hyaluronate periarticular injections: Topics by Science.gov

Sample records for hyaluronate periarticular injections

Will a single periarticular lidocaine-corticosteroid injection improve the clinical efficacy of intraarticular hyaluronic acid treatment of symptomatic knee osteoarthritis?

PubMed

Ertürk, Cemil; Altay, Mehmet Akif; Altay, Nuray; Kalender, Ali Murat; Öztürk, İbrahim Avşin

2016-11-01

A local injection of corticosteroid-lidocaine into the periarticular soft tissue structures is used commonly for rapid pain relief. It is hypothesized that knee pain associated with knee osteoarthritis would be relieved quickly and effectively in patients receiving intraarticular hyaluronic acid combined with a periarticular lidocaine-corticosteroid injection. To test this hypothesis, the clinical effect of the combined treatment with hyaluronic acid injection alone in patients with symptomatic knee osteoarthritis as compared in this prospective single-blinded randomized trial. This study included 70 patients. Group 1 (n = 35) received intraarticular hyaluronic acid injections only, whereas group 2 (n = 35) received intraarticular hyaluronic acid injections combined with a single local injection of corticosteroid-lidocaine. Injections were administered to the most painful areas of the anterior or posterior medial condyle of the femur or tibia. The outcome was measured by independent assessors (blinded to treatment) using a linear VAS pain scale and WOMAC and HSS knee scores. Assessments were performed at baseline and at 1, 3, 6, 12, 26, and 52 weeks. During the first 3 weeks, group 2 patients showed significantly better all scores than did group 1 patients (p < 0.01). However, no significant differences were detected at 6, 12, 26 or 52 weeks (n.s.). The combined treatment may lead to earlier pain relief compared with intraarticular hyaluronic acid alone in patients with knee osteoarthritis and can be considered a useful adjunctive treatment modality. This combined method may provide early return to patient's daily activity. Therapeutic study, Level I.
Fluoroscopically Guided Sacroiliac Joint Injections: Comparison of the Effects of Intraarticular and Periarticular Injections on Immediate and Short-Term Pain Relief.

PubMed

Nacey, Nicholas C; Patrie, James T; Fox, Michael G

2016-11-01

The purpose of this study was to determine whether intraarticular sacroiliac joint injections provide greater immediate and short-term pain relief than periarticular sacroiliac joint injections do. The records of all fluoroscopically guided sacroiliac joint injections performed over a 4-year period were identified. Patients who received an injection of 0.5 mL of bupivacaine and 0.5 mL (20 mg) of triamcinolone and who had preinjection, immediate, and 1-week postinjection pain scores (0-10 numeric scale) were included. Images from the procedures were retrospectively reviewed by two musculoskeletal radiologists to determine intraarticular or periarticular administration of the injection with discrepancies resolved by consensus. One hundred thirteen injections in 99 patients (65 women, 34 men; mean age, 59.4 years) met the inclusion criteria. There were 55 intraarticular and 58 periarticular injections. The mean preinjection, immediate, and 1-week postinjection pain scores for the intraarticular injections were 6.0, 1.6, and 4.1 and for the periarticular injections were 6.1, 2.0, and 4.2. The mean immediate and 1-week postinjection pain reduction were statistically significant in both groups (p < 0.001). After adjustment for age, sex, preinjection pain score, time of year, and indication for injection, no significant difference in the preinjection to immediately postinjection change in pain between intraarticular and periarticular injections (mean change, 0.37; p = 0.319) or in the preinjection to 1-week postinjection change in pain (mean change, 0.06; p = 0.888) was noted. The mean fluoroscopy times were 42.4 seconds for intraarticular injections and 60.5 seconds for periarticular injections (p = 0.32). Although both intraarticular and periarticular sacroiliac joint injections provide statistically significant immediate and 1-week postinjection pain relief, no significant difference in the degree of pain relief achieved with intraarticular and periarticular injections
Intra-operative periarticular multimodal injection in total knee arthroplasty: a local hospital experience in Hong Kong.

PubMed

Fan, J Ch

2018-04-01

Data from a local report revealed the superior outcome of regional anaesthesia and analgesia compared with general anaesthesia and intravenous patient-controlled analgesia in total knee arthroplasty. This retrospective study aimed to assess the efficacy of intra-operative periarticular multimodal injection in improving postoperative pain and reducing morphine consumption with patient-controlled analgesia after total knee arthroplasty in patients with knee osteoarthritis. From July 2005 to May 2009, 213 total knee arthroplasties without intra-operative periarticular multimodal injection (control group) were performed at a local hospital. From June 2009 to December 2012, 185 total knee arthroplasties were performed with intra-operative periarticular multimodal injection (cocktail group). The inclusion criteria were osteoarthritis of the knee, single method of anaesthesia (general or neuraxial), simple total knee arthroplasty without any metal augmentation or constraint, and postoperative patient-controlled analgesia. Postoperative patient-controlled morphine doses were compared. A total of 152 total knee arthroplasties were recruited to the cocktail group, and 89 to the control group. Duration of tourniquet application and preoperative knee score did not significantly correlate with morphine consumption by patient-controlled analgesia. Multimodal injection significantly decreased such consumption for 36 h. When injection was separately analysed for general and neuraxial anaesthesia, the effect lasted for 42 h and 24 h, respectively. Intra-operative periarticular multimodal injection decreased morphine consumption for up to 42 h postoperatively.
Postoperative epidural analgesia compared with intraoperative periarticular injection for pain control following total knee arthroplasty under spinal anesthesia: a randomized controlled trial.

PubMed

Tsukada, Sachiyuki; Wakui, Motohiro; Hoshino, Akiho

2014-09-03

Although epidural analgesia has been used for postoperative pain control after total knee arthroplasty, its usefulness is being reevaluated because of possible adverse effects. Recent studies have proven the efficacy of periarticular analgesic injection and its low prevalence of adverse effects. The present study compares the clinical efficacies of epidural analgesia and periarticular injection after total knee arthroplasty. This is a prospective, single-center, randomized controlled trial involving patients scheduled for unilateral total knee arthroplasty. One hundred and eleven patients were randomly assigned to periarticular injection or epidural analgesia groups. All patients were managed with spinal anesthesia. The surgical technique and postoperative medication protocol were identical in both groups. The primary outcome was postoperative pain at rest, quantified as the area under the curve of the scores on a visual analog pain scale to seventy-two hours postoperatively. The Student t test and chi-square test were used to compare the data between groups. In the intention-to-treat analysis, the periarticular injection group had a significantly lower area under the curve for pain score at rest (788.0 versus 1065.9; p = 0.0059). In the periarticular injection group, the mean knee flexion angle was small but significantly better at postoperative day 1 (64.2° versus 54.6°; p = 0.0072) and postoperative day 2 (70.3° versus 64.6°; p = 0.021) than in the epidural analgesia group. The incidence of nausea at postoperative day 1 was significantly lower in the periarticular injection group (4.0% versus 44.3%; p < 0.0001). Transient peroneal nerve palsy was frequently seen in the periarticular injection group (12.0% versus 1.6%; p = 0.026). Compared with epidural analgesia, periarticular injection offers better postoperative pain relief, earlier recovery of knee flexion angle, and lower incidence of nausea. Care should be taken to avoid transient peroneal nerve palsy
The safety of peri-articular local anaesthetic injection for patients undergoing total knee replacement with autologous blood transfusion: a randomised trial.

PubMed

Wallace, D F; Emmett, S R; Kang, K K; Chahal, G S; Hiskens, R; Balasubramanian, S; McGuinness, K; Parsons, H; Achten, J; Costa, M L

2012-12-01

Intra-operative, peri-articular injection of local anaesthesia is an increasingly popular way of controlling pain following total knee replacement. At the same time, the problems associated with allogenic blood transfusion have led to interest in alternative methods for managing blood loss after total knee replacement, including the use of auto-transfusion of fluid from the patient's surgical drain. It is safe to combine peri-articular infiltration with auto-transfusion from the drain. We performed a randomised clinical trial to compare the concentration of local anaesthetic in the blood and in the fluid collected in the knee drain in patients having either a peri-articular injection or a femoral nerve block. Clinically relevant concentrations of local anaesthetic were found in the fluid from the drains of patients having peri-articular injections (4.92 μg/ml (sd 3.151)). However, none of the patients having femoral nerve blockade had detectable levels. None of the patients in either group had clinically relevant concentrations of local anaesthetic in their blood after re-transfusion. The evidence from this study suggests that it is safe to use peri-articular injection in combination with auto-transfusion of blood from peri-articular drains during knee replacement surgery.
The AAHKS Clinical Research Award: Liposomal Bupivacaine and Periarticular Injection Are Not Superior to Single-Shot Intra-articular Injection for Pain Control in Total Knee Arthroplasty.

PubMed

Jain, Rajesh K; Porat, Manny D; Klingenstein, Greg G; Reid, Jeremy J; Post, Robert E; Schoifet, Scott D

2016-09-01

Intraoperative injections can help reduce early postoperative pain in total knee arthroplasty. We proposed that liposomal bupivacaine would not be superior to more common and cheaper injections. A single-blinded prospective randomized study with 207 consecutive patients was completed. Patients were randomized to treatment with periarticular liposomal bupivacaine injection, periarticular injection of bupivacaine/morphine, or intra-articular injection of bupivacaine/morphine at the conclusion of the procedure. Postoperative visual analog pain scores and narcotic consumption were recorded and analyzed. There was no significant difference in postoperative visual analog pain scores or narcotic consumption among the 3 study groups. Intra-articular injection of bupivacaine and morphine is as effective for postoperative pain control in total knee arthroplasty as periarticular bupivacaine/morphine injection and liposomal bupivacaine. Use of liposomal bupivacaine in total knee arthroplasty is costly and not justified. Copyright © 2016 Elsevier Inc. All rights reserved.
Development and validation of a periarticular injection technique of the sacroiliac joint in horses.

PubMed

Engeli, E; Haussler, K K; Erb, H N

2004-05-01

Sacroiliac joint osteoarthritis has been recognised as a significant cause of poor performance in competition and racehorses. Reliable diagnostic tools are currently lacking. The diagnosis has been based typically on exclusion of other possible causes of poor performance, back pain and hindlimb lameness. To develop a safe, reliable and minimally invasive periarticular or intra-articular injection technique of potential use for diagnosis and therapy of sacroiliac joint disease in horses. Twenty-six horses were used to develop and assess a medial approach to the sacroiliac joint with a 15 gauge, 25 cm long spinal needle. In Part I, the cadaveric study, the spinal needle was introduced cranial to the contralateral tuber sacrale and advanced along the medial aspect of the ipsilateral iliac wing until the dorsal surface of the sacrum was encountered. One ml methylene blue (MB) was injected in both sacroiliac joint regions of the sacropelvic specimens. The location of MB-stained tissues relative to the sacroiliac joints was recorded after dissection and disarticulation of the sacroiliac joint. In Part II, the in vivo study, 18 horses were used to validate the in vivo application of the sacroiliac joint injection technique. Horses were restrained in stocks and sedated in preparation for needle placement. One ml MB was injected bilaterally prior to euthanasia. Stained tissues were identified and recorded at necropsy. Successful joint injections were characterised as having MB located intra-articularly or < or = 2 cm periarticularly from the sacroiliac joint margin and localised to the middle or caudal third of the sacroiliac joint. Intra-articular MB was not observed in any specimen. However, MB-stained tissue was identified periarticularly in all injection sites (n = 48). Based on the predetermined success criteria, 96% of the methylene blue depots were located at the middle or caudal third of the sacroiliac joint. Dye-stained tissue was located < or = 2 cm from the
The effect of intra-articular hyaluronate and tramadol injection on patients with adhesive capsulitis of the shoulder.

PubMed

Kim, Kyung-Hee; Suh, Jung-Woo; Oh, Ki Young

2017-08-03

Local administration of opioids causes effective analgesia without adverse effects related to the central nervous system. After the beneficial demonstration of peripheral opioid receptors in joint synovia, intra-articular opioid injections were used for pain treatment. Clinical studies have reported the safety and efficacy of hyaluronate injection in the shoulder joint of patients with osteoarthritis, periarthritis, rotator cuff tears, and adhesive capsulitis. To estimate the efficacy of intra-articular hyaluronate and tramadol injection for adhesive capsulitis of the shoulder compared with that of intra-articular hyaluronate injection alone. Thirty patients with adhesive capsulitis of the shoulder were randomized to the hyaluronate group (n= 16) or the tramadol group (n= 14). Hyaluronate group members were administered five weekly intra-articular hyaluronate injections; tramadol group members were administered three weekly intra-articular hyaluronate and tramadol injections and then two weekly intra-articular injections of hyaluronate. Visual Analog Scale (VAS), passive range of motion (PROM) of the shoulder joint, and Shoulder Pain and Disability Index (SPADI) scores were assessed at baseline and weeks 1, 2, 3, 4, and 6 after the initial injection. A significant improvement was observed in VAS, PROM, and SPADI scores between time points in both groups. In comparison in both groups at weeks 1 and 2 after the initial injection the VAS scores of the tramadol group were significantly lower than those of the hyaluronate group. Intra-articular hyaluronate with tramadol showed more rapid and strong analgesic effects than intra-articular hyaluronate alone and did not induce any adverse effects.
Knee Viscosupplementation: Cost-Effectiveness Analysis between Stabilized Hyaluronic Acid in a Single Injection versus Five Injections of Standard Hyaluronic Acid.

PubMed

Estades-Rubio, Francisco J; Reyes-Martín, Alvaro; Morales-Marcos, Victor; García-Piriz, Mercedes; García-Vera, Juan J; Perán, Macarena; Marchal, Juan A; Montañez-Heredia, Elvira

2017-03-17

Given the wide difference in price per vial between various presentations of hyaluronic acid, this study seeks to compare the effectiveness and treatment cost of stabilized hyaluronic acid (NASHA) in a single injection with standard preparations of hyaluronic acid (HA) in five injections in osteoarthritis (OA) of the knee. Fifty-four patients with knee osteoarthritis (Kellgren-Lawrence Grade II and III) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score greater than 7, with a homogeneous distribution of age, sex, BMI, and duration of disease, were included in this study. Patients were randomized into two groups: Group I was treated with NASHA (Durolane ® ) and Group II with HA (Go-ON ® ). Patient's evolution was followed up at the 1st, 2nd, 4th, 8th, 12th, and 26th week after treatment. A statistically significant improvement in WOMAC score was observed for patients treated with NASHA versus those who received HA at Week 26. In addition, the need for analgesia was significantly reduced at Week 26 in the NASHA-treated group. Finally, the economic analysis showed an increased cost of overall treatment with HA injections. Our data support the use of the NASHA class of products in the treatment of knee OA.
[Crosslinking sodium hyaluronate gel with different ratio of molecular weight for subcutaneous injection: animal experimental study and clinical trials subcutaneous injection].

PubMed

Ran, Weizhi; Wang, Xiaoli; Hu, Yuefei; Gao, Songying; Yang, Yahong; Sun, Jian; Sun, Shuming; Liu, Zhongmei; Wang, Jiangling

2015-05-01

To investigate the biocompatibility and degradation rate of crosslinking sodium hyaluronate gel with different ratio of molecular weight, so as to choose the effective, safe and totally degraded hyaluronate gel for aesthetic injection. (1) Compound colloid was formed by cross-linking the divinyl sulphone and sodium hyaluronate with different molecular weight (4 x 10(5), 8 x 10(5), 10 x 10(5), 12 x 10(5)). (2) Healthy level KM mice was randomly divided into two groups to receive hyaluronic acid gel or liquid injection. Each group was subdivided into three subgroup to receive hyaluronic acid with different molecular weight. The biocompatibility and degradation rate, of hyaluronate were observed at 7, 90, 180 days after injection. At the same time, different molecular weight of sodium hyaluronate gel is sealed or exposed respectively under the low temperature preservation to observe its natural degradation rate. (3) The most stable colloid was selected as aesthetic injector for volunteers to observe the aesthetic effect. The sodium hyaluronate gel with molecular of 4 x 10(5) was completely degraded 90 days later. The sodium hyaluronate gel with molecular of 8 x 10(5) was completely degraded 180 days later. The sodium hyaluronate gel with molecular of 10 x 10(5) was degraded to 90.0% after 180 days. The sodium hyaluronate liquid can be degraded completely within 7 days. The colloid could be kept for at least 12 months when sealed under low temperature, but was totally degraded when exposed for I d. Sodium hyaluronate gel with molecular 10 x 10(5) was confirmed to be kept for at least 6 months in animal experiment and clinical trials. Under the same condition of material ratio, the higher the molecular weight is, the lower the degradation rate is. But the liquidity of gel is not good for injection when molecular weight is too large. It suggests that Sodium hyaluronate gel with molecular 10 x 10(5) maybe the best choice in cosmetic injections.
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.
Human glans penis augmentation using injectable hyaluronic acid gel.

PubMed

Kim, J J; Kwak, T I; Jeon, B G; Cheon, J; Moon, D G

2003-12-01

Although augmentation phalloplasty is not an established procedure, some patients still need enlargement of their penis. Current penile augmentation is girth enhancement of penile body by dermofat graft. We performed this study to identify the efficacy and the patient's satisfaction of human glans penis augmentation with injectable hyaluronic acid gel. In 100 patients of subjective small penis (Group I) and 87 patients of small glans after dermofat graft (Group II), 2 cm(3) of hyaluronic acid gel was injected into the glans penis, subcutaneously. At 1 y after injection, changes of glandular diameter were measured by tapeline. Patient's visual estimation of glandular size (Gr 0-4) and patient's satisfaction (Grade (Gr) 0-4) were evaluated, respectively. Any adverse reactions were also evaluated. The mean age of patients was 42.2 (30-70) y in Group I and 42.13 (28-61) y in Group II. The maximal glandular circumference was significantly increased compared to basal circumference of 9.13+/-0.64 cm in Group I (P<0.01) and 9.49+/-1.05 cm in Group II (P<0.01) at 1 y after injection. Net increase of maximal glandular circumference after glans augmentation was 14.93+/-0.80 mm in Group I and 14.78+/-0.89 mm in Group II. In patient's visual estimation, more than 50% of injected volume was maintained in 95% of Group 1 and 100% of Group II. The percentage of postoperative satisfaction (Gr 4, 5) was 77% in Group 1 and 69% in Group II. There was no abnormal reaction in area feeling, texture, and color. In most cases, initial discoloration by glandular swelling recovered to normal within 2 weeks. There were no signs of inflammation and no serious adverse reactions in all cases. These results suggest that injectable hyaluronic acid gel is a safe and effective material for augmentation of glans penis.
Intraocular Pressure Increases After Intraarticular Knee Injection With Triamcinolone but Not Hyaluronic Acid.

PubMed

Taliaferro, Kevin; Crawford, Alexander; Jabara, Justin; Lynch, Jonathan; Jung, Edward; Zvirbulis, Raimonds; Banka, Trevor

2018-07-01

Intraarticular steroid injections are a common first-line therapy for severe osteoarthritis, which affects an estimated 27 million people in the United States. Although topical, oral, intranasal, and inhalational steroids are known to increase intraocular pressure in some patients, the effect of intraarticular steroid injections on intraocular pressure has not been investigated, to the best of our knowledge. If elevated intraocular pressure is sustained for long periods of time or is of sufficient magnitude acutely, permanent loss of the visual field can occur. How does intraocular pressure change 1 week after an intraarticular knee injection either with triamcinolone acetonide or hyaluronic acid? A nonrandomized, nonblinded prospective cohort study was conducted at an outpatient, ambulatory orthopaedic clinic. This study compared intraocular pressure elevation before and 1 week after intraarticular knee injection of triamcinolone acetonide versus hyaluronic acid for management of primary osteoarthritis of the knee. Patients self-selected to be injected in their knee with either triamcinolone acetonide or hyaluronic acid before being informed of the study. The primary endpoint was intraocular pressure elevation of ≥ 7 mm Hg 1 week after injection. This cutoff is determined as the minimum significant pressure change in the ophthalmology literature recognized as an intermediate responder to steroids. Intraocular pressure was measured using a handheld Tono-Pen® applanation device. This device is frequently used in intraocular pressure measurement in clinical and research settings; 10 sequential measurements are obtained and averaged with a confidence interval. Only measurements with a 95% confidence interval were used. Over a 6-month period, a total of 96 patients were approached to enroll in the study. Sixty-two patients out of 96 approached (65%) agreed. Thirty-one (50%) were injected with triamcinolone and 31 (50%) were injected with hyaluronic acid. Patients
Is There a Difference in Intra-Articular Injections of Corticosteroids, Hyaluronate, or Placebo for Temporomandibular Osteoarthritis?

PubMed

Liu, Yan; Wu, Jiashun; Fei, Wei; Cen, Xiao; Xiong, Yi; Wang, Shasha; Tang, Yaling; Liang, Xinhua

2018-03-01

Corticosteroids are widely used for treatment of temporomandibular joint (TMJ) osteoarthritis (OA). This study investigated the effects of corticosteroids on TMJOA compared with placebo or hyaluronate. The authors designed and implemented a systematic review and meta-analysis to compare the effects of intra-articular injection of corticosteroid, hyaluronate, or placebo for patients with TMJOA. The authors searched related randomized controlled studies electronically in multiple English- and Chinese-language electronic databases. The predictor variable was intra-articular injection with corticosteroid, hyaluronate, or placebo. Primary outcome variables were pain intensity and maximal mouth opening. Other variables included success rate and adverse events. Meta-analyses were performed with Rev Man 5.3. Eight studies met the inclusion criteria. Meta-analysis showed that corticosteroid injections after arthrocentesis were superior to placebo in relieving pain as assessed with the visual analog scale (mean difference [MD], -0.74; 95% confidence interval [CI], -1.34 to -0.13; P = .02; I 2 = 0%) in the long-term, but was inferior in increasing maximal mouth opening (MD, -2.06; 95% CI, -2.76 to -1.36; P < .00001; I 2 = 28%). Although corticosteroid and hyaluronate injections without arthrocentesis decreased pain and improved maximal mouth opening, the corticosteroid group had a significantly lower success rate (odds ratio = 0.41; 95% CI, 0.17-1.00; P = .05; I 2 = 0%) than the hyaluronate group in the short term. Corticosteroid injections after arthrocentesis are recommended for patients with TMJOA to relieve joint pain rather than increase maximal mouth opening. Corticosteroid and hyaluronate have marked effectiveness on TMJOA; however, hyaluronate might be the better alternative to some extent. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.
[Facial injections of hyaluronic acid-based fillers for malformations. Preliminary study regarding scar tissue improvement and cosmetic betterment].

PubMed

Franchi, G; Neiva-Vaz, C; Picard, A; Vazquez, M-P

2018-06-01

Cross-linked hyaluronic acid-based fillers have gained rapid acceptance for treating facial wrinkles, deep tissue folds and sunken areas due to aging. This study evaluates, in addition to space-filling properties, their effects on softness and elasticity as a secondary effect, following injection of 3 commercially available cross-linked hyaluronic acid-based fillers (15mg/mL, 17,5mg/mL and 20mg/mL) in patients presenting with congenital or acquired facial malformations. We started injecting gels of cross-linked hyaluronic acid-based fillers in those cases in 2013; we performed 46 sessions of injections in 32 patients, aged from 13-32. Clinical assessment was performed by the patient himself and by a plastic surgeon, 15 days after injections and 6-18 months later. Cross-linked hyaluronic acid-based fillers offered very subtle cosmetic results and supplemented surgery with a very high level of satisfaction of the patients. When injected in fibrosis, the first session enhanced softness and elasticity; the second session enhanced the volume. Cross-linked hyaluronic acid-based fillers fill sunken areas and better softness and elasticity of scar tissues. In addition to their well-understood space-filling function, as a secondary effect, the authors demonstrate that cross-linked hyaluronic acid-based fillers improve softness and elasticity of scarring tissues. Many experimental studies support our observations, showing that cross-linked hyaluronic acid stimulates the production of several extra-cellular matrix components, including dermal collagen and elastin. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
Hyaluronic Acid Gel Injection to Prevent Thermal Injury of Adjacent Gastrointestinal Tract during Percutaneous Liver Radiofrequency Ablation

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

Hasegawa, Takaaki, E-mail: hasegawat@clin.medic.mie-u.ac.jp; Takaki, Haruyuki; Miyagi, Hideki

2013-08-01

This study evaluated the safety, feasibility, and clinical utility of hyaluronic acid gel injection to separate the gastrointestinal tract from the tumor during liver radiofrequency ablation (RFA). Eleven patients with liver tumors measuring 0.9-3.5 cm (mean {+-} standard deviation, 2.1 {+-} 0.8 cm) that were adjacent to the gastrointestinal tracts received RFA after the mixture of hyaluronic acid gel and contrast material (volume, 26.4 {+-} 14.5 mL; range, 10-60 mL) was injected between the tumor and the gastrointestinal tract under computed tomographic-fluoroscopic guidance. Each tumor was separated from the gastrointestinal tract by 1.0-1.5 cm (distance, 1.2 {+-} 0.2 cm) aftermore » injection of hyaluronic acid gel, and subsequent RFA was performed without any complications in all patients. Although tumor enhancement disappeared in all patients, local tumor progression was found in a patient (9.1 %, 1 of 11) during the follow-up of 5.5 {+-} 3.2 months (range, 0.4-9.9 months). In conclusion, hyaluronic acid gel injection is a safe and useful technique to avoid thermal injury of the adjacent gastrointestinal tract during liver RFA.« less
Effectiveness of intra-articular injections of sodium hyaluronate-chondroitin sulfate in knee osteoarthritis: a multicenter prospective study.

