNA levels of antioxidant enzymes and pro-inflammatory cytokines were detected using quantitative real-time polymerase chain reaction. A senescence-associated β-galactosidase (SA-β-gal) staining kit was used to assess senescent cells. 23-HTA showed antioxidant capacity mediated by ROS scavenging and regulation of antioxidant-related gene expression. Further, the SA-β-gal analysis and mRNA expression of matrix metalloproteinases and type I procollagen suggested that 23-HTA regulates the gene expression of ECM proteins and cellular senescence under UVA-irradiated conditions. In conclusion, 23-HTA protects against and attenuates UVA-induced oxidative stress in NHDFs likely via the nuclear factor erythroid-derived 2-like 2 signaling pathway. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Coriander Leaf Extract Exerts Antioxidant Activity and Protects Against UVB-Induced Photoaging of Skin by Regulation of Procollagen Type I and MMP-1 Expression

PubMed Central

Hwang, Eunson; Lee, Do-Gyeong; Park, Sin Hee; Oh, Myung Sook

2014-01-01

Abstract Ultraviolet (UV) radiation causes photodamage to the skin, which, in turn, leads to depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkles are associated with collagen synthesis and matrix metalloproteinase-1 (MMP-1) activity. Coriandrum sativum L. (coriander leaf, cilantro; CS) has been used as a herbal medicine for the treatment of diabetes, hyperlipidemia, liver disease, and cancer. In this study, we examined whether CS ethanol extract (CSE) has protective effects against UVB-induced skin photoaging in normal human dermal fibroblasts (NHDF) in vitro and in the skin of hairless mice in vivo. The main component of CSE, linolenic acid, was determined by gas chromatography-mass spectroscopy. We measured the cellular levels of procollagen type I and MMP-1 using ELISA in NHDF cells after UVB irradiation. NHDF cells that were treated with CSE after UVB irradiation exhibited higher procollagen type I production and lower levels of MMP-1 than untreated cells. We found that the activity of transcription factor activator protein-1 (AP-1) was also inhibited by CSE treatment. We measured the epidermal thickness, dermal collagen fiber density, and procollagen type I and MMP-1 levels in photo-aged mouse skin in vivo using histological staining and western blot analysis. Our results showed that CSE-treated mice had thinner epidermal layers and denser dermal collagen fibers than untreated mice. On a molecular level, it was further confirmed that CSE-treated mice had lower MMP-1 levels and higher procollagen type I levels than untreated mice. Our results support the potential of C. sativum L. to prevent skin photoaging. PMID:25019675

Coriander leaf extract exerts antioxidant activity and protects against UVB-induced photoaging of skin by regulation of procollagen type I and MMP-1 expression.

PubMed

Hwang, Eunson; Lee, Do-Gyeong; Park, Sin Hee; Oh, Myung Sook; Kim, Sun Yeou

2014-09-01

Ultraviolet (UV) radiation causes photodamage to the skin, which, in turn, leads to depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkles are associated with collagen synthesis and matrix metalloproteinase-1 (MMP-1) activity. Coriandrum sativum L. (coriander leaf, cilantro; CS) has been used as a herbal medicine for the treatment of diabetes, hyperlipidemia, liver disease, and cancer. In this study, we examined whether CS ethanol extract (CSE) has protective effects against UVB-induced skin photoaging in normal human dermal fibroblasts (NHDF) in vitro and in the skin of hairless mice in vivo. The main component of CSE, linolenic acid, was determined by gas chromatography-mass spectroscopy. We measured the cellular levels of procollagen type I and MMP-1 using ELISA in NHDF cells after UVB irradiation. NHDF cells that were treated with CSE after UVB irradiation exhibited higher procollagen type I production and lower levels of MMP-1 than untreated cells. We found that the activity of transcription factor activator protein-1 (AP-1) was also inhibited by CSE treatment. We measured the epidermal thickness, dermal collagen fiber density, and procollagen type I and MMP-1 levels in photo-aged mouse skin in vivo using histological staining and western blot analysis. Our results showed that CSE-treated mice had thinner epidermal layers and denser dermal collagen fibers than untreated mice. On a molecular level, it was further confirmed that CSE-treated mice had lower MMP-1 levels and higher procollagen type I levels than untreated mice. Our results support the potential of C. sativum L. to prevent skin photoaging.

Pericellular Versican Regulates the Fibroblast-Myofibroblast Transition

PubMed Central

Hattori, Noriko; Carrino, David A.; Lauer, Mark E.; Vasanji, Amit; Wylie, James D.; Nelson, Courtney M.; Apte, Suneel S.

2011-01-01

The cell and its glycosaminoglycan-rich pericellular matrix (PCM) comprise a functional unit. Because modification of PCM influences cell behavior, we investigated molecular mechanisms that regulate PCM volume and composition. In fibroblasts and other cells, aggregates of hyaluronan and versican are found in the PCM. Dermal fibroblasts from Adamts5−/− mice, which lack a versican-degrading protease, ADAMTS5, had reduced versican proteolysis, increased PCM, altered cell shape, enhanced α-smooth muscle actin (SMA) expression and increased contractility within three-dimensional collagen gels. The myofibroblast-like phenotype was associated with activation of TGFβ signaling. We tested the hypothesis that fibroblast-myofibroblast transition in Adamts5−/− cells resulted from versican accumulation in PCM. First, we noted that versican overexpression in human dermal fibroblasts led to increased SMA expression, enhanced contractility, and increased Smad2 phosphorylation. In contrast, dermal fibroblasts from Vcan haploinsufficient (Vcanhdf/+) mice had reduced contractility relative to wild type fibroblasts. Using a genetic approach to directly test if myofibroblast transition in Adamts5−/− cells resulted from increased PCM versican content, we generated Adamts5−/−;Vcanhdf/+ mice and isolated their dermal fibroblasts for comparison with dermal fibroblasts from Adamts5−/− mice. In Adamts5−/− fibroblasts, Vcan haploinsufficiency or exogenous ADAMTS5 restored normal fibroblast contractility. These findings demonstrate that altering PCM versican content through proteolytic activity of ADAMTS5 profoundly influenced the dermal fibroblast phenotype and may regulate a phenotypic continuum between the fibroblast and its alter ego, the myofibroblast. We propose that a physiological function of ADAMTS5 in dermal fibroblasts is to maintain optimal versican content and PCM volume by continually trimming versican in hyaluronan-versican aggregates. PMID:21828051

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

Periodontal soft tissue root coverage procedures: a systematic review from the AAP Regeneration Workshop.

PubMed

Chambrone, Leandro; Tatakis, Dimitris N

2015-02-01

This paper aims to create a "bridge" between research and practice by developing a practical, extensive, and clinically relevant study that translates evidence-based findings on soft tissue root coverage (RC) of recession-type defects to daily clinical practice. This review is prepared in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement based on the proposed focused questions. A literature search with no restrictions regarding status or the language of publication was performed for MEDLINE and EMBASE databases up to and including June 2013. Systematic reviews (SRs), randomized clinical trials, controlled clinical trials, case series, and case reports evaluating recession areas that were treated by means of RC procedures were considered eligible for inclusion through the three parts of the study (part I, an overview of the base of SRs; part II, an alternative random-effects meta-analyses on mean percentage of RC and sites exhibiting complete RC; and part III, an SR of non-randomized trials exploring other conditions not extensively evaluated by previous SRs). Data on Class I, II, III, and IV recessions, type of histologic attachment achieved with treatment, recipient- and donor-site anatomic characteristics, smoking-related outcomes, root surface conditions, tooth type and location, long-term effectiveness outcomes, unusual conditions that may be reported during conventional daily practice, and patient-centered outcomes were assessed as well. Of the 2,456 potentially eligible trials, 234 were included. Data on Class I, II, III, and IV gingival recessions, histologic attachment achieved after treatment, recipient- and donor-site anatomic characteristics, smoking-related outcomes, root surface conditions/biomodification, tooth type and location, long-term effectiveness outcomes and unusual conditions that may be reported during conventional daily practice, and patient-centered outcomes (i.e., esthetic, visual analog scale, complications, hypersensitivity, patients perceptions) were assessed. Subepithelial connective tissue (CT)-based procedures and coronally advanced flap plus acellular dermal matrix grafts, enamel matrix derivative, or collagen matrix led to the best improvements of recession depth, clinical attachment level (CAL) gain, and keratinized tissue (KT). Some conditions, such as smoking and use of magnification, may affect RC outcomes. All RC procedures can provide significant reduction in recession depth and CAL gain for Miller Class I and II recession-type defects. Subepithelial CT graft-based procedures provided the best outcomes for clinical practice because of their superior percentages of mean and complete RC, as well as significant increase of KT.

Synthesis and Characterization of a Model Extracellular Matrix that Induces Partial Regeneration of Adult Mammalian Skin

NASA Astrophysics Data System (ADS)

Yannas, I. V.; Lee, E.; Orgill, D. P.; Skrabut, E. M.; Murphy, G. F.

1989-02-01

Regeneration of the dermis does not occur spontaneously in the adult mammal. The epidermis is regenerated spontaneously provided there is a dermal substrate over which it can migrate. Certain highly porous, crosslinked collagen--glycosaminoglycan copolymers have induced partial morphogenesis of skin when seeded with dermal and epidermal cells and then grafted on standard, full-thickness skin wounds in the adult guinea pig. A mature epidermis and a nearly physiological dermis, which lacked hair follicles but was demonstrably different from scar, were regenerated over areas as large as 16 cm2. These chemical analogs of extracellular matrices were morphogenetically active provided that the average pore diameter ranged between 20 and 125 μ m, the resistance to degradation by collagenase exceeded a critical limit, and the density of autologous dermal and epidermal cells inoculated therein was >5 × 104 cells per cm2 of wound area. Unseeded copolymers with physical structures that were within these limits delayed the onset of wound contraction by about 10 days but did not eventually prevent it. Seeded copolymers not only delayed contraction but eventually arrested and reversed it while new skin was being regenerated. The data identify a model extracellular matrix that acts as if it were an insoluble growth factor with narrowly specified physicochemical structure, functioning as a transient basal lamina during morphogenesis of skin.

Reconstruction of full-thickness defects with bovine-derived collagen/elastin matrix: a series of challenging cases and the first reported post-burn facial reconstruction.

PubMed

Haik, Josef; Weissman, Oren; Hundeshagen, Gabriel; Farber, Nimrod; Harats, Moti; Rozenblatt, Shira M; Kamolz, Lars Peter; Winkler, Eyal; Zilinsky, Isaac

2012-07-01

Reconstruction of full-thickness defects may benefit from integration of dermal substitutes, which serve as a foundation for split-thickness skin grafts, thus enhancing short and long-term results. We present a series of 7 patients who were treated between 2010 and 2012 for complicated full-thickness defects by the second-generation collagen/elastin matrix Matriderm® covered by a split-thickness skin graft. The defects resulted from malignancy resection, trauma, and post-burn scar reconstruction. Overall graft take was excellent and no complications were noted regarding the dermal substitute. Graft quality was close to normal skin in terms of elasticity, pliability, texture, and color. Good contour and cushioning of defects in weight bearing areas was also achieved. Matriderm was found to be a useful adjunct to full-thickness defect reconstruction, especially in difficult areas where the desired result is a scar of the highest quality possible.

Root coverage with cultured gingival dermal substitute composed of gingival fibroblasts and matrix: a case series.

PubMed

Murata, Masashi; Okuda, Kazuhiro; Momose, Manabu; Kubo, Kentarou; Kuroyanagi, Yoshimitsu; Wolff, Larry F

2008-10-01

Cultured gingival dermal substitute (CGDS), composed of gingival fibroblasts and matrix and fabricated using tissue-engineering techniques, has been used for root coverage procedures. Fourteen sites from four patients with > or = 2 mm of Miller Class I or II facial gingival tissue recession were treated. The autologous CGDS sheet, prepared prior to surgical treatment, was grafted over the teeth with gingival recession and then covered with a coronally positioned flap. Vertical and horizontal recession was measured at baseline (prior to the surgical procedure) and 13 to 40 weeks (average: 30.7 +/- 9.6 weeks) after surgery. The average vertical and horizontal root coverage after surgery was 79.1% +/- 25.7% and 75.2% +/- 31.4%, respectively. Moreover, there was a significant increase of keratinized and attached gingival tissue at the final clinical evaluation compared with preoperative measurements (P < .05). These results demonstrate CGDS as a promising grafting material for use with root coverage procedures in periodontal therapy.

Dermal wound healing processes with curcumin incorporated collagen films.

PubMed

Gopinath, D; Ahmed, M Rafiuddin; Gomathi, K; Chitra, K; Sehgal, P K; Jayakumar, R

2004-05-01

The wound healing process involves extensive oxidative stress to the system, which generally inhibits tissue remodeling. In the present study, an improvement in the quality of wound healing was attempted by slow delivery of antioxidants like curcumin from collagen, which also acts as a supportive matrix for the regenerative tissue. Curcumin incorporated collagen matrix (CICM) treated groups were compared with control and collagen treated rats. Biochemical parameters and histological analysis revealed that increased wound reduction, enhanced cell proliferation and efficient free radical scavenging in CICM group. The higher shrinkage temperature of CICM films suggests increased hydrothermal stability when compared to normal collagen films. Spectroscopic studies revealed that curcumin was bound to the collagen without affecting its triple helicity. Further we adopted the antioxidant assay using 2,2'-azobisisobutyronitrile to assess in vitro antioxidant activity of CICM. The antioxidant studies indicated that CICM quenches free radicals more efficiently. This study provides a rationale for the topical application of CICM as a feasible and productive approach to support dermal wound healing.

Collagen XII and XIV, new partners of cartilage oligomeric matrix protein in the skin extracellular matrix suprastructure.

PubMed

Agarwal, Pallavi; Zwolanek, Daniela; Keene, Douglas R; Schulz, Jan-Niklas; Blumbach, Katrin; Heinegård, Dick; Zaucke, Frank; Paulsson, Mats; Krieg, Thomas; Koch, Manuel; Eckes, Beate

2012-06-29

The tensile and scaffolding properties of skin rely on the complex extracellular matrix (ECM) that surrounds cells, vasculature, nerves, and adnexus structures and supports the epidermis. In the skin, collagen I fibrils are the major structural component of the dermal ECM, decorated by proteoglycans and by fibril-associated collagens with interrupted triple helices such as collagens XII and XIV. Here we show that the cartilage oligomeric matrix protein (COMP), an abundant component of cartilage ECM, is expressed in healthy human skin. COMP expression is detected in the dermal compartment of skin and in cultured fibroblasts, whereas epidermis and HaCaT cells are negative. In addition to binding collagen I, COMP binds to collagens XII and XIV via their C-terminal collagenous domains. All three proteins codistribute in a characteristic narrow zone in the superficial papillary dermis of healthy human skin. Ultrastructural analysis by immunogold labeling confirmed colocalization and further revealed the presence of COMP along with collagens XII and XIV in anchoring plaques. On the basis of these observations, we postulate that COMP functions as an adapter protein in human skin, similar to its function in cartilage ECM, by organizing collagen I fibrils into a suprastructure, mainly in the vicinity of anchoring plaques that stabilize the cohesion between the upper dermis and the basement membrane zone.

Collagen XII and XIV, New Partners of Cartilage Oligomeric Matrix Protein in the Skin Extracellular Matrix Suprastructure*

PubMed Central

Agarwal, Pallavi; Zwolanek, Daniela; Keene, Douglas R.; Schulz, Jan-Niklas; Blumbach, Katrin; Heinegård, Dick; Zaucke, Frank; Paulsson, Mats; Krieg, Thomas; Koch, Manuel; Eckes, Beate

2012-01-01

The tensile and scaffolding properties of skin rely on the complex extracellular matrix (ECM) that surrounds cells, vasculature, nerves, and adnexus structures and supports the epidermis. In the skin, collagen I fibrils are the major structural component of the dermal ECM, decorated by proteoglycans and by fibril-associated collagens with interrupted triple helices such as collagens XII and XIV. Here we show that the cartilage oligomeric matrix protein (COMP), an abundant component of cartilage ECM, is expressed in healthy human skin. COMP expression is detected in the dermal compartment of skin and in cultured fibroblasts, whereas epidermis and HaCaT cells are negative. In addition to binding collagen I, COMP binds to collagens XII and XIV via their C-terminal collagenous domains. All three proteins codistribute in a characteristic narrow zone in the superficial papillary dermis of healthy human skin. Ultrastructural analysis by immunogold labeling confirmed colocalization and further revealed the presence of COMP along with collagens XII and XIV in anchoring plaques. On the basis of these observations, we postulate that COMP functions as an adapter protein in human skin, similar to its function in cartilage ECM, by organizing collagen I fibrils into a suprastructure, mainly in the vicinity of anchoring plaques that stabilize the cohesion between the upper dermis and the basement membrane zone. PMID:22573329

Reconstruction of living bilayer human skin equivalent utilizing human fibrin as a scaffold.

PubMed

Mazlyzam, A L; Aminuddin, B S; Fuzina, N H; Norhayati, M M; Fauziah, O; Isa, M R; Saim, L; Ruszymah, B H I

2007-05-01

Our aim of this study was to develop a new methodology for constructing a bilayer human skin equivalent to create a more clinical compliance skin graft composite for the treatment of various skin defects. We utilized human plasma derived fibrin as the scaffold for the development of a living bilayer human skin equivalent: fibrin-fibroblast and fibrin-keratinocyte (B-FF/FK SE). Skin cells from six consented patients were culture-expanded to passage 1. For B-FF/FK SE formation, human fibroblasts were embedded in human fibrin matrix and subsequently another layer of human keratinocytes in human fibrin matrix was stacked on top. The B-FF/FK SE was then transplanted to athymic mice model for 4 weeks to evaluate its regeneration and clinical performance. The in vivo B-FF/FK SE has similar properties as native human skin by histological analysis and expression of basal Keratin 14 gene in the epidermal layer and Collagen type I gene in the dermal layer. Electron microscopy analysis of in vivo B-FF/FK SE showed well-formed and continuous epidermal-dermal junction. We have successfully developed a technique to engineer living bilayer human skin equivalent using human fibrin matrix. The utilization of culture-expanded human skin cells and fibrin matrix from human blood will allow a fully autologous human skin equivalent construction.

A Mixture of Extracts of Kochia scoparia and Rosa multiflora with PPAR α/γ Dual Agonistic Effects Prevents Photoaging in Hairless Mice

PubMed Central

Jeon, Hyerin; Kim, Dong Hye; Nho, Youn-Hwa; Park, Ji-Eun; Kim, Su-Nam; Choi, Eung Ho

2016-01-01

Activation of peroxisome proliferator-activated receptors (PPAR) α/γ is known to inhibit the increases in matrix metalloproteinase (MMP) and reactive oxygen species (ROS) induced by ultraviolet light (UV). Extracts of natural herbs, such as Kochia scoparia and Rosa multiflora, have a PPAR α/γ dual agonistic effect. Therefore, we investigated whether and how they have an antiaging effect on photoaging skin. Eighteen-week-old hairless mice were irradiated with UVA 14 J/cm2 and UVB 40 mJ/cm2 three times a week for 8 weeks. A mixture of extracts of Kochia scoparia and Rosa multiflora (KR) was topically applied on the dorsal skin of photoaging mice twice a day for 8 weeks. Tesaglitazar, a known PPAR α/γ agonist, and vehicle (propylene glycol:ethanol = 7:3, v/v) were applied as positive and negative controls, respectively. Dermal effects (including dermal thickness, collagen density, dermal expression of procollagen 1 and collagenase 13) and epidermal effects (including skin barrier function, epidermal proliferation, epidermal differentiation, and epidermal cytokines) were measured and compared. In photoaging murine skin, KR resulted in a significant recovery of dermal thickness as well as dermal fibroblasts, although it did not change dermal collagen density. KR increased the expression of dermal transforming growth factor (TGF)-β. The dermal effects of KR were explained by an increase in procollagen 1 expression, induced by TGF-β, and a decrease in MMP-13 expression. KR did not affect basal transepidermal water loss (TEWL) or stratum corneum (SC) integrity, but did decrease SC hydration. It also did not affect epidermal proliferation or epidermal differentiation. KR decreased the expression of epidermal interleukin (IL)-1α. Collectively, KR showed possible utility as a therapeutic agent for photoaging skin, with few epidermal side effects such as epidermal hyperplasia or poor differentiation. PMID:27854351

A Mixture of Extracts of Kochia scoparia and Rosa multiflora with PPAR α/γ Dual Agonistic Effects Prevents Photoaging in Hairless Mice.

PubMed

Jeon, Hyerin; Kim, Dong Hye; Nho, Youn-Hwa; Park, Ji-Eun; Kim, Su-Nam; Choi, Eung Ho

2016-11-16

Activation of peroxisome proliferator-activated receptors (PPAR) α/γ is known to inhibit the increases in matrix metalloproteinase (MMP) and reactive oxygen species (ROS) induced by ultraviolet light (UV). Extracts of natural herbs, such as Kochia scoparia and Rosa multiflora , have a PPAR α/γ dual agonistic effect. Therefore, we investigated whether and how they have an antiaging effect on photoaging skin. Eighteen-week-old hairless mice were irradiated with UVA 14 J/cm² and UVB 40 mJ/cm² three times a week for 8 weeks. A mixture of extracts of Kochia scoparia and Rosa multiflora (KR) was topically applied on the dorsal skin of photoaging mice twice a day for 8 weeks. Tesaglitazar, a known PPAR α/γ agonist, and vehicle (propylene glycol:ethanol = 7:3, v / v ) were applied as positive and negative controls, respectively. Dermal effects (including dermal thickness, collagen density, dermal expression of procollagen 1 and collagenase 13) and epidermal effects (including skin barrier function, epidermal proliferation, epidermal differentiation, and epidermal cytokines) were measured and compared. In photoaging murine skin, KR resulted in a significant recovery of dermal thickness as well as dermal fibroblasts, although it did not change dermal collagen density. KR increased the expression of dermal transforming growth factor (TGF)-β. The dermal effects of KR were explained by an increase in procollagen 1 expression, induced by TGF-β, and a decrease in MMP-13 expression. KR did not affect basal transepidermal water loss (TEWL) or stratum corneum (SC) integrity, but did decrease SC hydration. It also did not affect epidermal proliferation or epidermal differentiation. KR decreased the expression of epidermal interleukin (IL)-1α. Collectively, KR showed possible utility as a therapeutic agent for photoaging skin, with few epidermal side effects such as epidermal hyperplasia or poor differentiation.

Perfusion decellularization of a human limb: A novel platform for composite tissue engineering and reconstructive surgery.

PubMed

Gerli, Mattia Francesco Maria; Guyette, Jacques Paul; Evangelista-Leite, Daniele; Ghoshhajra, Brian Burns; Ott, Harald Christian

2018-01-01

Muscle and fasciocutaneous flaps taken from autologous donor sites are currently the most utilized approach for trauma repair, accounting annually for 4.5 million procedures in the US alone. However, the donor tissue size is limited and the complications related to these surgical techniques lead to morbidities, often involving the donor sites. Alternatively, recent reports indicated that extracellular matrix (ECM) scaffolds boost the regenerative potential of the injured site, as shown in a small cohort of volumetric muscle loss patients. Perfusion decellularization is a bioengineering technology that allows the generation of clinical-scale ECM scaffolds with preserved complex architecture and with an intact vascular template, from a variety of donor organs and tissues. We recently reported that this technology is amenable to generate full composite tissue scaffolds from rat and non-human primate limbs. Translating this platform to human extremities could substantially benefit soft tissue and volumetric muscle loss patients providing tissue- and species-specific grafts. In this proof-of-concept study, we show the successful generation a large-scale, acellular composite tissue scaffold from a full cadaveric human upper extremity. This construct retained its morphological architecture and perfusable vascular conduits. Histological and biochemical validation confirmed the successful removal of nuclear and cellular components, and highlighted the preservation of the native extracellular matrix components. Our results indicate that perfusion decellularization can be applied to produce human composite tissue acellular scaffolds. With its preserved structure and vascular template, these biocompatible constructs, could have significant advantages over the currently implanted matrices by means of nutrient distribution, size-scalability and immunological response.

Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

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

Puente, Pilar de la, E-mail: pilardelapuentegarcia@gmail.com; Ludeña, Dolores; López, Marta

2013-02-01

Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12more » pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.« less

[Decellularized fish skin: characteristics that support tissue repair].