PubMed

Rivera, Fabrizio; Bertignone, Luca; Grandi, Giancarlo; Camisassa, Roberto; Comaschi, Guido; Trentini, Diego; Zanone, Marco; Teppex, Giuseppe; Vasario, Gabriele; Fortina, Giorgio

2016-03-01

Intra-articular injection of hyaluronic acid is a well-established therapy for the treatment of knee osteoarthritis. The aim of the study was to assess the effectiveness and safety of the use of Arthrum HCS(®) (40 mg hyaluronic acid and 40 mg chondroitin sulfate in 2 mL). This was an open, multicenter, prospective study. Men or women over 40 years of age with documented knee osteoarthritis and WOMAC subscore A (severity of pain) ≥25 were enrolled. They received three weekly intra-articular injections of sodium hyaluronate 2 % and chondroitin sulfate 2 % in combination. WOMAC subscore A was assessed at 1, 3 and 6 months after the last injection. One hundred and twelve patients were included (women, 66 %). The mean (SD) WOMAC subscore A decreased from 52.1 (15.2) at inclusion to 20.5 (19.7) at month 6 (P < 0.0001). The mean subscore was already significantly decreased 1 month after the last injection at 25.7 (P < 0.0001). Pain relief and consumption of analgesic drugs, both assessed with visual analogic scale (VAS), consistently decreased. The investigators were satisfied/very satisfied as regards the therapeutic effectiveness of sodium hyaluronate-chondroitin sulfate in reducing pain (77 %), improving mobility (78 %) and reducing the consumption of analgesics (74 %). Only one adverse effect was reported by one patient (knee tumefaction). These results suggest that intra-articular injections of Arthrum HCS(®) (sodium hyaluronate plus chondroitin sulfate) in patients with knee osteoarthritis are efficient and safe. These results should be confirmed in a randomized controlled study. IV.
Efficacy of Periarticular Injection With a Long-Acting Local Analgesic in Joint Arthroplasty.

PubMed

Barrington, John W

2015-10-01

Attention to patient satisfaction is critical in today's health care environment-satisfaction surveys inform the development of hospital performance standards and can influence an institution's rankings and reimbursement. The effectiveness of postoperative pain management can affect clinical outcomes and also influence the patient's perception of the overall surgical experience. Ample clinical- trial data now exist that demonstrate the benefits of periarticular injections as part of a multimodal regimen in patients undergoing joint arthroplasty. One option that surgeons now use widely is bupivacaine liposome injectable suspension (EXPAREL®, Pacira Pharmaceuticals, Inc), a long-acting local analgesic that the orthopedic surgeon can administer intraoperatively. The US Food and Drug Administration has approved liposomal bupivacaine for injection into the surgical site to produce postsurgical analgesia. The safety and efficacy of liposomal bupivacaine has been demonstrated in clinical studies in multiple types of surgical procedure, including double-blind, randomized, controlled clinical trials that involved over 1300 patients. In a case-control study comparing clinical and economic parameters before and after the introduction of liposomal bupivacaine as a component of the multimodal perioperative pain regimen for total joint arthroplasty, liposomal bupivacaine provided improved overall pain scores, an increase in patients reporting a pain score of 0, increased patient satisfaction, decreased length of stay, and a decrease in overall costs.
Impact of Clinical Practice Guidelines on Use of Intra-Articular Hyaluronic Acid and Corticosteroid Injections for Knee Osteoarthritis.

PubMed

Bedard, Nicholas A; DeMik, David E; Glass, Natalie A; Burnett, Robert A; Bozic, Kevin J; Callaghan, John J

2018-05-16

The efficacy of corticosteroid and hyaluronic acid injections for knee osteoarthritis has been questioned. The purpose of this study was to determine the impact of the American Academy of Orthopaedic Surgeons (AAOS) clinical practice guidelines on the use of these injections in the United States and determine if utilization differed by provider specialty. Patients with knee osteoarthritis were identified within the Humana database from 2007 to 2015, and the percentage of patients receiving a knee injection relative to the number of patients having an encounter for knee osteoarthritis was calculated and was trended for the study period. The impact of each edition of the AAOS clinical practice guidelines on injection use was evaluated with segmented regression analysis. Injection trends were also analyzed relative to the specialty of the provider performing the injection. Of 1,065,175 patients with knee osteoarthritis, 405,101 (38.0%) received a corticosteroid injection and 137,005 (12.9%) received a hyaluronic acid injection. The rate of increase in hyaluronic acid use, per 100 patients with knee osteoarthritis, decreased from 0.15 to 0.07 injection per quarter year (p = 0.02) after the first clinical practice guideline, and the increase changed to a decrease at a rate of -0.12 injection per quarter (p < 0.001) after the second clinical practice guideline. After the first clinical practice guideline, the rate of increase in utilization of corticosteroids, per 100 patients with knee osteoarthritis, significantly lessened to 0.12 injection per quarter (p < 0.001), and after the second clinical practice guideline, corticosteroid injection use plateaued (p = 0.72). The trend in use of hyaluronic acid injections by orthopaedic surgeons and pain specialists decreased with time following the second-edition clinical practice guideline but did not change for primary care physicians or nonoperative musculoskeletal providers. Subtle but significant changes in hyaluronic acid
Pain reduction and improvement of function following ultrasound-guided intra-articular injections of triamcinolone hexacetonide and hyaluronic acid in hip osteoarthritis.

PubMed

Araújo, J P; Silva, L; Andrade, R; Paços, M; Moreira, H; Migueis, N; Pereira, R; Sarmento, A; Pereira, H; Loureiro, N; Espregueira-Mendes, J

2016-01-01

The scientific literature has shown positive results regarding intra-articular injections of hyaluronic acid in osteoarthritic joints. When injecting in the hip joint, the guidance of ultrasound can provide higher injection accuracy and repeatability. However, due to the methodological limitations in the current available literature, its recommendation in the current practice is still controversial. This study shows that ultrasound-guided intra-articular injections of triamcinolone hexacetonide and hyaluronic acid can improve pain, function and quality of life in patients with symptomatic and radiographic hip osteoarthritis. In addition, the administration of triamcinolone hexacetonide and hyaluronic acid to the hip joint in these patients can delay the need for interventional surgery.

75 FR 1274 - Implantation or Injectable Dosage Form New Animal Drugs; Hyaluronate Sodium

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... safety warning for use of hyaluronate sodium injectable solution in horses. DATES: This rule is effective... human food safety warning on product labeling. The supplemental NADA is approved as of December 11, 2009...
Changes of synovial fluid protein concentrations in supra-patellar bursitis patients after the injection of different molecular weights of hyaluronic acid.

PubMed

Chen, Carl P C; Hsu, Chih Chin; Pei, Yu-Cheng; Chen, Ruo Li; Zhou, Shaobo; Shen, Hsuan-Chen; Lin, Shih-Cherng; Tsai, Wen Chung

2014-04-01

Knee pain is commonly seen in orthopedic and rehabilitation outpatient clinical settings, and in the aging population. Bursitis of the knee joint, especially when the volume of the synovial fluid is large enough, can compress and distend the nearby soft tissues, causing pain in the knee joint. Out of all the bursae surrounding the knee joint, supra-patellar bursitis is most often associated with knee pain. Treatment strategies in managing supra-patellar bursitis include the aspiration of joint synovial fluid and then followed by steroid injection into the bursa. When supra-patellar bursitis is caused by degenerative disorders, the concept of viscosupplementation treatment may be effective by injecting hyaluronic acid into the bursa. However, the rheology or the changes in the concentrations of proteins (biomarkers) that are related to the development of bursitis in the synovial fluid is virtually unexplored. Therefore, this study aimed to identify the concentration changes in the synovial fluid total protein amount and individual proteins associated with supra-patellar bursitis using the Bradford protein assay and western immunoglobulin methods. A total of 20 patients were divided into two groups with 10 patients in each group. One group received the high molecular weight hyaluronic acid product of Synvisc Hylan G-F 20 and the other group received the low molecular weight hyaluronic acid product of Hya-Joint Synovial Fluid Supplement once per week injection into the bursa for a total of 3 weeks. Significant decreases in the synovial fluid total protein concentrations were observed after the second dosage of high molecular weight hyaluronic acid injections. Apolipoprotein A-I, interleukin 1 beta, alpha 1 antitrypsin, and matrix metalloproteinase 1 proteins revealed a trend of decreasing western immunoblotting band densities after hyaluronic acid injections. The decreases in apolipoprotein A-I and interleukin 1 beta protein band densities were significant in the high
[The usefullness of hyaluronate injection in patients with RA].

PubMed

Saito, Seiji

2003-06-01

In this seminar, we reported the usefulness of hyaluronate injection in clinical application with patients of RA. In basic research areas, however, the mechanisms responsible for the reported beneficial clinical effects of these treatments remain unclear. There is accumulating experimental evidence to show that the receptors of HA, eg, CD-44, accelerate the inflammation of joint. Administration high molecular weight HA may modulate CD-44 sensitive macromolecular in joint inflammation in part to reduce the activity of proteinases such as MMP-9.
Febrile urinary tract infections after ureteroneocystostomy and subureteral injection of dextranomer/hyaluronic acid for vesicoureteral reflux--do choice of procedure and success matter?

PubMed

Dwyer, Moira E; Husmann, Douglas A; Rathbun, Suzanne R; Weight, Christopher J; Kramer, Stephen A

2013-01-01

Despite success rates favoring ureteroneocystostomy over subureteral injection of dextranomer/hyaluronic acid for correction of vesicoureteral reflux, the reported incidence of postoperative febrile urinary tract infection favors the latter. We evaluated contemporary treatment cohorts for an association between correction of vesicoureteral reflux and risk of postoperative febrile urinary tract infection. We retrospectively reviewed the records of 396 consecutive patients who underwent ureteroneocystostomy or subureteral injection of dextranomer/hyaluronic acid between 1994 and 2008. Time to event multivariate analyses included preoperative grade of vesicoureteral reflux and bladder/bowel dysfunction. Of 316 patients meeting study criteria 210 underwent ureteroneocystostomy (356 ureters) and 106 underwent subureteral injection of dextranomer/hyaluronic acid (167). Median patient age was 5.7 years (IQR 3.4 to 8.3). Median followup was 28 months (IQR 8 to 61). Ureteral success was significantly greater after ureteroneocystostomy (88%, 314 of 356 cases) vs subureteral injection of dextranomer/hyaluronic acid (74%, 124 of 167, p = 0.0001). When controlling for preoperative grade of vesicoureteral reflux and bladder/bowel dysfunction, the risk of persistent reflux was 2.8 times greater after subureteral injection of dextranomer/hyaluronic acid (95% CI 1.7-4.7, p <0.0001). The incidence of febrile urinary tract infection did not significantly differ between ureteroneocystostomy (8%, 16 of 210 cases) and subureteral injection of dextranomer/hyaluronic acid (4%, 4 of 106; HR 1.96, 95% CI 0.64-5.9, p = 0.24) even when controlling for preoperative grade of vesicoureteral reflux, a predictor of postoperative febrile urinary tract infection on multivariate analysis (HR 2.2 per increase in grade, 95% CI 1.3-3.6, p = 0.0022). Persistent reflux was not a predictor of postoperative febrile urinary tract infection (HR 0.81, 95% CI 0.22-2.9, p = 0.75 for ureteroneocystostomy vs HR 1
Prospective study of polydimethylsiloxane vs dextranomer/hyaluronic acid injection for treatment of vesicoureteral reflux.

PubMed

Moore, Katherine; Bolduc, Stéphane

2014-12-01

Endoscopic injection of a bulking agent is becoming a first-line treatment for low grade vesicoureteral reflux. We prospectively compared the efficacy of 2 such products commercially available in Canada. A total of 275 patients with documented grade I to V vesicoureteral reflux were prospectively enrolled in a comparative study between April 2005 and February 2011 to be randomly treated endoscopically with either polydimethylsiloxane (Macroplastique®) or dextranomer/hyaluronic acid copolymer (Deflux®). Of the ureters 202 were treated with polydimethylsiloxane and 197 with dextranomer/hyaluronic acid copolymer. Patients were followed with voiding cystourethrography at 3 months and renal ultrasonography at 3 months and at 1 year. Median followup was 4.3 years. The primary outcome was surgical success (resolution vs nonresolution), and secondary outcomes included occurrence of adverse events. Vesicoureteral reflux was fully corrected in 182 of 202 ureters (90%) treated with polydimethylsiloxane, compared to 159 of 197 (81%) treated with dextranomer/hyaluronic acid copolymer (p <0.05). Obstruction was found in 5 ureters. Univariate and multivariate analyses did not allow identification of any characteristics that could explain the significant difference in the success rates except for the type of product used. We present the largest known prospective evaluation comparing 2 bulking agents for the treatment of vesicoureteral reflux. Endoscopic injection of polydimethylsiloxane resulted in a better success rate than dextranomer/hyaluronic acid copolymer. The rate of resolution obtained with the latter is lower than those previously published due to the inclusion of high grade reflux. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Periarticular Injection of Liposomal Bupivacaine Offers No Benefit Over Standard Bupivacaine in Total Knee Arthroplasty: A Prospective, Randomized, Controlled Trial.

PubMed

Alijanipour, Pouya; Tan, Timothy L; Matthews, Christopher N; Viola, Jessica R; Purtill, James J; Rothman, Richard H; Parvizi, Javad; Austin, Matthew S

2017-02-01

Periarticular injection of liposomal bupivacaine has been adopted as part of multimodal pain management after total knee arthroplasty (TKA). In this prospective, randomized clinical trial, we enrolled 162 patients undergoing primary TKA in a single institution between January 2014 and May 2015. Eighty-seven patients were randomized to liposomal bupivacaine (experimental group), and 75 patients were randomized to free bupivacaine (control group). All patients received spinal anesthesia and otherwise identical surgical approaches, pain management, and rehabilitation protocols. Outcomes evaluated include the patient-reported visual analog pain scores, narcotic consumption, and narcotic-related side effects (Brief Pain Inventory) within 96 hours after surgery as well as functional outcomes using the Knee Society Score and the Short-Form 12 measured preoperatively and at 4-6 weeks after surgery. There were no statistically significant differences between the groups in terms of postoperative daily pain scores, narcotic consumption (by-day and overall), or narcotic-related side effects. There were no statistically significant differences between the groups in terms of surgical (P = .76) and medical complications or length of hospital stay (P = .35). There were no statistically significant differences in satisfaction between the groups (P = .56) or between the groups in postoperative Knee Society Score (P = .53) and the Short-Form 12 at 4-6 weeks (P = .82, P = .66). As part of multimodal pain management protocol, periarticular injection of liposomal bupivacaine compared with bupivacaine HCl did not result in any clinically or statistically significant improvement of the measured outcomes following TKA. Copyright © 2016 Elsevier Inc. All rights reserved.
Injectable and body temperature sensitive hydrogels based on chitosan and hyaluronic acid for pH sensitive drug release.

PubMed

Zhang, Wei; Jin, Xin; Li, Heng; Zhang, Run-Run; Wu, Cheng-Wei

2018-04-15

Hydrogels based on chitosan/hyaluronic acid/β-sodium glycerophosphate demonstrate injectability, body temperature sensitivity, pH sensitive drug release and adhesion to cancer cell. The drug (doxorubicin) loaded hydrogel precursor solutions are injectable and turn to hydrogels when the temperature is increased to body temperature. The acidic condition (pH 4.00) can trigger the release of drug and the cancer cell (Hela) can adhere to the surface of the hydrogels, which will be beneficial for tumor site-specific administration of drug. The mechanical strength, the gelation temperature, and the drug release behavior can be tuned by varying hyaluronic acid content. The mechanisms were characterized using dynamic mechanical analysis, Fourier transform infrared spectroscopy, scanning electron microscopy and fluorescence microscopy. The carboxyl group in hyaluronic acid can form the hydrogen bondings with the protonated amine in chitosan, which promotes the increase of mechanical strength of the hydrogels and depresses the initial burst release of drug from the hydrogel. Copyright © 2018 Elsevier Ltd. All rights reserved.
Dextranomer/hyaluronic acid endoscopic injection is effective in the treatment of intermediate and high grade vesicoureteral reflux in patients with complete duplex systems.

PubMed

Hunziker, Manuela; Mohanan, Nochiparambil; Puri, Prem

2013-05-01

Endoscopic subureteral injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis or surgical treatment for vesicoureteral reflux. We evaluated the effectiveness of endoscopic injection of dextranomer/hyaluronic acid in intermediate and high grade vesicoureteral reflux in patients with complete duplex collecting systems. A total of 123 children underwent endoscopic correction of intermediate or high grade vesicoureteral reflux using injection of dextranomer/hyaluronic acid into complete duplex systems between 2001 and 2010. Vesicoureteral reflux was diagnosed by voiding cystourethrogram, and dimercapto-succinic acid scan was performed to evaluate the presence of renal scarring. Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure and renal ultrasound thereafter every 2 years. Mean followup was 6.7 years. Complete duplex systems were unilateral in 110 patients and bilateral in 13. Reflux severity in the 136 refluxing units was grade II in 1 (0.7%), III in 52 (38.2%), IV in 61 (44.9%) and V in 22 (16.2%). Dimercapto-succinic acid scan revealed renal functional abnormalities in 63 children (51.2%). Vesicoureteral reflux resolved after the first endoscopic injection of dextranomer/hyaluronic acid in 93 ureters (68.4%), after a second injection in 35 (25.7%) and after a third injection in 8 (5.9%). Febrile urinary tract infection developed in 5 patients (4.1%) during followup. No patient required ureteral reimplantation or experienced significant complications. Our results confirm the safety and efficacy of endoscopic injection of dextranomer/hyaluronic acid in eradicating intermediate and high grade vesicoureteral reflux in patients with complete duplex systems. We recommend this minimally invasive, 15-minute outpatient procedure as a viable option for treating intermediate and high grade vesicoureteral reflux in patients with complete duplex collecting systems
Treatment of Stress Velopharyngeal Incompetence With Injection of Hyaluronic Acid.

PubMed

Koprowski, Steven; VanLue, Michael J; McCormick, Michael E

2018-04-01

Stress velopharyngeal incompetence (VPI) is a challenging clinical entity that can be managed by a variety of surgical and nonsurgical approaches. We describe the case of a clarinetist who presented with nasal air escape while playing. She had successful improvement in her symptoms after targeted injection of a hyaluronic acid compound to her posterior pharyngeal wall. Our objective is to describe the safety and efficacy of this technique, to emphasize the multidisciplinary management of patients with stress VPI, and to review the importance of both nasopharyngoscopy and videofluoroscopy in their evaluation.
Can combined use of low-level lasers and hyaluronic acid injections prolong the longevity of degenerative knee joints?

PubMed Central

Ip, David; Fu, Nga Yue

2015-01-01

Background This study evaluated whether half-yearly hyaluronic acid injection together with low-level laser therapy in addition to standard conventional physical therapy can successfully postpone the need for joint replacement surgery in elderly patients with bilateral symptomatic tricompartmental knee arthritis. Methods In this prospective, double-blind, placebo-controlled study, 70 consecutive unselected elderly patients with bilateral tricompartmental knee arthritis were assigned at random to either one of two conservative treatment protocols to either one of the painful knees. Protocol A consisted of conventional physical therapy plus a sham light source plus saline injection, and protocol B consisted of protocol A with addition of half-yearly hyaluronic acid injection as well as low-level laser treatment instead of using saline and a sham light source. Treatment failure was defined as breakthrough pain necessitating joint replacement. Results Among the 140 painful knees treated with either protocol A or protocol B, only one of the 70 painful knees treated by protocol B required joint replacement, whereas 15 of the 70 painful knees treated by protocol A needed joint replacement surgery (P<0.05). Conclusion We conclude that half-yearly hyaluronic acid injections together with low-level laser therapy should be incorporated into the standard conservative treatment protocol for symptomatic knee arthritis, because it may prolong the longevity of the knee joint without the need for joint replacement. PMID:26346122
Oral Glucosamine Hydrochloride Combined With Hyaluronate Sodium Intra-Articular Injection for Temporomandibular Joint Osteoarthritis: A Double-Blind Randomized Controlled Trial.

PubMed

Yang, Wenbin; Liu, Wei; Miao, Cheng; Sun, Haibin; Li, Longjiang; Li, Chunjie

2018-06-02

Temporomandibular joint (TMJ) disorders occur in many people and osteoarthritis (OA) is a severe form of this disease. Glucosamine has been used to treat OA of the large joints for many years and has been proved effective. A double-blinded randomized controlled trial was designed to investigate the effectiveness and safety of oral glucosamine hydrochloride pills combined with hyaluronate sodium intra-articular injection in TMJ OA. One hundred forty-four participants with TMJ OA were randomized to 4 hyaluronate sodium injections and oral glucosamine hydrochloride (1.44 g/day) for 3 months (group A) or 4 hyaluronate sodium injections and oral placebo for 3 months (group B). All participants were followed for 1 year. Eighteen participants were lost to follow-up. The intention-to-treat analysis showed that group A had similar maximal interincisal mouth opening and pain intensity during TMJ function at months 1 and 6 (P > .05). However, during long-term follow-up, group A had significantly greater maximal interincisal mouth opening compared with group B at month 12 (41.5 vs 37.9 mm; P < .001). For pain intensity, group A showed obviously lower visual analog scale scores than group B at month 6 (20.6 vs 29.2 mm; P = .007) and month 12 (17.4 vs 28.6 mm; P = .001). Twenty-four participants had gastrointestinal tract side effects, fatigue, and rash. Of these, 23 had slight side effects that were not correlated with glucosamine. There was no significant difference between the 2 groups (P > .05). The results of this study suggest that, compared with hyaluronate sodium injection alone, glucosamine hydrochloride pills added to hyaluronate sodium injection had no meaningful effect on TMJ OA in the short-term but did relieve the pain caused by TMJ OA and improved TMJ functions in the long-term. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.
Clinical effects of image-guided hyaluronate injections for the osteochondral lesions of ankle in sport active population.

PubMed

DI Gesù, Marco; Fusco, Augusto; Vetro, Angelo; Iosa, Marco; Mantia, Fabrizio; Iovane, Angelo; Mantia, Roberto

2016-11-01

Hyaluronic acid injections are effective as intra-articular treatment, but their use in the ankle has been hindered for the difficulty of execution in this area. Use of a guidance of musculo-skeleletal ultrasound could improve the success rate and the subsequent clinical outcome, for the ameliorating placement of the needle tip. The aim of this pilot study was to assess the short-term efficacy in terms of functional outcomes and pain of a image-guided intra-articular hyaluronic acid injections of post-traumatic osteochondral lesions (OLs) of the ankle. Thirty sport active patients (21 males; mean age 27.6±7.46) with a clinical and radiological diagnosis of post-traumatic ankle OLs at initial stage, received a course of three injections within a month. Patients were evaluated for pain (with Numerical Rating Scale, NRS) e function (Ankle-Hindfoot Scale, AHS, and range of motion, ROM) before every injection and ninety days after the last injection (T0-T3). Pain showed a significant and clinically relevant improvement during the period of treatment (P<0.001), even if pain was still presented at last follow-up assessment. Also for AHS e ROM, it was recorded a similar positive trend during time (P<0.001 for both measurements). Before intervention, pain and function resulted correlated (P<0.001), while at follow-up assessment these correlations were reduced, remaining only between pain at rest and plantar-flexion range. These results showed positive effects of the intra-articular hyaluronic acid for the osteochondral lesions, with a full recovery of the functional activity and a significant reduction of pain.
An injectable oxidated hyaluronic acid/adipic acid dihydrazide hydrogel as a vitreous substitute.

PubMed

Su, Wen-Yu; Chen, Ko-Hua; Chen, Yu-Chun; Lee, Yen-Hsien; Tseng, Ching-Li; Lin, Feng-Huei

2011-01-01

Vitrectomy is a common procedure for treating ocular-related diseases. The surgery involves removing the vitreous humor from the center of the eye, and vitreous substitutes are needed to replace the vitreous humor after vitrectomy. In the present study, we developed a colorless, transparent and injectable hydrogel with appropriate refractive index as a vitreous substitute. The hydrogel is formed by oxidated hyaluronic acid (oxi-HA) cross-linked with adipic acid dihydrazide (ADH). Hyaluronic acid (HA) was oxidized by sodium periodate to create aldehyde functional groups, which could be cross-linked by ADH. The refractive index of this hydrogel ranged between 1.3420 and 1.3442, which is quite similar to human vitreous humor (1.3345). The degradation tests demonstrated that the hydrogel could maintain the gel matrix over 35 days, depending on the ADH concentration. In addition, the cytotoxicity was evaluated on retina pigmented epithelium (RPE) cells cultivated following the ISO standard (tests for in vitro cytotoxicity), and the hydrogel was found to be non-toxic. In a preliminary animal study, the oxi-HA/ADH hydrogel was injected into the vitreous cavity of rabbit eyes. The evaluations of slit-lamp observation, intraocular pressure, cornea thickness and histological examination showed no significant abnormal biological reactions for 3 weeks. This study suggests that the injectable oxi-HA/ADH hydrogel should be a potential vitreous substitute. Koninklijke Brill NV, Leiden, 2011
Comparison of patient outcomes in periarticular and intraarticular local anaesthetic infiltration techniques in total knee arthroplasty.

PubMed

Perret, Michael; Fletcher, Philip; Firth, Laura; Yates, Piers

2015-07-31

The use of local infiltration analgesia in the setting of knee arthroplasty is well established. There are no studies to date which have directly compared differences in infiltration techniques. The purpose of this study is to establish if a difference in patient outcomes exists when the infiltrate is injected into the periarticular tissues or directly into the joint. One hundred and forty-two consecutive patients waitlisted for primary total knee arthroplasty were enrolled after primary exclusion criteria were applied. These included the following: allergy to study drugs, inability to receive spinal anaesthesia, and planned bilateral surgery. Patients were divided into two groups, a periarticular infiltration group (group A) and an intraarticular infiltration group (group B). Secondary exclusion criteria of regular opioid use, psychiatric illness, and serious medical comorbidity left a total of 47 patients in group A and 54 patients in group B. Both groups received a combination of 30 mg ketorolac, 500 μg of adrenaline, and 300 mg of ropivacaine, and normal saline. This was either injected into the periarticular tissues during surgery (group A) or intraarticularly after closure of the wound (group B). Primary outcome measures included opioid consumption during the first 24 h postoperatively and over the total admission, and visual analogue scales (VAS) on postoperative day 1 and at discharge. Secondary measures included Oxford Knee Score, knee flexion, length of stay, haemoglobin drop, and transfusion requirement. Ethics approval was granted by the hospital review board. The trial is registered in the Australian New Zealand Clinical Trials Registry, registration ACTRN12615000488505 . No statistically significant differences in postoperative analgesic use were observed between the two groups. However, there was a trend toward decreased postoperative patient-controlled analgesia use in the periarticular group (mean 53.1 vs 68.3 mg morphine equivalents; p�
Efficacy and safety of single injection of cross-linked sodium hyaluronate vs. three injections of high molecular weight sodium hyaluronate for osteoarthritis of the knee: a double-blind, randomized, multi-center, non-inferiority study.

PubMed

Ha, Chul-Won; Park, Yong-Beom; Choi, Chong-Hyuk; Kyung, Hee-Soo; Lee, Ju-Hong; Yoo, Jae Doo; Yoo, Ju-Hyung; Choi, Choong-Hyeok; Kim, Chang-Wan; Kim, Hee-Chun; Oh, Kwang-Jun; Bin, Seong-Il; Lee, Myung Chul

2017-05-26

This randomized, double-blind, multi-center, non-inferiority trial was conducted to assess the efficacy and safety of a cross-linked hyaluronate (XLHA, single injection form) compared with a linear high molecular hyaluronate (HMWHA, thrice injection form) in patients with symptomatic knee osteoarthritis. Two hundred eighty seven patients with osteoarthritis (Kellgren-Lawrence grade I to III) were randomized to each group. Three weekly injections were given in both groups but two times of saline injections preceded XLHA injection to maintain double-blindness. Primary endpoint was the change of weight-bearing pain (WBP) at 12 weeks after the last injection. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis index; patient's and investigator's global assessment; pain at rest, at night, or in motion; OMERACT-OARSI responder rate; proportion of patients achieving at least 20 mm or 40% decrease in WBP; and rate of rescue medicine use and its total consumption. Mean changes of WBP at 12 weeks after the last injection were -33.3 mm with XLHA and -29.2 mm with HMWHA, proving non-inferiority of XLHA to HMWHA as the lower bound of 95% CI (-1.9 mm, 10.1 mm) was well above the predefined margin (-10 mm). There were no significant between-group differences in all secondary endpoints. Injection site pain was the most common adverse event and no remarkable safety issue was identified. This study demonstrated that a single injection of XLHA was non-inferior to three weekly injections of HMWHA in terms of WBP reduction, and supports XLHA as an effective and safe treatment for knee osteoarthritis. ClinicalTrials.gov ( NCT01510535 ). This trial was registered on January 6, 2012.
Injectable In Situ Forming Biodegradable Chitosan-Hyaluronic acid Based Hydrogels for Cartilage Tissue Engineering

PubMed Central

Tan, Huaping; Chu, Constance R.; Payne, Karin; Marra, Kacey G.

2009-01-01

Injectable, biodegradable scaffolds are important biomaterials for tissue engineering and drug delivery. Hydrogels derived from natural polysaccharides are ideal scaffolds as they resemble the extracellular matrices of tissues comprised of various glycosaminoglycans (GAG). Here, we report a new class of biocompatible and biodegradable composite hydrogels derived from water-soluble chitosan and oxidized hyaluronic acid upon mixing, without the addition of a chemical crosslinking agent. The gelation is attributed to the Schiff-base reaction between amino and aldehyde groups of polysaccharide derivatives. In the current work, N-succinyl-chitosan (S-CS) and aldehyde hyaluronic acid (A-HA) were synthesized for preparation of the composite hydrogels. The polysaccharide derivatives and composite hydrogels were characterized by FTIR spectroscopy. The effect of the ratio of S-CS and A-HA on the gelation time, microstructure, surface morphology, equilibrium swelling, compressive modulus, and in vitro degradation of composite hydrogels was examined. The potential of the composite hydrogel as an injectable scaffold was demonstrated by encapsulation of bovine articular chondrocytes within the composite hydrogel matrix in vitro. The results demonstrated that the composite hydrogel supported cell survival and the cells retained chondrocytic morphology. These characteristics provide a potential opportunity to use the injectable, composite hydrogels in tissue engineering applications. PMID:19167750
Intraoperative Adductor Canal Block for Augmentation of Periarticular Injection in Total Knee Arthroplasty: A Cadaveric Study.

PubMed

Pepper, Andrew M; North, Trevor W; Sunderland, Adam M; Davis, Jason J

2016-09-01

Function is often sacrificed for pain control after total knee arthroplasty. Motor-sparing blocks, including adductor canal block (ACB) and periarticular injection (PAI), have gained interest to address this compromise. Our study evaluates the anatomic feasibility, accuracy, and safety of intraoperative ACB as an adjunct to PAI by analyzing 3 different injection orientations and needle configurations. Eleven cadaveric knees underwent a standard medial parapatellar arthrotomy. Blunt dissection through the suprapatellar recess was performed. Using a 10-mL syringe, various colors of dyed liquid gelatin were injected toward the proximal and distal adductor canal (AC) using 3 needle configurations. Medial dissection of the knee for each specimen was performed. The position of each needle and location of injected dye was identified and described relative to the AC. Accuracy of each injection orientation and/or needle configuration was different: 86% for a blunt needle in the distal AC, 57% for blunt needle in the proximal AC, and 14% for a spinal needle in the proximal AC. Puncture of the femoral artery was observed with the spinal needle 43% of the time and had the closest average proximity to the femoral artery with a distance of 5.9 mm. There were no vascular punctures using blunt needles, and the average distance from the femoral artery with proximal and distal orientation was 10.2 mm and 15.4 mm, respectively. Intraoperative ACB augmentation of PAI appears to be anatomically feasible and safe. There was decreased accuracy and increased risk of vascular puncture using a 3.5-inch spinal needle. A blunt 1.5-inch needle directed toward the distal AC had the highest accuracy while minimizing vascular injury. Copyright © 2016 Elsevier Inc. All rights reserved.
LOCAL PERIARTICULAR ANALGESIA IN TOTAL KNEE ARTHROPLASTY

PubMed Central

Sadigursky, David; Simões, Daniel Pereira; de Albuquerque, Raphael Araújo; Silva, Monize Zórnio; Fernandes, Rogério Jamil Carneiro; Colavolpe, Paulo Oliveira

2017-01-01

ABSTRACT Objective: To evaluate the use of infiltration of periarticular analgesic agents intraoperatively in total knee arthroplasty (TKA), with regard to benefits, reduction of pain, opioid consumption, improvement of range of motion and early ambulation. Methods: To analyze the benefits of periarticular drug infiltration, the patients submitted to TKA were evaluated, being separated into two groups. One group received the local periarticular infiltration protocol containing 0.5% bupivacaine (400mg/20ml), 1/1000 epinephrine (0.3ml), triamcinolone hexacetonide (20mg/1ml), clonidine (150mcg/1ml) and 20 ml of saline (0.9% SS) and, the other group underwent conventional intravenous analgesia. The results were compared and the variables analyzed were age, sex, BMI, comorbidities, postoperative complications, pain, functional capacity, range of motion, transfusion and rescue opioids for analgesia. Results: The mean age of the patients was 68 years and most were female and presented involvement of the left knee. Postoperatively, patients who had received periarticular infiltration showed improvement of pain as well as functional capacity. Conclusion: The analysis of data obtained demonstrated that the periarticular infiltration of analgesic agents is significantly effective for pain control and functional recovery.Level of Evidence II, Prospective Comparative Study. PMID:28642656
Evaluation of injection augmentation treatment of hyaluronic acid based materials on rabbit vocal folds viscoelasticity.

PubMed

Borzacchiello, A; Mayol, L; Gärskog, O; Dahlqvist, A; Ambrosio, L

2005-06-01

The viscoelastic properties of vocal folds after injection of hyaluronic acid (hyaluronan, HA) based materials have been studied in an animal model (rabbit) six months after injection. The results indicate that the viscoelastic properties of the vocal folds injected with the HA based materials are similar to the healthy vocal folds (non-injected samples) used as control. Histological analysis has been also performed to investigate on the fate of the injected materials after six months from the implant. The HA based materials remain up to six months and they recruited fibroblasts that induce the ingrowth of new connective tissue resulting in an endogenous soft tissue augmentation. The HA based compounds are good candidate for further studies aimed at restoring/preserving the vibratory capacity of the vocal folds with injection treatment in glottal insufficiency.
Joint lavage followed by intra-articular injection of hyaluronic acid and/or corticosteroids in patients with severe hemophilic arthropathy of the knee: Is this intervention really effective?

PubMed

Rodriguez-Merchan, E Carlos; Valentino, Leonard A

2018-05-10

The aim of this review is to explore the scientific rationale and evidence for a potential benefit of joint lavage followed by intra-articular injection of hyaluronic acid and/or corticosteroids in patients with severe hemophilic arthropathy of the knee (SHAK). Areas covered: This article is a narrative review of the evidence for potential benefits of joint lavage followed by intra-articular injection of hyaluronic acid and corticosteroids in SHAK compared with osteoarthritis of the knee in non-hemophilia patients. Expert commentary: Although some reports on hemophilic arthropathy with a low-grade of evidence seem to indicate a benefit of joint lavage followed by intra-articular injection of hyaluronic acid and/or corticosteroids in patients with SHAK, the short-lived improvements afforded by hyaluronic acid, and the doubtful benefits of corticosteroids and joint lavage in hemophilia, do not warrant their use in hemophilic patients. The scientific rationale of these procedures is poor and they are not recommended.

The Hyaluronic Acid Fillers: Current Understanding of the Tissue Device Interface.

PubMed

Greene, Jacqueline J; Sidle, Douglas M

2015-11-01

The article is a detailed update regarding cosmetic injectable fillers, specifically focusing on hyaluronic acid fillers. Hyaluronic acid-injectable fillers are used extensively for soft tissue volumizing and contouring. Many different hyaluronic acid-injectable fillers are available on the market and differ in terms of hyaluronic acid concentration, particle size, cross-linking density, requisite needle size, duration, stiffness, hydration, presence of lidocaine, type of cross-linking technology, and cost. Hyaluronic acid is a natural component of many soft tissues, is identical across species minimizing immunogenicity has been linked to wound healing and skin regeneration, and is currently actively being studied for tissue engineering purposes. The biomechanical and biochemical effects of HA on the local microenvironment of the injected site are key to its success as a soft tissue filler. Knowledge of the tissue-device interface will help guide the facial practitioner and lead to optimal outcomes for patients. Copyright © 2015 Elsevier Inc. All rights reserved.
Effect analysis of intradermal hyaluronic acid injection to treat enlarged facial pores.

PubMed

Qian, Wei; Zhang, Yan-Kun; Hou, Ying; Lyu, Wei; Cao, Qian; Li, Yan-Qi; Fan, Ju-Feng

2017-08-08

To investigate the clinical application and efficacy of intradermal injection of low molecular weight hyaluronic acid (LMW-HA) for treating enlarged facial pores. From January 2015 to May 2016, 42 subjects who sought aesthetic treatment underwent intradermal injection of LMW-HA to improve enlarged facial pores. For each treatment, 2.5 mL (25 mg) of LMW-HA was injected into the skin of the full face. The treatment was repeated 2-5 times with an interval of 1 to 1.5 months between consecutive treatments. The postoperative follow-up period was 1 to 6 months. Statistical analysis was used to compare the degree of enlargement of facial pores before and after injection. The clinical efficacy and adverse effects were recorded. The enlarged facial pores before and after treatment were categorized and subjected to the Wilcoxon matched-pairs signed-rank test. The difference was statistically significant (P<.01). The improvement rate was 40.03±18.41%. No infection, nodules, or pigmentation was reported at the injection sites in the subjects who sought aesthetic treatment. The overall satisfaction rate was 92.8%. Intradermal injection of LMW-HA can significantly improve skin texture, reduce pore size, and enhance skin radiance. The injection technique was simple, safe, and effective and could easily be extended to clinical practice. © 2017 Wiley Periodicals, Inc.
Periarticular local anesthesia does not improve pain or mobility after THA.

PubMed

Dobie, I; Bennett, D; Spence, D J; Murray, J M; Beverland, D E

2012-07-01

Periarticular infiltration of local anesthetic, NSAIDs, and adrenaline have been reported to reduce postoperative pain, improve mobility, and reduce hospital stay for patients having THAs, but available studies have not determined whether local anesthetic infiltration alone achieves similar improvements. We therefore asked whether periarticular injection of a local anesthetic during THA reduced postoperative pain and opioid requirements and improved postoperative mobility. We randomized 96 patients to either treatment (n = 50) or control groups (n = 46). Before wound closure, the treatment group received local infiltration of 160 mL of levobupivacaine with adrenaline. The control group received no local infiltration. We assessed postoperative morphine consumption and pain during the 24 hours after surgery. Mobilization was assessed 24 hours postoperatively with supine-to-sit and sit-to-stand transfers, timed 10-m walk test, and timed stair ascent and descent. Patients and assessing physiotherapists were blind to study status. We observed no differences in postoperative morphine consumption, time to ascend and descend stairs, or ability to transfer between treatment and control groups. The treatment group reported more pain 7 to 12 hours postoperatively, but there were no differences in pain scores between groups at all other postoperative intervals. The treatment group showed increased postoperative walking speed greater than 6 m, but not greater than 10 m, compared with the control group. Periarticular infiltration of local anesthetic during THA did not reduce postoperative pain or length of hospital stay and did not improve early postoperative mobilization.
Single center experience with endoscopic subureteral dextranomer/hyaluronic acid injection as first line treatment in 1,551 children with intermediate and high grade vesicoureteral reflux.

PubMed

Puri, Prem; Kutasy, Balazs; Colhoun, Eric; Hunziker, Manuela

2012-10-01

In recent years the endoscopic injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis and the surgical management of vesicoureteral reflux. We determined the safety and effectiveness of the endoscopic injection of dextranomer/hyaluronic acid as first line treatment for high grade vesicoureteral reflux. Between 2001 and 2010, 1,551 children (496 male, 1,055 female, median age 1.6 years) underwent endoscopic correction of intermediate and high grade vesicoureteral reflux using dextranomer/hyaluronic acid soon after the diagnosis of vesicoureteral reflux on initial voiding cystourethrogram. Vesicoureteral reflux was unilateral in 761 children and bilateral in 790. Renal scarring was detected in 369 (26.7%) of the 1,384 patients who underwent dimercapto-succinic acid imaging. Reflux grade in the 2,341 ureters was II in 98 (4.2%), III in 1,340 (57.3%), IV in 818 (34.9%) and V in 85 (3.6%). Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure, and renal ultrasound was performed annually thereafter. Patients were followed for 3 months to 10 years (median 5.6 years). Vesicoureteral reflux resolved after the first, second and third endoscopic injection of dextranomer/hyaluronic acid in 2,039 (87.1%), 264 (11.3%) and 38 (1.6%) ureters, respectively. Febrile urinary tract infections developed during followup in 69 (4.6%) patients. None of the patients in the series needed reimplantation of ureters or experienced any significant complications. Our results confirm the safety and efficacy of the endoscopic injection of dextranomer/hyaluronic acid in the eradication of high grade vesicoureteral reflux. We recommend this 15-minute outpatient procedure as the first line of treatment for high grade vesicoureteral reflux. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Comparative effectiveness of intra-articular prolotherapy versus peri-articular prolotherapy on pain reduction and improving function in patients with knee osteoarthritis: A randomized clinical trial.

PubMed

Farpour, Hamid Reza; Fereydooni, Farzane

2017-11-01

Osteoarthritis is a common degenerative disease. Prolotherapy is an alternative therapy used in multiple musculoskeletal disorders. To compare the effectiveness of intra-articular dextrose injection versus peri-articular prolotherapy in patients with knee osteoarthritis (KOA). Fifty-two adults with painful primary knee osteoarthritis for at least three months were randomized to intra- and peri-articular injection groups. Prolotherapy was done twice with two week intervals. The outcome measures included the Oxford Knee Scale (OKS), Western Ontario McMaster University Osteoarthritis Index (WOMAC), and Visual Analogue Scale (VAS), which were obtained from patients before the first injection at the base line and after the second injection at the fourth and eighth weeks. There were no statistically significant differences between demographic characteristics; before the injection, pain intensity, OKS, and WOMAC scores were approximately equal between the two groups. After dextrose prolotherapy, VAS, OKS, and WOMAC scores improved from baseline through the fourth and eighth weeks in both groups without any superiority between the two methods of injections (p<0.001). Dextrose prolotherapy either intra- or peri-articular injection resulted in significant improvement, so it could be an inexpensive and effective management of knee osteoarthritis. The study protocol was registered as a clinical trial under registration ID of IRCT2016091229795N1 at the Iranian Registry of Clinical Trials (http://www.irct.ir). The authors received no financial support for the research, authorship, or publication of this article.
Severe visual loss and cerebral infarction after injection of hyaluronic acid gel.

PubMed

Kim, Eung Gyu; Eom, Tae Kyung; Kang, Seok Joo

2014-01-01

We report a case of a 23-year-old man with cerebral infarction and permanent visual loss after injection of a hyaluronic acid gel filler for augmentation rhinoplasty. The patient was admitted to the hospital with complaints of loss of vision in the right eye, facial paralysis on the right side, and paralysis of the left limbs with severe pain during augmentation rhinoplasty with filler injection. Brain magnetic resonance imaging and computed tomography showed ophthalmic artery obstruction and right middle cerebral artery infarction. Acute thrombolysis was performed to treat the infarction; however, the patient's condition did not improve. Intracerebral hemorrhage in the right temporal/frontal/occipital/parietal lobe, subarachnoid hemorrhage, and midline shifting were observed on brain computed tomography after 24 hours after thrombolysis. Emergency decompressive craniectomy was performed. After the surgery, the patient continued to experience drowsiness, with no improvement in visual loss and motor weakness. Three months later, he could walk with cane. This case indicates that surgeons who administer filler injections should be familiar with the possibility of accidental intravascular injection and should explain the adverse effects of fillers to patients before surgery.
A Meta-Analysis Comparing Liposomal Bupivacaine and Traditional Periarticular Injection for Pain Control after Total Knee Arthroplasty.

PubMed

Sun, Hao; Huang, Zhiyu; Zhang, Zhiqi; Liao, Weiming

2018-04-04

Liposomal bupivacaine is a novel method for pain control after total knee arthroplasty (TKA), but recent studies showed no advantage for patients undergoing TKA compared with traditional periarticular injection (PAI). The purpose of this analysis was to compare the clinical outcomes between liposomal bupivacaine treatment and traditional PAI. We retrospectively reviewed data from 16 clinical trials in published databases from their inception to June 2017. The primary outcome was postoperative Visual Analogue Scale (VAS) score and secondary outcomes included opiate usage, narcotic consumption, range of motion, and length of stay. Nine randomized controlled trials and seven nonrandomized controlled trials involving 924 liposomal bupivacaine cases and 1,293 traditional PAI cases were eligible for inclusion in the meta-analysis. No differences were detected in most of the clinical outcomes, except for postoperative VAS within 12 hours and length of stay. This analysis showed that liposomal bupivacaine is not associated with significant improvement in postoperative pain control or other outcomes in TKA compared with PAI. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Endoscopic Injection of Dextranomer/Hyaluronic Acid as First-Line Treatment in 851 Consecutive Children with High Grade Vesicoureteral Reflux: Efficacy and Long-Term Results.

PubMed

Friedmacher, Florian; Colhoun, Eric; Puri, Prem

2018-03-15

Endoscopic injection of dextranomer/hyaluronic is widely acknowledged as first-line treatment of lower grade vesicoureteral reflux. We demonstrate its long-term efficacy and safety in eradicating high grade reflux. A total of 518 girls and 333 boys with a median age of 2.3 years (range 2 months to 13.7 years) underwent endoscopic correction of high grade vesicoureteral reflux using dextranomer/hyaluronic acid. Reflux was unilateral in 415 cases and bilateral in 436, comprising 1,287 refluxing units. Reflux was grade IV in 1,153 ureters (89.6%) and grade V in 134 (10.4%). 99m Technetium dimercaptosuccinic acid scintigraphy identified renal scarring in 317 patients (37.3%). Followup ultrasound and voiding cystourethrogram were performed 3 months after intervention and renal ultrasound yearly thereafter. Median followup was 8.5 years (range 6 months to 16 years). Overall resolution rate after the first endoscopic injection was 69.5% (895 of 1,287 cases), with resolution in 70.4% of grade IV and 61.9% of grade V cases. Reflux resolved after a second injection in 259 cases (20.1%) and after a third injection in 133 (10.4%). Persistent reflux after initial treatment was significantly more common in patients younger than age 1 year and in individuals with renal scarring. No significant postoperative complications were observed and no patient required ureteral reimplantation. Following reflux resolution febrile urinary tract infection developed in 43 children (5.1%), including 24 (55.8%) during the first year, 15 (34.9%) during the second year and 4 (9.3%) during year 3 or later. Of these patients 6 had reflux recurrence and 8 had neocontralateral grade III reflux, which was successfully treated with a single endoscopic injection of dextranomer/hyaluronic acid. Endoscopic injection of dextranomer/hyaluronic acid is an efficient and safe long-term treatment for grade IV and V vesicoureteral reflux, and can easily be repeated in patients with treatment failure, with a high
Desire for penile girth enhancement and the effects of the self-injection of hyaluronic Acid gel.

PubMed

Coskuner, Enis Rauf; Canter, Halil Ibrahim

2012-07-01

Penile girth enhancement is a controversial subject but demands for enhancement are increasing steadily. Although various fillers have been widely used for soft tissue augmentation, there is no reliable material for this particular situation. Here we report a case of an acute hypersensitivity reaction in a man after his first self-injection of a filler material, which, he claimed, was hyaluronic acid gel for penile girth enhancement and glans penis augmentation.
Periarticular regional analgesia in total knee arthroplasty: a review of the neuroanatomy and injection technique.

PubMed

Guild, George N; Galindo, Rubin P; Marino, Joseph; Cushner, Fred D; Scuderi, Giles R

2015-01-01

Postoperative pain control after total knee arthroplasty may be insufficient, resulting in insomnia, antalgic ambulation, and difficulty with rehabilitation. Current strategies, including the use of femoral nerve catheters, may control pain but have been associated with falls, motor blockade, and quadriceps inhibition. Periarticular infiltration using the appropriate technique and knowledge of intraarticular knee anatomy may increase pain control and maximize rehabilitation. Copyright © 2015 Elsevier Inc. All rights reserved.
Efficacy and durability of hyaluronic acid fillers for malar enhancement: A prospective, randomized, split-face clinical controlled trial.