PubMed

Magnússon, Skúli; Baldursson, Baldur Tumi; Kjartansson, Hilmar; Thorlacius, Guðný Ella; Axelsson, Ívar; Rolfsson, Óttar; Petersen, Pétur Henry; Sigurjónsson, Guðmundur Fertram

2015-12-01

Acellular fish skin of the Atlantic cod (Gadus morhua) is being used to treat chronic wounds. The prevalence of diabetes and the comorbidity of chronic wounds is increasing globally. The aim of the study was to assess the biocompatibility and biological characteristics of acellular fish skin, important for tissue repair. The structure of the acellular fish skin was examined with microscopy. Biocompatibility of the graft was conducted by a specialized certified laboratory. Protein extracts from the material were analyzed using gel electrophoresis. Cytokine levels were measured with an enzyme linked immunosorbent assay (ELISA). Angiogenic properties were assessed with a chick chorioallantoic membrane (chick CAM) assay. The structure of acellular fish skin is porous and the material is biocompatible. Electrophoresis revealed proteins around the size 115-130 kDa, indicative of collagens. The material did not have significant effect on IL-10, IL-12p40, IL-6 or TNF-α secretion from monocytes or macrophages. Acellular fish skin has significant effect on angiogenesis in the chick CAM assay. The acellular fish skin is not toxic and is not likely to promote inflammatory responses. The graft contains collagen I, promotes angiogenesis and supports cellular ingrowth. Compared to similar products made from mammalian sources, acellular fish skin does not confer a disease risk and contains more bioactive compounds, due to less severe processing.

Gingival Fibroblasts Display Reduced Adhesion and Spreading on Extracellular Matrix: A Possible Basis for Scarless Tissue Repair?

PubMed Central

Guo, Fen; Carter, David E.; Mukhopadhyay, Anuradha; Leask, Andrew

2011-01-01

Unlike skin, oral gingiva do not scar in response to injury. The basis of this difference is likely to be revealed by comparing the responses of dermal and gingival fibroblasts to fibrogenic stimuli. Previously, we showed that, compared to dermal fibroblasts, gingival fibroblasts are less responsive to the potent pro-fibrotic cytokine TGFβ, due to a reduced production of endothelin-1 (ET-1). In this report, we show that, compared to dermal fibroblasts, human gingival fibroblasts show reduced expression of pro-adhesive mRNAs and proteins including integrins α2 and α4 and focal adhesion kinase (FAK). Consistent with these observations, gingival fibroblasts are less able to adhere to and spread on both fibronectin and type I collagen. Moreover, the enhanced production of ET-1 mRNA and protein in dermal fibroblasts is reduced by the FAK/src inhibitor PP2. Given our previous observations suggesting that fibrotic fibroblasts display elevated adhesive properties, our data suggest that scarring potential may be based, at least in part, on differences in adhesive properties among fibroblasts resident in connective tissue. Controlling adhesive properties may be of benefit in controlling scarring in response to tissue injury. PMID:22073262

The hallmarks of fibroblast ageing.

PubMed

Tigges, Julia; Krutmann, Jean; Fritsche, Ellen; Haendeler, Judith; Schaal, Heiner; Fischer, Jens W; Kalfalah, Faiza; Reinke, Hans; Reifenberger, Guido; Stühler, Kai; Ventura, Natascia; Gundermann, Sabrina; Boukamp, Petra; Boege, Fritz

2014-06-01

Ageing is influenced by the intrinsic disposition delineating what is maximally possible and extrinsic factors determining how that frame is individually exploited. Intrinsic and extrinsic ageing processes act on the dermis, a post-mitotic skin compartment mainly consisting of extracellular matrix and fibroblasts. Dermal fibroblasts are long-lived cells constantly undergoing damage accumulation and (mal-)adaptation, thus constituting a powerful indicator system for human ageing. Here, we use the systematic of ubiquitous hallmarks of ageing (Lopez-Otin et al., 2013, Cell 153) to categorise the available knowledge regarding dermal fibroblast ageing. We discriminate processes inducible in culture from phenomena apparent in skin biopsies or primary cells from old donors, coming to the following conclusions: (i) Fibroblasts aged in culture exhibit most of the established, ubiquitous hallmarks of ageing. (ii) Not all of these hallmarks have been detected or investigated in fibroblasts aged in situ (in the skin). (iii) Dermal fibroblasts aged in vitro and in vivo exhibit additional features currently not considered ubiquitous hallmarks of ageing. (iv) The ageing process of dermal fibroblasts in their physiological tissue environment has only been partially elucidated, although these cells have been a preferred model of cell ageing in vitro for decades. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Integrin-linked kinase is required for TGF-β1 induction of dermal myofibroblast differentiation.

PubMed

Vi, Linda; de Lasa, Cristina; DiGuglielmo, Gianni M; Dagnino, Lina

2011-03-01

Cutaneous repair after injury requires activation of resident dermal fibroblasts and their transition to myofibroblasts. The key stimuli for myofibroblast formation are activation of transforming growth factor-β (TGF-β) receptors and mechanotransduction mediated by integrins and associated proteins. We investigated the role of integrin-linked kinase (ILK) in TGF-β1 induction of dermal fibroblast transition to myofibroblasts. ILK-deficient fibroblasts treated with TGF-β1 exhibited attenuation of Smad 2 and 3 phosphorylation, accompanied by impaired transcriptional activation of Smad targets, such as α-smooth muscle actin. These alterations were not limited to Smad-associated TGF-β1 responses, as stimulation of noncanonical mitogen-activated protein kinase pathways by this growth factor was also diminished in the absence of ILK. ILK-deficient fibroblasts exhibited abnormalities in the actin cytoskeleton, and did not form supermature focal adhesions or contractile F-actin stress fibers, indicating a severe impairment in their capacity to differentiate into myofibroblasts. These defects extended to the inability of cells to contract extracellular matrices when embedded in collagen lattices. We conclude that ILK is necessary to transduce signals implicated in the transition of dermal fibroblasts to myofibroblasts originating from matrix substrates and TGF-β1.

Hip arthroscopy for excision of osteoid osteoma and for the application of a collagen cartilage implant: Case report in a professional athlete, and literature review.

PubMed

von Engelhardt, Lars Victor; El Tabbakh, Mohammed Roshdy; Engers, Rainer; Lahner, Matthias; Jerosch, Jörg

2016-11-14

Osteoid osteoma is an osteoblastic benign bone tumor usually affecting young adolescents. Intra-articular lesions are not common; usually the diagnosis is delayed. A lot of studies report difficulties and complications in the management of osteoid osteoma of the hip joint using imaging guided techniques or open surgical procedures. Only few published cases have described that it can be treated precisely using hip arthroscopy. Additionally, the use of hip arthroscopy to apply the Chondrofiller®, an acellular collagen matrix for the management of articular cartilage defects of the hip joint, has not yet been described. This report presents an osteoid osteoma of the femoral neck. A 20-year-old female professional basketball player presented with pain in the left groin since more than 12 months. On magnetic resonance and computed tomography imaging, an osteoid osteoma was suggested. The lesion was successfully removed using arthroscopy. During surgery, a concomitant grade 4 cartilage lesion on the femoral head was detected. For the treatment of this severe defect we used the Chondrofiller®, which is a new acellular collagen implant for auto-regeneration of articular cartilage. This matrix was filled into the prepared and dried defect using CO2 arthroscopy. After the hardening of the matrix the surgery was finished. The patient was pain free shortly after the operation and returned to sports within 16 weeks. Return to high-performance sports 8 months after surgery was without of any sign of complaints. This article demonstrates that hip arthroscopy is a valuable tool for biopsy and excision of intra-articular osteoid osteoma affecting the hip joint, as well as for addressing other concomitant pathologies such as a severe synovitis or cartilage defects. CO2 arthroscopy provided good conditions for the drying and filling of the cartilage defect with the Chondrofiller®.

Comparative Biology of Decellularized Lung Matrix: Implications of Species Mismatch in Regenerative Medicine

PubMed Central

Balestrini, Jenna L.; Gard, Ashley L.; Gerhold, Kristin A.; Wilcox, Elise C.; Liu, Angela; Schwan, Jonas; Le, Andrew V.; Baevova, Pavlina; Dimitrievska, Sashka; Zhao, Liping; Sundaram, Sumati; Sun, Huanxing; Rittié, Laure; Dyal, Rachel; Broekelmann, Tom J.; Mecham, Robert P.; Schwartz, Martin A.; Niklason, Laura E.; White, Eric S.

2016-01-01

Lung engineering is a promising technology, relying on re-seeding of either human or xenographic decellularized matrices with patient-derived pulmonary cells. Little is known about the species-specificity of decellularization in various models of lung regeneration, or if species dependent cell-matrix interactions exist within these systems. Therefore decellularized scaffolds were produced from rat, pig, primate and human lungs, and assessed by measuring residual DNA, mechanical properties, and key matrix proteins (collagen, elastin, glycosaminoglycans). To study intrinsic matrix biologic cues, human endothelial cells were seeded onto acellular slices and analyzed for markers of cell health and inflammation. Despite similar levels of collagen after decellularization, human and primate lungs were stiffer, contained more elastin, and retained fewer glycosaminoglycans than pig or rat lung scaffolds. Human endothelial cells seeded onto human and primate lung tissue demonstrated less expression of vascular cell adhesion molecule and activation of nuclear factor-κB compared to those seeded onto rodent or porcine tissue. Adhesion of endothelial cells was markedly enhanced on human and primate tissues. Our work suggests that species-dependent biologic cues intrinsic to lung extracellular matrix could have profound effects on attempts at lung regeneration. PMID:27344365

Interleukin-1β Attenuates Myofibroblast Formation and Extracellular Matrix Production in Dermal and Lung Fibroblasts Exposed to Transforming Growth Factor-β1

PubMed Central

Mia, Masum M.; Boersema, Miriam; Bank, Ruud A.

2014-01-01

One of the most potent pro-fibrotic cytokines is transforming growth factor (TGFβ). TGFβ is involved in the activation of fibroblasts into myofibroblasts, resulting in the hallmark of fibrosis: the pathological accumulation of collagen. Interleukin-1β (IL1β) can influence the severity of fibrosis, however much less is known about the direct effects on fibroblasts. Using lung and dermal fibroblasts, we have investigated the effects of IL1β, TGFβ1, and IL1β in combination with TGFβ1 on myofibroblast formation, collagen synthesis and collagen modification (including prolyl hydroxylase, lysyl hydroxylase and lysyl oxidase), and matrix metalloproteinases (MMPs). We found that IL1β alone has no obvious pro-fibrotic effect on fibroblasts. However, IL1β is able to inhibit the TGFβ1-induced myofibroblast formation as well as collagen synthesis. Glioma-associated oncogene homolog 1 (GLI1), the Hedgehog transcription factor that is involved in the transformation of fibroblasts into myofibroblasts is upregulated by TGFβ1. The addition of IL1β reduced the expression of GLI1 and thereby also indirectly inhibits myofibroblast formation. Other potentially anti-fibrotic effects of IL1β that were observed are the increased levels of MMP1, −2, −9 and −14 produced by fibroblasts exposed to TGFβ1/IL1β in comparison with fibroblasts exposed to TGFβ1 alone. In addition, IL1β decreased the TGFβ1-induced upregulation of lysyl oxidase, an enzyme involved in collagen cross-linking. Furthermore, we found that lung and dermal fibroblasts do not always behave identically towards IL1β. Suppression of COL1A1 by IL1β in the presence of TGFβ1 is more pronounced in lung fibroblasts compared to dermal fibroblasts, whereas a higher upregulation of MMP1 is seen in dermal fibroblasts. The role of IL1β in fibrosis should be reconsidered, and the differences in phenotypical properties of fibroblasts derived from different organs should be taken into account in future anti-fibrotic treatment regimes. PMID:24622053

Short-term effects of vacuum massage on epidermal and dermal thickness and density in burn scars: an experimental study.

PubMed

Meirte, Jill; Moortgat, Peter; Anthonissen, Mieke; Maertens, Koen; Lafaire, Cynthia; De Cuyper, Lieve; Hubens, Guy; Van Daele, Ulrike

2016-01-01

Vacuum massage is a non-invasive mechanical massage technique invented to treat burns and scars. To date, no effects of vacuum massage on thickness and density of human scar tissue have been reported. The process in which external stimuli are converted into biochemical responses in the cell is known as mechanotransduction. In the skin endothelial cells, fibroblasts and myofibroblasts embedded in the extracellular matrix (ECM) sense mechanical stimuli (created by vacuum massage) and may promote intracellular processes leading to matrix remodelling. Since mechanotransduction could be a plausible working mechanism for vacuum massage as an anti-scarring therapy, this study aims to investigate the short-term effects of vacuum massage on thickness and density of epidermis and dermis in burn scars in order to find proof of ECM remodelling. A one group experimental study was performed. Patients with burn scars on upper extremities, lower extremities, and trunk were recruited for participation in this study. The DUB®cutis 22 MHz ultrasound scanner was used to assess thickness and density of the epidermal and dermal skin layers. After baseline measurements, vacuum massage was performed according to a pre-defined protocol. Measurements were carried out at 5 min, 30 min, 1 h, and 2 h post-intervention. Thirteen scar sites from 9 different patients were investigated. In 8 out of the 13 scar sites, a disruption of the epidermis was noticed after the vacuum massage. Five minutes after the intervention, epidermal density decreased statistically significantly (p = .022) and dermal thickness increased (p = .018). Both changes lasted for more than 1 h, but after 2 h, the changes were no longer statistically significant. Dermal density decreased significantly (p = .048) immediately after the intervention, and this decrease was still present after 2 h (p = .011). Preliminary results show that the disruption of the epidermis may indicate that vacuum massage could be able to actually breach the skin barrier. The statistically significant changes in the dermal layers could suggest an increased ECM production after vacuum massage.

The Economics of Prepectoral Breast Reconstruction.

PubMed

Glasberg, Scot Bradley

2017-12-01

The world of breast reconstruction over the last several years has seen a dramatic shift in focus to discussion and the application of placing tissue expanders and implants back into the prepectoral space. Although this technique failed during the early advent of breast reconstruction, newer technologies such as advances in fat grafting, improved acellular dermal matrices, better methods of assessing breast flap viability, and enhanced implants appear to have set the stage for the resurgence and positive early results seen with this technique. The main benefits of a switch to prepectoral breast reconstruction clinically appears to be less associated pain, lower incidence of animation deformities, and its associated symptoms as well as presumably better aesthetics. Early data suggest that the results are extremely promising and early adopters have attempted to define the ideal patients for prepectoral breast reconstruction. As with any new operative procedure, an assessment of finances and costs are crucial to its successful implementation. Although current data are minimal, this article attempts to build the fundamentals of an economic model that exhibits and displays potential savings through the use of prepectoral breast reconstruction.

In vivo performance of an acellular disc-like angle ply structure (DAPS) for total disc replacement in a small animal model.

PubMed

Martin, John T; Kim, Dong Hwa; Milby, Andrew H; Pfeifer, Christian G; Smith, Lachlan J; Elliott, Dawn M; Smith, Harvey E; Mauck, Robert L

2017-01-01

Total intervertebral disc replacement with a biologic engineered disc may be an alternative to spinal fusion for treating end-stage disc disease. In previous work, we developed disc-like angle ply structures (DAPS) that replicate the structure and function of the native disc and a rat tail model to evaluate DAPS in vivo. Here, we evaluated a strategy in which, after in vivo implantation, endogenous cells could colonize the acellular DAPS and form an extracellular matrix organized by the DAPS topographical template. To do so, acellular DAPS were implanted into the caudal spines of rats and evaluated over 12 weeks by mechanical testing, histology, and microcomputed tomography. An external fixation device was used to stabilize the implant site and various control groups were included to evaluate the effect of immobilization. There was robust tissue formation within the DAPS after implantation and compressive mechanical properties of the implant matched that of the native motion segment. Immobilization provided a stable site for fibrous tissue formation after either a discectomy or a DAPS implantation, but bony fusion eventually resulted, with segments showing intervertebral bridging after long-term implantation, a process that was accelerated by the implanted DAPS. Thus, while compressive mechanical properties were replicated after DAPS implantation, methods to actively prevent fusion must be developed. Future work will focus on limiting fusion by remobilizing the motion segment after a period of integration, delivering pro-chondrogenic factors, and pre-seeding DAPS with cells prior to implantation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:23-31, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Keratocyte Apoptosis and Not Myofibroblast Differentiation Mark the Graft/Host Interface at Early Time-Points Post-DSAEK in a Cat Model

PubMed Central

Weis, Adam J.; Huxlin, Krystel R.; Callan, Christine L.; DeMagistris, Margaret A.; Hindman, Holly B.

2013-01-01

Purpose To evaluate myofibroblast differentiation as an etiology of haze at the graft-host interface in a cat model of Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK). Methods DSAEK was performed on 10 eyes of 5 adult domestic short-hair cats. In vivo corneal imaging with slit lamp, confocal, and optical coherence tomography (OCT) were performed twice weekly. Cats were sacrificed and corneas harvested 4 hours, and 2, 4, 6, and 9 days post-DSAEK. Corneal sections were stained with the TUNEL method and immunohistochemistry was performed for α-smooth muscle actin (α-SMA) and fibronectin with DAPI counterstain. Results At all in vivo imaging time-points, corneal OCT revealed an increase in backscatter of light and confocal imaging revealed an acellular zone at the graft-host interface. At all post-mortem time-points, immunohistochemistry revealed a complete absence of α-SMA staining at the graft-host interface. At 4 hours, extracellular fibronectin staining was identified along the graft-host interface and both fibronectin and TUNEL assay were positive within adjacent cells extending into the host stroma. By day 2, fibronectin and TUNEL staining diminished and a distinct acellular zone was present in the region of previously TUNEL-positive cells. Conclusions OCT imaging consistently showed increased reflectivity at the graft-host interface in cat corneas in the days post-DSAEK. This was not associated with myofibroblast differentiation at the graft-host interface, but rather with apoptosis and the development of a subsequent acellular zone. The roles of extracellular matrix changes and keratocyte cell death and repopulation should be investigated further as potential contributors to the interface optical changes. PMID:24098706

Fabrication of Cardiac Patch with Decellularized Porcine Myocardial Scaffold and Bone Marrow Mononuclear Cells

PubMed Central

Wang, Bo; Borazjani, Ali; Tahai, Mina; de Jongh Curry, Amy L.; Simionescu, Dan T.; Guan, Jianjun; To, Filip; Elder, Steve H.; Liao, Jun

2010-01-01

Tissue engineered cardiac grafts are a promising therapeutic mode for ventricular wall reconstruction. Recently, it has been found that acellular tissue scaffolds provide natural ultrastructural, mechanical, and compositional cues for recellularization and tissue remodeling. We thus assess the potential of decellularized porcine myocardium as a scaffold for thick cardiac patch tissue engineering. Myocardial sections with 2 mm thickness were decellularized using 0.1% sodium dodecyl sulfate (SDS), and then reseeded with differentiated bone marrow mononuclear cells. We found that thorough decellularization could be achieved after 2.5 weeks treatment. Reseeded cells were found to infiltrate and proliferate in the tissue constructs. Immunohistological staining studies showed that the reseeded cells maintained cardiomyocyte-like phenotype and possible endothelialization was found in locations close to vasculature channels, indicating angiogenesis potential. Both biaxial and uniaxial mechanical testing showed a stiffer mechanical response of the acellular myocardial scaffolds; however, tissue extensibility and tensile modulus were found to recover in the constructs along with the culture time, as expected from increased cellular content. The cardiac patch that we envision for clinical application will benefit from the natural architecture of myocardial extracellular matrix, which has the potential to promote stem cell differentiation, cardiac regeneration, and angiogenesis. PMID:20694977

Licensed pertussis vaccines in the United States. History and current state.

PubMed

Klein, Nicola P

2014-01-01

The United States switched from whole cell to acellular pertussis vaccines in the 1990s following global concerns with the safety of the whole cell vaccines. Despite high levels of acellular pertussis vaccine coverage, the United States and other countries are experiencing large pertussis outbreaks. The aim of this article is to describe the historical context which led to acellular pertussis vaccine development, focusing on vaccines currently licensed in the US, and to review evidence that waning protection following licensed acellular pertussis vaccines have been significant factors in the widespread reappearance of pertussis.

New Insights on the Composition and the Structure of the Acellular Extrinsic Fiber Cementum by Raman Analysis

PubMed Central

Colard, Thomas; Falgayrac, Guillaume; Bertrand, Benoit; Naji, Stephan; Devos, Olivier; Balsack, Clara; Delannoy, Yann; Penel, Guillaume

2016-01-01

Acellular extrinsic fiber cementum is a mineralized tissue that covers the cervical half of the tooth root surface. It contains mainly extrinsic or Sharpey’s fibers that run perpendicular to the root surface to anchor the tooth via the periodontal ligament. Acellular cementum is continuously and slowly produced throughout life and exhibits an alternating bright and dark pattern under light microscopy. However, although a better understanding of the structural background of acellular cementum is relevant to many fields, such as cementochronology, periodontology and tissue engineering, acellular cementum remains rarely studied and poorly understood. In this work, we studied the acellular cementum at the incremental line scale of five human mandibular canines using polarized Raman spectroscopy. We provided Raman imaging analysis and polarized acquisitions as a function of the angular orientation of the sample. The results showed that mineral crystals were always parallel to collagen fibrils, and at a larger scale, we proposed an organizational model in which we found radial collagen fibers, “orthogonal” to the cementum surface, and “non-orthogonal” fibers, which consist of branching and bending radial fibers. Concerning the alternating pattern, we observed that the dark lines corresponded to smaller, more mineralized and probably more organized bands, which is consistent with the zoological assumption that incremental lines are produced during a winter rest period of acellular cementum growth. PMID:27936010

Intrarectal negative pressure system in the management of open abdomen with colorectal fistula: A case report.

PubMed

Yetişir, Fahri; Salman, A Ebru; Mamedov, Ruslan; Aksoy, Mustafa; Yalcin, Abdussamet; Kayaalp, Cüneyt

2014-01-01

To present the management of open abdomen with colorectal fistula by application of intrarectal negative pressure system (NPS) in addition to abdominal NPS. Twenty-year old man had a history of injuries by a close-range gunshot to the abdomen eight days ago and he had been treated by bowel repairs, resections, jejunal anastomosis and Hartman's procedure. He was referred to our center after deterioration, evisceration with open abdomen and enteric fistula in septic shock. There were edematous, fibrinous bowels and large multiple fistulas from the edematous rectal stump. APACHE II, Mannheim Peritoneal Index and Björck scores were 18, 33 and 3, respectively (expected mortality 100%). After intensive care for 5 days, he was treated by abdominal and intrarectal NPS. NPS repeated for 5 times and the fistula was recovered on day 18 completely. Fascial closure was facilitated with a dynamic abdominal closure system (ABRA) and he was discharged on day 33 uneventfully. There was no herniation and any other problem after 12 months follow-up. Management of fistula in OA can be extremely challenging. Floating stoma, fistula VAC, nipple VAC, ring and silo VAC, fistula intubation systems are used for isolation of the enteric effluent from OA. Several biologic dressings such as acellular dermal matrix, pedicled flaps have been used to seal the fistula opening with various success. Resection of the involved enteric loop and a new anastomosis of the intestine is very hard and rarely possible. In all of these reports, usually patients are left to heal with a giant hernia. In contrast to this, there is no hernia in our case during one year follow up period. Combination of intra and extra luminal negative pressure systems and ABRA is a safe and successful method to manage open abdomen with colorectal fistula. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Open and Laparo-Endoscopic Repair of Incarcerated Abdominal Wall Hernias by the Use of Biological and Biosynthetic Meshes.

PubMed

Fortelny, René H; Hofmann, Anna; May, Christopher; Köckerling, Ferdinand

2016-01-01

Although recently published guidelines recommend against the use of synthetic non-absorbable materials in cases of potentially contaminated or contaminated surgical fields due to the increased risk of infection (1, 2), the use of bio-prosthetic meshes for abdominal wall or ventral hernia repair is still controversially discussed in such cases. Bio-prosthetic meshes have been recommended due to less susceptibility for infection and the decreased risk of subsequent mesh explantation. The purpose of this review is to elucidate if there are any indications for the use of biological and biosynthetic meshes in incarcerated abdominal wall hernias based on the recently published literature. A literature search of the Medline database using the PubMed search engine, using the keywords returned 486 articles up to June 2015. The full text of 486 articles was assessed and 13 relevant papers were identified including 5 retrospective case cohort studies, 2 case-controlled studies, and 6 case series. The results of Franklin et al. (3-5) included the highest number of biological mesh repairs (Surgisis(®)) by laparoscopic IPOM in infected fields, which demonstrated a very low incidence of infection and recurrence (0.7 and 5.2%). Han et al. (6) reported in his retrospective study, the highest number of treated patients due to incarcerated hernias by open approach using acellular dermal matrix (ADM(®)) with very low rate of infection as well as recurrences (1.6 and 15.9%). Both studies achieved acceptable outcome in a follow-up of at least 3.5 years compared to the use of synthetic mesh in this high-risk population (7). Currently, there is a very limited evidence for the use of biological and biosynthetic meshes in strangulated hernias in either open or laparo-endoscopic repair. Finally, there is an urgent need to start with randomized controlled comparative trials as well as to support registries with data to achieve more knowledge for tailored indication for the use of biological meshes.

Migration ability and Toll-like receptor expression of human mesenchymal stem cells improves significantly after three-dimensional culture.

PubMed

Zhou, Panpan; Liu, Zilin; Li, Xue; Zhang, Bing; Wang, Xiaoyuan; Lan, Jing; Shi, Qing; Li, Dong; Ju, Xiuli

2017-09-16

While the conventional two-dimensional (2D) culture protocol is well accepted for the culture of mesenchymal stem cells (MSCs), this method fails to recapitulate the in vivo native three-dimensional (3D) cellular microenvironment, and may result in phenotypic changes, and homing and migration capacity impairments. MSC preparation in 3D culture systems has been considered an attractive preparatory and delivery method recently. We seeded human umbilical cord-derived MSCs (hUCMSCs) in a 3D culture system with porcine acellular dermal matrix (PADM), and investigated the phenotypic changes, the expression changes of some important receptors, including Toll-like receptors (TLRs) and C-X-C chemokine receptor type 4 (CXCR4) when hUCMSCs were transferred from 2D to 3D systems, as well as the alterations in in vivo homing and migration potential. It was found that the percentage of CD105-positive cells decreased significantly, whereas that of CD34- and CD271-positive cells increased significantly in 3D culture, compared to that in 2D culture. The mRNA and protein expression levels of TLR2, TLR3, TLR4, TLR6, and CXCR4 in hUCMSCs were increased significantly upon culturing with PADM for 3 days, compared to the levels in 2D culture. The numbers of migratory 3D hUCMSCs in the heart, liver, spleen, and bone marrow were significantly greater than the numbers of 2D hUCMSCs, and the worst migration occurred in 3D + AMD3100 (CXCR4 antagonist) hUCMSCs. These results suggested that 3D culture of hUCMSCs with PADM could alter the phenotypic characteristics of hUCMSCs, increase their TLR and CXCR4 expression levels, and promote their migratory and homing capacity in which CXCR4 plays an important role. Copyright © 2017 Elsevier Inc. All rights reserved.

Creation of a Bioengineered Skin Flap Scaffold with a Perfusable Vascular Pedicle.

PubMed

Jank, Bernhard J; Goverman, Jeremy; Guyette, Jacques P; Charest, Jon M; Randolph, Mark; Gaudette, Glenn R; Gershlak, Joshua R; Purschke, Martin; Javorsky, Emilia; Nazarian, Rosalynn M; Leonard, David A; Cetrulo, Curtis L; Austen, William G; Ott, Harald C

2017-07-01

Full-thickness skin loss is a challenging problem due to limited reconstructive options, demanding 75 million surgical procedures annually in the United States. Autologous skin grafting is the gold standard treatment, but results in donor-site morbidity and poor aesthetics. Numerous skin substitutes are available on the market to date, however, none truly functions as full-thickness skin due to lack of a vascular network. The creation of an autologous full-thickness skin analogue with a vascular pedicle would result in a paradigm shift in the management of wounds and in reconstruction of full-thickness skin defects. To create a clinically relevant foundation, we generated an acellular skin flap scaffold (SFS) with a perfusable vascular pedicle of clinically relevant size by perfusion decellularization of porcine fasciocutaneous flaps. We then analyzed the yielded SFS for mechanical properties, biocompatibility, and regenerative potential in vitro and in vivo. Furthermore, we assessed the immunological response using an in vivo model. Finally, we recellularized the vascular compartment of an SFS and reconnected it to a recipient's blood supply to test for perfusability. Perfusion decellularization removed all cellular components with preservation of native extracellular matrix composition and architecture. Biaxial testing revealed preserved mechanical properties. Immunologic response and biocompatibility assessed via implantation and compared with native xenogenic skin and commercially available dermal substitutes revealed rapid neovascularization and complete tissue integration. Composition of infiltrating immune cells showed no evidence of allorejection and resembled the inflammatory phase of wound healing. Implantation into full-thickness skin defects demonstrated good tissue integration and skin regeneration without cicatrization. We have developed a protocol for the generation of an SFS of clinically relevant size, containing a vascular pedicle, which can be utilized for perfusion decellularization and, ultimately, anastomosis to the recipient vascular system after precellularization. The observed favorable immunological response and good tissue integration indicate the substantial regenerative potential of this platform.

Conservative mastectomies and immediate reconstruction with the use of ADMs.

PubMed

Govshievich, Alexander; Somogyi, Ron B; Brown, Mitchell H

2015-12-01

In recent years, a novel approach to immediate breast reconstruction has been introduced with the advent of acellular dermal matrix (ADM). In the setting of conservative mastectomies where the native skin envelope is preserved, placement of ADM at the lower pole in continuity with the pectoralis major muscle (PMM) provides additional support, allowing direct-to-implant breast reconstruction. The following manuscript presents the senior author's experience with ADM-assisted reconstruction and provides a detailed description of surgical technique along with a comprehensive discussion of patient selection and potential complications. A retrospective chart review of patients undergoing direct-to-implant breast reconstruction following skin sparing or nipple sparing mastectomy with the use of ADM (AlloDerm; LifeCell Corp., Branchburg, USA) was conducted at Women's College Hospital in Toronto over a 5-year period [2008-2013]. Demographic data, previous radiation therapy and post-operative complications were recorded. A total of 72 patients representing 119 breasts were identified. Average follow-up was 16 months (range, 3-51 months). Twenty-seven complications were recorded for a complication rate of 22.7% (27/119). Complications included six cases of capsular contracture (Baker III/IV), five cases of red skin syndrome, four cases of rippling, three cases of dehiscence and two cases of seroma. Overall, direct-to-implant reconstruction was successfully completed in 97.5% of breasts (116/119). One case of infection was treated with explantation and conversion to autogenous reconstruction. Two breasts with tissue necrosis or dehiscence had the implants removed and replaced with tissue expanders. Overall reoperation rate was 9.7% (7/72 patients). ADM assisted direct-to-implant breast reconstruction has been shown to be a safe option for women who are candidates for skin sparing or nipple sparing mastectomies. Judicious patient selection, effective collaboration between the oncologic and reconstructive surgeon, careful evaluation of post-mastectomy skin flaps and precise surgical technique are paramount to the success of this technique.

[Experimental study on vagina reconstruction with tissue-engineering biological material.].

PubMed

Zhou, Hui-Mei; Lang, Jing-He; Zhu, Lan

2009-11-01

To investigate the effect of vagina reconstruction using tissue-engineering biological material (acellular dermal matrix) in an animal model. Vagina excision and vagina reconstruction with tissue-engineering biological material were performed in 12 Chinese experimental miniature pigs. The control group was matched with two of normal vagina specimens resected. At week 1, 2, 4, 6, 8, 12 after surgery, the animals were sacrificed, respectively, and the neovaginas were prepared for immunohistochemical and Van Gieson (VG) staining to evaluate the status of various layer growth of vagina. Epithelial broad spectrum of monoclonal antibodies of AE1/AE3 and alpha-actin were used to test the existence of epithelial and smooth muscle tissue by immunohistochemical staining. The ultrastructure of neovagina was studied by transmission electron microscope at week 1 and 12 after surgery. Contractile function of isolated smooth muscle of neovagina was evaluated by chemical and electronic stimulation after 12 weeks' reconstruction. (1) Epithelization of 2/3 neovaginal mucosa was observed within 1 week. Only 1 - 2 layer epitheliums were observed under the light microscopy and epithelial cells with characteristics of loose and disarrangement were shown with the electron microscopy. Within 4 - 6 weeks, epithelization in mucosa of neovaginal canal was intensified to 4 - 5 layers. After 12 weeks, the differences between the neovagina and the native vagina were harldy noted either in the gross or microscopically. (2) After 4 weeks, a few smooth muscle cells were observed with VG and immunohistochemical staining, and homogeneous muscle bundle was formed. (3) After 12 weeks, similar contractile responses between neovagina and native vagina were observed when KCl and electrical stimulation with different frequency and voltage were given [(2.96 +/- 0.29) g vs. (3.14 +/- 0.30) g, (3.43 +/- 0.34) g vs. (4.65 +/- 0.73) g, (4.92 +/- 0.38) g vs. (4.89 +/- 0.44) g]. The tissue-engineering biological material might be an ideal graft used in the reconstruction of vagina.

Cross-linked electrospun cartilage acellular matrix/poly(caprolactone-co-lactide-co-glycolide) nanofiber as an antiadhesive barrier.

PubMed

Lee, Jin Woo; Park, Joon Yeong; Park, Seung Hun; Kim, Min Ju; Song, Bo Ram; Yun, Hee-Woong; Kang, Tae Woong; Choi, Hak Soo; Kim, Young Jick; Min, Byoung Hyun; Kim, Moon Suk

2018-07-01

In this work, we chose cartilage acellular matrix (CAM) as a promising antiadhesive material because CAM effectively inhibits the formation of blood vessels, and we used electrospinning to prepare antiadhesive barriers. Additionally, we synthesized N-hydroxysuccinimide (NHS)-poly(caprolactone-co-lactide-co-glycolide)-NHS (MP) copolymers (to tune degradation) as a cross-linking agent for CAM. This is the first report on the development of electrospun cross-linked (Cx) CAM/MP (CA/P) nanofiber (NF) (Cx-CA/P-NF) with a tunable degradation period as an antiadhesive barrier. Compared with the CA/P-NF before cross-linking, the electrospun Cx-CA/P-NF after cross-linking showed different biodegradation. Cx-CA/P-NF significantly inhibited the in vitro attachment and proliferation of human umbilical vein endothelial cells (HUVECs), as confirmed by an MTT assay and scanning electron microscopy images. Cx-CA/P-NFs implanted between a surgically damaged peritoneal wall and cecum gradually degraded in 7 days; this process was monitored by NIR imaging. The in vivo evaluation of the anti-tissue adhesive effect of Cx-CA/P-NFs revealed little adhesion, few blood vessels, and negligible inflammation at 7 days determined by hematoxylin and eosin staining. ED1 staining of Cx-CA/P-NFs showed infiltration of few macrophages because of the inflammatory response to the Cx-CA/P-NF as compared with an untreated injury model. Additionally, Cx-CA/P-NFs significantly suppressed the formation of blood vessels between the peritoneal wall and cecum, according to CD31 staining. Overall, Cx-CA/P-NFs yielded little adhesion, infiltration by macrophages, or formation of blood vessels in a postoperative antiadhesion assay. Thus, it is reasonable to conclude that the Cx-CA/P-NF designed herein successfully works as an antiadhesive barrier with a tunable degradation period. The cartilage acellular matrix (CAM) can inhibit the formation of fibrous tissue bridges and blood vessels between the tissue at an injured site and the surrounding healthy tissues. However, CAM has not been rigorously investigated as an antiadhesive barrier. In this manuscript, the cross-linked CAM nanofiber (Cx-CA/P-NF) designed herein successfully works as an antiadhesive barrier. Cx-CA/P-NFs yielded little adhesion, infiltration by macrophages, or formation of blood vessels in a postoperative antiadhesion assay. Moreover, we demonstrated the suitable properties of Cx-CA/P-NF such as easy cross-linking by maintaining the antiadhesive properties, controllable biodegradation, and in vivo antiadhesive effect of Cx-CA/P-NF. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Global Gene Expression Analysis in PKCα-/- Mouse Skin Reveals Structural Changes in the Dermis and Defective Wound Granulation Tissue.

PubMed

Cooper, Nichola H; Balachandra, Jeya P; Hardman, Matthew J

2015-12-01

The skin's mechanical integrity is maintained by an organized and robust dermal extracellular matrix (ECM). Resistance to mechanical disruption hinges primarily on homeostasis of the dermal collagen fibril architecture, which is regulated, at least in part, by members of the small leucine-rich proteoglycan (SLRP) family. Here we present data linking protein kinase C alpha (PKCα) to the regulated expression of multiple ECM components including SLRPs. Global microarray profiling reveals deficiencies in ECM gene expression in PKCα-/- skin correlating with abnormal collagen fibril morphology, disorganized dermal architecture, and reduced skin strength. Detailed analysis of the skin and wounds from wild-type and PKCα-/- mice reveals a failure to upregulate collagen and other ECM components in response to injury, resulting in delayed granulation tissue deposition in PKCα-/- wounds. Thus, our data reveal a previously unappreciated role for PKCα in the regulation of ECM structure and deposition during skin wound healing.

Approach to quantify human dermal skin aging using multiphoton laser scanning microscopy

NASA Astrophysics Data System (ADS)

Puschmann, Stefan; Rahn, Christian-Dennis; Wenck, Horst; Gallinat, Stefan; Fischer, Frank

2012-03-01

Extracellular skin structures in human skin are impaired during intrinsic and extrinsic aging. Assessment of these dermal changes is conducted by subjective clinical evaluation and histological and molecular analysis. We aimed to develop a new parameter for the noninvasive quantitative determination of dermal skin alterations utilizing the high-resolution three-dimensional multiphoton laser scanning microscopy (MPLSM) technique. To quantify structural differences between chronically sun-exposed and sun-protected human skin, the respective collagen-specific second harmonic generation and the elastin-specific autofluorescence signals were recorded in young and elderly volunteers using the MPLSM technique. After image processing, the elastin-to-collagen ratio (ELCOR) was calculated. Results show that the ELCOR parameter of volar forearm skin significantly increases with age. For elderly volunteers, the ELCOR value calculated for the chronically sun-exposed temple area is significantly augmented compared to the sun-protected upper arm area. Based on the MPLSM technology, we introduce the ELCOR parameter as a new means to quantify accurately age-associated alterations in the extracellular matrix.

Invasive macrodystrophia lipomatosa of the hand.

PubMed

Colonna, M R; Guarneri, C; do Stagno d'Alcontres, F; Risitano, G; Cavallari, V; Ribuffo, D

2014-01-01

The Authors point out the interest of differential diagnosis and conservative surgical treatment of a rare case of digital and ulnar side of the hand gigantism, with massive fatty infiltration of soft tissues and a neurovascular bundle, to be included into Macrodystrophia Lipomatosa with fibrolipomatous hamartomata. Excision of the mass included 4th ray disarticulation (the fifth had been amputated several years ago) as well as microsurgical external and internal neurolysis of the ulnar nerve, the ulnar neurovascular bundle being exposed and covered with dermal substitute INTEGRATM, with a good result both from a cosmetic and functional point of view at three year follow up. This is the first report of INTEGRATM covering of a neurovascular bundle. Samples taken from the dermal substitute matrix interface at day 6 and day 25 were examined with transmission Electron Microscopy: a newly formed tissue, rich in precursor cells, was detected. Conservative surgery, requiring particular microsurgical skills and use of dermal templates, plays an outstanding role in treatment of these rare but aggressive soft tissues masses of the upper limb.

Characterization of acute and long-term pathologies of superficial and deep dermal sulfur mustard skin lesions in the hairless guinea pig model.

PubMed

Dachir, Shlomit; Cohen, Maayan; Kamus-Elimeleh, Dikla; Fishbine, Eliezer; Sahar, Rita; Gez, Rellie; Brandeis, Rachel; Horwitz, Vered; Kadar, Tamar

2012-01-01

Sulfur mustard induces severe acute and prolonged damage to the skin and only partially effective treatments are available. We have previously validated the use of hairless guinea pigs as an experimental model for skin lesions. The present study aimed to characterize a model of a deep dermal lesion and to compare it with the previously described superficial lesion. Clinical evaluation of the lesions was conducted using reflectance colorimetry, trans-epidermal water loss and wound area measurements. Prostaglandin E(2) content, matrix metalloproteinase-2 and 9 activity, and histopathology were conducted up to 4 weeks post-exposure. Sulfur mustard skin injury, including erythema and edema, impairment of skin barrier and wounds developed in a dose-dependent manner. Prostaglandin E(2) content and matrix metalloproteinase-2 and 9 activities were elevated during the wound development and the healing process. Histological evaluation revealed severe damage to the epidermis and deep dermis and vesications. At 4 weeks postexposure, healing was not completed: significantly impaired stratum corneum, absence of hair follicles, and epidermal hyperplasia were observed. These results confirm the use of the superficial and deep dermal skin injuries in the hairless guinea pigs as suitable models that can be utilized for the investigation of the pathological processes of acute as well as long-term injuries. These models will be further used to develop treatments to improve the healing process and prevent skin damage and long-term effects. © 2012 by the Wound Healing Society.

Development and manufacture of an investigational human living dermal equivalent (ICX-SKN).

PubMed

Flasza, Marzena; Kemp, Paul; Shering, David; Qiao, Jizeng; Marshall, Damian; Bokta, Ausha; Johnson, Penny A

2007-11-01

To design and manufacture an investigational living skin graft replacement (ICX-SKN) that is able to incorporate into the host, providing healing by primary intent without the need for a second intervention. The ICX-SKN skin graft replacement has been designed as an allogeneic dermal substitute comprising an extracellular matrix composed largely of human collagen and human dermal fibroblast cells (HDFs). ICX-SKN is first formed by casting a provisional matrix of fibrin, into which HDFs are seeded. Through a process of maturation, HDFs are induced to lay down collagen and other extracellular matrix materials and, as the construct matures, the original fibrin is largely replaced by collagen, which provides tensile strength and flexibility to the construct. In order to design a product and manufacturing system that lends itself to large-scale production the process was developed as a discontinuous process consisting of four stages: 1. batch casting and maturation of the initial construct (pSKN), 2. freeze-drying of pSKN to produce a second intermediate (dSKN), 3. sterilization by gamma-irradiation of dSKN to produce a third intermediate (sSKN), and finally, 4. repopulation of sSKN by fresh HDFs to produce the final product, ICX-SKN skin graft replacement. Preliminary characterization of ICX-SKN and its application in a preclinical model are described. The 7-week maturation period resulted in a construct (pSKN) with robust handling properties, which was composed mainly of human collagen I. Following development of a process for freeze-drying and subsequent sterilization, the matrix was successfully repopulated with fresh HDFs. In addition, it was demonstrated that human keratinocytes attached and differentiated on the matrix. Application of human keratinocytes to the repopulated constructs (ICX-SKN) resulted in expression of markers of basement membranes that was largely dependent on the presence of living HDFs on the constructs. ICX-SKN graft replacements applied to excision wounds in mice healed and were rapidly re-epithelialized. ICX-SKN has been developed as a platform product that can be used as a skin graft replacement and the process by which it is manufactured has been designed for the product to be available to the end-user off-the-shelf and for ease-of-use in practice.

Reactogenicity of tetanus, diphtheria, 5-component acellular pertussis vaccine administered as a sixth consecutive acellular pertussis vaccine dose to adolescents.

PubMed

Liese, Johannes G; Rieber, Nikolaus; Malzer, Thomas; Ocak, Marion; Johnson, David R; Decker, Michael D

2010-12-01

Safety of a sixth consecutive dose of acellular pertussis vaccine in adolescents was assessed in a 2-armed, randomized study. Adolescents who had received 5 doses of acellular pertussis vaccine combined with diphtheria and tetanus toxoids (6-dose group) received 1 dose of reduced 5-component acellular pertussis vaccine combined with tetanus toxoid and reduced diphtheria toxoid (Tdap). Adolescents who had received a primary series of 3 doses of whole-cell pertussis and 1 acellular or whole-cell pertussis booster received 1 dose of Tdap vaccine (5-dose group). Of 214 participants, 176 (82%) reported an injection-site reaction with pain (80%), erythema (22%), and swelling (19%) most frequently reported. A systemic reaction was reported by 169 of 214 (79%) with myalgia (66%), headache (42%), malaise (39%), and fever (9%) most frequently reported. The overall rate of solicited reactions was lower in the 6-dose group than in the 5-dose group (for injection-site reactions: 76.1% vs. 89.7%; for systemic reactions 72.6% vs. 86.6%). Significant differences were observed for injection-site pain, erythema, and for grade 1 or grade 2 increases in arm circumference. Fever, myalgia, and headache were reported at a significantly lower rate in the 6-dose group. Swelling >10 cm was observed in 5 patients (2%), 4 in the 5-dose group. Tdap vaccine was safe when given to adolescents who had received 5 prior doses of acellular pertussis vaccine.

Fibroblasts Protect Melanoma Cells from the Cytotoxic Effects of Doxorubicin

PubMed Central

Tiago, Manoela; de Oliveira, Edson Mendes; Brohem, Carla Abdo; Pennacchi, Paula Comune; Paes, Rafael Duarte; Haga, Raquel Brandão; Campa, Ana; de Moraes Barros, Silvia Berlanga; Smalley, Keiran S.

2014-01-01

Melanoma is the most aggressive form of skin cancer and until recently, it was extremely resistant to radio-, immuno-, and chemotherapy. Despite the latest success of BRAF V600E-targeted therapies, responses are typically short lived and relapse is all but certain. Furthermore, a percentage (40%) of melanoma cells is BRAF wild type. Emerging evidence suggests a role for normal host cells in the occurrence of drug resistance. In the current study, we compared a variety of cell culture models with an organotypic incomplete skin culture model (the “dermal equivalent”) to investigate the role of the tissue microenvironment in the response of melanoma cells to the chemotherapeutic agent doxorubicin (Dox). In the dermal equivalent model, consisting of fibroblasts embedded in type I collagen matrix, melanoma cells showed a decreased cytotoxic response when compared with less complex culture conditions, such as seeding on plastic cell culture plate (as monolayers cultures) or on collagen gel. We further investigated the role of the microenvironment in p53 induction and caspase 3 and 9 cleavage. Melanoma cell lines cultured on dermal equivalent showed decreased expression of p53 after Dox treatment, and this outcome was accompanied by induction of interleukin IL-6, IL-8, and matrix metalloproteinases 2 and 9. Here, we show that the growth of melanoma cells in the dermal equivalent model inflects drug responses by recapitulating important pro-survival features of the tumor microenvironment. These studies indicate that the presence of stroma enhances the drug resistance of melanoma in vitro, more closely mirroring the in vivo phenotype. Our data, thus, demonstrate the utility of organotypic cell culture models in providing essential context-dependent information critical for the development of new therapeutic strategies for melanoma. We believe that the organotypic model represents an improved screening platform to investigate novel anti-cancer agents, as it provides important insights into tumor-stromal interactions, thus assisting in the elucidation of chemoresistance mechanisms. PMID:24548268

Porcine wound healing in full-thickness skin defects using Integra™ with and without fibrin glue with keratinocytes

PubMed Central

Melendez, Mark M; Martinez, Rodrigo R; Dagum, Alexander B; McClain, Steve A; Simon, Marcia; Sobanko, Joseph; Zimmerman, Thomas; Wetterau, Meredith; Muller, Douglas; Xu, Xiaoti; Singer, Adam J; Arora, Balvantray

2008-01-01

BACKGROUND: An artificial dermal matrix such as Integra (Integra Life Sciences Corporation, USA) provides a wound bed template for vascular and fibrocyte ingrowth as well as collagen remodelling. Dermal repair leads to epidermal and basement membrane regeneration. Burn wounds in particular have been shown to benefit from Integra by enhanced wound healing. OBJECTIVE: To evaluate the effect of fibrin glue to modify the integration of Integra in large excised cutaneous wounds. It was hypothesized that applying fibrin glue on a wound bed would reduce the time needed for matrix vascularization and incorporation of Integra and take of the cultured keratinocytes. METHODS: Four separate full-thickness wounds were created on the dorsum of two swine. Wound beds were randomly assigned to either application of fibrin glue or no application of fibrin glue before application of Integra. Full-thickness biopsies were performed at days 7, 14, 21, 29 and 35. On day 21, keratinocytes were applied either as sheets or aerosolized fibrin glue suspension. RESULTS: Histological analysis revealed a wave of inflammatory cells and early granulation tissue ingrowth into the Integra from the fascia below on day 7. Only this initial phase was augmented by application of fibrin glue to the wound bed. By day 14, most and by day 21, all of the Integra thickness was incorporated. Accelerated dermal repair proceeded from the base with new collagen deposition in Integra spaces. There was no evidence of keratinocyte engraftment, although re-epithelialization occurred at wound edges extending onto the incorporated Integra. CONCLUSIONS: It appears there is an acceleration of early phase (day 7 to day 21) dermal incorporation with fibrin glue application to the wound bed, perhaps secondary to increased cellular migration. Day 21 appears to be too early to apply cultured keratinocytes either as sheets or aerosolized suspension. PMID:19721792

Angelica archangelia Prevented Collagen Degradation by Blocking Production of Matrix Metalloproteinases in UVB-exposed Dermal Fibroblasts.