PubMed

Jeong, Ki Heon; Gwak, Min Jae; Moon, Sung Kyung; Lee, Sang Jun; Shin, Min Kyung

2018-06-01

Various hyaluronic acid fillers can be used for facial attenuation and rejuvenation. The efficacy and durability of hyaluronic acid fillers are of major concern to dermatologists and patients. This study aimed to evaluate three-dimensional morphology, tissue distribution, and changes in volume after injection of two different hyaluronic acid fillers. Ten Korean women were enrolled in this study. Each subject was injected with monophasic hyaluronic acid filler in one malar area and biphasic filler in the other. Clinical outcome was measured before and after injection, and after 2, 4, 6, 8, 12, and 24 weeks, using the Global Aesthetic Improvement Scale, photographs and Moire's topography. Facial magnetic resonance imaging (MRI) was performed twice over six months. Both products showed good results after injection and demonstrated good durability over time. MRI was a useful modality for assessing tissue distribution and volume changes. The effects and durability after injection of monophasic hyaluronic acid filler and biphasic hyaluronic acid filler are generally comparable.
Glans Penis Augmentation Using Hyaluronic Acid Gel as an Injectable Filler

PubMed Central

Kwak, Tae Il; Kim, Je Jong

2015-01-01

Glans penis augmentation (GPA) has received little attention from experts despite the existence of a subset of patients who may be dissatisfied with a small glans or poor tumescence of the glans during erection. Recently, GPA using an injectable filler or implantation of a graft or filler has been developed. Despite a demanding injection technique and inevitable uneven undulation of the glandular surface, GPA using injectable hyaluronic acid (HA) gel is a novel and useful therapy and an effective and safe procedure for soft tissue enhancement. For long-term presence of implants, timed supplementation can be used similar to that for fascial plasty. In complications such as mucosal necrosis of the glans penis, most cases occur from the use of non-HA gel or an unpurified form and misunderstanding of the management protocol for immediate side effects. Currently, GPA using injectable HA gel is not recommended in the International Society for Sexual Medicine guideline due to possible sensory loss. In a 5-year long-term follow-up of GPA by subcutaneous injection of HA gel, the residual volume of implants decreased by 15% of the maximal glandular circumference, but was still effective for alleviating the hypersensitivity of the glans penis in premature ejaculation patients. For efficacy in premature ejaculation, selection of appropriate candidates is the most important factor for success. GPA does not harm erectile function and is less invasive and irreversible compared to dorsal neurectomy. To refine the procedure, more interest and well-designed studies are required for the establishment of the procedure. PMID:26331121
Glans Penis Augmentation Using Hyaluronic Acid Gel as an Injectable Filler.

PubMed

Moon, Du Geon; Kwak, Tae Il; Kim, Je Jong

2015-08-01

Glans penis augmentation (GPA) has received little attention from experts despite the existence of a subset of patients who may be dissatisfied with a small glans or poor tumescence of the glans during erection. Recently, GPA using an injectable filler or implantation of a graft or filler has been developed. Despite a demanding injection technique and inevitable uneven undulation of the glandular surface, GPA using injectable hyaluronic acid (HA) gel is a novel and useful therapy and an effective and safe procedure for soft tissue enhancement. For long-term presence of implants, timed supplementation can be used similar to that for fascial plasty. In complications such as mucosal necrosis of the glans penis, most cases occur from the use of non-HA gel or an unpurified form and misunderstanding of the management protocol for immediate side effects. Currently, GPA using injectable HA gel is not recommended in the International Society for Sexual Medicine guideline due to possible sensory loss. In a 5-year long-term follow-up of GPA by subcutaneous injection of HA gel, the residual volume of implants decreased by 15% of the maximal glandular circumference, but was still effective for alleviating the hypersensitivity of the glans penis in premature ejaculation patients. For efficacy in premature ejaculation, selection of appropriate candidates is the most important factor for success. GPA does not harm erectile function and is less invasive and irreversible compared to dorsal neurectomy. To refine the procedure, more interest and well-designed studies are required for the establishment of the procedure.
Desire for Penile Girth Enhancement and the Effects of the Self-Injection of Hyaluronic Acid Gel

PubMed Central

Coskuner, Enis Rauf; Canter, Halil Ibrahim

2012-01-01

Penile girth enhancement is a controversial subject but demands for enhancement are increasing steadily. Although various fillers have been widely used for soft tissue augmentation, there is no reliable material for this particular situation. Here we report a case of an acute hypersensitivity reaction in a man after his first self-injection of a filler material, which, he claimed, was hyaluronic acid gel for penile girth enhancement and glans penis augmentation. PMID:23112518
Enzymatically Cross-linked Alginic-Hyaluronic acid Composite Hydrogels As Cell Delivery Vehicles

PubMed Central

Ganesh, Nitya; Hanna, Craig; Nair, Shantikumar V.; Nair, Lakshmi S.

2013-01-01

An injectable composite gel was developed from alginic and hyaluronic acid. The ezymatically cross-linked injectable gels were prepared via the oxidative coupling of tyramine modified sodium algiante and sodium hyaluronate in the presence of horse radish peroxidase (HRP) and hydrogen peroxide (H2O2). The composite gels were prepared by mixing equal parts of the two tryaminated polymer solutions in 10U HRP and treating with 1.0% H2O2. The properties of the alginate gels were significanly affected by the addition of hyaluronic acid. The percentage water absorption and storage modulus of the composite gels were found to be lower than the alginate gels. The alginate and composite gels showed lower protein release compared to hyaluronate gels in the absence of hyaluronidase. Even hyaluronate gels showed only approximately 10% protein release after 14 days incubation in phosphate buffer solution. ATDC-5 cells encapsulated in the injectable gels showed high cell viability. The composite gels showed the presence of enlarged spherical cells with significantly higher metabolic activity compared to cells in hyaluronic and alginic acid gels. The results suggest the potential of the composite approach to develop covalently cross-linked hydrogels with tuneable physical, mechanical, and biological properties. PMID:23357799
The duration of hyaluronidase and optimal timing of hyaluronic acid (HA) filler reinjection after hyaluronidase injection.

PubMed

Kim, H J; Kwon, S B; Whang, K U; Lee, J S; Park, Y L; Lee, S Y

2018-02-01

Hyaluronidase injection is a commonly performed treatment for overcorrection or misplacement of hyaluronic acid (HA) filler. Many patients often wants the HA filler reinjection after the use of hyaluronidase, though the optimal timing of reinjection of HA filler still remains unknown. To provide the optimal time interval between hyaluronidase injections and HA filler reinjections. 6 Sprague-Dawley rats were injected with single monophasic HA filler. 1 week after injection, the injected sites were treated with hyaluronidase. Then, HA fillers were reinjected sequentially with differing time intervals from 30 minutes to 14 days. 1 hour after the reinjection of the last HA filler, all injection sites were excised for histologic evaluation. 3 hours after reinjection of HA filler, the appearance of filler material became evident again, retaining its shape and volume. 6 hours after reinjection, the filler materials restored almost its original volume and there were no significant differences from the positive control. Our data suggest that the hyaluronidase loses its effect in dermis and subcutaneous tissue within 3-6 hours after the injection and successful engraftment of reinjected HA filler can be accomplished 6 hours after the injection.
Macrolane (large particle biphasic hyaluronic acid) filler injection for correction of defect contour after liposuction.

PubMed

Cerqua, Sandro; Angelucci, Francesco

2013-08-01

In a minority of patients undergoing liposuction, superficial irregularities (or skin depression) in the operated area may occur. Macrolane is a gel composed of hyaluronic acid (HA), used for volume restoration of soft tissues. In this study, the authors investigated the effectiveness, maintenance, and safety of Macrolane as a "non-surgical" treatment to correct skin depression after liposuction. Twelve female patients were included. Macrolane was injected at a subdermal superficial plane using an intramuscular or spinal needle. In all patients, Macrolane was successful in correcting skin depression. No relevant side effects were observed. At 8 months post-injection, a persistence of correction of 60-70% was still present in 90% of the patients. In conclusion, Macrolane filler injections are a predictable, safe, and long-lasting non-surgical procedure to fill contour defects that arise after liposuction, and represent a good option for patients who refuse to undergo an additional surgery to fill the arisen skin depressions.
The treatment of vesicoureteral reflux in children by endoscopic sub-mucosal intra-ureteral injection of dextranomer/hyaluronic acid: A case-series, multi-centre study.

PubMed

Bawazir, Osama

2017-04-01

Vesicoureteral reflux is a risk factor for progressive renal damage. In addition to long-term antibiotic prophylaxis and open surgical re-implantation, endoscopic sub-mucosal intra-ureteral injection of implant material is a therapeutic alternative that gained a world-wide preference. The aim of this study was to determine the effectiveness and safety of the implant material, dextranomer/hyaluronic acid, in a cohort of Saudi children with vesicoureteral reflux. In this case-series study, 61 patients with vesicoureteral reflux, who were 7 months to 10 years old (mean age 2.6 years), underwent sub-mucosal intra-ureteral injection of dextranomer/hyaluronic acid at our institutions in the period from October 2003 to October 2013. The operative protocol was the same in all institutions. Dextranomer/hyaluronic acid was injected submucosally within the intramural ureter (modified STING). Renal ultrasonography was performed to detect the presence of hydronephrosis. At 6 weeks' fluoroscopic voiding cystourethrograms were used to evaluate the success of the technique. Data were analysed by SPSS version 19 using Pearson Chi square, Fisher's Exact and Cramér's V test. Reflux was corrected in 44 patients out of 61 (72.13%) and in 60 (75.00%) out of 80 ureteric units. Statistically, there was no significant difference (p>0.05) in success rate of the technique according to gender, age group and unilateral vs. bilateral cases. The success rate was significantly (p=0.025) higher in the lower grades (I-III) (87.50%) compared to grade IV (73.53%) and grade V (50.00%). No complications related to the technique were reported. The technique had failed in 17 patients (27.87%) or 20 ureters (25.00%). These cases underwent open surgery. Sub-mucosal intra-ureteral implantation with dextranomer/hyaluronic acid by the modified STING technique is a simple, safe and effective outpatient procedure for vesicoureteral reflux.
Technique for Periarticular Local Infiltrative Anesthesia Delivery Using Liposomal Bupivacaine in Total Knee Arthroplasty.

PubMed

Connelly, Jacob O; Edwards, Paul K; Mears, Simon C; Barnes, C Lowry

2015-01-01

Postoperative pain control after total knee arthroplasty is a major contributing factor to patient satisfaction, rehabilitation, and length of stay. Current clinical practice guidelines recommend a multimodal pain management protocol, including the use of regional anesthesia. Periarticular injection (PAI) has been shown to provide excellent pain relief after total knee arthroplasty. Recently, liposomal bupivacaine has been introduced as a long-acting alternative to traditional local anesthetics, such as bupivacaine or ropivacaine. Liposomal bupivacaine is a sustained-release preparation designed to provide local analgesia up to 72 hours after initial application. The efficacy of PAI relies significantly on a meticulous, systematic injection technique. This article details recommendations for solution preparation and injection during total knee arthroplasty on the basis of the experience of a high-volume orthopaedic reconstruction service.
Effect of Intra-articular Hyaluronic Acid Injection on Hemiplegic Shoulder Pain After Stroke.

PubMed

Jang, Myung Hun; Lee, Chang-Hyung; Shin, Yong-Il; Kim, Soo-Yeon; Huh, Sung Chul

2016-10-01

To evaluate the efficacy of intra-articular hyaluronic acid (IAHA) injection for hemiplegic shoulder pain (HSP) after stroke. Thirty-one patients with HSP and limited range of motion (ROM) without spasticity of upper extremity were recruited. All subjects were randomly allocated to group A (n=15) for three weekly IAHA injection or group B (n=16) for a single intra-articular steroid (IAS) injection. All injections were administered by an expert physician until the 8th week using a posterior ultrasonography-guided approach. Shoulder joint pain was measured using the Wong-Baker Scale (WBS), while passive ROM was measured in the supine position by an expert physician. There were no significant intergroup differences in WBS or ROM at the 8th week. Improvements in forward flexion and external rotation were observed from the 4th week in the IAHA group and the 8th week in the IAS group. Subjects experienced a statistically significant improvement in pain from the 1st week in the IAS and from the 8th week in IAHA group, respectively. IAHA seems to have a less potent ability to reduce movement pain compared to steroid in the early period. However, there was no statistically significant intergroup difference in WBS and ROM improvements at the 8th week. IAHA might be a good alternative to steroid for managing HSP when the use of steroid is limited.

Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome.

PubMed

Saturveithan, C; Premganesh, G; Fakhrizzaki, S; Mahathir, M; Karuna, K; Rauf, K; William, H; Akmal, H; Sivapathasundaram, N; Jaspreet, K

2016-07-01

Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option.
Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome

PubMed Central

Premganesh, G; Fakhrizzaki, S; Mahathir, M; Karuna, K; Rauf, K; William, H; Akmal, H; Sivapathasundaram, N; Jaspreet, K

2016-01-01

Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option. PMID:28435559
Hyaluronic Acid (HA)-Polyethylene glycol (PEG) as injectable hydrogel for intervertebral disc degeneration patients therapy

NASA Astrophysics Data System (ADS)

Putri Kwarta, Cityta; Widiyanti, Prihartini; Siswanto

2017-05-01

Chronic Low Back Pain (CLBP) is one health problem that is often encountered in a community. Inject-able hydrogels are the newest way to restore the disc thickness and hydration caused by disc degeneration by means of minimally invasive surgery. Thus, polymers can be combined to improve the characteristic properties of inject-able hydrogels, leading to use of Hyaluronic Acid (a natural polymer) and Polyethylene glycol (PEG) with Horse Radish Peroxide (HRP) cross linker enzymes. The swelling test results, which approaches were the ideal disc values, were sampled with variation of enzyme concentrations of 0.25 µmol/min/mL. The enzyme concentrations were 33.95%. The degradation test proved that the sample degradation increased along with the decrease of the HRP enzyme concentration. The results of the cytotoxicity assay with MTT assay method showed that all samples resulted in the 90% of living cells are not toxic. In vitro injection, models demonstrated that higher concentration of the enzymes was less state of gel which would rupture when released from the agarose gel. The functional group characterization shows the cross linking bonding in sample with enzyme adding. The conclusion of this study is PEG-HA-HRP enzyme are safe polymer composites which have a potential to be applied as an injectable hydrogel for intervertebral disc degeneration.
Severe Acute Local Reactions to a Hyaluronic Acid-derived Dermal Filler

PubMed Central

Hays, Geoffrey P.; Caglia, Anthony E.; Caglia, Michael

2010-01-01

Injectable fillers are normally well tolerated by patients with little or no adverse effects. The most common side effects include swelling, redness, bruising, and pain at the injection site. This report describes three cases in which patients injected with a hyaluronic acid-derived injectable filler that is premixed with lidocaine developed adverse reactions including persistent swelling, pain, and nodule formation. Two of the three patients' abscesses were cultured for aerobic and anaerobic bacteria and mycobacterium. All three cultures were negative. Abscess persistence in all cases necessitated physical removal and/or enzymatic degradation with hyaluronidase. The effects subsided only after the product had been removed. Two of these patients were subsequently treated with other hyaluronic acid-derived dermal fillers without adverse events. PMID:20725567
[Intra-articular injections of hyaluronic acid for anterior disc displacement of temporomandibular joint].

PubMed

Long, X

2017-03-09

Anterior disc displacement (ADD) of temporomandibular joint (TMJ) is regarded as one of the major findings in temporomandibular disorders (TMD). It is related to joint noise, pain, mandibular dysfunction, degenerative change and osteoarthritis. In the mean time, the pathological changes were found in synovial membrane and synovial fluid. Hyaluronic acid is a principal component of the synovial fluid which plays an important role in nutrition, lubrication, anti-inflammation and cartilage repair. The synthesis, molecule weight, and concentration of hyaluronic acid are decreased during TMD and cause TMJ degenerative changes. The clinical conditions, pathological changes, the mechanism of action for hyaluronic acid and the treatment of anterior disc displacement of TMJ are discussed in this article.
Intra-articular viscosupplementation of hyaluronic acids in an experimental osteoarthritis model.

PubMed

Oliveira, Marcello Zaia; Albano, Mauro Batista; Stirma, Guilherme Augusto; Namba, Mario Massatomo; Vidigal, Leandro; Cunha, Luiz Antonio Munhoz da

2018-01-01

To analyze, from the immunohistochemical perspective, the effects of hyaluronic acid of different molecular weights in an experimental model of osteoarthritis in rabbits. Forty-four male California rabbits were randomly assigned to three different groups (PR, S, and P) and submitted to the resection of the anterior cruciate ligament of the right knee. Three weeks after the surgical procedure, three intra-articular weekly injections were carried out with low-molecular-weight native hyaluronic acid (Hyalgan ® ) to PR group, high molecular weight branched chain hyaluronic acid (Synvisc ® ) to group S, and saline solution 0.9% to group P. All animals were sacrificed 12 weeks after the surgical procedure, and the tibial plateaus of the infiltrated knees were then dissected. Histological sections of cartilage from the tibial plateau support areas were stained with immunohistochemical markers in order to investigate the amount of metalloproteases (MMPs 3 and 13) and their inhibitors (TIMPs 1 and 3). The staining intensity was quantified on a Zeiss Imager.Z2 Metasystems microscope and analyzed by Metafer4 Msearch software. The chondroprotective effect of the hyaluronic acids used in the study was demonstrated when compared to the control group. However, the comparison between them presented no significant statistical difference regarding chondroprotection. The injection of saline solution demonstrated signs of OA development, while adding native hyaluronic acid of low molecular weight (Hyalgan ® ) and hyaluronic acid of high molecular weight (Synvisc ® ) protected the articular cartilage in this model of OA.
Crosslinking method of hyaluronic-based hydrogel for biomedical applications

PubMed Central

Khunmanee, Sureerat; Jeong, Younghyen; Park, Hansoo

2017-01-01

In the field of tissue engineering, there is a need for advancement beyond conventional scaffolds and preformed hydrogels. Injectable hydrogels have gained wider admiration among researchers as they can be used in minimally invasive surgical procedures. Injectable gels completely fill the defect area and have good permeability and hence are promising biomaterials. The technique can be effectively applied to deliver a wide range of bioactive agents, such as drugs, proteins, growth factors, and even living cells. Hyaluronic acid is a promising candidate for the tissue engineering field because of its unique physicochemical and biological properties. Thus, this review provides an overview of various methods of chemical and physical crosslinking using different linkers that have been investigated to develop the mechanical properties, biodegradation, and biocompatibility of hyaluronic acid as an injectable hydrogel in cell scaffolds, drug delivery systems, and wound healing applications. PMID:28912946
A skincare containing retinol adenosine and hyaluronic acid optimises the benefits from a type A botulinum toxin injection.

PubMed

Ascher, Benjamin; Fanchon, Chantal; Kanoun-Copy, Leila; Bouloc, Anne; Benech, Florence

2012-10-01

A monocentre double-blind two parallel group clinical study was conducted to assess whether a new skincare regimen containing retinol, adenosine and hyaluronic acid, applied after the injection of botulinum toxin A to the glabellar area, provided a beneficial effect. Standardised photographs acquired using LifeViz cameras and zoomed pictures of the glabella and of the crow's feet areas were analysed with automatic well-defined procedures. Perceived efficacy and tolerance were also analysed by comparison between the two groups. A beneficial effect versus placebo-treated group was proven in the group having topically applied the new skincare regimen for 2 months following botulinum toxin A injection with no touch up after 1 month. 3D image analysis showed more rapid results on D10 and enhanced efficacy on M2. Moreover, a beneficial effect independent of injection was measured in the crow's feet area, and analysis of the self-evaluation questionnaire showed enhanced efficacy perceived by the volunteers. A specially developed skincare regimen applied immediately after botulinum toxin A injection completes the beneficial effect of the injection on the glabellar area and offers clinical benefits in fine lines, wrinkles and smoothness on the whole face.
Intra-articular hyaluronic acid compared to intra-articular triamcinolone hexacetonide in inflammatory knee osteoarthritis.

PubMed

Jones, A C; Pattrick, M; Doherty, S; Doherty, M

1995-12-01

The aim of this study was to determine the comparative efficacy and safety of intra-articular (i/a) triamcinolone. hexacetonide (TH) and i/a hyaluronic acid (HA) in inflammatory knee osteoarthritis. A randomized double-blind comparative trail was carried out in a rheumatology outpatient department. There were 63 patients (24 male, 39 female, mean age 70.5 years) with bilateral symptomatic knee osteoarthritis with effusion. Each was given five HA injections at weekly intervals; or 20 mg TH followed by four placebo (saline) injections. Patients were examined weekly during the treatment period and then at monthly intervals for a further 6 months. Assessment included recording of: visual analog scores (VAS) for pain; duration of stiffness; range of movement; joint effusion; local heat; synovial thickening; joint-line and periarticular tenderness. The principal outcome measure was pain on a self-selected activity assessed by Vas. The two groups were comparable at entry and no significant differences between the groups developed at any time during the treatment period. However, there was a high drop-out rate and intention to treat analysis failed to demonstrate statistically significant differences between the groups. In patients remaining in the study, significantly less pain was experienced by the HA group during the 6 month follow-up period. Other parameters showed a similar trend in favor of experienced by the HA group during the 6 month follow-up period. Other parameters showed a similar trend in favor of HA. We could not, however, demonstrate significant differences between the placebo and active treatments. HA may therefore be a useful additional therapy for symptomatic knee osteoarthritis and may have a long duration of action.
Office-Based Intracordal Hyaluronate Injections Improve Quality of Life in Thoracic-Surgery-Related Unilateral Vocal Fold Paralysis.

PubMed

Fang, Tuan-Jen; Hsin, Li-Jen; Chung, Hsiu-Feng; Chiang, Hui-Chen; Li, Hsueh-Yu; Wong, Alice M K; Pei, Yu-Chen

2015-10-01

Thoracic-surgery-related unilateral vocal fold paralysis (UVFP) may cause severe morbidity and can cause profound functional impairment and psychosocial stress in patients with pre-existing thoracic diseases. In-office intracordal hyaluronate (HA) injections have recently been applied to improve voice and quality of life in patients with vocal incompetence, but their effect on thoracic-surgery-related UVFP remains inconclusive. We therefore conducted a prospective study to clarify the effect of early HA injection on voice and quality of life in patients with thoracic-surgery-related UVFP. Patients with UVFP within 3 months after thoracic surgery who received office-based HA injection were recruited. Quantitative laryngeal electromyography, videolaryngostroboscopy, voice-related life quality (voice outcome survey), laboratory voice analysis, and health-related quality of life (SF-36) were evaluated at baseline, and at 1 month postinjection. A total of 104 consecutive patients accepted office-based HA intracordal injection during the study period, 34 of whom were treated in relation to thoracic surgery and were eligible for inclusion. Voice-related life quality, voice laboratory analysis, and most generic quality of life domains were significantly improved at 1 month after in-office HA intracordal injection. No HA-related complications were reported. Single office-based HA intracordal injection is a safe and effective treatment for thoracic-surgery-related UVFP, resulting in immediate improvements in patient quality of life, voice quality, and swallowing ability.
Injectable gentamicin-loaded thermo-responsive hyaluronic acid derivative prevents infection in a rabbit model.

PubMed

Ter Boo, Gert-Jan A; Arens, Daniel; Metsemakers, Willem-Jan; Zeiter, Stephan; Richards, R Geoff; Grijpma, Dirk W; Eglin, David; Moriarty, T Fintan

2016-10-01

Despite the use of systemic antibiotic prophylaxis, the surgical fixation of open fractures with osteosynthesis implants is associated with high infection rates. Antibiotic-loaded biomaterials (ALBs) are increasingly used in implant surgeries across medical specialties to deliver high concentrations of antibiotics to the surgical site and reduce the risk of implant-associated infection. ALBs which are either less or not restricted in terms of spatial distribution and which may be applied throughout complex wounds could offer improved protection against infection in open fracture care. A thermo-responsive hyaluronic acid derivative (hyaluronic acid-poly(N-isopropylacrylamide) (HApN)) was prepared by a direct amidation reaction between the tetrabutyl ammonium (TBA) salt of hyaluronic acid and amine-terminated poly(N-isopropylacrylamide) (pN). The degree of grafting, and gelation properties of this gel were characterized, and the composition was loaded with gentamicin. The rheological- and release properties of this gentamicin-loaded HApN composition were tested in vitro and its efficacy in preventing infection was tested in a rabbit model of osteosynthesis contaminated with Staphylococcus aureus. The gentamicin-loaded HApN composition was able to prevent bacterial colonization of the implant site as shown by quantitative bacteriology. This finding was supported by histopathological evaluation of the humeri samples where no bacteria were found in the stained sections. In conclusion, this gentamicin-loaded HApN hydrogel effectively prevents infection in a complex wound, simulating a contaminated fracture treated with plating osteosynthesis. Fracture fixation after trauma is associated with high infection rates. Antibiotic loaded biomaterials (ALBs) can provide high local concentrations without systemic side effects. However, the currently available ALBs have limited accessibility to contaminated tissues in open fractures because of predetermined shape. Thus, a novel
Symposium: evidence for the use of intra-articular cortisone or hyaluronic acid injection in the hip

PubMed Central

Chandrasekaran, Sivashankar; Lodhia, Parth; Suarez-Ahedo, Carlos; Vemula, S. Pavan; Martin, Timothy J.; Domb, Benjamin G.