PubMed

Sun, Zhengwang; Hwang, Eunson; Park, Sang Yong; Zhang, Mengyang; Gao, Wei; Lin, Pei; Yi, Tae-Hoo

2016-07-01

Angelica archangelia (AA), a traditional herb, has attracted attention as an agent with potential for use in the prevention of chronic skin diseases. This study examined the photoprotective effects of AA on the inhibition of matrix metalloproteinases (MMPs) and collagen degradation in UVB-irradiated normal human dermal fibroblasts. Our results showed that AA markedly blocked collagen degradation by restraining the production of MMPs in UVB-exposed fibroblasts. We also investigated the underlying mechanism behind the effects of AA. AA attenuated UVB-triggered interleukin-6 (IL-6) and promoted the expression of transforming growth factor β1. Application of AA extract (10, 100 μg mL(-1) ) significantly diminished UVB-induced extracellular signal-regulated kinase and Jun-N-terminal kinase phosphorylation, which consequently reduced phosphorylated c-Fos and c-Jun. Our results indicated that AA inhibited the UVB-induced expression of MMPs by inhibiting mitogen-activated protein kinase signaling pathways and activator protein-1 activation. Our results suggest that AA is a promising botanical agent for use against skin photoaging. © 2016 The American Society of Photobiology.

Dermal arteritis of the nasal philtrum in a Giant Schnauzer and three Saint Bernard dogs.

PubMed

Torres, Sheila M F; Brien, Timothy O; Scott, Danny W

2002-10-01

Arteritis of the nasal philtrum is described in four dogs. Two of the Saint Bernards were related. The lesions were solitary, well-circumscribed, linear ulcers that were neither pruritic nor painful. The age of the dogs at the time the owners first noticed the lesion ranged from 3 to 6 years. The ulcers had been present for 0.5-5 years before diagnosis was pursued. Three of the dogs experienced repeated, mild episodes of arterial bleeding from the ulcers. Two dogs also experienced a severe episode of bleeding that required surgical intervention. Histopathological findings included a V-shaped ulcer, neutrophilic dermal inflammation subjacent to the ulcer and lymphoplasmacytic dermatitis bordering the ulcer. The most remarkable pathological findings were present in the deep dermal arteries and arterioles subjacent to the ulcer. The changes were characterized by subendothelial spindle cell proliferation with marked extracellular matrix deposition that stained blue with Alcian Blue (mucin) and Masson's trichrome (collagen) and resulted in intimal thickening, and stenosis of dermal arteries and arterioles. Immunohistochemical studies suggested that the proliferating spindle cells were of either myofibroblast or smooth muscle origin (actin and vimentin positive). Anti-inflammatory therapy (glucocorticoids; tetracycline and niacinamide; fish oil) may be beneficial for long-term control of this condition, however, long-term maintenance treatment appears to be necessary.

Novel aspects of intrinsic and extrinsic aging of human skin: beneficial effects of soy extract.

PubMed

Südel, Kirstin M; Venzke, Kirsten; Mielke, Heiko; Breitenbach, Ute; Mundt, Claudia; Jaspers, Sören; Koop, Urte; Sauermann, Kirsten; Knussman-Hartig, Elke; Moll, Ingrid; Gercken, Günther; Young, Anthony R; Stäb, Franz; Wenck, Horst; Gallinat, Stefan

2005-01-01

Biochemical and structural changes of the dermal connective tissue substantially contribute to the phenotype of aging skin. To study connective tissue metabolism with respect to ultraviolet (UV) exposure, we performed an in vitro (human dermal fibroblasts) and an in vivo complementary DNA array study in combination with protein analysis in young and old volunteers. Several genes of the collagen metabolism such as Collagen I, III and VI as well as heat shock protein 47 and matrix metalloproteinase-1 are expressed differentially, indicating UV-mediated effects on collagen expression, processing and degradation. In particular, Collagen I is time and age dependently reduced after a single UV exposure in human skin in vivo. Moreover, older subjects display a lower baseline level and a shorter UV-mediated increase in hyaluronan (HA) levels. To counteract these age-dependent changes, cultured fibroblasts were treated with a specific soy extract. This treatment resulted in increased collagen and HA synthesis. In a placebo-controlled in vivo study, topical application of an isoflavone-containing emulsion significantly enhanced the number of dermal papillae per area after 2 weeks. Because the flattening of the dermal-epidermal junction is the most reproducible structural change in aged skin, this soy extract appears to rejuvenate the structure of mature skin.

Promoting Wound Healing Using Low Molecular Weight Fucoidan in a Full-Thickness Dermal Excision Rat Model

PubMed Central

Park, Jun-Hyeong; Choi, Seong-Hun; Park, Soo-Jin; Lee, Young Joon; Park, Jong Hyun; Song, Phil Hyun; Cho, Chang-Mo; Ku, Sae-Kwang; Song, Chang-Hyun

2017-01-01

Low molecular weight fucoidan (LMF) has been reported to possess anti-inflammatory and antioxidant activities. Thus, we examined the effects of LMF extracted from Undaria pinnatifida on dermal wounds. Five round dermal wounds were created on the dorsal back of rats, and they were then treated topically with distilled water (DW), Madecasol Care™ (MC) or LMF at 200, 100 and 50 mg/mL, twice a day for a week. There were dose-dependent increases in wound contraction in the groups receiving LMF but not in the MC group, compared with the DW. Histopathological examination revealed that LMF treatment accelerated wound healing, which was supported by increases in granular tissue formation on day four post-treatment but a decrease on day seven, accompanied by an evident reduction in inflammatory cells. In the LMF-treated wounds, collagen distribution and angiogenesis were increased in the granular tissue on days four and seven post-treatment. Immunoreactive cells for transforming growth factor-β1, vascular endothelial growth factor receptor-2 or matrix metalloproteinases 9 were also increased, probably due to tissue remodeling. Furthermore, LMF treatment reduced lipid peroxidation and increased antioxidant activities. These suggested that LMF promotes dermal wound healing via complex and coordinated antioxidant, anti-inflammatory and growth factor-dependent activities. PMID:28387729

Polyesterurethane and acellular matrix based hybrid biomaterial for bladder engineering.

PubMed

Horst, Maya; Milleret, Vincent; Noetzli, Sarah; Gobet, Rita; Sulser, Tullio; Eberli, Daniel

2017-04-01

Poly(lactic-co-glycolic acid) (PLGA) based biomaterials for soft tissue engineering have inherent disadvantages, such as a relative rigidity and a limited variability in the mechanical properties and degradation rates. In this study, a novel electrospun biomaterial based on degradable polyesterurethane (PEU) (DegraPol ® ) was investigated for potential use for bladder engineering in vitro and in vivo. Hybrid microfibrous PEU and PLGA scaffolds were produced by direct electrospinning of the polymer onto a bladder acellular matrix. The scaffold morphology of the scaffold was analyzed, and the biological performance was tested in vitro and in vivo using a rat cystoplasty model. Anatomical and functional outcomes after implantation were analyzed macroscopically, histologically and by cystometry, respectively. Scanning electron microscopy analysis showed that PEU samples had a lower porosity (p < 0.001) and were slightly thinner (p = 0.009) than the PGLA samples. Proliferation and survival of the seeded smooth muscle cells in vitro were comparable on PEU and PLGA scaffolds. After 8 weeks in vivo, the PEU scaffolds exhibited no shrinkage. However, cystometry of the reconstructed bladders exhibited a slightly greater functional bladder capacity in the PLGA group. Morphometric analyses revealed significantly better tissue healing (p < 0.05) and, in particular, better smooth muscle regeneration, as well as a lower rate of inflammatory responses at 8 weeks in the PEU group. Collectively, the results indicated that PEU-hybrid scaffolds promote bladder tissue formation with excellent tissue integration and a low inflammatory reaction in vivo. PEU is a promising biomaterial, particularly with regard to functional tissue engineering of the bladder and other hollow organs. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 658-667, 2017. © 2015 Wiley Periodicals, Inc.

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

Carneiro, Karina M. M.; Zhai, Halei; Zhu, Li

We report that enamel, the outermost layer of teeth, is an acellular mineralized tissue that cannot regenerate; the mature tissue is composed of high aspect ratio apatite nanocrystals organized into rods and inter-rod regions. Amelogenin constitutes 90% of the protein matrix in developing enamel and plays a central role in guiding the hierarchical organization of apatite crystals observed in mature enamel. To date, a convincing link between amelogenin supramolecular structures and mature enamel has yet to be described, in part because the protein matrix is degraded during tissue maturation. Here we show compelling evidence that amelogenin self-assembles into an amyloid-likemore » structure in vitro and in vivo. We show that enamel matrices stain positive for amyloids and we identify a specific region within amelogenin that self-assembles into β-sheets. Lastly, we propose that amelogenin nanoribbons template the growth of apatite mineral in human enamel. This is a paradigm shift from the current model of enamel development.« less

Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

PubMed Central

Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.

2011-01-01

Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979

Interactions between Skeletal Muscle Myoblasts and their Extracellular Matrix Revealed by a Serum Free Culture System.

PubMed

Chaturvedi, Vishal; Dye, Danielle E; Kinnear, Beverley F; van Kuppevelt, Toin H; Grounds, Miranda D; Coombe, Deirdre R

2015-01-01

Decellularisation of skeletal muscle provides a system to study the interactions of myoblasts with muscle extracellular matrix (ECM). This study describes the efficient decellularisation of quadriceps muscle with the retention of matrix components and the use of this matrix for myoblast proliferation and differentiation under serum free culture conditions. Three decellularisation approaches were examined; the most effective was phospholipase A2 treatment, which removed cellular material while maximizing the retention of ECM components. Decellularised muscle matrices were then solubilized and used as substrates for C2C12 mouse myoblast serum free cultures. The muscle matrix supported myoblast proliferation and differentiation equally as well as collagen and fibronectin. Immunofluorescence analyses revealed that myoblasts seeded on muscle matrix and fibronectin differentiated to form long, well-aligned myotubes, while myoblasts seeded on collagen were less organized. qPCR analyses showed a time dependent increase in genes involved in skeletal muscle differentiation and suggested that muscle-derived matrix may stimulate an increased rate of differentiation compared to collagen and fibronectin. Decellularized whole muscle three-dimensional scaffolds also supported cell adhesion and spreading, with myoblasts aligning along specific tracts of matrix proteins within the scaffolds. Thus, under serum free conditions, intact acellular muscle matrices provided cues to direct myoblast adhesion and migration. In addition, myoblasts were shown to rapidly secrete and organise their own matrix glycoproteins to create a localized ECM microenvironment. This serum free culture system has revealed that the correct muscle ECM facilitates more rapid cell organisation and differentiation than single matrix glycoprotein substrates.

Lithospermum erythrorhizon extract protects keratinocytes and fibroblasts against oxidative stress.

PubMed

Yoo, Hee Geun; Lee, Bong Han; Kim, Wooki; Lee, Jong Suk; Kim, Gun Hee; Chun, Ock K; Koo, Sung I; Kim, Dae-Ok

2014-11-01

Oxidative stress damages dermal and epidermal cells and degrades extracellular matrix proteins, such as collagen, ultimately leading to skin aging. The present study evaluated the potential protective effect of the aqueous methanolic extract obtained from Lithospermum erythrorhizon (LE) against oxidative stress, induced by H2O2 and ultraviolet (UV) irradiation, on human keratinocyte (HaCaT) and human dermal fibroblast-neonatal (HDF-n) cells. Exposure of cells to H2O2 or UVB irradiation markedly increased oxidative stress and reduced cell viability. However, pretreatment of cells with the LE extract not only increased cell viability (up to 84.5%), but also significantly decreased oxidative stress. Further, the LE extract downregulated the expression of matrix metalloproteinase-1, an endopeptidase that degrades extracellular matrix collagen. In contrast, treatment with the LE extract did not affect the expression of procollagen type 1 in HDF-n cells exposed to UVA irradiation. Thirteen phenolic compounds, including derivatives of shikonin and caffeic acid, were identified by ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. These results suggest that LE-derived extracts may protect oxidative-stress-induced skin aging by inhibiting degradation of skin collagen, and that this protection may derive at least in part from the antioxidant phenolics present in these extracts. Further studies are warranted to determine the potential utility of LE-derived extracts in both therapeutic and cosmetic applications.

Epilobium angustifolium extract demonstrates multiple effects on dermal fibroblasts in vitro and skin photo-protection in vivo.

PubMed

Ruszová, Ema; Cheel, José; Pávek, Stanislav; Moravcová, Martina; Hermannová, Martina; Matějková, Ilona; Spilková, Jiřina; Velebný, Vladimír; Kubala, Lukáš

2013-09-01

Stress-induced fibroblast senescence is thought to contribute to skin aging. Ultraviolet light (UV) radiation is the most potent environmental risk factor in these processes. An Epilobium angustifolium (EA) extract was evaluated for its capacity to reverse the senescent response of normal human dermal fibroblasts (NHDF) in vitro and to exhibit skin photo-protection in vivo. The HPLC-UV-MS analysis of the EA preparation identified three major polyphenol groups: tannins (oenothein B), phenolic acids (gallic and chlorogenic acids) and flavonoids. EA extract increased the cell viability of senescent NHDF induced by serum deprivation. It diminished connective tissue growth factor and fibronectin gene expressions in senescent NHDF. Down-regulation of the UV-induced release of both matrix metalloproteinase-1 and -3 and the tissue inhibitor of matrix metalloproteinases-1 and -2, and also down-regulation of the gene expression of hyaluronidase 2 were observed in repeatedly UV-irradiated NHDF after EA extract treatment. Interestingly, EA extract diminished the down-regulation of sirtuin 1 dampened by UV-irradiation. The application of EA extract using a sub-irritating dose protected skin against UV-induced erythema formation in vivo. In summary, EA extract diminished stress-induced effects on NHDF, particularly on connective tissue growth factor, fibronectin and matrix metalloproteinases. These results collectively suggest that EA extract may possess anti-aging properties and that the EA polyphenols might account for these benefits.

p-Coumaric Acid Attenuates UVB-Induced Release of Stratifin from Keratinocytes and Indirectly Regulates Matrix Metalloproteinase 1 Release from Fibroblasts

PubMed Central

Seok, Jin Kyung

2015-01-01

Ultraviolet (UV) radiation-induced loss of dermal extracellular matrix is associated with skin photoaging. Recent studies demonstrated that keratinocyte-releasable stratifin (SFN) plays a critical role in skin collagen metabolism by inducing matrix metalloproteinase 1 (MMP1) expression in target fibroblasts. In the present study, we examined whether SFN released from UVB-irradiated epidermal keratinocytes increases MMP1 release from dermal fibroblasts, and whether these events are affected by p-coumaric acid (p-CA), a natural phenolic compound with UVB-shielding and antioxidant properties. HaCaT cells were exposed to UVB in the absence and presence of p-CA, and the conditioned medium was used to stimulate fibroblasts in medium transfer experiments. The cells and media were analyzed to determine the expressions/releases of SFN and MMP1. UVB exposure increased SFN release from keratinocytes into the medium. The conditioned medium of UVB-irradiated keratinocytes increased MMP1 release from fibroblasts. The depletion of SFN using a siRNA rendered the conditioned medium of UVB-irradiated keratinocytes ineffective at stimulating fibroblasts to release MMP1. p-CA mitigated UVB-induced SFN expression in keratinocytes, and attenuated the MMP1 release by fibroblasts in medium transfer experiments. In conclusion, the present study demonstrated that the use of UV absorbers such as p-CA would reduce UV-induced SFN-centered signaling events involved in skin photoaging. PMID:25954129

p-Coumaric Acid Attenuates UVB-Induced Release of Stratifin from Keratinocytes and Indirectly Regulates Matrix Metalloproteinase 1 Release from Fibroblasts.

PubMed

Seok, Jin Kyung; Boo, Yong Chool

2015-05-01

Ultraviolet (UV) radiation-induced loss of dermal extracellular matrix is associated with skin photoaging. Recent studies demonstrated that keratinocyte-releasable stratifin (SFN) plays a critical role in skin collagen metabolism by inducing matrix metalloproteinase 1 (MMP1) expression in target fibroblasts. In the present study, we examined whether SFN released from UVB-irradiated epidermal keratinocytes increases MMP1 release from dermal fibroblasts, and whether these events are affected by p-coumaric acid (p-CA), a natural phenolic compound with UVB-shielding and antioxidant properties. HaCaT cells were exposed to UVB in the absence and presence of p-CA, and the conditioned medium was used to stimulate fibroblasts in medium transfer experiments. The cells and media were analyzed to determine the expressions/releases of SFN and MMP1. UVB exposure increased SFN release from keratinocytes into the medium. The conditioned medium of UVB-irradiated keratinocytes increased MMP1 release from fibroblasts. The depletion of SFN using a siRNA rendered the conditioned medium of UVB-irradiated keratinocytes ineffective at stimulating fibroblasts to release MMP1. p-CA mitigated UVB-induced SFN expression in keratinocytes, and attenuated the MMP1 release by fibroblasts in medium transfer experiments. In conclusion, the present study demonstrated that the use of UV absorbers such as p-CA would reduce UV-induced SFN-centered signaling events involved in skin photoaging.

The dynamics of adult haematopoiesis in the bone and bone marrow environment.

PubMed

Ho, Miriel S H; Medcalf, Robert L; Livesey, Stephen A; Traianedes, Kathy

2015-08-01

This review explores the dynamic relationship between bone and bone marrow in the genesis and regulation of adult haematopoiesis and will provide an overview of the haematopoietic hierarchical system. This will include the haematopoietic stem cell (HSC) and its niches, as well as discuss emerging evidence of the reciprocal interplay between bone and bone marrow, and support of the pleiotropic role played by bone cells in the regulation of HSC proliferation, differentiation and function. In addition, this review will present demineralized bone matrix as a unique acellular matrix platform that permits the generation of ectopic de novo bone and bone marrow and provides a means of investigating the temporal sequence of bone and bone marrow regeneration. It is anticipated that the utilization of this matrix-based approach will help researchers in gaining deeper insights into the major events leading to adult haematopoiesis in the bone marrow. Furthermore, this model may potentially offer new avenues to manipulate the HSC niche and hence influence the functional output of the haematopoietic system. © 2015 John Wiley & Sons Ltd.

The Bioactivity of Cartilage Extracellular Matrix in Articular Cartilage Regeneration

PubMed Central

Sutherland, Amanda J.; Converse, Gabriel L.; Hopkins, Richard A.; Detamore, Michael S.

2014-01-01

Cartilage matrix is a particularly promising acellular material for cartilage regeneration given the evidence supporting its chondroinductive character. The ‘raw materials’ of cartilage matrix can serve as building blocks and signals for enhanced tissue regeneration. These matrices can be created by chemical or physical methods: physical methods disrupt cellular membranes and nuclei but may not fully remove all cell components and DNA, whereas chemical methods when combined with physical methods are particularly effective in fully decellularizing such materials. Critical endpoints include no detectable residual DNA or immunogenic antigens. It is important to first delineate between the sources of the cartilage matrix, i.e., derived from matrix produced by cells in vitro or from native tissue, and then to further characterize the cartilage matrix based on the processing method, i.e., decellularization or devitalization. With these distinctions, four types of cartilage matrices exist: decellularized native cartilage (DCC), devitalized native cartilage (DVC), decellularized cell derived matrix (DCCM), and devitalized cell derived matrix (DVCM). Delivery of cartilage matrix may be a straightforward approach without the need for additional cells or growth factors. Without additional biological additives, cartilage matrix may be attractive from a regulatory and commercialization standpoint. Source and delivery method are important considerations for clinical translation. Only one currently marketed cartilage matrix medical device is decellularized, although trends in filed patents suggest additional decellularized products may be available in the future. To choose the most relevant source and processing for cartilage matrix, qualifying testing needs to include targeting the desired application, optimizing delivery of the material, identify relevant FDA regulations, assess availability of raw materials, and immunogenic properties of the product. PMID:25044502

Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine

MedlinePlus

Certiva® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Daptacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

Koraxitrachitic syndrome: a syndromic form of self-healing collodion baby with residual dappled atrophy of the derma.

PubMed

Verloes, A; Hermanns-Lê, T; Lesenfants, S; Lombet, J; Lamotte, P J; Crèvecoeur-Liégeois, C; Duchesne, B; Piérard, G E

1999-10-29

We report on a child with a generalized skin disorder associated with other minor anomalies. At birth, the child presented as a collodion baby, with patchy erythema, generalized irregular dermal atrophy, alopecia, absent eyelashes and eyebrows, and conjunctival pannus. He also had hypertelorism, prominent nasal root, large mouth, micrognathia, brachydactyly, syndactyly involving all interdigital spaces, and camptodactyly of fingers III-V. The hyperkeratotic membrane thinned progressively, leaving a mottled reticulated skin atrophy, with patchy areas of yellowish hyperpigmentation and papyraceous areas. Hair and nails were dystrophic. Mental development was borderline normal. The histological hallmarks of the skin manifestations combined orthokeratotic hyperkeratosis and marked atrophy of the dermis. The dermal extracellular matrix was immature, and factor XIII-a positive dendrocytes were rare and globular rather than dendritic. We frame as a hypothesis that the disease is due to or associated with a defect in maturation of a subset of dermal dendrocytes during fetal life. This entity may be designed as the koraxitrachitic syndrome (kappaomicronrhoalphaxi:grapnel- taurhoalphachiiotatauepsilonsigma: roughness) Copyright 1999 Wiley-Liss, Inc.

Perlecan and vascular endothelial growth factor-encoding DNA-loaded chitosan scaffolds promote angiogenesis and wound healing.

PubMed

Lord, Megan S; Ellis, April L; Farrugia, Brooke L; Whitelock, John M; Grenett, Hernan; Li, Chuanyu; O'Grady, Robert L; DeCarlo, Arthur A

2017-03-28

The repair of dermal wounds, particularly in the diabetic population, poses a significant healthcare burden. The impaired wound healing of diabetic wounds is attributed to low levels of endogenous growth factors, including vascular endothelial growth factor (VEGF), that normally stimulate multiple phases of wound healing. In this study, chitosan scaffolds were prepared via freeze drying and loaded with plasmid DNA encoding perlecan domain I and VEGF189 and analyzed in vivo for their ability to promote dermal wound healing. The plasmid DNA encoding perlecan domain I and VEGF189 loaded scaffolds promoted dermal wound healing in normal and diabetic rats. This treatment resulted in an increase in the number of blood vessels and sub-epithelial connective tissue matrix components within the wound beds compared to wounds treated with chitosan scaffolds containing control DNA or wounded controls. These results suggest that chitosan scaffolds containing plasmid DNA encoding VEGF189 and perlecan domain I have the potential to induce angiogenesis and wound healing. Copyright © 2017 Elsevier B.V. All rights reserved.

75 FR 7281 - Pediatric Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-18

... and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine), Pentacel [Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b...

Novel use of a flowable collagen-glycosaminoglycan matrix (Integra™ Flowable Wound Matrix) combined with percutaneous cannula scar tissue release in treatment of post-burn malfunction of the hand--A preliminary 6 month follow-up.

PubMed

Hirche, C; Senghaas, A; Fischer, S; Hollenbeck, S T; Kremer, T; Kneser, U

2016-02-01

Long-term function following severe burns to the hand may be poor secondary to scar adhesions to the underlying tendons, webspaces, and joints. In this pilot study, we report the feasibility of applying a pasty dermal matrix combined with percutaneous cannula teno- and adhesiolysis. In this 6 month follow-up pilot study, we included eight hands in five patients with hand burns undergoing minimal-invasive, percutaneous cannula adhesiolysis and injection of INTEGRA™ Flowable Wound Matrix for a pilot study of this new concept. The flowable collagen-glycosaminoglycan wound matrix (FCGWM) was applied with a buttoned 2mm cannula to induce formation of a neo-gliding plane. Post treatment follow-up was performed to assess active range of motion (AROM), grip strength, Disabilities of the Arm, Shoulder and Hand (DASH) score, Vancouver Scar Scale (VSS) and quality of life Short-Form (SF)-36 questionnaire. No complications were detected associated with the treatment of FCGWM injection. The mean improvement (AROM) at 6 months was 30.6° for digits 2-5. The improvement in the DASH score was a mean of 9 points out of 100. The VSS improved by a mean of 2 points out of 14. The study demonstrates the feasibility and safety of percutaneous FCGWM for dermal augmentation after burn. Results from this pilot study show improvements in AROM for digits 2-5, functional scores from the patient's perspective (DASH) and scar quality (VSS). The flowable form of established INTEGRA™ wound matrix offers the advantage of minimal-invasive injection after scar release in the post-burned hand with a reduction in the risk of postsurgical re-scarring. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Reconstruction of peripheral nerves using acellular nerve grafts with implanted cultured Schwann cells.

PubMed

Frerichs, Onno; Fansa, Hisham; Schicht, Christoph; Wolf, Gerald; Schneider, Wolfgang; Keilhoff, Gerburg

2002-01-01

The bridging of nerve gaps is still one of the major problems in peripheral nerve surgery. The present experiment describes our attempt to engineer different biologic nerve grafts in a rat sciatic nerve model: cultured isogenic Schwann cells were implanted into 2-cm autologous acellular nerve grafts or autologous predegenerated nerve grafts. Autologous nerve grafts and predegenerated or acellular nerve grafts without implanted Schwann cells served as controls. The regenerated nerves were assessed histologically and morphometrically after 6 weeks. Predegenerated grafts showed results superior in regard to axon count and histologic appearance in comparison to standard grafts and acellular grafts. The acellular nerve grafts showed the worst histologic picture, but axon counts were in the range of standard grafts. The implantation of Schwann cells did not yield significant improvements in any group. In conclusion, the status of activation of Schwann cells and the stadium of Wallerian degeneration in a nerve graft might be key factors for regeneration, rather than total number of Schwann cells. Predegenerated nerve grafts are therefore superior to standard grafts in the rat model. Acellular grafts are able to bridge nerve gaps of up to 2 cm in the rat model, but even the addition of cultivated Schwann cells did not lead to results as good as in the group with autologous nerve grafts. Copyright 2002 Wiley-Liss, Inc. MICROSURGERY 22:311-315 2002

Real-time three-dimensional imaging of epidermal splitting and removal by high-definition optical coherence tomography.

PubMed

Boone, Marc; Draye, Jean Pierre; Verween, Gunther; Pirnay, Jean-Paul; Verbeken, Gilbert; De Vos, Daniel; Rose, Thomas; Jennes, Serge; Jemec, Gregor B E; Del Marmol, Véronique

2014-10-01

While real-time 3-D evaluation of human skin constructs is needed, only 2-D non-invasive imaging techniques are available. The aim of this paper is to evaluate the potential of high-definition optical coherence tomography (HD-OCT) for real-time 3-D assessment of the epidermal splitting and decellularization. Human skin samples were incubated with four different agents: Dispase II, NaCl 1 M, sodium dodecyl sulphate (SDS) and Triton X-100. Epidermal splitting, dermo-epidermal junction, acellularity and 3-D architecture of dermal matrices were evaluated by High-definition optical coherence tomography before and after incubation. Real-time 3-D HD-OCT assessment was compared with 2-D en face assessment by reflectance confocal microscopy (RCM). (Immuno) histopathology was used as control. HD-OCT imaging allowed real-time 3-D visualization of the impact of selected agents on epidermal splitting, dermo-epidermal junction, dermal architecture, vascular spaces and cellularity. RCM has a better resolution (1 μm) than HD-OCT (3 μm), permitting differentiation of different collagen fibres, but HD-OCT imaging has deeper penetration (570 μm) than RCM imaging (200 μm). Dispase II and NaCl treatments were found to be equally efficient in the removal of the epidermis from human split-thickness skin allografts. However, a different epidermal splitting level at the dermo-epidermal junction could be observed and confirmed by immunolabelling of collagen type IV and type VII. Epidermal splitting occurred at the level of the lamina densa with dispase II and above the lamina densa (in the lamina lucida) with NaCl. The 3-D architecture of dermal papillae and dermis was more affected by Dispase II on HD-OCT which corresponded with histopathologic (orcein staining) fragmentation of elastic fibres. With SDS treatment, the epidermal removal was incomplete as remnants of the epidermal basal cell layer remained attached to the basement membrane on the dermis. With Triton X-100 treatment, the epidermis was not removed. In conclusion, HD-OCT imaging permits real-time 3-D visualization of the impact of selected agents on human skin allografts. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mesenchymal-epithelial interactions during hair follicle morphogenesis and cycling

PubMed Central

Sennett, Rachel; Rendl, Michael

2012-01-01

Embryonic hair follicle induction and formation are regulated by mesenchymal-epithelial interactions between specialized dermal cells and epidermal stem cells that switch to a hair fate. Similarly, during postnatal hair growth, communication between mesenchymal dermal papilla cells and surrounding epithelial matrix cells coordinates hair shaft production. Adult hair follicle regeneration in the hair cycle again is thought to be controlled by activating signals originating from the mesenchymal compartment and acting on hair follicle stem cells. Although many signaling pathways are implicated in hair follicle formation and growth, the precise nature, timing, and intersection of these inductive and regulatory signals remains elusive. The goal of this review is to summarize our current understanding and to discuss recent new insights into mesenchymal-epithelial interactions during hair follicle morphogenesis and cycling. PMID:22960356

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 stem cells and decellularized dermal matrix natural scaffolds in rat diabetic wound models. The authors of this research article have been working on stem cells and tissue engineering scaffolds for years. According to our knowledge, there is a lack of an efficient system for the treatment of skin defects using tissue engineering strategy. Since the rates of angiogenesis, re-epithelization and granulation tissue are directly correlated with full thickness wound healing, the proposed HUCPVCs-loaded DDM scaffolds perfectly fills the niche neglected by current treatment strategies. This pre-clinical study demonstrates the proof-of-concept that necessitates clinical evaluations. PMID:27591919

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 decellularized dermal matrix natural scaffolds in rat diabetic wound models. The authors of this research article have been working on stem cells and tissue engineering scaffolds for years. According to our knowledge, there is a lack of an efficient system for the treatment of skin defects using tissue engineering strategy. Since the rates of angiogenesis, re-epithelization and granulation tissue are directly correlated with full thickness wound healing, the proposed HUCPVCs-loaded DDM scaffolds perfectly fills the niche neglected by current treatment strategies. This pre-clinical study demonstrates the proof-of-concept that necessitates clinical evaluations. Copyright © 2016. Published by Elsevier Ltd.

Full-Thickness Skin Wound Healing Using Human Placenta-Derived Extracellular Matrix Containing Bioactive Molecules

PubMed Central

Choi, Ji Suk; Kim, Jae Dong; Yoon, Hyun Soo

2013-01-01

The human placenta, a complex organ, which facilitates exchange between the fetus and the mother, contains abundant extracellular matrix (ECM) components and well-preserved endogenous growth factors. In this study, we designed a new dermal substitute from human placentas for full-thickness wound healing. Highly porous, decellularized ECM sheets were fabricated from human placentas via homogenization, centrifugation, chemical and enzymatic treatments, molding, and freeze-drying. The physical structure and biological composition of human placenta-derived ECM sheets dramatically supported the regeneration of full-thickness wound in vivo. At the early stage, the ECM sheet efficiently absorbed wound exudates and tightly attached to the wound surface. Four weeks after implantation, the wound was completely closed, epidermic cells were well arranged and the bilayer structure of the epidermis and dermis was restored. Moreover, hair follicles and microvessels were newly formed in the ECM sheet-implanted wounds. Overall, the ECM sheet produced a dermal substitute with similar cellular organization to that of normal skin. These results suggest that human placenta-derived ECM sheets provide a microenvironment favorable to the growth and differentiation of cells, and positive modulate the healing of full-thickness wounds. PMID:22891853

The protective effects of fucosterol against skin damage in UVB-irradiated human dermal fibroblasts.

PubMed

Hwang, Eunson; Park, Sang-Yong; Sun, Zheng-wang; Shin, Heon-Sub; Lee, Don-Gil; Yi, Tae Hoo

2014-06-01

Exposure to ultraviolet (UV) light causes matrix metalloproteinase (MMP) overexpression and extracellular matrix depletion, leading to skin photoaging. The activation of MMP is related to increased interlukin-6 (IL-6) and type I procollagen production, which is regulated by transforming growth factor-β1 (TGF-β1). Activator protein-1 (AP-1) activation induces MMP-1 production and reduces type I procollagen secretion. Fucosterol, which is extracted and purified from the brown algae Hizikia fusiformis, is a phytosterol. We assessed the effects of fucosterol on photodamage and investigated its molecular mechanism of action in UVB-irradiated normal human dermal fibroblasts by using enzyme-linked immunosorbent assay, Western blot analysis, and reverse transcription-polymerase chain reaction. Our results showed that fucosterol significantly decreased the UVB-induced expression of MMP-1, IL-6, p-c-Jun, and p-c-Fos. Additionally, fucosterol markedly increased the UVB-induced production of type I procollagen and TGF-β1. Our results indicate that fucosterol regulates MMP-1 and type I procollagen expression by modulating AP-1 and TGF-β1 signaling and that MMP-1 activation is correlated with IL-6. These data suggest that fucosterol is a promising botanical agent to protect against skin photodamage.

Shell extracts of the edible mussel and oyster induce an enhancement of the catabolic pathway of human skin fibroblasts, in vitro.

PubMed

Latire, Thomas; Legendre, Florence; Bouyoucef, Mouloud; Marin, Frédéric; Carreiras, Franck; Rigot-Jolivet, Muriel; Lebel, Jean-Marc; Galéra, Philippe; Serpentini, Antoine

2017-10-01

Mollusc shells are composed of more than 95% calcium carbonate and less than 5% organic matrix consisting mostly of proteins, glycoproteins and polysaccharides. In this study, we investigated the effects of matrix macromolecular components extracted from the shells of two edible molluscs of economic interest, i.e., the blue mussel Mytilus edulis and the Pacific oyster Crassostrea gigas. The potential biological activities of these organic molecules were analysed on human dermal fibroblasts in primary culture. Our results demonstrate that shell extracts of the two studied molluscs modulate the metabolic activities of the cells. In addition, the extracts caused a decrease of type I collagen and a concomitant increase of active MMP-1, both at the mRNA and the protein levels. Therefore, our results suggest that shell extracts from M. edulis and C. gigas contain molecules that promote the catabolic pathway of human dermal fibroblasts. This work emphasises the potential use of these shell matrices in the context of anti-fibrotic strategies, particularly against scleroderma. More generally, it stresses the usefulness to valorise bivalve shells that are coproducts of shellfish farming activity.

Anti-Photoaging Effect of Jeju Putgyul (Unripe Citrus) Extracts on Human Dermal Fibroblasts and Ultraviolet B-induced Hairless Mouse Skin.

PubMed

Choi, Seung-Hyun; Choi, Sun-Il; Jung, Tae-Dong; Cho, Bong-Yeon; Lee, Jin-Ha; Kim, Seung-Hyung; Yoon, Seon-A; Ham, Young-Min; Yoon, Weon-Jong; Cho, Ju-Hyun; Lee, Ok-Hawn

2017-09-25

Ultraviolet (UV) radiation stimulates the expression of matrix metalloproteinases (MMPs) and inflammatory cytokines. These signaling pathways participate in the degradation of the extracellular matrix and induce inflammatory responses that lead to photoaging. This study evaluated the antioxidant activity and the effect on MMPs and procollagen of putgyul extract in vitro. The anti-photoaging activity of putgyul extracts was estimated in vivo using hairless mice (HR-1). The putgyul extracts reduced MMP-1 production and increased the content of procollagen type I carboxy-terminal peptide in human dermal fibroblasts. Ultravilot-B (UVB)-induced expression of inflammatory cytokines and MMPs was detected in mice, and putgyul extracts suppressed the expression. These results suggest that putgyul extract inhibits photoaging by inhibiting the expression of MMPs that degrade collagen and inhibiting cytokines that induce inflammatory responses. The mouse model also demonstrated that oral administration of putgyul extracts decreased wrinkle depth, epidermal thickness, collagen degradation, and trans-epidermal water loss, and increased β-glucosidase activity on UVB exposed skin. Putgyul extract protects against UVB-induced damage of skin and could be valuable in the prevention of photoaging.

Anti-Photoaging Effect of Jeju Putgyul (Unripe Citrus) Extracts on Human Dermal Fibroblasts and Ultraviolet B-induced Hairless Mouse Skin

PubMed Central

Choi, Seung-Hyun; Choi, Sun-Il; Jung, Tae-Dong; Cho, Bong-Yeon; Lee, Jin-Ha; Kim, Seung-Hyung; Yoon, Seon-A; Ham, Young-Min; Yoon, Weon-Jong; Cho, Ju-Hyun; Lee, Ok-Hawn

2017-01-01

Ultraviolet (UV) radiation stimulates the expression of matrix metalloproteinases (MMPs) and inflammatory cytokines. These signaling pathways participate in the degradation of the extracellular matrix and induce inflammatory responses that lead to photoaging. This study evaluated the antioxidant activity and the effect on MMPs and procollagen of putgyul extract in vitro. The anti-photoaging activity of putgyul extracts was estimated in vivo using hairless mice (HR-1). The putgyul extracts reduced MMP-1 production and increased the content of procollagen type I carboxy-terminal peptide in human dermal fibroblasts. Ultravilot-B (UVB)-induced expression of inflammatory cytokines and MMPs was detected in mice, and putgyul extracts suppressed the expression. These results suggest that putgyul extract inhibits photoaging by inhibiting the expression of MMPs that degrade collagen and inhibiting cytokines that induce inflammatory responses. The mouse model also demonstrated that oral administration of putgyul extracts decreased wrinkle depth, epidermal thickness, collagen degradation, and trans-epidermal water loss, and increased β-glucosidase activity on UVB exposed skin. Putgyul extract protects against UVB-induced damage of skin and could be valuable in the prevention of photoaging. PMID:28946661

Dinitrotoluene exposure in the copper mining industry and renal cancer: a case-cohort study.

PubMed

Seidler, Andreas; Harth, Volker; Taeger, Dirk; Möhner, Matthias; Gawrych, Katarzyna; Bergmann, Annekatrin; Haerting, Johannes; Kahmann, Hans-Joachim; Bolt, Hermann Maximilian; Straif, Kurt; Brüning, Thomas

2014-04-01

To evaluate the association between dinitrotoluene (DNT) exposure and renal cancer in a case-cohort study. This case-cohort study was conducted among men born between 1920 and 1974 (n=16 441) who were gainfully employed between 1953 and 1990 in one of two copper mines in Mansfeld, Saxony-Anhalt, former German Democratic Republic, and followed up till 31 December 2006. The study included 109 cases with renal cancer identified by record linkage with the Common Cancer Registry of the New Federal States of Germany (GKR) or by a network of pathology institutes. A comparison subcohort of 999 cohort members was selected at random from the total cohort. Duration and intensity of inhalation and dermal exposure to DNT were assessed on the basis of a job exposure matrix. A time-dependent Cox proportional hazards model modified for case-cohort design was used to assess the relationship between cumulative inhalation and dermal DNT exposure and renal cancer. Elevated risks were found for medium (HR=2.73; 95% CI 1.00 to 7.42) and high (HR=1.81; 95% CI 0.75 to 4.33) dermal exposure to DNT. Relative risks for medium inhalation exposure to DNT were not increased (HR=0.93; 95% CI 0.48 to 1.79) while relative risks for high inhalation exposure to DNT were elevated to 1.36 (95% CI 0.84 to 2.21). We found a statistically significant HR of 2.12 (95% CI 1.03 to 4.37) for combined medium or high inhalation and medium or high dermal exposure to DNT. According to our case-cohort study, dermal and inhalation exposure to DNT is associated with increased renal cancer risk.

Ureter Regeneration–The Proper Scaffold Has to Be Defined

PubMed Central

Kowalczyk, Tomasz; Nowacki, Maciej; Bodnar, Magdalena; Marszałek, Andrzej; Pokrywczyńska, Marta; Frontczak-Baniewicz, Małgorzata; Kowalewski, Tomasz A.; Chłosta, Piotr; Drewa, Tomasz

2014-01-01

The aim of this study was to compare two different acellular scaffolds: natural and synthetic, for urinary conduit construction and ureter segment reconstruction. Acellular aortic arch (AAM) and poly(L-lactide-co-caprolactone) (PLCL) were used in 24 rats for ureter reconstruction in both tested groups. Follow-up period was 4 weeks. Intravenous pyelography, histological and immunohistochemical analysis were performed. All animals survived surgical procedures. Patent uretero-conduit junction was observed only in one case using PLCL. In case of ureter segment reconstruction ureters were patent in one case using AAM and in four cases using PLCL scaffolds. Regeneration of urothelium layer and focal regeneration of smooth muscle layer was observed on both tested scaffolds. Obtained results indicates that synthetic acellular PLCL scaffolds showed better properties for ureter reconstruction than naturally derived acellular aortic arch. PMID:25162415

Development of sampling and analytical methods for concerted determination of commonly used chloroacetanilide, chlorotriazine, and 2,4-D herbicides in hand-wash, dermal-patch, and air samples.

PubMed

Tucker, S P; Reynolds, J M; Wickman, D C; Hines, C J; Perkins, J B

2001-06-01

Sampling and analytical methods were developed for commonly used chloroacetanilide, chlorotriazine, and 2,4-D herbicides in hand washes, on dermal patches, and in air. Eight herbicides selected for study were alachlor, atrazine, cyanazine, 2,4-dichlorophenoxyacetic acid (2,4-D), metolachlor, simazine, and two esters of 2,4-D, the 2-butoxyethyl ester (2,4-D, BE) and the 2-ethylhexyl ester (2,4-D, EH). The hand-wash method consisted of shaking the worker's hand in 150 mL of isopropanol in a polyethylene bag for 30 seconds. The dermal-patch method entailed attaching a 10-cm x 10-cm x 0.6-cm polyurethane foam (PUF) patch to the worker for exposure; recovery of the herbicides was achieved by extraction with 40 mL of isopropanol. The air method involved sampling with an OVS-2 tube (which contained an 11-mm quartz fiber filter and two beds of XAD-2 resin) and recovery with 2 mL of 10:90 methanol:methyl t-butyl ether. Analysis of each of the three sample types was performed by gas chromatography with an electron-capture detector. Diazomethane in solution was employed to convert 2,4-D as the free acid to the methyl ester in each of the three methods for ease of gas chromatography. Silicic acid was added to sample solutions to quench excess diazomethane. Limits of detection for all eight herbicides were matrix-dependent and, generally, less than 1 microgram per sample for each matrix. Sampling and analytical methods met NIOSH evaluation criteria for all herbicides in hand-wash samples, for seven herbicides in air samples (all herbicides except cyanazine), and for six herbicides in dermal-patch samples (all herbicides except cyanazine and 2,4-D). Speciation of 2,4-D esters and simultaneous determination of 2,4-D acid were possible without losses of the esters or of other herbicides (acetanilides and triazines) being determined.

Age-associated reduction of cellular spreading/mechanical force up-regulates matrix metalloproteinase-1 expression and collagen fibril fragmentation via c-Jun/AP-1 in human dermal fibroblasts.

PubMed

Qin, Zhaoping; Voorhees, John J; Fisher, Gary J; Quan, Taihao

2014-12-01

The dermal compartment of human skin is largely composed of dense collagen-rich fibrils, which provide structural and mechanical support. Skin dermal fibroblasts, the major collagen-producing cells, are interact with collagen fibrils to maintain cell spreading and mechanical force for function. A characteristic feature of aged human skin is fragmentation of collagen fibrils, which is initiated by matrix metalloproteinase 1 (MMP-1). Fragmentation impairs fibroblast attachment and thereby reduces spreading. Here, we investigated the relationship among fibroblast spreading, mechanical force, MMP-1 expression, and collagen fibril fragmentation. Reduced fibroblast spreading due to cytoskeletal disruption was associated with reduced cellular mechanical force, as determined by atomic force microscopy. These reductions substantially induced MMP-1 expression, which led to collagen fibril fragmentation and disorganization in three-dimensional collagen lattices. Constraining fibroblast size by culturing on slides coated with collagen micropatterns also significantly induced MMP-1 expression. Reduced spreading/mechanical force induced transcription factor c-Jun and its binding to a canonical AP-1 binding site in the MMP-1 proximal promoter. Blocking c-Jun function with dominant negative mutant c-Jun significantly reduced induction of MMP-1 expression in response to reduced spreading/mechanical force. Furthermore, restoration of fibroblast spreading/mechanical force led to decline of c-Jun and MMP-1 levels and eliminated collagen fibril fragmentation and disorganization. These data reveal a novel mechanism by which alteration of fibroblast shape/mechanical force regulates c-Jun/AP-1-dependent expression of MMP-1 and consequent collagen fibril fragmentation. This mechanism provides a foundation for understanding the cellular and molecular basis of age-related collagen fragmentation in human skin. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Delayed osteon formation in long-bone diaphysis of an 11-year-old giant cow with dermal dysplasia.

PubMed

Mori, R; Kodaka, T; Naito, Y

1999-02-01

The transverse sections of radius diaphysis in an 11-year-old giant Holstein cow with dermal dysplasia of a collagen disorder-related skin fragility (Cow 1), probably based on increasing turnover of the dermal collagen as reported previously, were morphologically and physico-chemically investigated. Cow 1 had about one and a half times as much as the body weight of normal Holstein cows, aged 5 to 6.5 years with stabilized growth. The bone samples were compared with those of a 12-year-old Holstein cow as controls (Cow 2). It has been reported that the long-bone diaphysis of young calves and some herbivorous dinosaurs are occupied with laminar bone showing a concentric appositional formation, and that such a laminar bone is characteristically seen during the growing period of some farm animals and large dogs that show very rapid growth rates. Cow 1 had a smaller number of osteons than Cow 2 in the outer-half layer of the diaphysis, and showed an intermediate type between Cow 2 and a 1-year-old Holstein ox in the entire layers, although their bone volumes were similar among them. There were no significant differences in Ca and P concentrations and the Vickers microhardness values between the bone matrix of Cow 1 and Cow 2. The bone-collagen fibrils of Cow 1 showed uneven diameters and a disordered arrangement. Thus, there may be some relation in collagen formation between the bone matrix of Cow 1 and the dermis. From the remaining volume of laminar bone, Cow 1, aged 11 years, had probably shown growth until quite recently, so that we consider that Cow 1 became a giant animal, in the same way as some herbivorous dinosaurs.

Properties of dehydrated human amnion/chorion composite grafts: Implications for wound repair and soft tissue regeneration.

PubMed

Koob, Thomas J; Lim, Jeremy J; Massee, Michelle; Zabek, Nicole; Denozière, Guilhem

2014-08-01

PURION(®) processed dehydrated human amnion/chorion membrane (dHACM; MiMedx Group, Marietta, GA) tissue products were analyzed for the effectiveness of the PURION(®) process in retaining the native composition of the amniotic membrane and preserving bioactivity in the resulting products. dHACM was analyzed for extracellular matrix (ECM) composition through histological staining and for growth factor content via multiplex ELISA arrays. Bioactivity was assessed by evaluating endogenous growth factor production by human dermal fibroblasts in response to dHACM and for thermal stability by mechanical tests and in vitro cell proliferation assays. Histology of dHACM demonstrated preservation of the native amnion and chorion layers with intact, nonviable cells, collagen, proteoglycan, and elastic fibers distributed in the individual layers. An array of 36 cytokines known to regulate processes involved in inflammation and wound healing were identified in dHACM. When treated with dHACM extracts, bioactivity was demonstrated through an upregulation of basic fibroblast growth factor, granulocyte colony-stimulating factor, and placental growth factor biosynthesis, three growth factors involved in wound healing, by dermal fibroblasts in vitro. After conditioning at temperatures ranging from -78.7 to +73.5°C, dHACM retained its tensile strength and ability to promote proliferation of dermal fibroblasts in vitro. Elution experiments demonstrated a soluble fraction of growth factors that eluted from the tissue and another fraction sequestered within the matrix. The PURION(®) process retains the native composition of ECM and signaling molecules and preserves bioactivity. The array of cytokines preserved in dHACM are in part responsible for its therapeutic efficacy in treating chronic wounds by orchestrating a "symphony of signals" to promote healing. © 2014 Wiley Periodicals, Inc.

Apigenin inhibits UVA-induced cytotoxicity in vitro and prevents signs of skin aging in vivo.