2016-01-01

The primary purpose of this review article is to discuss the role of diagnostic, corticosteroid, hyaluronic acid (HA) and platelet rich plasma (PRP) in the treatment of osteoarthritis (OA) and femoroacetabular impingement (FIA). These treatments play an important biological role in the non-operative management of these conditions. Two independent reviewers performed an search of PubMed for articles that contained at least one of the following search terms pertaining to intra-articular hip injection—local anaesthetic, diagnostic, ultrasound, fluoroscopic, image guided, corticosteroid, HA, PRP, OA, labral tears and FAI. Seventy-two full text articles were suitable for inclusion. There were 18 articles addressing the efficacy of diagnostic intra-articular hip injections. With respect to efficacy in OA there were 25 articles pertaining to efficacy of corticosteroid, 22 of HA and 4 of PRP. There were three articles addressing the efficacy of biologics in FAI. Diagnostic intra-articular hip injections are sensitive and specific for differentiating between intra-articular, extra-articular and spinal causes of hip symptoms. Ultrasound and fluoroscopy improves the precision of intra-articular positioning of diagnostic injections. Corticosteroids are more effective than HA and PRP in alleviating pain from hip OA. A higher dose of corticosteroids produces a longer benefit but volume of injection has no significant effect. Intra-articular corticosteroids do not increase infection rates of subsequent arthroplasty. There is currently limited evidence to warrant the routine use of therapeutic injections in the management of labral tears and FIA. PMID:27026814
Hyaluronic acid injections protect patellar tendon from detraining-associated damage.

PubMed

Frizziero, Antonio; Salamanna, Francesca; Giavaresi, Gianluca; Ferrari, Andrea; Martini, Lucia; Marini, Marina; Veicsteinas, Arsenio; Maffulli, Nicola; Masiero, Stefano; Fini, Milena

2015-09-01

Having previously demonstrated that detraining affects patellar tendon (PT) proteoglycan content and collagen fiber organization, we undertook the present study with two aims: to improve knowledge on the adaptation of PT and its enthesis to detraining from a histological and histomorphometric point of view, and to investigate the hypothesis that repeated peri-patellar injections of hyaluronic acid (HA) on detrained PT may reduce and limit detrained associated-damage. Twenty-four male Sprague-Dawley rats were divided into 3 groups: Untrained (n=6), Trained (n=6) (10 wks-treadmill) and Detrained (n=12). In the detrained rats, the left tendon was untreated while the right tendon received repeated peri-patellar injections of either HA or saline (NaCl). Structure and morphology of PTs (modified Movin score, tear density, collagen type I and III) and enthesis (cell morphology, chondrocyte cluster formation, tidemark integrity, matrix staining and vascularization) were evaluated. The left PT and enthesis of the Detrained groups showed altered structure and morphology with the highest Movin score values, the highest percentage of collagen III and the lowest of collagen I; the lowest score values were observed in the Trained and Detrained-HA groups. Detrained-NaCl PTs showed the highest collagen III and the lowest collagen I values with respect to Detrained-HA PTs. This study strengthens previously published data showing the alteration in tendon and enthesis morphology due to discontinuation of training, and provides new data showing that treatment with HA is effective in the maintenance of the structural properties of PT and enthesis in Detrained rats. Such beneficial effects could play a significant role in the management of conservative and rehabilitation strategies in athletes that change type, intensity and duration of training.
Platelet-rich plasma injection is more effective than hyaluronic acid in the treatment of knee osteoarthritis.

PubMed

Say, F; Gürler, D; Yener, K; Bülbül, M; Malkoc, M

2013-01-01

There is increasing use of platelet-rich plasma (PRP) in orthopaedics as it is a simple, cheap and minimally invasive technique. This study aimed to compare the effects of the use of PRP and hyaluronic acid (HA) injections in the knee of patients diagnosed with and being followed-up for degenerative arthritis. This prospective study included 90 patients with complaints of knee pain with findings of mild or moderate degenerative arthritis. In the PRP group (n=45), one intra-articular injection was applied and in the HA group (n=45), three doses of intra-articular injection were applied. Clinical evaluation was made by Knee Injury and Osteoarthritis Outcome Score (KOOS) and a visual pain scale. No severe adverse events was observed. Statistically significant better results in the KOOS score and visual pain scale was determined in PRP group than HA group at 3 months and 6 months follow up. The cost of the application for the PRP group was lower than that of the HA group. The results of this study have shown the application of single dose PRP to be a safe, effective and low-cost method for treating OA. However, further studies are required for a more clear result.
Comparison of histological effects of polydeoxyribonucleic acid and hyaluronic acid in experimentally induced osteoarthritis of the knee joints of rats

PubMed Central

Karahan, Nazım; Arslan, İlyas; Orak, Müfit; Midi, Ahmet; Yücel, İstemi

2017-01-01

Aim: The histological effects of intra-articular polydeoxyribonucleic acid and hyaluronic acid in experimentally induced osteoarthritis of the knee joints of rats were investigated. Methods: Thirty rats were divided into three groups, i.e. polydeoxyribonucleic acid group, hyaluronic acid group and saline group. Osteoarthritis of the knee joints of the rats were induced by acl- transection. The polydeoxyribonucleic group was injected with 100 µg (0.05 cc) polydeoxyribonucleic acid. The hyaluronic acid group was injected with 100 µg (0.05 cc) hyaluronic acid, and the saline group was injected with 50 µl (0.05 cc) of 0.9% sodium chloride solution. All of the rats were sacrificed on day 29 and the right knee joints were prepared, and evaluated histologically by Mankin classification. Findings: The differences in total Mankin scores between the three groups were statistically significant (P < 0.01). The differences in total Mankin scores between the polydeoxyribonucleic acid group and the hyaluronic acid group were statistically significant (P < 0.01). The differences in total Mankin scores between hyaluronic acid group and saline group were statistically significant (P < 0.01). Tidemark continuity in all the specimens of the polydeoxyribonucleic acid group was noteworthy. Conclusion: The present study shows that more chondroprotective effect and less degeneration was observed with intra-articularly delivered polydeoxyribonucleic acid compared to hyaluronic acid and saline solution in the experimentally induced osteoarthritis of the knee joints of rats.
Ultrasound-guided subacromial injections of sodium hyaluronate for the management of rotator cuff tendinopathy: a prospective comparative study with rehabilitation therapy.

PubMed

Merolla, G; Bianchi, P; Porcellini, G

2013-06-01

Rotator cuff (RC) tendinopathy is a common cause of pain and shoulder dysfunction. The literature evidence suggests that a combination of overuse and extrinsic compression may induce chronic RC tendinopathy. Aim of the current study was to compare the results of subacromial sodium hyaluronate injections with rehabilitation therapy. We enrolled 48 patients (M/F: 26/22; mean age: 50 years; shoulder right/left: 29/19) with persistent shoulder pain for at least 4 months. Exclusion criteria were as follows: RC tear, calcifying tendinitis, glenohumeral instability, osteoarthritis, rheumatic diseases, physical therapy and/or injection in the previous 4 months, shoulder surgery, anesthetic nerve block, trauma, and severe medical diseases. The included subjects received either two ultrasound-guided subacromial hyaluronic acid (HA) injections (25 patients, HA group) at baseline and 14 days, or underwent rehabilitation therapy (23 patients, Physio group) including active shoulder mobilization, soft tissue stretching and humeral head positioner and propeller muscles strengthening for 30 days (3 sessions every week). Clinical assessment of shoulder function was performed with visual analog scale score for pain (0-100), Oxford Shoulder Score (OSS), and Constant-Murley Score (CS). Overall, patients were examined at baseline, week 2, week 4, week 12, and week 24. Statistical significance was set at 5 % (p < 0.05). Reduction in overall pain in the HA group was statistically significant at week 2 (p < 0.05) week 4 (p < 0.05), week 12 comparing to baseline. Similarly, pain subscores (at night and with activity) were significantly lower at week 2 (p < 0.05), week 4 (p < 0.05), and week 12 (p < 0.05), respectively. In the Physio group, pain decreased significantly at week 2 (p < 0.05) but not maintained at week 4 (p > 0.05), week 12 (p > 0.05), and week 24 (p > 0.05). CS and OSS in the HA group increased significantly at week 2 (p < 0.05), week 4 (p < 0
Comparison of the 3 Different Injection Techniques Used in a Randomized Controlled Study Evaluating a Cross-Linked Sodium Hyaluronate Combined With Triamcinolone Hexacetonide (Cingal) for Osteoarthritis of the Knee: A Subgroup Analysis.

PubMed

McCormack, Robert; Lamontagne, Martin; Vannabouathong, Christopher; Deakon, Robert T; Belzile, Etienne L

2017-01-01

A recent trial demonstrated that patients with knee osteoarthritis treated with a sodium hyaluronate and corticosteroid combination (Cingal) experienced greater pain reductions compared with those treated with sodium hyaluronate alone (Monovisc) or saline up to 3 weeks postinjection. In this study, injections were administered by 1 of 3 approaches; however, there is currently no consensus on which, if any, of these techniques produce a more favorable outcome. To provide additional insight on this topic, the results of the previous trial were reanalyzed to determine whether (1) the effect of Cingal was significant within each injection technique and (2) pain reductions were similar between injection techniques across all treatment groups. Greater pain reductions with Cingal up to 3 weeks were only significant in the anteromedial subgroup. Across all therapies, both the anteromedial and anterolateral techniques demonstrated significantly greater pain reductions than the lateral midpatellar approach at 18 and 26 weeks.
Comparison of the 3 Different Injection Techniques Used in a Randomized Controlled Study Evaluating a Cross-Linked Sodium Hyaluronate Combined With Triamcinolone Hexacetonide (Cingal) for Osteoarthritis of the Knee: A Subgroup Analysis

PubMed Central

McCormack, Robert; Lamontagne, Martin; Vannabouathong, Christopher; Deakon, Robert T; Belzile, Etienne L

2017-01-01

A recent trial demonstrated that patients with knee osteoarthritis treated with a sodium hyaluronate and corticosteroid combination (Cingal) experienced greater pain reductions compared with those treated with sodium hyaluronate alone (Monovisc) or saline up to 3 weeks postinjection. In this study, injections were administered by 1 of 3 approaches; however, there is currently no consensus on which, if any, of these techniques produce a more favorable outcome. To provide additional insight on this topic, the results of the previous trial were reanalyzed to determine whether (1) the effect of Cingal was significant within each injection technique and (2) pain reductions were similar between injection techniques across all treatment groups. Greater pain reductions with Cingal up to 3 weeks were only significant in the anteromedial subgroup. Across all therapies, both the anteromedial and anterolateral techniques demonstrated significantly greater pain reductions than the lateral midpatellar approach at 18 and 26 weeks. PMID:28839449
Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

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

Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr; EMR3738, Université Lyon 1, Lyon; Decullier, Evelyne

Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Eventsmore » version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.« less
Adelmidrol, in combination with hyaluronic acid, displays increased anti-inflammatory and analgesic effects against monosodium iodoacetate-induced osteoarthritis in rats.

PubMed

Di Paola, Rosanna; Fusco, Roberta; Impellizzeri, Daniela; Cordaro, Marika; Britti, Domenico; Morittu, Valeria Maria; Evangelista, Maurizio; Cuzzocrea, Salvatore

2016-12-12

Osteoarthritis (OA) is a degenerative joint disease produced by a cascade of events that can ultimately lead to joint damage. The aim of this study was to evaluate the effect of adelmidrol, a synthetic palmitoylethanolamide analogue, combined with hyaluronic acid on pain severity and modulation of the inflammatory response in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. OA was induced by intra-articular injection of MIA in the knee joint. On day 21 post-MIA administration, the knee joint was analyzed. Rats subjected to OA were treated by intra-articular injection of adelmidrol in combination with sodium hyaluronate at different doses and time points after MIA induction. Limb nociception was assessed by the paw withdrawal latency and threshold measurement. Samples were examined macroscopically, histologically, and by immunohistochemistry. At day 21 post-MIA injection, the MIA + solvent and MIA + 1.0% sodium hyaluronate groups showed irregularities and fibrillation in the surface layer, a decrease in blood cells and multilayering in transition and radial zones, no pannus formation, and modified Mankin scores significantly higher than sham knees. The combination of hyaluronic acid and adelmidrol dose-dependently (adelmidrol 0.6% + 1.0% sodium hyaluronate and adelmidrol 2% + 1.0% sodium hyaluronate) reduced the histological alterations induced by MIA. Moreover, degeneration of articular cartilage, mast cell infiltration, and pro-inflammatory cytokine and chemokine plasma levels were significantly downregulated by treatment with a combination of hyaluronic acid and adelmidrol at the above doses. Our results clearly demonstrate that the combination of hyaluronic acid and adelmidrol improves the signs of OA induced by MIA.

Adipose‑derived stem cells and hyaluronic acid based gel compatibility, studied in vitro.

PubMed

Guo, Jiayan; Guo, Shu; Wang, Yuxin; Yu, Yanqiu

2017-10-01

Minimally invasive aesthetic and cosmetic procedures have increased in popularity. Injectable dermal fillers provide soft tissue augmentation, improve facial rejuvenation and wrinkles, and correct tissue defects. To investigate the use of adipose‑derived stem cells integrated with a hyaluronic acid based gel as a dermal filler, the present study used cytotoxicity studies, proliferation studies, adipogenic and osteogenic differentiation, apoptosis assays and scanning electron microscopy. Although hyaluronic acid induced low levels of apoptosis in adipose‑derived stem cells, its significantly promoted proliferation of adipose‑derived stem cells. Hyaluronic acid demonstrates little toxicity against adipose‑derived stem cells. Adipose‑derived stem cells were able to differentiate into adipocytes and osteoblasts. Furthermore, scanning electron microscopy revealed that adipose‑derived stem cells maintained intact structures on the surface of hyaluronic acid as well as in it, and demonstrated abundant cell attachments. The present study demonstrated the compatibility of adipose‑derived stem cells and hyaluronic acid based gels in vitro.
The efficacy of multiple versus single hyaluronic acid injections: a systematic review and meta-analysis.

PubMed

Concoff, Andrew; Sancheti, Parag; Niazi, Faizan; Shaw, Peter; Rosen, Jeffrey

2017-12-21

Intra-articular hyaluronic acid (IA-HA) is a common therapy used to treat knee pain and suppress knee inflammation in knee osteoarthritis (OA), typically prescribed in regimens ranging from a single injection to 5 weekly injections given once weekly. We conducted a systematic review to determine the efficacy of IA-HA, with subgroup analyses to explore the differences in knee pain and adverse events (AEs) across different dosing regimens. We conducted a systematic search of the literature to identify studies evaluating IA-HA for the management of knee OA compared to IA-saline. Primary outcome measure was the mean knee pain score at 13 Weeks (3 months) or 26 weeks (6 months). Secondary outcome was the number of treatment-related AEs and treatment-related serious adverse events (SAEs). We evaluated differences in levels of pain and AEs/SAEs between dosing regimens compared to IA-Saline. Thirty articles were included. Overall, IA-HA injections were associated with less knee pain compared to IA-Saline injections for all dosing regimens. 2-4 injections of IA-HA vs. IA-Saline produced the largest effect size at both 3-months and 6-months (Standard mean difference [SMD] = -0.76; -0.98 to -0.53, 95% CI, P < 0.00001, and SMD = -0.36; -0.63 to -0.09 95% CI, P = 0.008, respectively). Additionally, single injection studies yielded a non-significant treatment effect at 3 and 6 months, while ≥5 5 injections demonstrated a significant improvement in pain only at 6 months. Five or more injections of IA-HA were associated with a higher risk of treatment-related AEs compared to IA-Saline (Risk ratio [RR] = 1.67; 1.09 to 2.56 95% CI, p = 0.02), which was a result not seen within the 1 and 2-4 injection subgroups. Overall, 2-4 and ≥5 injection regimens provided pain relief over IA-Saline, while single injection did not. Intra-articular injections of HA used in a 2-4 injection treatment regimen provided the greatest benefit when compared to IA
Intravenous Hyaluronidase with Urokinase as Treatment for Rabbit Retinal Artery Hyaluronic Acid Embolism.

PubMed

Chiang, ChengAn; Zhou, ShuangBai; Chen, ChuHsin; Ho, Dave S; Zhang, HuiZhong; Liu, Kai

2016-12-01

Although various salvage methods have been proposed to treat intraretinal artery hyaluronic acid embolism, their applications are still limited by various factors. The authors investigated the effectiveness of intravenous hyaluronidase with urokinase for resolving retinal artery hyaluronic acid embolism. The anatomy of rabbit ophthalmic and fundus arteries (retinal and choroid artery) was studied. Approximately 0.35 ml of hyaluronic acid was injected into the ophthalmic artery to create a retinal artery embolism model. The rabbits were grouped randomly (groups A, B, C, D, E, and F) and given hyaluronidase with urokinase intravenously at different postobstruction time points (10, 20, 30, 40, 50, and 60 minutes). Saline was given to the control group. Fundus vascular (retinal and choroid artery) reperfusion status and the effectiveness of the solution on the obstruction of each group were observed for 5 days. The animal model closely imitated actual hyaluronic acid ophthalmic/retinal artery obstructions. Three vascular conditions were observed after hyaluronidase with urokinase injection: total, partial, and no reperfusion. Groups A, B, and C showed a significantly higher overall solution effectiveness rate (total/partial reperfusion) compared with the control group (p = 0.001, p = 0.001, and p = 0.005, respectively). Solution effectiveness in groups D, E, and F showed no difference compared with the control group (p = 0.628, p = 1.000, and p = 1.000, respectively). The effectiveness of the solution drops dramatically if given after 30 minutes of obstruction. The authors' method can indeed help resolve retinal artery hyaluronic acid obstruction. Intravenous hyaluronidase with urokinase technique shows possible potential to become a standardized treatment protocol for intraretinal artery hyaluronic acid embolism with further clinical tests.
Effects of sodium hyaluronate on tendon healing and adhesion formation in horses.

PubMed

Gaughan, E M; Nixon, A J; Krook, L P; Yeager, A E; Mann, K A; Mohammed, H; Bartel, D L

1991-05-01

Sodium hyaluronate reduces adhesions after tendon repair in rodents and dogs, and has been used in limited clinical trials in people. To evaluate its effect on tendon healing and adhesion formation in horses and to compare these effects with those of a compound of similar visco-elastic properties, a study was performed in horses, using a model of collagenase injection in the flexor tendons within the digital sheath. Eight clinically normal horses were randomly allotted to 2 groups. Adhesion formation between the deep digital flexor tendon and the tendon sheath at the pastern region was induced in the forelimbs of all horses. Using tenoscopic control, a 20-gauge needle was inserted into the deep digital flexor tendon of horses under general anesthesia and 0.2 ml of collagenase (2.5 mg/ml) was injected. The procedure was repeated proximally at 2 other sites, spaced 1.5 cm apart. A biopsy forceps was introduced, and a 5-mm tendon defect was created at each injection site. Group-A horses had 120 mg of sodium hyaluronate (NaHA) gel injected into the tendon sheath of one limb. Group-B horses had methylcellulose gel injected at the same sites. The contralateral limbs of horses in both groups served as surgical, but noninjected, controls. Horses were euthanatized after 8 weeks of stall rest. Ultrasonographic evaluation revealed improved tendon healing after NaHa injection, but no difference in peritendinous adhesion formation. Tendon sheath fluid volume and hyaluronic acid (HA) content were greater in NaHA-treated limbs. Gross pathologic examination revealed considerably fewer and smaller adhesions when limbs were treated with NaHA. However, significant difference in pull-out strengths was not evident between NaHA-treated and control limbs. Histologically, the deep digital flexor tendon from the NaHA-treated limbs had reduced inflammatory cell infiltration, improved tendon structure, and less intratendinous hemorrhage. Treatment with methylcullulose had no significant
Is the addition of a polyol to hyaluronic acid a significant advance in the treatment of osteoarthritis?

PubMed

Conrozier, Thierry

2017-07-10

Viscosupplementation with intra-articular injections of hyaluronic acid is recommended as a second line treatment for knee OA, after failure of non-pharmacological modalities and usual pain killers. Nevertheless there is still controversies regarding clinical relevance of its effects. Research is looking at the best means to improve the performance of viscosupplementation in order to obtain a faster, more sustainable and more marked effect. Antioxidants have been assessed in combination with hyaluronic acid because the injected hyaluronate is rapidly degraded by the reactive oxygen species present in large amounts in the OA synovial fluid, limiting its residence time into the joint. Sorbitol and mannitol which have intrinsic free radical scavenger properties have been the most studied antioxidants. Sodium hyaluronate and polyols develop together a complex based on a dense network of hydrogen bonds that do not modify the visco-elsatic properties of hyaluronic acid. The oxygen free radicals neutralization by mannitol has been proven to delay the degradation of both linear and cross-linked HA in several in vitro models of oxidative stress. The antioxidant effect of these polyols may also play a role in accelerate onset of analgesia, as demonstrated in a double blind controlled trial comparing a mannitol-modified viscosupplement to regular hyaluronic acid. The addition of mannitol and sorbitol to hyaluronic acid does not alter the safety and local tolerability. In summary, adding a polyol to hyaluronic acid may improve the effects of viscosupplementation, by reducing the rate of degradation of HA that leads to an earlier effect on pain relief without increasing the risk of adverse effect. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
The self-crosslinking smart hyaluronic acid hydrogels as injectable three-dimensional scaffolds for cells culture.

PubMed

Bian, Shaoquan; He, Mengmeng; Sui, Junhui; Cai, Hanxu; Sun, Yong; Liang, Jie; Fan, Yujiang; Zhang, Xingdong

2016-04-01

Although the disulfide bond crosslinked hyaluronic acid hydrogels have been reported by many research groups, the major researches were focused on effectively forming hydrogels. However, few researchers paid attention to the potential significance of controlling the hydrogel formation and degradation, improving biocompatibility, reducing the toxicity of exogenous and providing convenience to the clinical operations later on. In this research, the novel controllable self-crosslinking smart hydrogels with in-situ gelation property was prepared by a single component, the thiolated hyaluronic acid derivative (HA-SH), and applied as a three-dimensional scaffold to mimic native extracellular matrix (ECM) for the culture of fibroblasts cells (L929) and chondrocytes. A series of HA-SH hydrogels were prepared depending on different degrees of thiol substitution (ranging from 10 to 60%) and molecule weights of HA (0.1, 0.3 and 1.0 MDa). The gelation time, swelling property and smart degradation behavior of HA-SH hydrogel were evaluated. The results showed that the gelation and degradation time of hydrogels could be controlled by adjusting the component of HA-SH polymers. The storage modulus of HA-SH hydrogels obtained by dynamic modulus analysis (DMA) could be up to 44.6 kPa. In addition, HA-SH hydrogels were investigated as a three-dimensional scaffold for the culture of fibroblasts cells (L929) and chondrocytes cells in vitro and as an injectable hydrogel for delivering chondrocytes cells in vivo. These results illustrated that HA-SH hydrogels with controllable gelation process, intelligent degradation behavior, excellent biocompatibility and convenient operational characteristics supplied potential clinical application capacity for tissue engineering and regenerative medicine. Copyright © 2016 Elsevier B.V. All rights reserved.
Effects of one-time and two-time intra-articular injection of hyaluronic acid sodium salt after joint surgery in dogs

PubMed Central

Boonsri, Burin; Sripratak, Thatdanai; Markmee, Patsanan

2013-01-01

Thirty-one dogs with patellar luxation (grades 2 and 3) were categorized into three groups. Group 1 (G.1; n = 12) had sodium hyaluronate (SHA) intra-articularly injected into the stifle joint that received surgery. Group 2 (G.2; n = 10) received SHA twice: first after surgery and then 1 week later. Group 3 (G.3; n = 9) served as a control, without injection. Blood was collected before injection and then once a week for 4 weeks after injection for evaluation of chondroitin sulfate (CS-WF6) and hyaluronan (HA). The results revealed significantly (p < 0.05) improved clinical scores by the end of week 4 in G.1 and G.2 relative to G.3; however, there was no significant difference between G.1 and G.2. There was a significant decrease (p < 0.05) in serum CS-WF6 levels beginning at week 2 in G.1 and G.2. At weeks 3 and 4, serum HA in G.1 and G.2 differed from that in G.3 (p < 0.05). No significant difference (p > 0.05) was observed in serum biomarkers between G.1 and G.2. In conclusion, intra-articular injection with SHA after joint surgery may improve homeostasis of the joint, retarding the process of OA. PMID:23814475
Carbon dioxide therapy and hyaluronic acid for cosmetic correction of the nasolabial folds.

PubMed

Nisi, Giuseppe; Cuomo, Roberto; Brandi, Cesare; Grimaldi, Luca; Sisti, Andrea; D'Aniello, Carlo

2016-06-01

The main application of hyaluronic acid filling, in esthetic medicine, is the augmentation of soft tissues. The carbon dioxide therapy, instead, improves quality and elasticity of the dermis and increases the oxygen release to the tissue through an enhancing of the Bohr's effect. The aim of the study was to compare the efficacy, tolerability, and effect duration of hyaluronic acid fillers and the use of carbon dioxide therapy plus hyaluronic acid in the cosmetic correction of nasolabial folds. Forty healthy female patients received a blinded and randomized treatment on nasolabial folds (hyaluronic acid in group A and hyaluronic acid plus subcutaneous injections of carbon dioxide in group B) for cosmetic correction of the nasolabial folds. The results were evaluated by two blinded plastic surgeons after the implant (1 week, 4 and 6 months) using a 1-5 graduated scale (GAIS), and at the same time, each patient was asked to express her opinion about the cosmetic result. Any long-term adverse reaction was reported. The blinded evaluation at 4 and 6 months from the implant shows in all patients a maintenance of a good cosmetic result higher for the side treated with carbon dioxide therapy plus hyaluronic acid. At the control visit, 6 months after the treatment, the patients treated with hyaluronic acid plus carbon dioxide therapy maintain a satisfactory esthetic result while the nasolabial fold treated only with hyaluronic acid shows, in almost all patients, a come back to pretreatment appearance. © 2016 Wiley Periodicals, Inc.
Using Hyaluronic Acid for Improving Vocal Function in a Prepubescent Boy With an Atrophied Right Vocal Fold.

PubMed

Cohen, Wendy; Wynne, David McGregor

2015-07-01

A single case study is reported of a child who underwent several surgical procedures as result of congenital grade III subglottic stenosis. The anterior aspect of the right vocal cord was damaged and underwent atrophy during one of these procedures. Now, an active 10-year-old, the patient has become increasingly aware of his vocal limitations on functional activities. Injection of hyaluronic acid into the vocal folds has been known to provide improved voice quality in adults although there are no known cases reported of this procedure in children. This article reports voice outcomes after injection of hyaluronic acid into the Reinke's space in a single case study. Voice recordings were made before, after, and 1 month after injection. The voice recordings were subject to acoustic and perceptual analysis. Post and follow-up voice recordings demonstrate decreased jitter, shimmer, and harmonics-to-noise ratio. Perceptual evaluation indicates improved voice quality. Injection of hyaluronic acid in children who require voice augmentation is possible and may contribute to increased vocal function and improved voice outcomes. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
Clinical comparison of oral administration and viscosupplementation of hyaluronic acid (HA) in early knee osteoarthritis.

PubMed

Ricci, M; Micheloni, G M; Berti, M; Perusi, F; Sambugaro, E; Vecchini, E; Magnan, B

2017-04-01

Osteoarthritis (OA) is a progressive, chronic and degenerative joint disease characterized by a loss of articular cartilage. Treatment of OA is largely palliative based on nonsteroidal anti-inflammatory drugs, opioids and injections of steroids. Regarding conservative treatment, intra-articular injections of hyaluronic acid (HA) can play a role in early symptomatic knee OA. Between August 2015 and September 2015, sixty patients (32 males and 28 females) between 40 and 70 years old were randomly allocated into two groups: Half were treated with three weekly intra-articular injections of hyaluronic acid 1.6 % (group A), while the others were treated with Syalox 300 Plus ® (hyaluronic acid 300 mg + Boswellia serrata extract 100 mg) 1 tab/die for 20 days and afterward Syalox 150 ® (hyaluronic acid 150 mg) 1 tab/die for other 20 days (group B). All patients were evaluated clinically with American Knee Society Score (AKSS) and visual analogue scale (VAS) for the pain before the treatment and after 3 months. AKSS of the patients in both groups was significantly increased by the treatment, and VAS score was significantly reduced. In both groups, two subgroups were created with patients older than 60 years and patients younger than 60 years. Better results are reported in younger patients of group A and older subjects in group B. Despite several limitations, the results of the study have shown that HA injection and oral administration may have beneficial therapeutic effects on patients with early osteoarthritis. Different outcomes in younger and older subject suggested a combined therapy first with local infiltrations and then with oral composition.
Hyaluronic acid in knee osteoarthritis: preliminary results using a four months administration schedule.

PubMed

Abate, Michele; Vanni, Daniele; Pantalone, Andrea; Salini, Vincenzo

2017-02-01

To evaluate the therapeutic trajectory of intra-articular injections of hyaluronic acid at high concentration (2%) performed at 4-month intervals. Subjects with knee osteoarthritis received, after a weekly injection of 32 mg/2 mL hyaluronic acid for 3 weeks, a single injection of 50 mg/2.5 mL hyaluronic acid (not cross-linked, molecular weight 800-1200 kDa) at 4-month interval (4, 8 and 12 months). Clinical assessment (visual analogic scale [VAS] for pain at rest and during activities, Lequesne Index [LI], Knee Injury and Osteoarthritis Outcome Score (KOOS), and monthly non-steroidal anti-inflammatory drug consumption) was performed at baseline, and after 1, 4, 6, 8, 12 and 14 months. In the 15 knees treated, pain decreased (baseline vs. 14 months: VAS at rest, 3.7 ± 1.7 vs. 1 ± 0.7 [P < 0.000]; VAS activities, 6.2 ± 1.7 vs. 2.6 ± 1.3 [P < 0.000]) and function improved (baseline vs. 14 months: KOOS, 51.9 ± 15.3 vs. 70.2 ± 13.7 [P < 0.000]; LI, 10 ± 3.8 vs. 5.4 ± 2.4 [P < 0.000]) significantly. This schedule provides persistent positive results in terms of reduced pain and improved function, optimizing the protective properties of the hyaluronic acid used. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.
An experimental study of tissue reaction to hyaluronic acid (Restylane) and polymethylmethacrylate (Metacrill) in the mouse.

PubMed

Rosa, Simone C; Macedo, Jefferson L S; Magalhães, Albino V

2012-10-01

The aging skin is a challenge for medical science. Plastic surgeons and dermatologists are called every day to solve problems like filling wrinkles or folds. The material used must be biocompatible because abnormal reactions may cause catastrophic results. This study analyzes the biological behavior of polymethylmethacrylate (Metacrill) and hyaluronic acid (Restylane), using a histopathologic study in mice. A prospective study was performed using 40 mice for each substance: polymethylmethacrylate or hyaluronic acid was injected into the right ear, the left ear been used as a control. Histopathologic analyses of the right ear, liver, and kidney were performed at intervals during the study and revealed the development of a granulomatous reaction with fibrosis and absorption of spheres and signs of liver and kidney sistematization for polymethylmethacrylate. A discrete cellular reaction, with less formation of fibrosis, and no giant cells were seen in the mice injected with hyaluronic acid.
Blinded evaluation of the effects of hyaluronic acid filler injections on first impressions.

PubMed

Dayan, Steven H; Arkins, John P; Gal, Thomas J

2010-11-01

Facial appearance has profound influence on the first impression that is projected to others. To determine the effects that complete correction of the nasolabial folds (NLFs) with hyaluronic acid (HA) filler has on the first impression one makes. Twenty-two subjects received injections of HA filler into the NLFs. Photographs of the face in a relaxed pose were taken at baseline, optimal correction visit, and 4 weeks after optimal correction. Three hundred four blinded evaluators completed a survey rating first impression on various measures of success for each photo. In total, 5,776 first impressions were recorded, totaling 46,208 individual assessments of first impression. Our findings indicate a significant improvement in mean first impression in the categories of dating success, attractiveness, financial success, relationship success, athletic success, and overall first impression at the optimal correction visit. At 4 weeks after the optimal correction visit, significance was observed in all categories measured: social skills, academic performance, dating success, occupational success, attractiveness, financial success, relationship success, athletic success, and overall first impression. Full correction of the NLFs with HA filler significantly and positively influences the first impression an individual projects. © 2010 by the American Society for Dermatologic Surgery, Inc.
The Efficacy of Liposomal Bupivacaine Using Periarticular Injection in Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.

PubMed

Kuang, Ming-Jie; Du, Yuren; Ma, Jian-Xiong; He, Weiwei; Fu, Lin; Ma, Xin-Long

2017-04-01

Total knee arthroplasty (TKA) is gradually emerging as the treatment of choice for end-stage osteoarthritis. In the past, the method of liposomal bupivacaine by periarticular injection (PAI) showed better effects on pain reduction and opioid consumption after surgery. However, some recent studies have reported that liposomal bupivacaine by PAI did not improve pain control and functional recovery in patients undergoing TKA. Therefore, this meta-analysis was conducted to determine whether liposomal bupivacaine provides better pain relief and functional recovery after TKA. Web of Science, PubMed, Embase, and the Cochrane Library were comprehensively searched. Randomized controlled trials, controlled clinical trials, and cohort studies were included in our meta-analysis. Eleven studies that compared liposomal bupivacaine using the PAI technique with the conventional PAI method were included in our meta-analysis. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and Cochrane Handbook were applied to assess the quality of the results published in all included studies to ensure that the results of our meta-analysis were reliable and veritable. Our pooled data analysis demonstrated that liposomal bupivacaine was as effective as the control group in terms of visual analog scale score at 24 hours (P = .46), 48 hours (P = .43), 72 hours (P = .21), total amount of opioid consumption (P = .25), range of motion (P = .28), length of hospital stay (P = .53), postoperative nausea (P = .34), and ambulation distance (P = .07). Compared with the conventional PAI method, liposomal bupivacaine shows similar pain control and functional recovery after TKA. Considering the cost for pain control, liposomal bupivacaine is not worthy of being recommended as a long-acting alternative analgesic agent using the PAI method. Copyright © 2016 Elsevier Inc. All rights reserved.
Comparison of intra-articular injections of hyaluronic acid and corticosteroid in the treatment of osteoarthritis of the hip in comparison with intra-articular injections of bupivacaine. Design of a prospective, randomized, controlled study with blinding of the patients and outcome assessors.

PubMed

Colen, Sascha; van den Bekerom, Michel P J; Bellemans, Johan; Mulier, Michiel

2010-11-16

Although intra-articular hyaluronic acid is well established as a treatment for osteoarthritis of the knee, its use in hip osteoarthritis is not based on large randomized controlled trials. There is a need for more rigorously designed studies on hip osteoarthritis treatment as this subject is still very much under debate. Randomized, controlled trial with a three-armed, parallel-group design. Approximately 315 patients complying with the inclusion and exclusion criteria will be randomized into one of the following treatment groups: infiltration of the hip joint with hyaluronic acid, with a corticosteroid or with 0.125% bupivacaine.The following outcome measure instruments will be assessed at baseline, i.e. before the intra-articular injection of one of the study products, and then again at six weeks, 3 and 6 months after the initial injection: Pain (100 mm VAS), Harris Hip Score and HOOS, patient assessment of their clinical status (worse, stable or better then at the time of enrollment) and intake of pain rescue medication (number per week). In addition patients will be asked if they have complications/adverse events. The six-month follow-up period for all patients will begin on the date the first injection is administered. This randomized, controlled, three-arm study will hopefully provide robust information on two of the intra-articular treatments used in hip osteoarthritis, in comparison to bupivacaine. NCT01079455.
Potential superiority of periarticular injection in analgesic effect and early mobilization ability over femoral nerve block following total knee arthroplasty.

PubMed

Fu, Huichao; Wang, Jiaxing; Zhang, Wen; Cheng, Tao; Zhang, Xianlong

2017-01-01

Pain management after total knee arthroplasty (TKA) should permit early knee mobilization with minimal pain. Periarticular injection (PAI) with local anaesthetics has been recently discussed as a protocol of pain control. The purpose of this review of the literature was to evaluate the efficacy of PAI in comparison with femoral nerve block (FNB). A literature search was performed in PubMed, EMBASE, the OVID database and the Cochrane Library databases. Risk of bias was assessed using the Cochrane collaboration tool. Outcomes of interest included narcotic consumption, pain score, early mobilization ability, length of stay and adverse effects or events. Research identified 918 articles, of which six with a total of 284 knees, met the inclusion criteria and were eligible for the current study. Conflicting evidence was found in terms of narcotic consumption on the postoperative day 1 and early mobilization ability. Total narcotic consumption, pain score in the first 2 days after surgery, length of stay and adverse effects or events showed no difference between two groups. Lower pain score on the day of surgery was detected after PAI. When compared to continuous FNB, patients in PAI group showed a tendency to achieving better ability of early mobilization. In consideration of its relatively simple practice and its potential in analgesic effects or early mobilization ability, PAI had superiority to FNB in the management of pain control after TKA. Before PAI could be widely used in clinical practice after TKAs, further investigations would be necessary to confirm or refute our observed results and to unify the protocol of PAI. I.
A potential relationship between skin hydration and stamp-type microneedle intradermal hyaluronic acid injection in middle-aged male face.

PubMed

Seok, Joon; Hong, Ji Yeon; Choi, Sun Young; Park, Kui Young; Kim, Beom Joon

2016-12-01

There is an increasing interest in skin rejuvenation using hyaluronic acid (HA) fillers beyond the improvement of deep wrinkles and volume deficiencies, which have been primary research foci in the past. We conducted a pilot study using a sample of six middle-aged male subjects. Using an automatic intradermal injector with 0.020 mL of material contained in each injection point with a total of 100 points, 2 mL of non-cross-HA filler was injected into the entire face at every treatment session. We administered injections of HA for a total of three sessions per subject at 2-week intervals and evaluated the results using a corneometer, TEWL, cutometer, measures of patient satisfaction, and the global aesthetic improvement scale (GAIS). Corneometer values increased steadily at each measurement, while the average value of TEWL increased in comparison with baseline after each application of the procedure. However, values returned to readings similar to those at 4 weeks after complete termination of the procedures. Cutometer values differed between the baseline and after procedures. All patients were assessed as "very much improved" or "much improved" according to GAIS, and all were pleased with the outcomes of treatment in terms of the enhancement of moisture, elasticity, and brightness. © 2016 Wiley Periodicals, Inc.
PMMA (polymethylmetacrylate) microspheres and stabilized hyaluronic acid as an injection laryngoplasty material for the treatment of glottal insufficiency: in vivo canine study.

PubMed

Lim, Jae-Yol; Kim, Han Su; Kim, Young-Ho; Kim, Kwang-Moon; Choi, Hong-Shik

2008-03-01

Both PMMA (polymethylmetacrylate) microspheres (PM) and stabilized hyaluronic acid (HA) are recently used for facial augmentation. The aim of this study was to test functional effect, durability, and safety of the injection of these two materials into true vocal folds, and test their availability as injection laryngoplasty materials in vivo canine model. The study was carried out with 16 beagle dogs (8 males and 8 females, average weight of 12.4 kg). No biological difference was detected between two groups; PM (Artecoll) injection and HA (Restylane) injection group. After inducing complete unilateral paralysis of the recurrent laryngeal nerve of the dogs, either PM or HA was injected into the paralyzed vocal fold. One, 3, 6, and 9 months after the injection, clinical outcomes and videostroboscopic findings were evaluated by investigators who were blind to the injection materials. Histological study and microscopic computerized augmentation dimension analysis were also performed. In HA injection group, up to 30% the HA was gradually resorbed over time. However, in PM group, the dimension of the augmented region after 9 months was similar to that after 1 month. In both groups, the mucosal waves of the vocal folds decreased in amplitude and periodicity, but they were still well detected during the follow-up periods. Acute immune reaction to HA was not detected, but some degree of foreign body reaction occurred in PM injection group. Both PM and HA are safe and relatively durable in vocal folds and they are considered as useful candidates for injection laryngoplasty.
Cohesive Polydensified Matrix® hyaluronic acid volumizer injected for cheek augmentation has additional positive effect on nasolabial folds.

PubMed

Gauglitz, Gerd; Steckmeier, Stephanie; Pötschke, Julian; Schwaiger, Hannah

2017-01-01

Cohesive Polydensified Matrix ® hyaluronic acid (CPM-HA) volumizer has been used successfully for several years to reverse biometric volume loss during facial aging. This observational study explored the additive effect on nasolabial folds when CPM-HA volumizer is injected into the neighboring cheek area. In this open-label, prospective, postmarketing noninterventional study, 18 adult patients seeking esthetic enhancement of the lateral cheek hollows and cheekbone area were injected with CPM-HA volumizer integrated with lidocaine (CPM-HA-VL) in the upper or lower cheek area. Safety and performance of CPM-HA-VL up to 12 months after injection with follow-up visits at week 4 and month 3, 6, and 12 were assessed. The primary endpoint was improvement of cheek fullness on the validated Merz Aesthetics Scales. Additionally, changes in nasolabial folds were quantified using a phaseshift rapid in vivo measurement of skin optical three-dimensional (3D) in vivo measurement device. Patients (94.4% female, median age 52 years, age range 39-69 years) were injected with a mean volume of 2.5±1.1 mL CPM-HA-VL per side. Immediately after injection, mean severity for upper and lower cheek fullness assessed on the validated MAS improved from 2.5±0.6 and 2.8±0.5, respectively, to 1.0±0.0, and remained unchanged through month 12. Improvement in relation to baseline was attested on the Global Aesthetics Improvement Scale for all assessments. Compared with baseline, the following assessments offered a statistical significance in the reduction of wrinkle depth of nasolabial folds (maximum depth reduction by 30.4% at 3 months) according to optical 3D in vivo measurements. Pain during injection was minimal and abated within 30 minutes. Treatment was well tolerated and led to great patient satisfaction. CPM-HA-VL injected into the upper and lower cheeks led to long-lasting satisfactory cosmetic results in cheek augmentation as well as in reducing depth of nasolabial folds adjacent to
Nonsurgical Rejuvenation of the Eyelids with Hyaluronic Acid Gel Injections

PubMed Central

Lee, Seongmu; Yen, Michael T.

2017-01-01

There has been an increased recognition for the role volume deflation plays in the aging periorbital area, and as such, rejuvenation strategies to augment and restore volume have developed and evolved. Hyaluronic acid fillers provide an efficient option for volume augmentation with good efficacy, longevity, and safety. An understanding of the changes in the upper and lower periocular area due to aging, the meticulous identification of focal hollows, and the precise delivery of filler to these areas can smooth contours and restore a rejuvenated periorbital area. PMID:28255285

Efficacy and safety of repeated courses of hyaluronic acid injections for knee osteoarthritis: A systematic review.

PubMed

Altman, Roy; Hackel, Josh; Niazi, Faizan; Shaw, Peter; Nicholls, Mathew

2018-01-31

Hyaluronic acid (HA) is a commonly prescribed intra-articular (IA) therapy for knee osteoarthritis (OA). While a single series of IA-HA has been well studied, the efficacy and safety of repeated courses of IA-HA injection therapy in knee OA patients have not been evaluated as frequently. A literature search was conducted using MEDLINE, EMBASE and PubMed databases. The primary outcome measure was knee pain reduction after each treatment course and/or last reported follow-up visit. Secondary outcomes were treatment-related adverse events (AEs) and serious adverse events (SAEs). A total of 17 articles (7 RCTs and 10 cohort studies) met the pre-defined inclusion criteria. Of the RCTs, six were double-blind with two trials including open label extension studies, and one was single-blind. Studies ranged from investigating a single reinjection cycle to four repeat injection cycles. Eleven studies evaluated one reinjection, five studies evaluated ≥2 repeated courses of IA-HA, and one study allowed either one or two repeated courses. All studies reported pain reduction from baseline in the IA-HA treatment group throughout the initial treatment cycle, and either sustained or further reduced pain throughout the repeated courses of treatment. The study with the longest follow-up repeated IA-HA injection every 6 months for 25 months. Pain decreased after the first course and continued to decrease until the end of the study, with an approximate 55% reduction in pain compared to baseline. Common AEs were joint swelling and arthralgia; there were no reported SAEs. All repeated courses were well tolerated, and the number of documented AEs and SAEs was similar to the primary injection regimens. Repeated courses of IA-HA injections are an effective and safe treatment for knee OA. Repeat courses were demonstrated to maintain or further improve pain reduction while introducing no increased safety risk. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
A new viscosupplement based on partially hydrophobic hyaluronic acid: a comparative study.

PubMed

Finelli, Ivana; Chiessi, Ester; Galesso, Devis; Renier, Davide; Paradossi, Gaio

2011-01-01

A novel partially hydrophobized derivative of hyaluronic acid (HYADD® 4), containing a low number of C16 side-chains per polysaccharide backbone, provides injectable hydrogels stabilized by side-chain hydrophobic interactions. The rheological properties of Hymovis®, a physical hydrogel based on the hyaluronic acid derivative HYADD® 4, were evaluated using as reference a solution of the parent natural polysaccharide, hyaluronic acid. The rheological measurements were performed both in flow and oscillation regimes at the physiological frequency values of the knee, typically spanning the range from 0.5 Hz (walking frequency) to 3 Hz (running frequency). Moreover, the viscoelastic features of Hymovis® were compared with the market-available viscosupplementation products in view of its use in joint diseases.The different behavior of the investigated materials in crossover frequency measurements and in structure recovery experiments can be explained on the basis of the structural and dynamic properties of the polymeric systems.
Preliminary study of highly cross-linked hyaluronic acid-based combination therapy for management of knee osteoarthritis-related pain

PubMed Central

Palmieri, Beniamino; Rottigni, Valentina; Iannitti, Tommaso

2013-01-01

Background Hyaluronic acid has been extensively used for treatment of knee osteoarthritis due to its anti-inflammatory properties and its ability to act as a synovial lubricant. Furthermore, it has found application in combination with other drugs in the dermatological field and in pre-clinical studies in animal models of osteoarthritis. Experimental evidence suggests that a combination of this macromolecule with other drugs may act as a slow-release depot. However, to date, to the best of our knowledge, no one has tested local intra-articular delivery of highly cross-linked hyaluronic acid combined with bisphosphonate or nonsteroidal anti-inflammatory drugs for management of knee osteoarthritis pain in the clinical setting. The aim of the present randomized double-blind study was to investigate, for the first time, the effect of a highly cross-linked hyaluronic acid, Variofill®, alone or in combination with diclofenac sodium or sodium clodronate, for management of bilateral knee osteoarthritis-related pain. Methods Sixty-two patients with symptomatic bilateral medial tibiofemoral knee osteoarthritis (Kellgren–Lawrence grade II and III) and pain in both knees corresponding to a daily visual analog scale (VAS) score ≥ 30 in the month before the beginning of the study were included in this investigation. Patients were divided into three groups: group 1, treated with an injection of hyaluronic acid alone (66 mg) into each knee; group 2, treated with an injection of hyaluronic acid (49.5 mg) plus diclofenac sodium (5 mg) into each knee; group 3, treated with an injection of hyaluronic acid (49.5 mg) plus sodium clodronate (5 mg) into each knee. Patients also underwent blood tests for measurement of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) immediately before and at 6-month follow-up. Results Hyaluronic acid alone and in combination with sodium clodronate or diclofenac sodium produced a significant improvement in mean VAS pain score at 3 and
Hyaluronic acid-based scaffolds for tissue engineering.

PubMed

Chircov, Cristina; Grumezescu, Alexandru Mihai; Bejenaru, Ludovic Everard

2018-01-01

Hyaluronic acid (HA) is a natural glycosaminoglycan found in the extracellular matrix of most connective tissues. Due to its chemical structure, HA is a hydrophilic polymer and it is characterized by a fast degradation rate. HA-based scaffolds for tissue engineering are intensively studied due to their increased biocompatibility, biodegradability and chemical modification. Depending on the processing technique, scaffolds can be prepared in the form of hydrogels, sponges, cryogels, and injectable hydrogels, all discussed in this review.
Intra-Articular Hyaluronic Acid Compared to Traditional Conservative Treatment in Dogs with Osteoarthritis Associated with Hip Dysplasia

PubMed Central

Carapeba, Gabriel O. L.; Cavaleti, Poliana; Brinholi, Rejane B.

2016-01-01

The purpose of this study was to compare the efficacy of the intra-articular (IA) hyaluronic acid injection to traditional conservative treatment (TCT) in dogs with osteoarthritis (OA) induced by hip dysplasia. Sixteen dogs were distributed into two groups: Hyal: IA injection of hyaluronic acid (5–10 mg), and Control: IA injection with saline solution (0.5–1.0 mL) in combination with a TCT using an oral nutraceutical (750–1000 mg every 12 h for 90 days) and carprofen (2.2 mg/kg every 12 h for 15 days). All dogs were assessed by a veterinarian on five occasions and the owner completed an assessment form (HCPI and CPBI) at the same time. The data were analyzed using unpaired t test, ANOVA, and Tukey's test (P < 0.05). Compared with baseline, lower scores were observed in both groups over the 90 days in the veterinarian evaluation, HCPI, and CPBI (P < 0.001). The Hyal group exhibited lower scores from 15 to 90 and 60 to 90 days, in the CBPI and in the veterinarian evaluation, respectively, compared to the Control group. Both treatments reduced the clinical signs associated with hip OA. However, more significant results were achieved with intra-articular hyaluronic acid injection. PMID:27847523
Biocompatibility of hyaluronic acid hydrogels prepared by porous hyaluronic acid microbeads

NASA Astrophysics Data System (ADS)

Kim, Jin-Tae; Lee, Deuk Yong; Kim, Tae-Hyung; Song, Yo-Seung; Cho, Nam-Ihn

2014-05-01

Hyaluronic acid hydrogels (HAHs) were synthesized by immersing HA microbeads crosslinked with divinyl sulfone in a phosphate buffered saline solution to evaluate the biocompatibility of the gels by means of cytotoxicity, genotoxicity ( in vitro chromosome aberration test, reverse mutation assay, and in vivo micronucleus test), skin sensitization, and intradermal reactivity. The HAHs induced no cytotoxicity or genotoxicity. In guinea pigs treated with grafts and prostheses, no animals died and there were no abnormal clinical signs. The sensitization scores were zero in all guinea pigs after 24 h and 48 h challenge, suggesting that the HAHs had no contact allergic sensitization in the guinea pig maximization test. No abnormal signs were found in New Zealand White rabbits during the 72 h observation period after the injection. There was no difference between the HAHs and negative control mean scores because skin reaction such as erythema or oedema was not observed after injection. Experimental results suggest that the HAHs would be suitable for soft tissue augmentation due to the absence of cytotoxicity, genotoxicity, skin sensitization, and intradermal reactivity.
Clinical benefit using sperm hyaluronic acid binding technique in ICSI cycles: a systematic review and meta-analysis.