PubMed

Choi, Sungjin; Youn, Jeungyeun; Kim, Karam; Joo, Da Hye; Shin, Shanghun; Lee, Jeongju; Lee, Hyun Kyung; An, In-Sook; Kwon, Seungbin; Youn, Hae Jeong; Ahn, Kyu Joong; An, Sungkwan; Cha, Hwa Jun

2016-08-01

Apigenin (4',5,7-trihydroxyflavone) is a flavone that has been reported to have anti-inflammatory, antioxidant and anti-carcinogenic properties. In this study, we investigated the protective effects of apigenin on skin and found that, in experiments using cells, apigenin restored the viability of normal human dermal fibroblasts (nHDFs), which had been decreased by exposure to ultraviolet (UV) radiation in the UVA range. Using a senescence-associated (SA)-β-gal assay, we also demonstrate that apigenin protects against the UVA-induced senescence of nHDFs. Furthermore, we found that apigenin decreased the expression of the collagenase, matrix metalloproteinase (MMP)-1, in UVA-irradiated nHDFs. UVA, which has been previously identified as a photoaging-inducing factor, has been shown to induce MMP-1 expression. The elevated expression of MMP-1 impairs the collagen matrix, leading to the loss of elasticity and skin dryness. Therefore, we examined the clinical efficacy of apigenin on aged skin, using an apigenin‑containing cream for clinical application. Specifically, we measured dermal density, skin elasticity and the length of fine wrinkles in subjects treated with apigenin cream or the control cream without apigenin. Additionally, we investigated the effects of the apigenin-containing cream on skin texture, moisture and transepidermal water loss (TEWL). From these experiments, we found that the apigenin‑containing cream increased dermal density and elasticity, and reduced fine wrinkle length. It also improved skin evenness, moisture content and TEWL. These results clearly demonstrate the biological effects of apigenin, demonstrating both its cellular and clinical efficacy, and suggest that this compound holds promise as an anti-aging cosmetic ingredient.

In Vivo Evaluation and Imaging of a Bilayered Self-Assembled Skin Substitute Using a Decellularized Dermal Matrix Grafted on Mice.

PubMed

Beaudoin Cloutier, Chanel; Goyer, Benjamin; Perron, Cindy; Guignard, Rina; Larouche, Danielle; Moulin, Véronique J; Germain, Lucie; Gauvin, Robert; Auger, François A

2017-04-01

As time to final coverage is the essence for better survival outcome in severely burned patients, we have continuously strived to reduce the duration for the preparation of our bilayered self-assembled skin substitutes (SASS). These SASS produced in vitro by the self-assembly approach have a structure and functionality very similar to native skin. Recently, we have shown that a decellularized dermal matrix preproduced by the self-assembly approach could be used as a template to further obtain self-assembled skin substitute using a decellularized dermal template (SASS-DM) in vitro. Thus, the production period with patient cells was then reduced to about 1 month. Herein, preclinical animal experiments have been performed to confirm the integration and evolution of such a graft and compare the maturation of SASS and SASS-DM in vivo. Both tissues, reconstructed from adult or newborn cells, were grafted on athymic mice. Green fluorescent protein-transfected keratinocytes were also used to follow grafted tissues weekly for 6 weeks using an in vivo imaging system (IVIS). Cell architecture and differentiation were studied with histological and immunofluorescence analyses at each time point. Graft integration, macroscopic evolution, histological analyses, and expression of skin differentiation markers were similar between both skin substitutes reconstructed from either newborn or adult cells, and IVIS observations confirmed the efficient engraftment of SASS-DM. In conclusion, our in vivo graft experiments on a mouse model demonstrated that the SASS-DM had equivalent macroscopic, histological, and differentiation evolution over a 6-week period, when compared with the SASS. The tissue-engineered SASS-DM could improve clinical availability and advantageously shorten the time necessary for the definitive wound coverage of severely burned patients.

Dynamic culture induces a cell type-dependent response impacting on the thickness of engineered connective tissues.

PubMed

Fortier, Guillaume Marceau; Gauvin, Robert; Proulx, Maryse; Vallée, Maud; Fradette, Julie

2013-04-01

Mesenchymal cells are central to connective tissue homeostasis and are widely used for tissue-engineering applications. Dermal fibroblasts and adipose-derived stromal cells (ASCs) allow successful tissue reconstruction by the self-assembly approach of tissue engineering. This method leads to the production of multilayered tissues, devoid of exogenous biomaterials, that can be used as stromal compartments for skin or vesical reconstruction. These tissues are formed by combining cell sheets, generated through cell stimulation with ascorbic acid, which favours the cell-derived production/organization of matrix components. Since media motion can impact on cell behaviour, we investigated the effect of dynamic culture on mesenchymal cells during tissue reconstruction, using the self-assembly method. Tissues produced using ASCs in the presence of a wave-like movement were nearly twice thicker than under standard conditions, while no difference was observed for tissues produced from dermal fibroblasts. The increased matrix deposition was not correlated with an increased proliferation of ASCs, or by higher transcript levels of fibronectin or collagens I and III. A 30% increase of type V collagen mRNA was observed. Interestingly, tissues engineered from dermal fibroblasts featured a four-fold higher level of MMP-1 transcripts under dynamic conditions. Mechanical properties were similar for tissues reconstructed using dynamic or static conditions. Finally, cell sheets produced using ASCs under dynamic conditions could readily be manipulated, resulting in a 2 week reduction of the production time (from 5 to 3 weeks). Our results describe a distinctive property of ASCs' response to media motion, indicating that their culture under dynamic conditions leads to optimized tissue engineering. Copyright © 2011 John Wiley & Sons, Ltd.

Natural Arctium lappa fruit extract improves the clinical signs of aging skin.

PubMed

Knott, Anja; Reuschlein, Katja; Mielke, Heiko; Wensorra, Ursula; Mummert, Christopher; Koop, Urte; Kausch, Martina; Kolbe, Ludger; Peters, Nils; Stäb, Franz; Wenck, Horst; Gallinat, Stefan

2008-12-01

Subclinical, chronic tissue inflammation involving the generation of cytokines (e.g., interleukin-6 and tumor necrosis factor-alpha) might contribute to the cutaneous aging process. This study aims to screen for an active ingredient with anti-inflammatory (i.e., reduction of interleukin-6 and tumor necrosis factor-alpha) and matrix-stimulating efficacy which improves the clinical signs of skin aging in vivo. In vitro studies with pure Arctiin were performed investigating the inhibition of cytokine induction and stimulation of collagen neo-synthesis. In vivo home-in-use studies using an Arctium lappa fruit extract-containing formulation were carried out to determine procollagen and hyaluronan synthesis, hyaluronan synthase-2 gene expression, and reduction of wrinkle volume after treatment. In vitro studies on human dermal fibroblasts and monocyte-derived dendritic cells supplemented with pure Arctiin showed relative to untreated control cells a stimulation of collagen synthesis and a decrease in interleukin-6 and tumor necrosis factor-alpha concentration, respectively. In addition, topical in vivo application of an A. lappa fruit extract-containing formulation for 12 weeks significantly stimulated procollagen synthesis and increased hyaluronan synthase-2 expression as well as hyaluronan levels compared to vehicle-treated control areas. Similarly, after a 4-week treatment with an A. lappa fruit extract-containing formulation, wrinkle volume in the crow's feet area was significantly reduced as compared to treatment with the vehicle. Our data show that topical treatment with a natural A. lappa fruit extract significantly improves the metabolism of the dermal extracellular matrix and leads to a visible wrinkle reduction in vivo. In conclusion, A. lappa fruit extract represents a targeted means to regenerate dermal structures and, thus, offers an effective treatment option for mature skin.

E- and P-cadherin expression during murine hair follicle morphogenesis and cycling.

PubMed

Müller-Röver, S; Tokura, Y; Welker, P; Furukawa, F; Wakita, H; Takigawa, M; Paus, R

1999-08-01

The role of adhesion molecules in the control of hair follicle (HF) morphogenesis, regression and cycling is still rather enigmatic. Since the adhesion molecules E- and P-cadherin (Ecad and Pcad) are functionally important, e.g. during embryonic pattern formation, we have studied their expression patterns during neonatal HF morphogenesis and cycling in C57/BL6 mice by immunohistology and semi-quantitative RT-PCR. The expression of both cadherins was strikingly hair cycle-dependent and restricted to distinct anatomical HF compartments. During HF morphogenesis, hair bud keratinocytes displayed strong Ecad and Pcad immunoreactivity (IR). While neonatal epidermis showed Ecad IR in all epidermal layers, Pcad IR was restricted to the basal layer. During later stages of HF morphogenesis and during anagen IV-VI of the adolescent murine hair cycle, the outer root sheath showed strong E- and Pcad IR. Instead, the outermost portion of the hair matrix and the inner root sheath displayed isolated Ecad IR, while the innermost portion of the hair matrix exhibited isolated Pcad IR. During telogen, all epidermal and follicular keratinocytes showed strong Ecad IR. This is in contrast to Pcad, whose IR was stringently restricted to matrix and secondary hair germ keratinocytes which are in closest proximity to the dermal papilla. These findings suggest that isolated or combined E- and/or Pcad expression is involved in follicular pattern formation by segregating HF keratinocytes into functionally distinct subpopulations; most notably, isolated Pcad expression may segregate those hair matrix keratinocytes into one functional epithelial tissue unit, which is particularly susceptible to growth control by dermal papilla-derived morphogens. The next challenge is to define which secreted agents implicated in hair growth control modulate these follicular cadherin expression patterns, and to define how these basic parameters of HF topobiology are altered during common hair growth disorders.

Acellular vaccines for preventing whooping cough in children.

PubMed

Zhang, Linjie; Prietsch, Sílvio Om; Axelsson, Inge; Halperin, Scott A

2011-01-19

Routine use of whole-cell pertussis vaccines was suspended in some countries in the 1970s/1980s because of concerns about adverse effects. There was a resurgence of whooping cough. Acellular pertussis vaccines (containing purified or recombinant Bordetella pertussis antigens) were developed in the hope that they would be as effective but less reactogenic than the whole-cell vaccines. To assess the efficacy and safety of acellular pertussis vaccines in children. We searched the Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 2) which contains the Acute Respiratory Infections Group's Specialised Register; MEDLINE (1950 to April week 2 2009) and EMBASE (1974 to April 2009). Double-blind randomised efficacy and safety trials of acellular pertussis vaccines in children up to six years old, with active follow-up of participants and laboratory verification of pertussis cases. Two review authors independently performed data extraction and study quality assessment. Differences in trial design precluded pooling of the efficacy data. The safety data from individual trials were pooled using the Cochrane statistical package Review Manager 5. Six efficacy trials and 52 safety trials were included. The efficacy of multi-component (≥ 3) vaccines varied from 84% to 85% in preventing typical whooping cough, and from 71% to 78% in preventing mild pertussis disease. In contrast, the efficacy of one- and two-component vaccines varied from 59% to 75% against typical whooping cough, and from 13% to 54% against mild pertussis disease. Multi-component acellular vaccines is more effective than low-efficacy whole-cell vaccines, but may be less effective than the highest-efficacy whole-cell vaccines. Most systemic and local adverse events were significantly less common with acellular than with whole-cell pertussis vaccines for the primary series as well as for the booster dose. Multi-component acellular pertussis vaccines are effective, and show less adverse effects than whole-cell pertussis vaccines for the primary series as well as for booster doses.

Amyloid-like ribbons of amelogenins in enamel mineralization

DOE PAGES

Carneiro, Karina M. M.; Zhai, Halei; Zhu, Li; ...

2016-03-24

We report that enamel, the outermost layer of teeth, is an acellular mineralized tissue that cannot regenerate; the mature tissue is composed of high aspect ratio apatite nanocrystals organized into rods and inter-rod regions. Amelogenin constitutes 90% of the protein matrix in developing enamel and plays a central role in guiding the hierarchical organization of apatite crystals observed in mature enamel. To date, a convincing link between amelogenin supramolecular structures and mature enamel has yet to be described, in part because the protein matrix is degraded during tissue maturation. Here we show compelling evidence that amelogenin self-assembles into an amyloid-likemore » structure in vitro and in vivo. We show that enamel matrices stain positive for amyloids and we identify a specific region within amelogenin that self-assembles into β-sheets. Lastly, we propose that amelogenin nanoribbons template the growth of apatite mineral in human enamel. This is a paradigm shift from the current model of enamel development.« less

Natural and Sun-Induced Aging of Human Skin

PubMed Central

Rittié, Laure; Fisher, Gary J.

2015-01-01

With worldwide expansion of the aging population, research on age-related pathologies is receiving growing interest. In this review, we discuss current knowledge regarding the decline of skin structure and function induced by the passage of time (chronological aging) and chronic exposure to solar UV irradiation (photoaging). Nearly every aspect of skin biology is affected by aging. The self-renewing capability of the epidermis, which provides vital barrier function, is diminished with age. Vital thermoregulation function of eccrine sweat glands is also altered with age. The dermal collagenous extracellular matrix, which comprises the bulk of skin and confers strength and resiliency, undergoes gradual fragmentation, which deleteriously impacts skin mechanical properties and dermal cell functions. Aging also affects wound repair, pigmentation, innervation, immunity, vasculature, and subcutaneous fat homeostasis. Altogether, age-related alterations of skin lead to age-related skin fragility and diseases. PMID:25561721

Long-pulsed 1064-nm Nd: YAG laser ameliorates LL-37-induced rosacea-like skin lesions through promoting collagen remodeling in BALB/c mice.

PubMed

Kim, Miri; Kim, Jongsic; Jeong, Seo-Won; Jo, Hyunmu; Park, Hyun Jeong

2018-02-01

Long-pulsed 1064-nm neodymium: yttrium-aluminum-garnet laser (LPND) effectively treats rosacea, although the underlying mechanism is unclear, to evaluate the histological effects and molecular mechanism of LPND on LL-37-induced rosacea-like skin lesions in mice. Intradermal injection of LL-37 was performed into the dorsal skin of BALB/c mice (n = 30) twice a day for 2 days. Fifteen mice were treated with LPND. After 48 h, the excised skin sample was stained for histology and type I collagen; transforming growth factor (TGF)-β, matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase (TIMP)-1, tumor necrosis factor (TNF)-α, and interleukin (IL)-1α mRNA levels were determined by real-time RT-PCR. Intradermal injection of LL-37 induced rosacea-like clinical features. LPND treatment significantly reduced erythema and increased dermal collagen production. Levels of Type I collagen, TGF-β, and MMP-1 mRNA were significantly higher in LPND-treated mice than in untreated mice. LPND may improve rosacea by ameliorating dermal connective tissue disorganization and elastosis through MMP-mediated dermal collagen remodeling.

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

Using genipin-crosslinked acellular porcine corneal stroma for cosmetic corneal lens implants.

PubMed

Liu, Zhao; Zhou, Qiang; Zhu, Jixiang; Xiao, Jianhui; Wan, Pengxia; Zhou, Chenjing; Huang, Zheqian; Qiang, Na; Zhang, Wei; Wu, Zheng; Quan, Daping; Wang, Zhichong

2012-10-01

Acellular porcine corneal stroma (APCS) has been proven to maintain the matrix microenvironment and is therefore an ideal biomaterial for the repair and reconstruction of corneal stroma. This study aims to develop a method to prepare cosmetic corneal lens implants for leukoma using genipin-crosslinked APCS (Gc-APCS). The Gc-APCS was prepared from APCS immersed in 1.0% genipin aqueous solution (pH 5.5) for 4 h at 37 °C, followed by lyophilization at -10 °C. The color of the Gc-APCS gradually deepened to dark-blue. The degree of crosslinking was 45.7 ± 4.6%, measured by the decrease of basic and hydroxy amino acids. The porous structure and ultrastructure of collagenous lamellae were maintained, and the porosity and BET SSA were 72.7 ± 4.6% and 23.01 ± 3.45 m(2)/g, respectively. The Gc-APCS rehydrated to the physiological water content within 5 min and was highly resistant to collagenase digestion. There were no significant differences in the areal modulus and curvature variation between Gc-APCS and nature porcine cornea. The dark-blue pigments were stable to pH, light and implantation in vivo. Gc-APCS extracts had no inhibitory effects on the proliferation of keratocytes. Corneal neovascularization, graft degradation and corneal rejection were not observed within 6 months. Copyright © 2012 Elsevier Ltd. All rights reserved.

Enamel formation and amelogenesis imperfecta.

PubMed

Hu, Jan C-C; Chun, Yong-Hee P; Al Hazzazzi, Turki; Simmer, James P

2007-01-01

Dental enamel is the epithelial-derived hard tissue covering the crowns of teeth. It is the most highly mineralized and hardest tissue in the body. Dental enamel is acellular and has no physiological means of repair outside of the protective and remineralization potential provided by saliva. Enamel is comprised of highly organized hydroxyapatite crystals that form in a defined extracellular space, the contents of which are supplied and regulated by ameloblasts. The entire process is under genetic instruction. The genetic control of amelogenesis is poorly understood, but requires the activities of multiple components that are uniquely important for dental enamel formation. Amelogenesis imperfecta (AI) is a collective designation for the variety of inherited conditions displaying isolated enamel malformations, but the designation is also used to indicate the presence of an enamel phenotype in syndromes. Recently, genetic studies have demonstrated the importance of genes encoding enamel matrix proteins in the etiology of isolated AI. Here we review the essential elements of dental enamel formation and the results of genetic analyses that have identified disease-causing mutations in genes encoding enamel matrix proteins. In addition, we provide a fresh perspective on the roles matrix proteins play in catalyzing the biomineralization of dental enamel. Copyright 2007 S. Karger AG, Basel.

Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

PubMed Central

Xiao, Yun; Ahadian, Samad

2017-01-01

Progress in biomaterial science and engineering and increasing knowledge in cell biology have enabled us to develop functional biomaterials providing appropriate biochemical and biophysical cues for tissue regeneration applications. Tissue regeneration is particularly important to treat chronic wounds of people with diabetes. Understanding and controlling the cellular microenvironment of the wound tissue are important to improve the wound healing process. In this study, we review different biochemical (e.g., growth factors, peptides, DNA, and RNA) and biophysical (e.g., topographical guidance, pressure, electrical stimulation, and pulsed electromagnetic field) cues providing a functional and instructive acellular matrix to heal diabetic chronic wounds. The biochemical and biophysical signals generally regulate cell–matrix interactions and cell behavior and function inducing the tissue regeneration for chronic wounds. Some technologies and devices have already been developed and used in the clinic employing biochemical and biophysical cues for wound healing applications. These technologies can be integrated with smart biomaterials to deliver therapeutic agents to the wound tissue in a precise and controllable manner. This review provides useful guidance in understanding molecular mechanisms and signals in the healing of diabetic chronic wounds and in designing instructive biomaterials to treat them. PMID:27405960

Quickening: Translational design of resorbable synthetic vascular grafts.

PubMed

Stowell, Chelsea E T; Wang, Yadong

2018-08-01

Traditional tissue-engineered vascular grafts have yet to gain wide clinical use. The difficulty of scaling production of these cell- or biologic-based products has hindered commercialization. In situ tissue engineering bypasses such logistical challenges by using acellular resorbable scaffolds. Upon implant, the scaffolds become remodeled by host cells. This review describes the scientific and translational advantages of acellular, synthetic vascular grafts. It surveys in vivo results obtained with acellular synthetics over their fifty years of technological development. Finally, it discusses emerging principles, highlights strategic considerations for designers, and identifies questions needing additional research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transition from Round to Shaped Implants in Immediate Breast Reconstruction: Our Preferred Approach and Clinical Outcomes.

PubMed

Imahiyerobo, Thomas A; Small, Kevin H; Sackeyfio, Robyn; Hoffman, Hannah; Talmor, Mia

2017-04-01

Smooth, round, silicone implants predominate device-based breast reconstruction in the USA; despite their prevalence, complications can include bottoming out, superior contour deformity, rippling, and/or lateral malposition. This complication profile increases the need for revision surgery and subsequent patient dissatisfaction. With the resurgence of shaped, textured, silicone implants in the USA, we report the senior author's success with these devices and outline a strategy to optimize outcomes in breast reconstruction surgery. A retrospective chart review was conducted on a prospectively collected IRB-approved database of nipple-sparing mastectomies (NSMs) with immediate breast reconstruction with smooth, round, silicone implants (Group A) in 2011 in comparison to textured, shaped, silicone implants (Group B) in 2012. Changes in operative technique were highlighted and extrapolated. Outcomes were reviewed. In Group A, 128 NSMs were performed in 76 patients. In Group B, 109 NSMs were performed in 59 patients. Thirteen percent of patients in Group A had direct to implant reconstruction as compared with 21% in Group B. Patients with textured, shaped implants were more likely to have acellular dermal matrix (61 vs 34%, p < 0.0001) than those with smooth, round implants. Patients who had smooth, round implants were more likely to have postoperative nipple malposition (18 vs 0%, p < 0.0001,) and rippling (29 vs 0%, p < 0.0001.) Patients with textured, shaped implants had fewer operative revision reconstructions as compared with those with smooth, round implants (36.71 vs 12.8%, p < 0.0001) Based on these results, our technique has evolved and has eight key technical modifications. With a few adaptations in surgical technique, the transition to textured, shaped, silicone devices for breast reconstruction can be seamless with superior breast contour and reduced complications/revision rates. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Abdominal Wall Reconstruction with Concomitant Ostomy-Associated Hernia Repair: Outcomes and Propensity Score Analysis.

PubMed

Mericli, Alexander F; Garvey, Patrick B; Giordano, Salvatore; Liu, Jun; Baumann, Donald P; Butler, Charles E

2017-03-01

The optimal strategy for abdominal wall reconstruction in the presence of a stomal-site hernia is unclear. We hypothesized that the rate of ventral hernia recurrence in patients undergoing a combined ventral hernia repair and stomal-site herniorraphy would not differ clinically from the ventral hernia recurrence rate in patients undergoing an isolated ventral hernia repair. We also hypothesized that bridged ventral hernia repairs result in worse outcomes compared with reinforced repairs, regardless of stomal hernia. We retrospectively reviewed prospectively collected data from consecutive abdominal wall reconstructions performed with acellular dermal matrix (ADM) at a single center between 2000 and 2015. We compared patients who underwent a ventral hernia repair alone (AWR) and those who underwent both a ventral hernia repair and ostomy-associated herniorraphy (AWR+O). We conducted a propensity score matched analysis to compare the outcomes between the 2 groups. Multivariable Cox proportional hazards and logistic regression models were used to study associations between potential predictive or protective reconstructive strategies and surgical outcomes. We included 499 patients (median follow-up 27.2 months; interquartile range [IQR] 12.4 to 46.6 months), 118 AWR+O and 381 AWR. After propensity score matching, 91 pairs were obtained. Ventral hernia recurrence was not statistically associated with ostomy-associated herniorraphy (adjusted hazard ratio [HR] 0.7; 95% CI 0.3 to 1.5; p = 0.34). However, the AWR+O group experienced a significantly higher percentage of surgical site occurrences (34.1%) than the AWR group (18.7%; adjusted odds ratio 2.3; 95% CI 1.4 to 3.7; p < 0.001). In the AWR group, there were significantly fewer ventral hernia recurrences when the repair was reinforced compared with bridged (5.3% vs 38.5%; p < 0.001). There was no statistically significant difference in ventral hernia recurrence between the AWR and AWR+O groups. Bridging was associated with an increased rate of hernia recurrence and should be avoided if possible. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Rates of Reconstruction Failure in Patients Undergoing Immediate Reconstruction With Tissue Expanders and/or Implants and Postmastectomy Radiation Therapy

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

Fowble, Barbara, E-mail: BFowble@radonc.ucsf.edu; Park, Catherine; Wang, Frederick

2015-07-01

Objectives: Mastectomy rates for breast cancer have increased, with a parallel increase in immediate reconstruction. For some women, tissue expander and implant (TE/I) reconstruction is the preferred or sole option. This retrospective study examined the rate of TE/I reconstruction failure (ie, removal of the TE or I with the inability to replace it resulting in no final reconstruction or autologous tissue reconstruction) in patients receiving postmastectomy radiation therapy (PMRT). Methods and Materials: Between 2004 and 2012, 99 women had skin-sparing mastectomies (SSM) or total nipple/areolar skin-sparing mastectomies (TSSM) with immediate TE/I reconstruction and PMRT for pathologic stage II to IIImore » breast cancer. Ninety-seven percent had chemotherapy (doxorubicin and taxane-based), 22% underwent targeted therapies, and 78% had endocrine therapy. Radiation consisted of 5000 cGy given in 180 to 200 cGy to the reconstructed breast with or without treatment to the supraclavicular nodes. Median follow-up was 3.8 years. Results: Total TE/I failure was 18% (12% without final reconstruction, 6% converted to autologous reconstruction). In univariate analysis, the strongest predictor of reconstruction failure (RF) was absence of total TE/I coverage (acellular dermal matrix and/or serratus muscle) at the time of radiation. RF occurred in 32.5% of patients without total coverage compared to 9% with coverage (P=.0069). For women with total coverage, the location of the mastectomy scar in the inframammary fold region was associated with higher RF (19% vs 0%, P=.0189). In multivariate analysis, weight was a significant factor for RF, with lower weight associated with a higher RF. Weight appeared to be a surrogate for the interaction of total coverage, thin skin flaps, interval to exchange, and location of the mastectomy scar. Conclusions: RFs in patients receiving PMRT were lowered with total TE/I coverage at the time of radiation by avoiding inframammary fold incisions and with a preferred interval of 6 months to exchange.« less

Basement membrane reconstruction in human skin equivalents is regulated by fibroblasts and/or exogenously activated keratinocytes.