PubMed

Beck-Fruchter, Ronit; Shalev, Eliezer; Weiss, Amir

2016-03-01

The human oocyte is surrounded by hyaluronic acid, which acts as a natural selector of spermatozoa. Human sperm that express hyaluronic acid receptors and bind to hyaluronic acid have normal shape, minimal DNA fragmentation and low frequency of chromosomal aneuploidies. Use of hyaluronic acid binding assays in intracytoplasmic sperm injection (ICSI) cycles to improve clinical outcomes has been studied, although none of these studies had sufficient statistical power. In this systematic review and meta-analysis, electronic databases were searched up to June 2015 to identify studies of ICSI cycles in which spermatozoa able to bind hyaluronic acid was selected. The main outcomes were fertilization rate and clinical pregnancy rate. Secondary outcomes included cleavage rate, embryo quality, implantation rate, spontaneous abortion and live birth rate. Seven studies and 1437 cycles were included. Use of hyaluronic acid binding sperm selection technique yielded no improvement in fertilization and pregnancy rates. A meta-analysis of all available studies showed an improvement in embryo quality and implantation rate; an analysis of prospective studies only showed an improvement in embryo quality. Evidence does not support routine use of hyaluronic acid binding assays in all ICSI cycles. Identification of patients that might benefit from this technique needs further study. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Analysis of anatomic periarticular tibial plate fit on normal adults.

PubMed

Goyal, Kanu S; Skalak, Anthony S; Marcus, Randall E; Vallier, Heather A; Cooperman, Daniel R

2007-08-01

Implant manufacturers are producing anatomically contoured periarticular plates to improve the treatment of proximal tibia fractures. We assessed the accuracy of the designation anatomic. We applied eight-hole medial and lateral anatomically contoured periarticular plates to 101 cadaveric tibiae. The tibiae and the plate fits were mapped, quantified, and analyzed using a MicroScribe G2LX digitizer, Rhinoceros software, and MATLAB software. By corresponding the clinical appearance of good fit with our digital findings, we created numerical criteria for plate fit in three planes: coronal (volume of free space between the plate and bone), sagittal (alignment with the tibial plateau and shaft), and axial (match in curvature between the proximal horizontal part of the plate and the tibial plateau). An anatomic fit should mirror the shape of the tibia in all three planes, and only four medial and four lateral plate fits qualified. Recognizing and understanding the substantial variations in fit that exist between anatomically contoured plates and the tibia may help lead to a more stable fixation and prevent malreduction of the fracture and/or soft tissue impingement.
Recent trends in the surgical management of primary vesicoureteral reflux in the era of dextranomer/hyaluronic acid.

PubMed

Herbst, Katherine W; Corbett, Sean T; Lendvay, Thomas S; Caldamone, Anthony A

2014-05-01

Since its inception as a technology in the United States, endoscopic correction of vesicoureteral reflux has become a popular treatment option in children with vesicoureteral reflux with reported wide use. We determined whether the increasing trend in use in the United States after the introduction of dextranomer/hyaluronic acid has been sustained. We abstracted data on pediatric patients treated with ureteral reimplantation or dextranomer/hyaluronic acid intervention for vesicoureteral reflux from 2004 to 2011 from the PHIS (Pediatric Health Information System) database. Patients with coding data indicating diagnoses other than primary vesicoureteral reflux and hospitals reporting less than 80% of ambulatory surgery cases by CPT code were excluded from study. We identified 14,430 patients (17,826 procedures), of whom 49% underwent reimplantation and 51% underwent dextranomer/hyaluronic acid injection. Of the patients 83% were female with a median age at surgery of 4.7 years (IQR 2.5-7.2). Linear regression showed a significant downward trend in the average total number of antireflux operations per institution during the study period. This was attributable to a decrease in the average rate of dextranomer/hyaluronic acid interventions because the average reimplantation rate remained stable during this time. At freestanding pediatric hospitals enrolled in the PHIS database there is a trend toward decreasing intervention for primary vesicoureteral reflux, which appears to be due to decreased use of injection therapy. This may reflect a philosophical change in reflux management by injection therapy. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Peritoneal adhesion prevention with a biodegradable and injectable N,O-carboxymethyl chitosan-aldehyde hyaluronic acid hydrogel in a rat repeated-injury model

NASA Astrophysics Data System (ADS)

Song, Linjiang; Li, Ling; He, Tao; Wang, Ning; Yang, Suleixin; Yang, Xi; Zeng, Yan; Zhang, Wenli; Yang, Li; Wu, Qinjie; Gong, Changyang

2016-11-01

Postoperative peritoneal adhesion is one of the serious issues because it induces severe clinical disorders. In this study, we prepared biodegradable and injectable hydrogel composed of N,O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA), and assessed its anti-adhesion effect in a rigorous and severe recurrent adhesion model which is closer to clinical conditions. The flexible hydrogel, which gelated in 66 seconds at 37 °C, was cross-linked by the schiff base derived from the amino groups of NOCC and aldehyde groups in AHA. In vitro cytotoxicity test showed the hydrogel was non-toxic. In vitro and in vivo degradation examinations demonstrated the biodegradable and biocompatibility properties of the hydrogel. The hydrogel discs could prevent the invasion of fibroblasts, whereas fibroblasts encapsulated in the porous 3-dimensional hydrogels could grow and proliferate well. Furthermore, the hydrogel was applied to evaluate the anti-adhesion efficacy in a more rigorous recurrent adhesion model. Compared with normal saline group and commercial hyaluronic acid (HA) hydrogel, the NOCC-AHA hydrogel exhibited significant reduction of peritoneal adhesion. Compared to control group, the blood and abdominal lavage level of tPA was increased in NOCC-AHA hydrogel group. These findings suggested that NOCC-AHA hydrogel had a great potential to serve as an anti-adhesion candidate.
High-fat diet exacerbates pain-like behaviors and periarticular bone loss in mice with CFA-induced knee arthritis.

PubMed

Loredo-Pérez, Aleyda A; Montalvo-Blanco, Carlos E; Hernández-González, Luis I; Anaya-Reyes, Maricruz; Fernández Del Valle-Laisequilla, Cecilia; Reyes-García, Juan G; Acosta-González, Rosa I; Martínez-Martínez, Arisai; Villarreal-Salcido, Jaira C; Vargas-Muñoz, Virginia M; Muñoz-Islas, Enriqueta; Ramírez-Rosas, Martha B; Jiménez-Andrade, Juan M

2016-05-01

Our aim was to quantify nociceptive spontaneous behaviors, knee edema, proinflammatory cytokines, bone density, and microarchitecture in high-fat diet (HFD)-fed mice with unilateral knee arthritis. ICR male mice were fed either standard diet (SD) or HFD starting at 3 weeks old. At 17 weeks, HFD and SD mice received intra-articular injections either with Complete Freund's Adjuvant (CFA) or saline into the right knee joint every 7 days for 4 weeks. Spontaneous pain-like behaviors and knee edema were assessed for 26 days. At day 26 post-first CFA injection, serum levels of IL-1β, IL-6, and RANKL were measured by ELISA, and microcomputed tomography analysis of knee joints was performed. HFD-fed mice injected with CFA showed greater spontaneous pain-like behaviors of the affected extremity as well as a decrease in the weight-bearing index compared to SD-fed mice injected with CFA. Knee edema was not significantly different between diets. HFD significantly exacerbated arthritis-induced bone loss at the distal femoral metaphysis but had no effect on femoral diaphyseal cortical bone. HFD did not modify serum levels of proinflammatory cytokines. HFD exacerbates pain-like behaviors and significantly increases the magnitude of periarticular trabecular bone loss in a murine model of unilateral arthritis. © 2016 The Obesity Society.
Efficacy and safety of injection with poly-L-lactic acid compared with hyaluronic acid for correction of nasolabial fold: a randomized, evaluator-blinded, comparative study.

PubMed

Hyun, M Y; Lee, Y; No, Y A; Yoo, K H; Kim, M N; Hong, C K; Chang, S E; Won, C H; Kim, B J

2015-03-01

Hyaluronic acid (HA) fillers and poly-L-lactic acid (PLA) fillers are frequently used to correct facial wrinkles. To compare the efficacy and safety of a novel injectable poly-L-lactic acid (PLA) filler and a well-studied biphasic HA filler for the treatment of moderate to severe nasolabial folds. In this multicentre, randomized, evaluator-blinded, comparative study, subjects were randomized for injections with PLA or HA into both nasolabial folds. Efficacy was determined by calculating the change in Wrinkle Severity Rating Scale (WSRS) relative to baseline. Local safety was assessed by reported adverse events. At week 24, mean improvement in WSRS from baseline was 2.09 ± 0.68 for the PLA side and 1.54 ± 0.65 for the HA side. Both injections were well tolerated, and the adverse reactions were mild and transient in most cases. PLA provides noninferior efficacy compared with HA 6 months after being used to treat moderate to severe nasolabial folds. © 2014 British Association of Dermatologists.
Retraction of the Plunger on a Syringe of Hyaluronic Acid Before Injection: Are We Safe?

PubMed

Carey, Wayne; Weinkle, Susan

2015-12-01

Controversy exists concerning the need for aspiration before injection with hyaluronic acid (HA) fillers. The authors undertook a study of HA products to determine if blood could be aspirated back into a syringe of HA when the needle has been primed or filled with HA. Two studies were set up to determine if or when blood could be withdrawn from a heparinized fresh tube of blood into the HA syringe. Two different techniques were tested; one using a slow-pull retraction of the plunger and up to a 5-second waiting time before release versus a rapid pullback and quick release. Review of these data demonstrates that the usual clinical method, which involves quick withdrawal and instant release of the syringe plunger does not allow for sufficient removal of the filler found intraluminal in the needle and may give rise to false negative results in vitro and likely in vivo with the exception being the Galderma/Medicis products. In summary, withdrawal of the syringe plunger with no visible blood in the syringe does not eliminate the possibility of intravascular placement of the syringe needle.
A comparative study on the impact of intra-articular injections of hyaluronic acid, tenoxicam and betametazon on the relief of temporomandibular joint disorder complaints.

PubMed

Gencer, Zeliha Kapusuz; Özkiriş, Mahmut; Okur, Aylin; Korkmaz, Murat; Saydam, Levent

2014-10-01

The aim of this study was to compare the efficacy of intra-articular injections of three different agents with well known anti-inflammatory properties. Between April 2010 and January 2013 a total of 100 patients who were diagnosed as temporomandibular joint disorder in the Department of Otolaryngology at Bozok University School of Medicine were prospectively studied. Patients with symptoms of jaw pain, limited or painful jaw movement, clicking or grating within the joint, were evaluated with temporomandibular CT to investigate the presence of cartilage or capsule degeneration. In the study group there were 55 female and 45 male patients who were non-responders to conventional anti-inflammatory treatment for TMJ complaints. The patients were randomly divided into four groups consisting of a control group and three different groups who underwent intra-articular injection of one given anti-inflammatory agent for each group. We injected saline solution to intra-articular space in the control group. Of three anti-inflammatory agents including hyaluronic acid (HA, Hyalgan intra-articular injection, Sodium hyaluronate 10 mg/ml, 2 ml injection syringe, Bilim Pharmaceutical Company, Istanbul, Turkey); betamethasone (CS, Diprospan flacon, 7.0 mg betamethasone/1 ml, Schering-Plough Pharmaceutical Company, Istanbul, Turkey) and; tenoxicam (TX, Tilcotil flacon, 20 mg tenoxicam/ml, Roche Pharmaceutical Company, Istanbul, Turkey) were administered intra-articularly under, ultrasonographic guidance. Following the completion of injections the, changes in subjective symptoms were compared with visual analogue scales, (VAS) scores at 1st and 6th weeks' follow-up visits between four groups. The HA group did significantly better pain relief scores compared to the, other groups at 1st and 6th weeks (p < 0.05). TX and CS groups' pain scores were better than control group values (p < 0.05, for both agents). The pain relief effect of TX was noted to decrease significantly between the 1st
Patient-Controlled Epidural Analgesia or Multimodal Pain Regimen with Periarticular Injection After Total Hip Arthroplasty

PubMed Central

Jules-Elysee, Kethy M.; Goon, Amanda K.; Westrich, Geoffrey H.; Padgett, Douglas E.; Mayman, David J.; Ranawat, Amar S.; Ranawat, Chitranjan S.; Lin, Yi; Kahn, Richard L.; Bhagat, Devan D.; Goytizolo, Enrique A.; Ma, Yan; Reid, Shane C.; Curren, Jodie; YaDeau, Jacques T.

2015-01-01

Background: The optimal postoperative analgesia after primary total hip arthroplasty remains in question. This randomized, double-blind, placebo-controlled study compared the use of patient-controlled epidural analgesia (PCEA) with use of a multimodal pain regimen including periarticular injection (PAI). We hypothesized that PAI would lead to earlier readiness for discharge, decreased opioid consumption, and lower pain scores. Methods: Forty-one patients received PAI, and forty-three patients received PCEA. Preoperatively, both groups were administered dexamethasone (6 mg, orally). The PAI group received a clonidine patch and sustained-release oxycodone (10 mg), while the PCEA group had placebo. Both groups received combined spinal-epidural anesthesia and used an epidural pain pump postoperatively; the PAI group had normal saline solution, while the PCEA group had bupivacaine and hydromorphone. The primary outcome, readiness for discharge, required the discontinuation of the epidural, a pain score of <4 (numeric rating scale) without parenteral narcotics, normal eating, minimal nausea, urination without a catheter, a dry surgical wound, no acute medical problems, and the ability to independently transfer and walk 12.2 m (40 ft). Results: The mean time to readiness for discharge (and standard deviation) was 2.4 ± 0.7 days (PAI) compared with 2.3 ± 0.8 days (PCEA) (p = 0.86). The mean length of stay was 3.0 ± 0.8 days (PAI) compared with 3.1 ± 0.7 days (PCEA) (p = 0.46). A significant mean difference in pain score of 0.74 with ambulation (p = 0.01; 95% confidence interval [CI], 0.18 to 1.31) and 0.80 during physical therapy (p = 0.03; 95% CI, 0.09 to 1.51) favored the PCEA group. The mean opioid consumption (oral morphine equivalents in milligrams) was significantly higher in the PAI group on postoperative day 0 (43 ± 21 compared with 28 ± 23; p = 0.002) and postoperative days 0 through 2 (136 ± 59 compared with 90 ± 79; p = 0.004). Opioid-Related Symptom
Injectable Drug Eluting Elastomeric Polymer: A Novel Submucosal Injection Material

PubMed Central

Tran, Richard T.; Palmer, Michael; Tang, Shou-Jiang; Abell, Thomas L.; Yang, Jian

2011-01-01

Background Biodegradable hydrogels can deliver therapeutic payloads with great potentials in endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) to yield improvements in efficacy and foster mucosal regeneration. Objective To assess the efficacy of an injectable drug eluting elastomeric polymer (iDEEP) as a submucosal injection material. Design Comparative study among 3 different solutions using material characterization tests, ex vivo and in vivo porcine models. Setting Academic hospital. Interventions 30 gastric submucosal cushions were achieved with saline (0.9%), sodium hyaluronate (0.4%), and iDEEP (n = 10) in ex vivo porcine stomachs. Four porcine gastric submucosal cushions were then performed in vivo using iDEEP. Main outcome measurements Maximum injection pressure, Rebamipide release rate, submucosal elevation duration, and assessment of in vivo efficacy by en bloc resection. Results No significant difference in injection pressures between iDEEP (28.9 ± 0.3 PSI) and sodium hyaluronate (29.5 ± 0.4 PSI, P > .05) was observed. iDEEP gels displayed a controlled release of Rebamipide up to 2 weeks in vitro. The elevation height of iDEEP (5.7 ± 0.5 mm) was higher than saline (2.8 ± 0.2 mm, P < .01) and SH (4.2 ± 0.2 mm, P < .05). All EMR procedures were successfully performed after injection of iDEEP, and a large gel cushion was noted after the resection procedure. Limitations Benchtop, ex vivo, and non-survival pig study. Conclusions A novel injection solution was evaluated for endoscopic resection. These results suggest that iDEEP may provide a significant step towards the realization of an ideal EMR and ESD injection material. PMID:22301346
The influence of polymeric component of bioactive glass-based nanocomposite paste on its rheological behaviors and in vitro responses: hyaluronic acid versus sodium alginate.

PubMed

Sohrabi, Mehri; Hesaraki, Saeed; Kazemzadeh, Asghar

2014-04-01

Different biocomposite pastes were prepared from a solid phase that was nanoparticles of sol-gel-derived bioactive glass and different liquid phases including 3% hyaluronic acid solution, sodium alginate solutions (3% and 10 %) or mixtures of hyaluronic acid and sodium alginate (3% or 10 %) solutions in 50:50 volume ratio. Rheological properties of the pastes were measured in both rotatory and oscillatory modes. The washout behavior and in vitro apatite formation of the pastes were determined by soaking them in simulated body fluid under dynamic situation for 14 days. The proliferation and alkaline phosphatase activity of MG-63 osteoblastic cells were also determined using extracts of the pastes. All pastes could be easily injected from the standard syringes with different tip diameters. All pastes exhibited visco-elastic character, but a nonthixotropic paste was obtained using hyaluronic acid in which the loss modulus was higher than the storage modulus. The thixotropy and storage modulus were increasingly improved by adding/using sodium alginate as mixing liquid. Moreover, the pastes in which the liquid phase was sodium alginate or mixture of hyaluronic acid and 10% sodium alginate solution revealed better apatite formation ability and washout resistance than that made of hyaluronic acid alone. No cytotoxicity effects were observed by extracts of the pastes on osteoblasts but better alkaline phosphatase activity was found for the pastes containing hyaluronic acid. Overall, injectable biocomposites can be produced by mixing bioactive glass nanoparticles and sodium alginate/hyaluronic acid polymers. They are potentially useful for hard and even soft tissues treatments. Copyright © 2013 Wiley Periodicals, Inc.
Peritoneal adhesion prevention with a biodegradable and injectable N,O-carboxymethyl chitosan-aldehyde hyaluronic acid hydrogel in a rat repeated-injury model

PubMed Central

Song, Linjiang; Li, Ling; He, Tao; Wang, Ning; Yang, Suleixin; Yang, Xi; Zeng, Yan; Zhang, Wenli; Yang, Li; Wu, Qinjie; Gong, Changyang

2016-01-01

Postoperative peritoneal adhesion is one of the serious issues because it induces severe clinical disorders. In this study, we prepared biodegradable and injectable hydrogel composed of N,O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA), and assessed its anti-adhesion effect in a rigorous and severe recurrent adhesion model which is closer to clinical conditions. The flexible hydrogel, which gelated in 66 seconds at 37 °C, was cross-linked by the schiff base derived from the amino groups of NOCC and aldehyde groups in AHA. In vitro cytotoxicity test showed the hydrogel was non-toxic. In vitro and in vivo degradation examinations demonstrated the biodegradable and biocompatibility properties of the hydrogel. The hydrogel discs could prevent the invasion of fibroblasts, whereas fibroblasts encapsulated in the porous 3-dimensional hydrogels could grow and proliferate well. Furthermore, the hydrogel was applied to evaluate the anti-adhesion efficacy in a more rigorous recurrent adhesion model. Compared with normal saline group and commercial hyaluronic acid (HA) hydrogel, the NOCC-AHA hydrogel exhibited significant reduction of peritoneal adhesion. Compared to control group, the blood and abdominal lavage level of tPA was increased in NOCC-AHA hydrogel group. These findings suggested that NOCC-AHA hydrogel had a great potential to serve as an anti-adhesion candidate. PMID:27869192
Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options.

PubMed

Duymus, Tahir Mutlu; Mutlu, Serhat; Dernek, Bahar; Komur, Baran; Aydogmus, Suavi; Kesiktas, Fatma Nur

2017-02-01

This study was performed to compare the efficacy of treatment in three groups of patients with knee osteoarthritis (OA) given an intra-articular injection of platelet-rich plasma (PRP), hyaluronic acid (HA) or ozone gas. A total of 102 patients with mild-moderate and moderate knee OA who presented at the polyclinic with at least a 1-year history of knee pain and VAS score ≥4 were randomly separated into three groups. Group 1 (PRP group) received intra-articular injection of PRP × 2 doses, Group 2 (HA group) received a single dose of HA, and Group 3 (Ozone group) received ozone × four doses. Weight-bearing anteroposterior-lateral and Merchant's radiographs of both knees were evaluated. WOMAC and VAS scores were applied to all patients on first presentation and at 1, 3, 6 and 12 months. At the end of the 1st month after injection, significant improvements were seen in all groups. In the 3rd month, the improvements in WOMAC and VAS scores were similar in Groups 1 and 2, while those in Group 3 were lower (p < 0.001). At the 6th month, while the clinical efficacies of PRP and HA were similar and continued, the clinical effect of ozone had disappeared (p < 0.001). At the end of the 12th month, PRP was determined to be both statistically and clinically superior to HA (p < 0.001). In the treatment of mild-moderate knee OA, PRP was more successful than HA and ozone injections, as the application alone was sufficient to provide at least 12 months of pain-free daily living activities. Therapeutic study, Level I.
Role of Bladder Hydrodistention and Intravesical Sodium Hyaluronate in the Treatment of Interstitial Cystitis.

PubMed

Yang, Jin-Yi; Wei, Wei; Lan, Yu-Long; Liu, Jun-Qiang; Wang, Hai-Bo; Li, Shao

2015-12-23

To evaluate the clinical efficacy of bladder hydrodistention and intravesical sodium hyaluronate in the treatment of interstitial cystitis (IC). Twenty-one patients with IC received intravesical sodium hyaluronate therapy under nerve block or intravenous anesthesia. Bladders were perfused with 100 cmH2O perfusion pressure and expanded for 10 min and were later injected with 40 mg/50 mL sodium hyaluronate through the catheter. After 1 h, the perfusion fluid was released. Perfusion was applied once per week, 4 to 6 times as a course of treatment. Under anesthesia, the average bladder capacity was 191.62 ± 88.67 mL, and after bladder expansion, the bladder capacity reached 425.33 ± 79.83 mL (P = .000). There were 2 suspected bladder ruptures after bladder expansion at 6.5 min and 7.2 min. After 10 min of bladder expansion, there were 19 cases of significantly gross hematuria. After treatment, the catheters of 17 patients were removed at 24 h; for the 2 cases of hematuria, catheters were removed at 72 h and for the 2 cases of suspected bladder rupture, catheters were removed after 4 days. After catheter removal, the pain threshold significantly decreased, and the maximum urinary output increased slightly. Compared with values before treatment, the day before the second injection of sodium hyaluronate, the frequency of urination decreased significantly (32.8 vs. 18.5 times/24 h), the maximum urinary output increased significantly (86.7 vs. 151.9 mL), the pain decreased significantly (8.7 vs. 3.0), and the O'Leary-Sant IC score and quality of life score were significantly decreased (30.0 vs. 17.0 and 5.9 vs. 2.4, respectively) (P = .000). Bladder hydrodistention under anesthesia for patients with severe intractable IC produces immediate effectiveness; sodium hyaluronic infusion can alleviate frequent urination and pain, and the efficacy was positively correlated with the duration of treatment.

Hyaluronic acid concentration in liver diseases.

PubMed

Gudowska, Monika; Gruszewska, Ewa; Panasiuk, Anatol; Cylwik, Bogdan; Flisiak, Robert; Świderska, Magdalena; Szmitkowski, Maciej; Chrostek, Lech

2016-11-01

The aim of this study was to evaluate the effect of liver diseases of different etiologies and clinical severity of liver cirrhosis on the serum level of hyaluronic acid. The results were compared with noninvasive markers of liver fibrosis: APRI, GAPRI, HAPRI, FIB-4 and Forn's index. Serum samples were obtained from 20 healthy volunteers and patients suffering from alcoholic cirrhosis (AC)-57 patients, non-alcoholic cirrhosis (NAC)-30 and toxic hepatitis (HT)-22. Cirrhotic patients were classified according to Child-Pugh score. Hyaluronic acid concentration was measured by the immunochemical method. Non-patented indicators were calculated using special formulas. The mean serum hyaluronic acid concentration was significantly higher in AC, NAC and HT group in comparison with the control group. There were significant differences in the serum hyaluronic acid levels between liver diseases, and in AC they were significantly higher than those in NAC and HT group. The serum hyaluronic acid level differs significantly due to the severity of cirrhosis and was the highest in Child-Pugh class C. The sensitivity, specificity, accuracy, positive and negative predictive values and the area under the ROC curve for hyaluronic acid and all non-patented algorithms were high and similar to each other. We conclude that the concentration of hyaluronic acid changes in liver diseases and is affected by the severity of liver cirrhosis. Serum hyaluronic acid should be considered as a good marker for noninvasive diagnosis of liver damage, but the combination of markers is more useful.
Relative ratios of collagen composition of periarticular tissue of joints of the upper limb.