PubMed

El Ghalbzouri, Abdoelwaheb; Jonkman, Marcel F; Dijkman, Remco; Ponec, Maria

2005-01-01

This study was undertaken to examine the role fibroblasts play in the formation of the basement membrane (BM) in human skin equivalents. For this purpose, keratinocytes were seeded on top of fibroblast-free or fibroblast-populated collagen matrix or de-epidermized dermis and cultured in the absence of serum and exogenous growth factors. The expression of various BM components was analyzed on the protein and mRNA level. Irrespective of the presence or absence of fibroblasts, keratin 14, hemidesmosomal proteins plectin, BP230 and BP180, and integrins alpha1beta1, alpha2beta1, alpha3beta1, and alpha6beta4 were expressed but laminin 1 was absent. Only in the presence of fibroblasts or of various growth factors, laminin 5 and laminin 10/11, nidogen, uncein, type IV and type VII collagen were decorating the dermal/epidermal junction. These findings indicate that the attachment of basal keratinocytes to the dermal matrix is most likely mediated by integrins alpha1beta1 and alpha2beta1, and not by laminins that bind to integrin alpha6beta4 and that the epithelial-mesenchymal cross-talk plays an important role in synthesis and deposition of various BM components.

Efficacy of a collagen-based dressing in an animal model of delayed wound healing.

PubMed

Guillemin, Y; Le Broc, D; Ségalen, C; Kurkdjian, E; Gouze, J N

2016-07-02

The aim of this study was to evaluate in vitro and in vivo the efficacy of GBT013, a collagen-based dressing, for the treatment of chronic wounds, in a db/db mouse model of diabetes. Macroscopic and histologic analyses of db/db mice wound healing with GBT013 or saline gauze were assessed. The mRNA expression and the proliferation of dermal fibroblast were investigated. Matrix metalloproteinases (MMP)-2 and MMP-9 activities were quantified. In db/db mice, GBT013 improves wound epithelialisation when compared with saline gauze. Histological analysis of scar tissue also shows an enhancement of remodelling associated with no sign of acute inflammation. In addition, GBT013 significantly decreases interleukin (IL)-6 and IL-8, significantly increases tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 fibroblast mRNA expression and significantly reduces in vitro MMP-2 and MMP-9 enzymatic activities. Moreover, GBT013 allows cell growth inside the matrix and stimulates proliferation of human dermal fibroblast. By contributing to restore MMPs/TIMPs balance, GBT013 may function in all key stages of wound healing, such as inflammation, proliferation and tissue remodelling, and ultimately may provide a favourable environment for skin repair. This work was supported by Genbiotech, the R&D subsidiary of Laboratoires Genévrier, a pharmaceutical company.

Matrix metalloproteinase-1 inhibitory activities of Morinda citrifolia seed extract and its constituents in UVA-irradiated human dermal fibroblasts.

PubMed

Masuda, Megumi; Murata, Kazuya; Naruto, Shunsuke; Uwaya, Akemi; Isami, Fumiyuki; Matsuda, Hideaki

2012-01-01

The objective of this study was to examine whether a 50% ethanolic extract (MCS-ext) of the seeds of Morinda citrifolia (noni) and its constituents have matrix metalloproteinase-1 (MMP-1) inhibitory activity in UVA-irradiated normal human dermal fibroblasts (NHDFs). The MCS-ext (10 μg/mL) inhibited MMP-1 secretion from UVA-irradiated NHDFs, without cytotoxic effects, at 48 h after UV exposure. The ethyl acetate-soluble fraction of MCS-ext was the most potent inhibitor of MMP-1 secretion. Among the constituents of the fraction, a lignan, 3,3'-bisdemethylpinoresinol (1), inhibited the MMP-1 secretion at a concentration of 0.3 μM without cytotoxic effects. Furthermore, 1 (0.3 μM) reduced the level of intracellular MMP-1 expression. Other constituents, namely americanin A (2), quercetin (3) and ursolic acid (4), were inactive. To elucidate inhibition mechanisms of MMP-1 expression and secretion, the effect of 1 on mitogen-activated protein kinases (MAPKs) phosphorylation was examined. Western blot analysis revealed that 1 (0.3 μM) reduced the phosphorylations of p38 and c-Jun-N-terminal kinase (JNK). These results suggested that 1 suppresses intracellular MMP-1 expression, and consequent secretion from UVA-irradiated NHDFs, by down-regulation of MAPKs phosphorylation.

Histological and Immunohistochemical Evaluation of the Efficacy of a New Cosmetic Formulation in the Treatment of Skin Photoaging

PubMed Central

Jiménez, N.; Miguel-Gomez, L.; Hermosa, A.; Sánchez-Neila, N.; Cuevas, J.

2017-01-01

Objective. Mechanism of action of cosmetic products is not often studied. The aim of this study is to determine the histological, immunohistochemical, and clinical changes of a new cosmetic formulation. Methods. Prospective, single-blind, patient-controlled, randomized study in 10 volunteers with mild to moderate skin photoaging on the back of their hands. The product was applied on one hand and a standard cream on the other hand, twice a day for three months. Standardized photographs were taken on basal (T0) and final visit (T1) and skin biopsies were performed. Changes on histological and immunohistochemical markers were studied. Subjective clinical changes were determined. Results. After treatment, a 26.3% improvement on epidermal thickness was detected and a significant increase on collagens I and III, elastin, and fibronectin fibers was achieved (p < 0.05). As the expression of MMPs remained stable, this improvement of dermal matrix was attributed to the stimulation of their synthesis. A significant clinical improvement on the treated hand was obtained, compared to control hand. Conclusion. This new cosmetic product with combination of three registered technologies (IFC-CAF, WGC, and RetinSphere), focused on regenerating dermal matrix and activating proliferation of skin cells, has shown to be efficient in the reversion of skin photoaging. PMID:28167957

Piper retrofractum Vahl. Extract, as a PPARδ and AMPK Activator, Suppresses UVB-Induced Photoaging through Mitochondrial Biogenesis and MMPs Inhibition in Human Dermal Fibroblasts and Hairless Mice

PubMed Central

2018-01-01

Photoaging occurs by UVB-irradiation and involves production of reactive oxygen species (ROS) and overexpression of matrix metalloproteinases (MMPs), leading to extracellular matrix damage. Piper retrofractum Vahl. is used as a traditional medicine for antiflatulence, expectorant, sedative, and anti-irritant; however, its antiphotoaging effect has not yet been studied. The current study investigated the antiphotoaging effect of standardized Piper retrofractum extract (PRE) on UVB-damaged human dermal fibroblasts and hairless mouse skin. PRE treatment activated the peroxisome proliferator-activated receptor delta (PPARδ) and the adenosine monophosphate-activated protein kinase (AMPK), consequently upregulating mitochondrial synthesis and reducing ROS production. Additionally, PRE inhibited MMPs expression via suppressing mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1). PRE downregulated UVB-induced inflammatory reactions by inhibiting the nuclear factor-kappa B (NF-κB) activity. PRE also enhanced transforming growth factor-beta (TGF-β) and the Smad signaling pathway, thereby promoting procollagen gene transcription. Furthermore, oral administration of PRE (300 mg/kg/day) similarly regulated the signaling pathways and increased antioxidant enzyme expression, thus attenuating physiological deformations, such as wrinkle formation and erythema response. Collectively, these results suggest that PRE acts as a potent antiphotoaging agent via PPARδ and AMPK activation. PMID:29619069

Piper retrofractum Vahl. Extract, as a PPARδ and AMPK Activator, Suppresses UVB-Induced Photoaging through Mitochondrial Biogenesis and MMPs Inhibition in Human Dermal Fibroblasts and Hairless Mice.

PubMed

Yun, Jungon; Kim, Changhee; Kim, Mi-Bo; Hwang, Jae-Kwan

2018-01-01

Photoaging occurs by UVB-irradiation and involves production of reactive oxygen species (ROS) and overexpression of matrix metalloproteinases (MMPs), leading to extracellular matrix damage. Piper retrofractum Vahl. is used as a traditional medicine for antiflatulence, expectorant, sedative, and anti-irritant; however, its antiphotoaging effect has not yet been studied. The current study investigated the antiphotoaging effect of standardized Piper retrofractum extract (PRE) on UVB-damaged human dermal fibroblasts and hairless mouse skin. PRE treatment activated the peroxisome proliferator-activated receptor delta (PPAR δ ) and the adenosine monophosphate-activated protein kinase (AMPK), consequently upregulating mitochondrial synthesis and reducing ROS production. Additionally, PRE inhibited MMPs expression via suppressing mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1). PRE downregulated UVB-induced inflammatory reactions by inhibiting the nuclear factor-kappa B (NF- κ B) activity. PRE also enhanced transforming growth factor-beta (TGF- β ) and the Smad signaling pathway, thereby promoting procollagen gene transcription. Furthermore, oral administration of PRE (300 mg/kg/day) similarly regulated the signaling pathways and increased antioxidant enzyme expression, thus attenuating physiological deformations, such as wrinkle formation and erythema response. Collectively, these results suggest that PRE acts as a potent antiphotoaging agent via PPAR δ and AMPK activation.

Analysis of human acellular nerve allograft reconstruction of 64 injured nerves in the hand and upper extremity: a 3 year follow-up study.

PubMed

Zhu, Shuang; Liu, Jianghui; Zheng, Canbin; Gu, Liqiang; Zhu, Qingtang; Xiang, Jianping; He, Bo; Zhou, Xiang; Liu, Xiaolin

2017-08-01

Human acellular nerve allografts have been increasingly applied in clinical practice. This study was undertaken to investigate the functional outcomes of nerve allograft reconstruction for nerve defects in the upper extremity. A total of 64 patients from 13 hospitals were available for this follow-up study after nerve repair using human acellular nerve allografts. Sensory and motor recovery was examined according to the international standards for motor and sensory nerve recovery. Subgroup analysis and logistic regression analysis were conducted to identify the relationship between the known factors and the outcomes of nerve repair. Mean follow-up time was 355 ± 158 (35-819) days; mean age was 35 ± 11 (14-68) years; average nerve gap length was 27 ± 13 (10-60) mm; no signs of infection, tissue rejection or extrusion were observed among the patients; 48/64 (75%) repaired nerves experienced meaningful recovery. Univariate analysis showed that site and gap length significantly influenced prognosis after nerve repair using nerve grafts. Delay had a marginally significant relationship with the outcome. A multivariate logistic regression model revealed that gap length was an independent predictor of nerve repair using human acellular nerve allografts. The results indicated that the human acellular nerve allograft facilitated safe and effective nerve reconstruction for nerve gaps 10-60 mm in length in the hand and upper extremity. Factors such as site and gap length had a statistically significant influence on the outcomes of nerve allograft reconstruction. Gap length was an independent predictor of nerve repair using human acellular nerve allografts. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Acellular pertussis vaccines effectiveness over time: A systematic review, meta-analysis and modeling study

PubMed Central

Chit, Ayman; Zivaripiran, Hossein; Shin, Thomas; Lee, Jason K. H.; Tomovici, Antigona; Macina, Denis; Johnson, David R.; Decker, Michael D.; Wu, Jianhong

2018-01-01

Background Acellular pertussis vaccine studies postulate that waning protection, particularly after the adolescent booster, is a major contributor to the increasing US pertussis incidence. However, these studies reported relative (ie, vs a population given prior doses of pertussis vaccine), not absolute (ie, vs a pertussis vaccine naïve population) efficacy following the adolescent booster. We aim to estimate the absolute protection offered by acellular pertussis vaccines. Methods We conducted a systematic review of acellular pertussis vaccine effectiveness (VE) publications. Studies had to comply with the US schedule, evaluate clinical outcomes, and report VE over discrete time points. VE after the 5-dose childhood series and after the adolescent sixth-dose booster were extracted separately and pooled. All relative VE estimates were transformed to absolute estimates. VE waning was estimated using meta-regression modeling. Findings Three studies reported VE after the childhood series and four after the adolescent booster. All booster studies reported relative VE (vs acellular pertussis vaccine-primed population). We estimate initial childhood series absolute VE is 91% (95% CI: 87% to 95%) and declines at 9.6% annually. Initial relative VE after adolescent boosting is 70% (95% CI: 54% to 86%) and declines at 45.3% annually. Initial absolute VE after adolescent boosting is 85% (95% CI: 84% to 86%) and declines at 11.7% (95% CI: 11.1% to 12.3%) annually. Interpretation Acellular pertussis vaccine efficacy is initially high and wanes over time. Observational VE studies of boosting failed to recognize that they were measuring relative, not absolute, VE and the absolute VE in the boosted population is better than appreciated. PMID:29912887

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

Human skin cell fractions fail to self-organize within a gellan gum/hyaluronic acid matrix but positively influence early wound healing.

PubMed

Cerqueira, Mariana T; da Silva, Lucília P; Santos, Tírcia C; Pirraco, Rogério P; Correlo, Vitor M; Marques, Alexandra P; Reis, Rui L

2014-05-01

Split-thickness autografts still are the current gold standard to treat skin, upon severe injuries. Nonetheless, autografts are dependent on donor site availability and often associated to poor quality neoskin. The generation of dermal-epidermal substitutes by tissue engineering is seen as a promising strategy to overcome this problematic. However, solutions that can be safely and conveniently transplanted in one single surgical intervention are still very challenging as their production normally requires long culture time, and graft survival is many times compromised by delayed vascularization upon transplantation. This work intended to propose a strategy that circumvents the prolonged and laborious preparation period of skin substitutes and allows skin cells self-organization toward improved healing. Human dermal/epidermal cell fractions were entrapped directly from isolation within a gellan gum/hyaluronic acid (GG-HA) spongy-like hydrogel formed from an off-the-shelf dried polymeric network. Upon transplantation into full-thickness mice wounds, the proposed constructs accelerated the wound closure rate and re-epithelialization, as well as tissue neovascularization. A synergistic effect of the GG-HA matrix and the transplanted cells over those processes was demonstrated at early time points. Despite the human-derived and chimeric blood vessels found, the proposed matrix did not succeed in prolonging cells residence time and in sustaining the self-organization of transplanted human cells possibly due to primitive degradation. Despite this, the herein proposed approach open the opportunity to tackle wound healing at early stages contributing to re-epithelialization and neovascularization.

Comparison of structural, architectural and mechanical aspects of cellular and acellular bone in two teleost fish.

PubMed

Cohen, Liat; Dean, Mason; Shipov, Anna; Atkins, Ayelet; Monsonego-Ornan, Efrat; Shahar, Ron

2012-06-01

The histological diversity of the skeletal tissues of fishes is impressive compared with that of other vertebrate groups, yet our understanding of the functional consequences of this diversity is limited. In particular, although it has been known since the mid-1800s that a large number of fish species possess acellular bones, the mechanical advantages and consequences of this structural characteristic - and therefore the nature of the evolution of this feature - remain unclear. Although several studies have examined the material properties of fish bone, these have used a variety of techniques and there have been no direct contrasts of acellular and cellular bone. We report on a comparison of the structural and mechanical properties of the ribs and opercula between two freshwater fish - the common carp Cyprinus carpio (a fish with cellular bone) and the tilapia Oreochromis aureus (a fish with acellular bone). We used light microscopy to show that the bones in both fish species exhibit poor blood supply and possess discrete tissue zones, with visible layering suggesting differences in the underlying collagen architecture. We performed identical micromechanical testing protocols on samples of the two bone types to determine the mechanical properties of the bone material of opercula and ribs. Our data support the consensus of literature values, indicating that Young's moduli of cellular and acellular bones are in the same range, and lower than Young's moduli of the bones of mammals and birds. Despite these similarities in mechanical properties between the bone tissues of the fish species tested here, cellular bone had significantly lower mineral content than acellular bone; furthermore, the percentage ash content and bone mineral density values (derived from micro-CT scans) show that the bone of these fishes is less mineralized than amniote bone. Although we cannot generalize from our data to the numerous remaining teleost species, the results presented here suggest that while cellular and acellular fish bone may perform similarly from a mechanical standpoint, there are previously unappreciated differences in the structure and composition of these bone types.

Combining nano-physical and computational investigations to understand the nature of "aging" in dermal collagen.

PubMed

Ahmed, Tarek; Nash, Anthony; Clark, Kristina En; Ghibaudo, Marion; de Leeuw, Nora H; Potter, Anne; Stratton, Richard; Birch, Helen L; Enea Casse, Ramona; Bozec, Laurent

2017-01-01

The extracellular matrix of the dermis is a complex, dynamic system with the various dermal components undergoing individual physiologic changes as we age. Age-related changes in the physical properties of collagen were investigated in particular by measuring the effect of aging, most likely due to the accumulation of advanced glycation end product (AGE) cross-links, on the nanomechanical properties of the collagen fibril using atomic force microscope nano-indentation. An age-related decrease in the Young's modulus of the transverse fibril was observed (from 8.11 to 4.19 GPa in young to old volunteers, respectively, P <0.001). It is proposed that this is due to a change in the fibril density caused by age-related differences in water retention within the fibrils. The new collagen-water interaction mechanism was verified by electronic structure calculations, showing it to be energetically feasible.

Three-dimensional organization of dermal fibroblasts by macromass culture.

PubMed

Deshpande, Manisha

2008-01-01

The three-dimensional organization of cells by high-cell-seeding-density culture, termed 'macromass culture', is described. By macromass culture, dermal fibroblasts can be made to organize themselves into a unified three-dimensional form without the aid of a scaffold, and macroscopic constructs, named macromasses, can be made wholly from cells. The sole factor causing three-dimensional organization is culture of cells at high cell seeding density per unit area. No scaffold or extraneous matrix is used for the generation of macromasses; they are of completely cellular origin. No other agents or external influences such as tissue-inducing chemicals, tissue-inducing growth factors, substratum with special properties, rotational culture, centrifugation etc. are employed for macromass formation, and all seeded cells become part of the cohesive construct. These three-dimensional constructs have the potential for use as in vitro tissue analogues, and a possible application for in vitro cytotoxicity testing is demonstrated.

Controlled release of an extract of Calendula officinalis flowers from a system based on the incorporation of gelatin-collagen microparticles into collagen I scaffolds: design and in vitro performance.

PubMed

Jiménez, Ronald A; Millán, Diana; Suesca, Edward; Sosnik, Alejandro; Fontanilla, Marta R

2015-06-01

Aiming to develop biological skin dresses with improved performance in the treatment of skin wounds, acellular collagen I scaffolds were modified with polymeric microparticles and the subsequent loading of a hydroglycolic extract of Calendula officinalis flowers. Microparticles made of gelatin-collagen were produced by a water-in-oil emulsion/cross-linking method. Thereafter, these microparticles were mixed with collagen suspensions at three increasing concentrations and the resulting mixtures lyophilized to make microparticle-loaded porous collagen scaffolds. Resistance to enzymatic degradation, ability to associate with the C. officinalis extract, and the extract release profile of the three gelatin-collagen microparticle-scaffold prototypes were assessed in vitro and compared to collagen scaffolds without microparticles used as control. Data indicated that the incorporation of gelatin-collagen microparticles increased the resistance of the scaffolds to in vitro enzymatic degradation, as well as their association with the C. officinalis flower extract. In addition, a sharp decrease in cytotoxicity, as well as more prolonged release of the extract, was attained. Overall results support the potential of these systems to develop innovative dermal substitutes with improved features. Furthermore, the gelatin-collagen mixture represents a low-cost and scalable alternative with high clinical transferability, especially appealing in developing countries.

Patch-Augmented Latissimus Dorsi Transfer and Open Reduction–Internal Fixation of Unstable Os Acromiale for Irreparable Massive Posterosuperior Rotator Cuff Tear

PubMed Central

Petri, Maximilian; Greenspoon, Joshua A.; Bhatia, Sanjeev; Millett, Peter J.

2015-01-01

Latissimus dorsi transfer is a reasonable treatment option for massive posterosuperior rotator cuff tears that can substantially improve chronically painful and dysfunctional shoulders. This report and accompanying video describe the treatment of an active 43-year-old man with severe pain and weakness in the right shoulder after 3 failed rotator cuff repairs. Preoperative imaging showed a massive posterosuperior rotator cuff tear retracted to the glenoid as well as a hypermobile os acromiale likely causing dynamic impingement and recurrent rotator cuff tears. After diagnostic arthroscopy, the latissimus tendon is harvested and augmented with a 3-mm human acellular dermal patch (ArthroFlex; Arthrex, Naples, FL). The native rotator cuff tissue is repaired as much as possible, and the latissimus tendon is passed underneath the deltoid and posterior to the teres minor. The patch-augmented tendon is then integrated into a double-row SpeedBridge repair of eight 4.75-mm BioComposite SwiveLock anchors (Arthrex). The bony surface of the os acromiale is prepared and then fixed to the acromion with 2 cannulated partially threaded screws and additional tension-band wiring. Postoperative rehabilitation initially focuses on early passive range of motion, followed by active and active-assisted motion and a biofeedback program starting at 6 weeks postoperatively. PMID:26697309

Axonal regeneration through acellular muscle grafts

PubMed Central

HALL, SUSAN

1997-01-01

The management of peripheral nerve injury remains a major clinical problem. Progress in this field will almost certainly depend upon manipulating the pathophysiological processes which are triggered by traumatic injuries. One of the most important determinants of functional outcome after the reconstruction of a transected peripheral nerve is the length of the gap between proximal and distal nerve stumps. Long defects (> 2 cm) must be bridged by a suitable conduit in order to support axonal regrowth. This review examines the cellular and acellular elements which facilitate axonal regrowth and the use of acellular muscle grafts in the repair of injuries in the peripheral nervous system. PMID:9034882

The relationship between mucosal immunity, nasopharyngeal carriage, asymptomatic transmission and the resurgence of Bordetella pertussis

PubMed Central

Gill, Christopher; Rohani, Pejman; Thea, Donald M

2017-01-01

The incidence of whooping cough in the US has been rising slowly since the 1970s, but the pace of this has accelerated sharply since acellular pertussis vaccines replaced the earlier whole cell vaccines in the late 1990s. A similar trend occurred in many other countries, including the UK, Canada, Australia, Ireland, and Spain, following the switch to acellular vaccines. The key question is why. Two leading theories (short duration of protective immunologic persistence and evolutionary shifts in the pathogen to evade the vaccine) explain some but not all of these shifts, suggesting that other factors may also be important. In this synthesis, we argue that sterilizing mucosal immunity that blocks or abbreviates the duration of nasopharyngeal carriage of Bordetella pertussis and impedes person-to-person transmission (including between asymptomatically infected individuals) is a critical factor in this dynamic. Moreover, we argue that the ability to induce such mucosal immunity is fundamentally what distinguishes whole cell and acellular pertussis vaccines and may be pivotal to understanding much of the resurgence of this disease in many countries that adopted acellular vaccines. Additionally, we offer the hypothesis that observed herd effects generated by acellular vaccines may reflect a modification of disease presentation leading to reduced potential for transmission by those already infected, as opposed to inducing resistance to infection among those who have been exposed. PMID:28928960

Regenerative and Antibacterial Properties of Acellular Fish Skin Grafts and Human Amnion/Chorion Membrane: Implications for Tissue Preservation in Combat Casualty Care.

PubMed

Magnusson, Skuli; Baldursson, Baldur Tumi; Kjartansson, Hilmar; Rolfsson, Ottar; Sigurjonsson, Gudmundur Fertram

2017-03-01

Improvised explosive devices and new directed energy weapons are changing warfare injuries from penetrating wounds to large surface area thermal and blast injuries. Acellular fish skin is used for tissue repair and during manufacturing subjected to gentle processing compared to biologic materials derived from mammals. This is due to the absence of viral and prion disease transmission risk, preserving natural structure and composition of the fish skin graft. The aim of this study was to assess properties of acellular fish skin relevant for severe battlefield injuries and to compare those properties with those of dehydrated human amnion/chorion membrane. We evaluated cell ingrowth capabilities of the biological materials with microscopy techniques. Bacterial barrier properties were tested with a 2-chamber model. The microstructure of the acellular fish skin is highly porous, whereas the microstructure of dehydrated human amnion/chorion membrane is mostly nonporous. The fish skin grafts show superior ability to support 3-dimensional ingrowth of cells compared to dehydrated human amnion/chorion membrane (p < 0.0001) and the fish skin is a bacterial barrier for 24 to 48 hours. The unique biomechanical properties of the acellular fish skin graft make it ideal to be used as a conformal cover for severe trauma and burn wounds in the battlefield. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Enzyme Replacement Therapy Prevents Dental Defects in a Model of Hypophosphatasia

PubMed Central

McKee, M.D.; Nakano, Y.; Masica, D.L.; Gray, J.J.; Lemire, I.; Heft, R.; Whyte, M.P.; Crine, P.; Millán, J.L.

2011-01-01

Hypophosphatasia (HPP) occurs from loss-of-function mutation in the tissue-non-specific alkaline phosphatase (TNALP) gene, resulting in extracellular pyrophosphate accumulation that inhibits skeletal and dental mineralization. TNALP-null mice (Akp2-/-) phenocopy human infantile hypophosphatasia; they develop rickets at 1 week of age, and die before being weaned, having severe skeletal and dental hypomineralization and episodes of apnea and vitamin B6-responsive seizures. Delay and defects in dentin mineralization, together with a deficiency in acellular cementum, are characteristic. We report the prevention of these dental abnormalities in Akp2-/- mice receiving treatment from birth with daily injections of a mineral-targeting, human TNALP (sALP-FcD10). sALP-FcD10 prevented hypomineralization of alveolar bone, dentin, and cementum as assessed by micro-computed tomography and histology. Osteopontin – a marker of acellular cementum – was immuno-localized along root surfaces, confirming that acellular cementum, typically missing or reduced in Akp2-/- mice, formed normally. Our findings provide insight concerning how acellular cementum is formed on tooth surfaces to effect periodontal ligament attachment to retain teeth in their osseous alveolar sockets. Furthermore, they provide evidence that this enzyme-replacement therapy, applied early in post-natal life – where the majority of tooth root development occurs, including acellular cementum formation – could prevent the accelerated tooth loss seen in individuals with HPP. PMID:21212313

Enzyme replacement therapy prevents dental defects in a model of hypophosphatasia.

PubMed

McKee, M D; Nakano, Y; Masica, D L; Gray, J J; Lemire, I; Heft, R; Whyte, M P; Crine, P; Millán, J L

2011-04-01

Hypophosphatasia (HPP) occurs from loss-of-function mutation in the tissue-non-specific alkaline phosphatase (TNALP) gene, resulting in extracellular pyrophosphate accumulation that inhibits skeletal and dental mineralization. TNALP-null mice (Akp2(-/-)) phenocopy human infantile hypophosphatasia; they develop rickets at 1 week of age, and die before being weaned, having severe skeletal and dental hypomineralization and episodes of apnea and vitamin B(6)-responsive seizures. Delay and defects in dentin mineralization, together with a deficiency in acellular cementum, are characteristic. We report the prevention of these dental abnormalities in Akp2(-/-) mice receiving treatment from birth with daily injections of a mineral-targeting, human TNALP (sALP-FcD(10)). sALP-FcD(10) prevented hypomineralization of alveolar bone, dentin, and cementum as assessed by micro-computed tomography and histology. Osteopontin--a marker of acellular cementum--was immuno-localized along root surfaces, confirming that acellular cementum, typically missing or reduced in Akp2(-/-) mice, formed normally. Our findings provide insight concerning how acellular cementum is formed on tooth surfaces to effect periodontal ligament attachment to retain teeth in their osseous alveolar sockets. Furthermore, they provide evidence that this enzyme-replacement therapy, applied early in post-natal life--where the majority of tooth root development occurs, including acellular cementum formation--could prevent the accelerated tooth loss seen in individuals with HPP.

Bioengineering Human Myocardium on Native Extracellular Matrix

PubMed Central

Guyette, Jacques P.; Charest, Jonathan M; Mills, Robert W; Jank, Bernhard J.; Moser, Philipp T.; Gilpin, Sarah E.; Gershlak, Joshua R.; Okamoto, Tatsuya; Gonzalez, Gabriel; Milan, David J.; Gaudette, Glenn R.; Ott, Harald C.

2015-01-01

Rationale More than 25 million individuals suffer from heart failure worldwide, with nearly 4,000 patients currently awaiting heart transplantation in the United States. Donor organ shortage and allograft rejection remain major limitations with only about 2,500 hearts transplanted each year. As a theoretical alternative to allotransplantation, patient-derived bioartificial myocardium could provide functional support and ultimately impact the treatment of heart failure. Objective The objective of this study is to translate previous work to human scale and clinically relevant cells, for the bioengineering of functional myocardial tissue based on the combination of human cardiac matrix and human iPS-derived cardiac myocytes. Methods and Results To provide a clinically relevant tissue scaffold, we translated perfusion-decellularization to human scale and obtained biocompatible human acellular cardiac scaffolds with preserved extracellular matrix composition, architecture, and perfusable coronary vasculature. We then repopulated this native human cardiac matrix with cardiac myocytes derived from non-transgenic human induced pluripotent stem cells (iPSCs) and generated tissues of increasing three-dimensional complexity. We maintained such cardiac tissue constructs in culture for 120 days to demonstrate definitive sarcomeric structure, cell and matrix deformation, contractile force, and electrical conduction. To show that functional myocardial tissue of human scale can be built on this platform, we then partially recellularized human whole heart scaffolds with human iPSC-derived cardiac myocytes. Under biomimetic culture, the seeded constructs developed force-generating human myocardial tissue, showed electrical conductivity, left ventricular pressure development, and metabolic function. Conclusions Native cardiac extracellular matrix scaffolds maintain matrix components and structure to support the seeding and engraftment of human iPS-derived cardiac myocytes, and enable the bioengineering of functional human myocardial-like tissue of multiple complexities. PMID:26503464

The chromene sargachromanol E inhibits ultraviolet A-induced ageing of skin in human dermal fibroblasts.

PubMed

Kim, J-A; Ahn, B-N; Kong, C-S; Kim, S-K

2013-05-01

Skin ageing is influenced by environmental factors such as ultraviolet (UV) radiation. The effects of UV radiation on skin functions should be investigated using human in vitro models to understand the mechanisms of skin ageing. Additionally, marine algae provide a valuable source for identifying and extracting biologically active substances. In this study, sargachromanol E was isolated from a marine brown alga, Sargassum horneri, and its inhibitory effect on skin ageing was investigated using UVA-irradiated dermal fibroblasts. Formation of intracellular reactive oxygen species (ROS), lipid peroxidation and protein oxidation induced by UVA irradiation were investigated in UVA-irradiated human dermal fibroblasts. The levels of matrix metalloproteinases (MMPs) were determined by reverse-transcriptase polymerase chain reaction and Western blot analysis. Sargachromanol E did not exhibit any significant cytotoxicity or phototoxicity in UVA-exposed dermal fibroblasts. Additionally, sargachromanol E suppressed intracellular formation of ROS, membrane protein oxidation, lipid peroxidation and expression of collagenases such as MMP-1, MMP-2 and MMP-9, all of which are caused by UVA exposure. It was further found that these inhibitions were related to an increase in the expression of the tissue inhibitor of metalloproteinase (TIMP) genes, TIMP1 and TIMP2. Moreover, we have shown that the transcriptional activation of activator protein 1 (AP-1) signalling caused by UVA irradiation was inhibited by treatment with sargachromanol E. This study suggests that UVA irradiation modulates MMP expression via the transcriptional activation of AP-1 signalling, whereas treatment with sargachromanol E protected cell damage caused by UVA irradiation. © 2013 The Authors. BJD © 2013 British Association of Dermatologists.

Pigment epithelium-derived factor as a multifunctional regulator of wound healing

PubMed Central

Wietecha, Mateusz S.; Król, Mateusz J.; Michalczyk, Elizabeth R.; Chen, Lin; Gettins, Peter G.

2015-01-01

During dermal wound repair, hypoxia-driven proliferation results in dense but highly permeable, disorganized microvascular networks, similar to those in solid tumors. Concurrently, activated dermal fibroblasts generate an angiopermissive, provisional extracellular matrix (ECM). Unlike cancers, wounds naturally resolve via blood vessel regression and ECM maturation, which are essential for reestablishing tissue homeostasis. Mechanisms guiding wound resolution are poorly understood; one candidate regulator is pigment epithelium-derived factor (PEDF), a secreted glycoprotein. PEDF is a potent antiangiogenic in models of pathological angiogenesis and a promising cancer and cardiovascular disease therapeutic, but little is known about its physiological function. To examine the roles of PEDF in physiological wound repair, we used a reproducible model of excisional skin wound healing in BALB/c mice. We show that PEDF is abundant in unwounded and healing skin, is produced primarily by dermal fibroblasts, binds to resident microvascular endothelial cells, and accumulates in dermal ECM and epidermis. PEDF transcript and protein levels were low during the inflammatory and proliferative phases of healing but increased in quantity and colocalization with microvasculature during wound resolution. Local antibody inhibition of endogenous PEDF delayed vessel regression and collagen maturation during the remodeling phase. Treatment of wounds with intradermal injections of exogenous, recombinant PEDF inhibited nascent angiogenesis by repressing endothelial proliferation, promoted vascular integrity and function, and increased collagen maturity. These results demonstrate that PEDF contributes to the resolution of healing wounds by causing regression of immature blood vessels and stimulating maturation of the vascular microenvironment, thus promoting a return to tissue homeostasis after injury. PMID:26163443

Evaluation of dermal wound healing activity of synthetic peptide SVVYGLR.

PubMed

Uchinaka, Ayako; Kawaguchi, Naomasa; Ban, Tsuyoshi; Hamada, Yoshinosuke; Mori, Seiji; Maeno, Yoshitaka; Sawa, Yoshiki; Nagata, Kohzo; Yamamoto, Hirofumi

2017-09-23

SVVYGLR peptide (SV peptide) is a 7-amino-acid sequence with angiogenic properties that is derived from osteopontin in the extracellular matrix and promotes differentiation of fibroblasts to myofibroblast-like cells and the production of collagen type Ⅲ by cardiac fibroblasts. However, the effects of SV peptide on dermal cells and tissue are unknown. In this study, we evaluated the effects of this peptide in a rat model of dermal wound healing. The synthetic SV peptide was added to dermal fibroblasts or keratinocytes, and their cellular motility was evaluated. In an in vivo wound healing exeriment, male rats aged 8 weeks were randomly assigned to the SV peptide treatment, non-treated control, or phosphate-buffered saline (PBS) groups. Wound healing was assessed by its repair rate and histological features. Scratch assay and cell migration assays using the Chemotaxicell method showed that SV peptide significantly promoted the cell migration in both fibroblasts and keratinocytes. In contrast the proliferation potency of these cells was not affected by SV peptide. In the rat model, wound healing progressed faster in the SV peptide-treated group than in the control and PBS groups. The histopathological analyses showed that the SV peptide treatment stimulated the migration of fibroblasts to the wound area and increased the number of myofibroblasts. Immunohistochemical staining showed a marked increase of von Willebland factor-positive neomicrovessels in the SV peptide-treated group. In conclusion, SV peptide has a beneficial function to promote wound healing by stimulating granulation via stimulating angiogenesis, cell migration, and the myofibroblastic differentiation of fibroblasts. Copyright © 2017 Elsevier Inc. All rights reserved.

Heterogeneous Pathology of Melasma and Its Clinical Implications.

PubMed

Kwon, Soon-Hyo; Hwang, Young-Ji; Lee, Soo-Keun; Park, Kyoung-Chan

2016-05-26

Melasma is a commonly acquired hypermelanosis that affects sun-exposed areas of the skin, with frequent facial involvement. Its histologic manifestations are evident in the epidermis, extracellular matrix, and dermis. In addition to epidermal pigmentation, pathologic findings of melasma include extracellular matrix abnormality, especially solar elastosis. The disrupted basement membrane has been described in melasma with variable incidences. In the dermis, an increase in vascularity and an increase in the number of mast cells were observed, indicating that dermal factors have critical roles in the pathogenesis of melasma, despite the fact that melasma is characterized by epidermal hyperpigmentation. This review discusses such histologic characteristics of melasma, with consideration to their implications for melasma treatment.

Heterogeneous Pathology of Melasma and Its Clinical Implications

PubMed Central

Kwon, Soon-Hyo; Hwang, Young-Ji; Lee, Soo-Keun; Park, Kyoung-Chan

2016-01-01

Melasma is a commonly acquired hypermelanosis that affects sun-exposed areas of the skin, with frequent facial involvement. Its histologic manifestations are evident in the epidermis, extracellular matrix, and dermis. In addition to epidermal pigmentation, pathologic findings of melasma include extracellular matrix abnormality, especially solar elastosis. The disrupted basement membrane has been described in melasma with variable incidences. In the dermis, an increase in vascularity and an increase in the number of mast cells were observed, indicating that dermal factors have critical roles in the pathogenesis of melasma, despite the fact that melasma is characterized by epidermal hyperpigmentation. This review discusses such histologic characteristics of melasma, with consideration to their implications for melasma treatment. PMID:27240341

Molecular basis of retinol anti-ageing properties in naturally aged human skin in vivo.

PubMed

Shao, Y; He, T; Fisher, G J; Voorhees, J J; Quan, T

2017-02-01

Retinoic acid has been shown to improve the aged-appearing skin. However, less is known about the anti-ageing effects of retinol (ROL, vitamin A), a precursor of retinoic acid, in aged human skin in vivo. This study aimed to investigate the molecular basis of ROL anti-ageing properties in naturally aged human skin in vivo. Sun-protected buttock skin (76 ± 6 years old, n = 12) was topically treated with 0.4% ROL and its vehicle for 7 days. The effects of topical ROL on skin epidermis and dermis were evaluated by immunohistochemistry, in situ hybridization, Northern analysis, real-time RT-PCR and Western analysis. Collagen fibrils nanoscale structure and surface topology were analysed by atomic force microscopy. Topical ROL shows remarkable anti-ageing effects through three major types of skin cells: epidermal keratinocytes, dermal endothelial cells and fibroblasts. Topical ROL significantly increased epidermal thickness by stimulating keratinocytes proliferation and upregulation of c-Jun transcription factor. In addition to epidermal changes, topical ROL significantly improved dermal extracellular matrix (ECM) microenvironment; increasing dermal vascularity by stimulating endothelial cells proliferation and ECM production (type I collagen, fibronectin and elastin) by activating dermal fibroblasts. Topical ROL also stimulates TGF-β/CTGF pathway, the major regulator of ECM homeostasis, and thus enriched the deposition of ECM in aged human skin in vivo. 0.4% topical ROL achieved similar results as seen with topical retinoic acid, the biologically active form of ROL, without causing noticeable signs of retinoid side effects. 0.4% topical ROL shows remarkable anti-ageing effects through improvement of the homeostasis of epidermis and dermis by stimulating the proliferation of keratinocytes and endothelial cells, and activating dermal fibroblasts. These data provide evidence that 0.4% topical ROL is a promising and safe treatment to improve the naturally aged human skin. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Gelatin/Carboxymethyl chitosan based scaffolds for dermal tissue engineering applications.

PubMed

Agarwal, Tarun; Narayan, Rajan; Maji, Somnath; Behera, Shubhanath; Kulanthaivel, Senthilguru; Maiti, Tapas Kumar; Banerjee, Indranil; Pal, Kunal; Giri, Supratim

2016-12-01

The present study delineates the preparation, characterization and application of gelatin-carboxymethyl chitosan scaffolds for dermal tissue engineering. The effect of carboxymethyl chitosan and gelatin ratio was evaluated for variations in their physico-chemical-biological characteristics and drug release kinetics. The scaffolds were prepared by freeze drying method and characterized by SEM and FTIR. The study revealed that the scaffolds were highly porous with pore size ranging between 90 and 170μm, had high water uptake (400-1100%) and water retention capacity (>300%). The collagenase mediated degradation of the scaffolds was dependent on the amount of gelatin present in the formulation. A slight yet significant variation in their biological characteristics was also observed. All the formulations supported adhesion, spreading, growth and proliferation of 3T3 mouse fibroblasts. The cells seeded on the scaffolds also demonstrated expression of collagen type I, HIF1α and VEGF, providing a clue regarding their growth and proliferation along with potential to support angiogenesis during wound healing. In addition, the scaffolds showed sustained ampicillin and bovine serum albumin release, confirming their suitability as a therapeutic delivery vehicle during wound healing. All together, the results suggest that gelatin-carboxymethyl chitosan based scaffolds could be a suitable matrix for dermal tissue engineering applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Generation of hyaline cartilaginous tissue from mouse adult dermal fibroblast culture by defined factors

PubMed Central

Hiramatsu, Kunihiko; Sasagawa, Satoru; Outani, Hidetatsu; Nakagawa, Kanako; Yoshikawa, Hideki; Tsumaki, Noriyuki

2011-01-01

Repair of cartilage injury with hyaline cartilage continues to be a challenging clinical problem. Because of the limited number of chondrocytes in vivo, coupled with in vitro de-differentiation of chondrocytes into fibrochondrocytes, which secrete type I collagen and have an altered matrix architecture and mechanical function, there is a need for a novel cell source that produces hyaline cartilage. The generation of induced pluripotent stem (iPS) cells has provided a tool for reprogramming dermal fibroblasts to an undifferentiated state by ectopic expression of reprogramming factors. Here, we show that retroviral expression of two reprogramming factors (c-Myc and Klf4) and one chondrogenic factor (SOX9) induces polygonal chondrogenic cells directly from adult dermal fibroblast cultures. Induced cells expressed marker genes for chondrocytes but not fibroblasts, i.e., the promoters of type I collagen genes were extensively methylated. Although some induced cell lines formed tumors when subcutaneously injected into nude mice, other induced cell lines generated stable homogenous hyaline cartilage–like tissue. Further, the doxycycline-inducible induction system demonstrated that induced cells are able to respond to chondrogenic medium by expressing endogenous Sox9 and maintain chondrogenic potential after substantial reduction of transgene expression. Thus, this approach could lead to the preparation of hyaline cartilage directly from skin, without generating iPS cells. PMID:21293062

Plasma Rich in Growth Factors Inhibits Ultraviolet B Induced Photoageing of the Skin in Human Dermal Fibroblast Culture.

PubMed

Anitua, Eduardo; Pino, Ander; Orive, Gorka

Ultraviolet irradiation is able to deeply penetrate into the dermis and alter fibroblast structure and function, leading to a degradation of the dermal extracellular matrix. The regenerative effect of plasma rich in growth factors (PRGF) on skin ageing was investigated using UVB photo-stressed human dermal fibroblasts as an in vitro culture model. PRGF was assessed over the main indicative features of ultraviolet B irradiation, including ROS formation, cell viability and death detection, apoptosis/ necrosis analysis and biosynthetic activity measurement. Four different UV irradiation protocols were tested in order to analyze the beneficial effects of PRGF. Ultraviolet irradiation exhibited a dose dependent cytotoxicity and dose of 400mJ/cm2 was selected for subsequent experiments. PRGF increased the cell viability and decreased the cell death comparing to the non-treated group. The apoptosis and necrosis were significantly lower in PRGF treated fibroblasts. ROS production after UV irradiation was significantly reduced in the presence of PRGF. Procollagen type I, hyaluronic acid and TIMP-1 levels were higher in the when treated with PRGF. This preliminary in vitro study suggests that PRGF is able to prevent UVB derived photooxidative stress and to diminish the cell damage caused by ultraviolet irradiation.

Improvement of the in vivo cellular repopulation of decellularized cardiovascular tissues by a detergent-free, non-proteolytic, actin-disassembling regimen.

PubMed

Assmann, Alexander; Struß, Marc; Schiffer, Franziska; Heidelberg, Friederike; Munakata, Hiroshi; Timchenko, Elena V; Timchenko, Pavel E; Kaufmann, Tim; Huynh, Khon; Sugimura, Yukiharu; Leidl, Quentin; Pinto, Antonio; Stoldt, Volker R; Lichtenberg, Artur; Akhyari, Payam

2017-12-01

Low immunogenicity and high repopulation capacity are crucial determinants for the functional and structural performance of acellular cardiovascular implants. The present study evaluates a detergent-free, non-proteolytic, actin-disassembling regimen (BIO) for decellularization of heart valve and vessel grafts, particularly focusing on their bio-functionality. Rat aortic conduits (rAoC; n = 89) and porcine aortic valve samples (n = 106) are decellularized using detergents (group DET) or the BIO regimen. BIO decellularization results in effective elimination of cellular proteins and significantly improves removal of DNA as compared with group DET, while the extracellular matrix (ECM) structure as well as mechanical properties are preserved. The architecture of rAoC in group BIO allows for improved bio-functionalization with fibronectin (FN) in a standardized rat implantation model: BIO treatment significantly increases speed and amount of autologous medial cellular repopulation in vivo (p < 0.001) and decreases the formation of hyperplastic intima (p < 0.001) as compared with FN-coated DET-decellularized grafts. Moreover, there are no signs of infiltration with inflammatory cells. The present biological, detergent-free, non-proteolytic regimen balances effective decellularization and ECM preservation in cardiovascular grafts, and provides optimized bio-functionality. Additionally, this study implies that the actin-disassembling regimen may be a promising approach for bioengineering of acellular scaffolds from other muscular tissues, as for example myocardium or intestine. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Kindler syndrome.

PubMed

Ashton, G H S

2004-03-01

Kindler syndrome is a rare, autosomal recessive skin fragility disorder characterized by blistering in infancy, followed by photosensitivity and progressive poikiloderma. Ultrastructural examination reveals marked basement membrane reduplication and variable levels of cleavage at the dermal-epidermal junction. The molecular pathology underlying Kindler syndrome has recently been shown to involve loss-of-function mutations in a novel gene, KIND1, encoding kindlin-1. Immunofluorescence, gene expression and cell biology studies have shown that kindlin-1 is expressed mainly in basal keratinocytes and plays a role in the attachment of the actin cytoskeleton via focal contacts to the extracellular matrix. Thus, Kindler syndrome is the first genodermatosis caused by a defect in actin-extracellular matrix linkage rather than the classic keratin-extracellular matrix linkage underlying the pathology of other inherited skin fragility disorders such as epidermolysis bullosa. This article reviews the clinical features as well as the molecular and cellular pathology of Kindler syndrome and highlights the importance of the new protein, kindlin-1, in cell-matrix adhesion and its intriguing link to photosensitivity.

Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS)

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-13-1-0309 TITLE: Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts...plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Thomas L. Smith, PhD RECIPIENT: Wake Forest University Health Sciences

The levels and kinetics of oxygen tension detectable at the surface of human dermal fibroblast cultures.

PubMed

Tokuda, Y; Crane, S; Yamaguchi, Y; Zhou, L; Falanga, V

2000-03-01

Low oxygen tension has recently been shown to stimulate cell growth and clonal expansion, as well as synthesis and transcription of certain growth factors and extracellular matrix components. These results have been obtained by exposing cell cultures to a hypoxic environment. Using an oxygen probe, we have now studied how experimental conditions affect the oxygen tension detectable at the cell surface. Dissolved oxygen tension was directly related to the height of the medium above the cell surface (r = 0.8793, P = 0.021), but was constant when no cells were present in the flask (r = -0. 9732, P = 0.001). In both human dermal fibroblasts and NIH/3T3 cultures, oxygen tension decreased linearly as cell density increased (r = -0.835, P < 0.0001; r = -0.916, P < 0.0001, respectively). When human dermal fibroblasts were exposed to 2% O(2), maximum hypoxic levels (0 mmHg) were achieved within approximately 15 min, and the recovery time was within a similar time frame. The addition of rotenone, an inhibitor of cellular respiration, blocked this decrease in oxygen tension at the cell surface, suggesting that cellular consumption of oxygen is responsible for the decline. Finally, we examined the cell-surface oxygen tension in control and acutely wounded human skin equivalents (HSE), consisting of a keratinocyte layer over a type I collagen matrix containing fibroblasts. We found that oxygen tension dropped significantly (P < 0.0001) in acutely wounded areas of HSE as compared to unwounded areas of HSE and that this drop was prevented by the addition of mitomycin C. These results indicate that cell-surface oxygen tension is indirectly related to cell density, and that the amount of detectable oxygen at the cell surface is a function of cell density, the oxygen tension in the incubator, and increased cellular activity, as occurs after injury. Copyright 2000 Wiley-Liss, Inc.