PubMed

Cheah, A; Harris, A; Le, W; Huang, Y; Yao, J

2017-07-01

We investigated the relative ratios of collagen composition of periarticular tissue of the elbow, wrist, metacarpophalangeal, proximal and distal interphalangeal joints. Periarticulat tissue, which we defined as the ligaments, palmar plate and capsule, was harvested from ten fresh-frozen cadaveric upper limbs, yielding 50 samples. The mean paired differences (95% confidence interval) of the relative ratios of collagen between the five different joints were estimated using mRNA expression of collagen in the periarticular tissue. We found that the relative collagen composition of the elbow was not significantly different to that of the proximal interphalangeal joint, nor between the proximal interphalangeal joint and distal interphalangeal joint, whereas the differences in collagen composition between all the other paired comparisons of the joints had confidence intervals that did not include zero.
Ultrasound screening of periarticular soft tissue abnormality around metal-on-metal bearings.

PubMed

Nishii, Takashi; Sakai, Takashi; Takao, Masaki; Yoshikawa, Hideki; Sugano, Nobuhiko

2012-06-01

Although metal hypersensitivity or pseudotumors are concerns for metal-on-metal (MoM) bearings, detailed pathologies of patterns, severity, and incidence of periprosthetic soft tissue lesions are incompletely understood. We examined the potential of ultrasound for screening of periarticular soft tissue lesions around MoM bearings. Ultrasound examinations were conducted in 88 hips (79 patients) with MoM hip resurfacings or MoM total hip arthroplasties with a large femoral head. Four qualitative ultrasound patterns were shown, including normal pattern in 69 hips, joint-expansion pattern in 11 hips, cystic pattern in 5 hips, and mass pattern in 3 hips. Hips with the latter 3 abnormal patterns showed significantly higher frequency of clinical symptoms, without significant differences of sex, duration of implantation, head sizes, and cup abduction/anteversion angles, compared with hips with normal pattern. Ultrasound examination provides sensitive screening of soft tissue reactions around MoM bearings and may be useful in monitoring progression and defining treatment for periarticular soft tissue abnormalities. Copyright © 2012 Elsevier Inc. All rights reserved.
Effectiveness of Bupivacaine Liposome Injectable Suspension for Postoperative Pain Control in Total Knee Arthroplasty: A Prospective, Randomized, Double Blind, Controlled Study.

PubMed

DeClaire, Jeffrey H; Aiello, Paige M; Warritay, Olayinka K; Freeman, Dwight C

2017-09-01

We compared the effectiveness of liposomal bupivacaine to ropivacaine, each as part of multimodal pain management, in total knee arthroplasty (TKA) postoperative pain control. This prospective, double blind study randomized 96 TKA patients into a control group (periarticular injection of ropivacaine, ketorolac, morphine, and epinephrine in saline; 100cc) or an experimental group (periarticular injection of bupivacaine, ketorolac, morphine, and epinephrine in saline; 80cc plus 1.3% liposomal bupivacaine 20cc; total injection 100cc). The postoperative use of narcotics, visual analog pain scores, hours to ambulate 100 feet, and length of hospital stay were recorded. There was no significant difference between the two groups (control N = 49, experiment N = 47) in mean narcotic use per hour, total narcotic use during hospital stay, time to ambulate 100 feet, length of hospital stay, or visual analog score for pain postoperatively. There is no benefit in the use of liposomal bupivacaine compared with ropivacaine for postoperative pain control in TKA. Copyright © 2017 Elsevier Inc. All rights reserved.
In vivo engineering of the vocal fold extracellular matrix with injectable hyaluronic acid hydrogels: early effects on tissue repair and biomechanics in a rabbit model.

PubMed

Hansen, Jennifer K; Thibeault, Susan L; Walsh, Jennifer F; Shu, Xiao Zheng; Prestwich, Glenn D

2005-09-01

A prospective, controlled animal study was performed to determine whether the use of injectable, chemically modified hyaluronic acid (HA) derivatives at the time of intentional vocal fold resection might facilitate wound repair and preserve the unique viscoelastic properties of the vocal fold extracellular matrix. We performed bilateral vocal fold biopsies on 33 rabbits. Two groups of rabbits were unilaterally treated with 2 different HA derivatives--Carbylan-SX and HA-DTPH-PEGDA--at the time of resection. Saline was injected as a control into the contralateral fold. The animals were painlessly sacrificed 3 weeks after biopsy and injection. The outcomes measured included histologic fibrosis level, tissue HA level, and tissue viscosity and elasticity. The Carbylan-SX-treated vocal folds were found to have significantly less fibrosis than the saline-treated controls. The levels of HA in the treated vocal folds were not significantly different from those in the controls at 3 weeks as measured by enzyme-linked immunosorbent assay. The Carbylan-SX-treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. The HA-DTPH-PEGDA injections yielded significantly improved viscosity, but not elasticity. Prophylactic in vivo manipulation of the extracellular matrix with an injectable Carbylan-SX hydrogel appears to induce vocal fold tissue regeneration to yield optimal tissue composition and biomechanical properties favorable for phonation.
Hyaluronic Acid: A Boon in Periodontal Therapy

PubMed Central

Dahiya, Parveen; Kamal, Reet

2013-01-01

Hyaluronic acid is a naturally occurring linear polysaccharide of the extracellular matrix of connective tissue, synovial fluid, and other tissues. Its use in the treatment of the inflammatory process is established in medical areas such as orthopedics, dermatology, and ophthalmology. The Pubmed/Medline database was searched for keywords “Hyaluronic acid and periodontal disease” and “Hyaluronic acid and gingivitis” which resulted in 89 and 22 articles respectively. Only highly relevant articles from electronic and manual search in English literature were selected for the present review article. In the field of dentistry, hyaluronic acid has shown anti-inflammatory and anti-bacterial effects in the treatment of periodontal diseases. Due to its tissue healing properties, it could be used as an adjunct to mechanical therapy in the treatment of periodontitis. Further studies are required to determine the clinical efficacy of hyaluronic acid in healing of periodontal lesion. The aim of the present review, article is to discuss the role of hyaluronic acid in periodontal therapy. PMID:23814761
Hyaluronate-binding proteins of murine brain.

PubMed

Marks, M S; Chi-Rosso, G; Toole, B P

1990-01-01

The distribution of hyaluronate-binding activity was determined in the soluble and membrane fractions derived from adult mouse brain by sonication in low-ionic-strength buffer. Approximately 60% of the total activity was recovered in the soluble fraction and 33% in membrane fractions. In both cases, the hyaluronate-binding activities were found to be of high affinity (KD = 10(-9) M), specific for hyaluronate, and glycoprotein in nature. Most of the hyaluronate-binding activity from the soluble fraction chromatographed in the void volume of Sepharose CL-4B and CL-6B. Approximately 50% of this activity was highly negatively charged, eluting from diethylaminoethyl (DEAE)-cellulose in 0.5 M NaCl, and contained chondroitin sulfate chains. This latter material also reacted with antibodies raised against cartilage link protein and the core protein of cartilage proteoglycan. Thus, the binding and physical characteristics of this hyaluronate-binding activity are consistent with those of a chondroitin sulfate proteoglycan aggregate similar to that found in cartilage. A 500-fold purification of this proteoglycan-like, hyaluronate-binding material was achieved by wheat germ agglutinin affinity chromatography, molecular sieve chromatography on Sepharose CL-6B, and ion exchange chromatography on DEAE-cellulose. Another class of hyaluronate-binding material (25-50% of that recovered) eluted from DEAE with 0.24 M NaCl; this material had the properties of a complex glycoprotein, did not contain chondroitin sulfate, and did not react with the antibodies against cartilage link protein and proteoglycan. Thus, adult mouse brain contains at least three different forms of hyaluronate-binding macromolecules. Two of these have properties similar to the link protein and proteoglycan of cartilage proteoglycan aggregates; the third is distinguishable from these entities.
Utilization and safety of sodium hyaluronate-carboxymethylcellulose adhesion barrier.

PubMed

Bashir, Shazia; Ananth, Cande V; Lewin, Sharyn N; Burke, William M; Lu, Yu-Shiang; Neugut, Alfred I; Herzog, Thomas J; Hershman, Dawn L; Wright, Jason D

2013-10-01

Little is known about the use and toxicity of antiadhesion substances such as sodium hyaluronate-carboxymethylcellulose. We analyzed the patterns of use and safety of sodium hyaluronate-carboxymethylcellulose in patients undergoing colectomy and gynecologic surgery. This is a retrospective cohort study. This study covered hospitals nationwide. All patients in the Premier Perspective database who underwent colectomy or hysterectomy from 2000 to 2010 were included in the analyses. Hyaluronate-carboxymethylcellulose use was determined by billing codes. For the primary outcome, we used hierarchical mixed-effects logistic regression models to determine the factors associated with the use of hyaluronate-carboxymethylcellulose, whereas a propensity score-matched analysis was used to secondarily assess the association between hyaluronate-carboxymethylcellulose use and toxicity (abscess, bowel and wound complications, peritonitis). We identified 382,355 patients who underwent hysterectomy and 267,368 who underwent colectomy. For hysterectomy, hyaluronate-carboxymethylcellulose use was 5.0% overall, increasing from 1.1% in 2000 to 9.8% in 2010. Hyaluronate-carboxymethylcellulose was used in 8.1% of those who underwent colectomy and increased from 6.2% in 2000 to 12.4% in 2010. The year of diagnosis and procedure volume of the attending surgeon were the strongest predictors of hyaluronate-carboxymethylcellulose use. After matching and risk adjustment, hyaluronate-carboxymethylcellulose use was not associated with abscess formation (1.5% vs 1.5%) (relative risk = 0.97; 95% CI, 0.84-1.12) in those who underwent hysterectomy. A patient receiving hyaluronate-carboxymethylcellulose had a 13% increased risk of abscess (17.4% vs 15.0%) (relative risk = 1.13; 95% CI, 1.08-1.17) after colectomy. This was an observational study. Hyaluronate-carboxymethylcellulose use has increased over the past decade for colectomy and hysterectomy. Although there is no association between hyaluronate
No Difference in Early Analgesia Between Liposomal Bupivacaine Injection and Intrathecal Morphine After TKA.

PubMed

Barrington, John W; Emerson, Roger H; Lovald, Scott T; Lombardi, Adolph V; Berend, Keith R

2017-01-01

Opioid analgesics have been a standard modality for postoperative pain management after total knee arthroplasty (TKA) but are also associated with increased risk of nausea, pruritus, vomiting, respiratory depression, prolonged ileus, and cognitive dysfunction. There is still a need for a method of anesthesia that can deliver effective long-term postoperative pain relief without incurring the high cost and health burden of opioids and nerve blocks. (1) Is liposomal bupivacaine-based periarticular injection (PAI) more effective than morphine-based spinal anesthesia or ropivacaine-based PAI in controlling postoperative pain after TKA? (2) Do patients treated with liposomal bupivacaine-based PAI experience fewer opioid-related adverse events compared with patients treated with morphine-based spinal anesthesia or ropivacaine-based PAI in controlling postoperative pain after TKA? This multicenter, blind trial randomized 119 patients undergoing TKA with spinal anesthesia to receive spinal anesthesia plus periarticular injection with liposomal bupivacaine (40 patients), spinal anesthesia with bupivacaine plus intrathecal morphine (41 patients) but no liposomal bupivacaine injection, or spinal anesthesia with bupivacaine (38 patients) and no liposomal bupivacaine injection. The two groups that did not receive periarticular liposomal bupivacaine did receive periarticular injection with ropivacaine, and all three groups had ketorolac (30 mg) plus epinephrine (1:1000) in the periarticular injections. Patients in all three groups received identical perioperative multimodal analgesic and antiemetic drugs. All patients were analyzed in the group to which they were randomized and no patients were lost to followup. The primary study endpoints were visual analog score (VAS) for pain and narcotic use during postoperative day 1. Secondary endpoints included side effects associated with narcotic administration during the hospital stay. Mean VAS pain in the liposomal bupivacaine PAI
Global Aesthetics Consensus: Avoidance and Management of Complications from Hyaluronic Acid Fillers—Evidence- and Opinion-Based Review and Consensus Recommendations

PubMed Central

Liew, Steven; Sundaram, Hema; De Boulle, Koenraad L.; Goodman, Greg J.; Monheit, Gary; Wu, Yan; Trindade de Almeida, Ada R.; Swift, Arthur; Vieira Braz, André

2016-01-01

Background: Although the safety profile of hyaluronic acid fillers is favorable, adverse reactions can occur. Clinicians and patients can benefit from ongoing guidance on adverse reactions to hyaluronic acid fillers and their management. Methods: A multinational, multidisciplinary group of experts in cosmetic medicine convened the Global Aesthetics Consensus Group to review the properties and clinical uses of Hylacross and Vycross hyaluronic acid products and develop updated consensus recommendations for early and late complications associated with hyaluronic acid fillers. Results: The consensus panel provided specific recommendations focusing on early and late complications of hyaluronic acid fillers and their management. The impact of patient-, product-, and technique-related factors on such reactions was described. Most of these were noted to be mild and transient. Serious adverse events are rare. Early adverse reactions to hyaluronic acid fillers include vascular infarction and compromise; inflammatory reactions; injection-related events; and inappropriate placement of filler material. Among late reactions are nodules, granulomas, and skin discoloration. Most adverse events can be avoided with proper planning and technique. Detailed understanding of facial anatomy, proper patient and product selection, and appropriate technique can further reduce the risks. Should adverse reactions occur, the clinician must be prepared and have tools available for effective treatment. Conclusions: Adverse reactions with hyaluronic acid fillers are uncommon. Clinicians should take steps to further reduce the risk and be prepared to treat any complications that arise. PMID:27219265
Therapeutic efficacy of three hyaluronic acid formulations in young and middle-aged patients with early-stage meniscal injuries

PubMed Central

Dernek, Bahar; Kesiktas, Fatma Nur; Duymus, Tahir Mutlu; Diracoglu, Demirhan; Aksoy, Cihan

2017-01-01

[Purpose] To investigate and compare the efficacy of three hyaluronic acid formulations in patients with early-stage meniscal injuries. [Subjects and Methods] Male and female patients who were admitted to our clinic between January 2013 and December 2013, diagnosed with early-stage meniscus lesions of the knee, and given a hyaluronic acid treatment were included in this retrospective study. Patients were categorized into 3 groups according to their treatments: MONOVISC, OSTENIL PLUS, or ORTHOVISC. Scores from a Visual Analog Scale and the Western Ontario and McMaster Universities Arthritis Index were evaluated at baseline and one, three, and six months after baseline. [Results] A total of 55 patients were included in this study. Most of the patients were female (55%), and the mean age of the patients was 42.4 (± 8.1) years. Based on the pre- and post-injection data, there was significant reductions both in the Visual Analog Scale score and the Western Ontario and McMaster Universities Arthritis Index score after the injections for all groups. According to intergroup comparisons, no significant difference was observed in terms of efficacy. [Conclusion] Three hyaluronic acid formulations produced a similar efficacy in patients with meniscal injuries, and further studies are needed to evaluate long-term results. PMID:28744035
The efficacy of intra-articular sodium hyaluronate in patients with reducing displaced disc of the temporomandibular joint.

PubMed

Hepguler, S; Akkoc, Y S; Pehlivan, M; Ozturk, C; Celebi, G; Saracoglu, A; Ozpinar, B

2002-01-01

In this clinical trial, we examined the efficacy of intra-articular hyaluronic acid (HA) treatment in 38 patients with reducing displaced disc of the temporomandibular joint (TMJ). Subjects received two unilateral upper space injections of HA or physiological saline solution with 1 week apart. Efficacy was based on the following measurements: pain and sound intensity of the joint measured by visual analogue scale (VAS), modified Helkimo's clinical dysfunction index and the intensity of joint vibration during opening and closing the mouth measured by accelerometers. These measurements were performed before the first injection and 1 and 6 months after the last injection. In the treatment group (n=19), all measurements improved significantly at month 1 and at month 6 compared with the baseline (P < 0.01). The same measurements, in the placebo group (n=19), did not show any change, except for the pain intensity which improved at month 1 and month 6 (P < 0.05). The change in baseline measurements of all of the efficacy criteria at month 1 and at month 6 in the treatment group was significantly better compared with the change obtained with placebo at the same time intervals. This study demonstrates that intra-articular sodium hyaluronate (Orthovisc) injection into the TMJ is an effective treatment for a reducing displaced disc.
Hyaluronic acid hydrogels for vocal fold wound healing.

PubMed

Gaston, Joel; Thibeault, Susan L

2013-01-01

The unique vibrational properties inherent to the human vocal fold have a significant detrimental impact on wound healing and scar formation. Hydrogels have taken prominence as a tissue engineered strategy to restore normal vocal structure and function as cellularity is low. The frequent vibrational and shear forces applied to, and present in this connective tissue make mechanical properties of such hydrogels a priority in this active area of research. Hyaluronic acid has been chemically modified in a variety of ways to address cell function while maintaining desirable tissue mechanical properties. These various modifications have had mixed results when injected in vivo typically resulting in better biomechanical function but not necessarily with a concomitant decrease in tissue fibrosis. Recent work has focused on seeding mesenchymal progenitor cells within 3D architecture of crosslinked hydrogels. The data from these studies demonstrate that this approach has a positive effect on cells in both early and late wound healing, but little work has been done regarding the biomechanical effects of these treatments. This paper provides an overview of the various hyaluronic acid derivatives, their crosslinking agents, and their effect when implanted into the vocal folds of various animal models.
Hyaluronic acid hydrogels for vocal fold wound healing

PubMed Central

Gaston, Joel; Thibeault, Susan L.

2013-01-01

The unique vibrational properties inherent to the human vocal fold have a significant detrimental impact on wound healing and scar formation. Hydrogels have taken prominence as a tissue engineered strategy to restore normal vocal structure and function as cellularity is low. The frequent vibrational and shear forces applied to, and present in this connective tissue make mechanical properties of such hydrogels a priority in this active area of research. Hyaluronic acid has been chemically modified in a variety of ways to address cell function while maintaining desirable tissue mechanical properties. These various modifications have had mixed results when injected in vivo typically resulting in better biomechanical function but not necessarily with a concomitant decrease in tissue fibrosis. Recent work has focused on seeding mesenchymal progenitor cells within 3D architecture of crosslinked hydrogels. The data from these studies demonstrate that this approach has a positive effect on cells in both early and late wound healing, but little work has been done regarding the biomechanical effects of these treatments. This paper provides an overview of the various hyaluronic acid derivatives, their crosslinking agents, and their effect when implanted into the vocal folds of various animal models. PMID:23507923
Evaluation of a Commercially Available Hyaluronic Acid Hydrogel (Restylane) as Injectable Scaffold for Dental Pulp Regeneration: An In Vitro Evaluation.

PubMed

Chrepa, Vanessa; Austah, Obadah; Diogenes, Anibal

2017-02-01

Regenerative endodontic procedures (REPs) are viable alternatives for treating immature teeth, yet these procedures do not predictably lead to pulp-dentin regeneration. A true bioengineering approach for dental pulp regeneration requires the incorporation of a scaffold conducive with the regeneration of the pulp-dentin complex. Several materials have been proposed as scaffolds for REPs; nonetheless, the majority are not eligible for immediate clinical chairside use. Thus, the aim of this study was to evaluate Restylane, a Food and Drug Administration-approved hyaluronic acid-based gel, as possible scaffold for REPs. Stem cells of the apical papilla (SCAP) were cultured either alone or in mixtures with either Restylane or Matrigel scaffolds. Groups were cultured in basal culture medium for 6, 24, and 72 hours, and cell viability was assessed. For the mineralizing differentiation experiments, groups were cultured in differentiation medium either for 7 days and processed for alkaline phosphatase activity or for 14 days and processed for gene expression by using quantitative reverse-transcription polymerase chain reaction. SCAP in basal medium served as control. Cell encapsulation in either Restylane or Matrigel demonstrated reduced cell viability compared with control. Nonetheless, cell viability significantly increased in the Restylane group in the course of 3 days, whereas it decreased significantly in the Matrigel group. Restylane promoted significantly greater alkaline phosphatase activity and upregulation of dentin sialophosphoprotein, dentin matrix acidic phosphoprotein-1, and matrix extracellular phosphoglycoprotein, compared with control. A Food and Drug Administration-approved hyaluronic acid-based injectable gel promoted SCAP survival, mineralization, and differentiation into an odontoblastic phenotype and may be a promising scaffold material for REPs. Published by Elsevier Inc.
Periarticular Liposomal Bupivacaine Injection Versus Intra-Articular Bupivacaine Infusion Catheter for Analgesia After Total Knee Arthroplasty: A Double-Blinded, Randomized Controlled Trial.

PubMed

Smith, Eric B; Kazarian, Gregory S; Maltenfort, Mitchell G; Lonner, Jess H; Sharkey, Peter F; Good, Robert P

2017-08-16

Intra-articular bupivacaine hydrochloride (HCl) infusion catheters and periarticular injections of liposomal bupivacaine are often used as postoperative local anesthetics. The purpose of this study was to compare the efficacies of these local anesthetics following total knee arthroplasty. This study was a superiority trial with a randomized, controlled, double-blinded design. Patients were randomly assigned to either delivery of bupivacaine HCl by the ON-Q* Pain Relief System pump (n = 96) or by an injection of Exparel (liposomal bupivacaine) (n = 104). The primary outcome of this study was cumulative narcotic consumption on postoperative days 0 through 3. Narcotic consumption data were collected retrospectively from in-hospital records while patients were in the hospital. Following discharge, narcotic consumption data were gathered from patient surveys, as were secondary outcomes measures. We did not identify greater narcotic use in the ON-Q* group compared with the Exparel group (p = 0.641). The mean difference between the groups was 0.5 morphine equivalent (95% confidence interval [CI] = -1.7 to +2.8), with the ON-Q* group consuming an average 10.4 morphine equivalents (95% CI = 8.7 to 12.0) compared with 10.9 (95% CI = 9.3 to 12.5) in the Exparel group. There were no significant differences between groups with regard to any of the secondary measures of pain with the exception of pain while walking and pain with physical therapy (p = 0.019 and p = 0.010, respectively), both of which showed an approximately 1-point difference in favor of the ON-Q* group on a visual analog scale (VAS). There were also no differences in the postoperative side effects, including nausea, constipation, or vomiting, or in the rates of study-related complications, patient satisfaction, or length of hospital stay. Exparel did not have superior efficacy compared with the ON-Q* Pain Relief System as reflected by narcotic consumption, our primary outcome. There were small significant
Serum hyaluronic acid in dogs with congenital portosystemic shunts.

PubMed

Seki, M; Asano, K; Sakai, M; Kanno, N; Teshima, K; Edamura, K; Tanaka, S

2010-05-01

To compare the serum level of hyaluronic acid in dogs with congenital portosystemic shunt with that in healthy dogs and to investigate the perioperative change in serum hyaluronic acid following shunt attenuation. Blood samples were obtained from 29 congenital portosystemic shunt dogs before the operation, and 2 and 4 weeks after the operation from 17 and 7 dogs, respectively. The serum hyaluronic acid level of these dogs was measured and compared with that of 10 healthy beagles. The median preoperative hyaluronic acid level in dogs with congenital portosystemic shunt was significantly elevated compared with that in healthy dogs. Furthermore, the median postoperative hyaluronic acid level significantly decreased compared with the median preoperative levels in congenital portosystemic shunt dogs. In the case of dogs with congenital portosystemic shunt, the reduction of intrahepatic portal blood flow might lower the clearance rate of hyaluronic acid in hepatic sinusoidal endothelial cells, so hyaluronic acid clearance could be improved by attenuation of a shunt vessel. Hence, serum hyaluronic acid levels might be useful to evaluate liver function and also have the potential to evaluate successful attenuation of a shunt vessel in dogs with congenital portosystemic shunt. Further investigations are required to clarify whether serum hyaluronic acid offers significant benefits over existing markers such as serum bile acid or ammonia concentrations.
Dietary Hyaluronic Acid Migrates into the Skin of Rats

PubMed Central

Mitsugi, Koichi; Odanaka, Wataru; Seino, Satoshi; Masuda, Yasunobu

2014-01-01

Hyaluronic acid is a constituent of the skin and helps to maintain hydration. The oral intake of hyaluronic acid increases water in the horny layer as demonstrated by human trials, but in vivo kinetics has not been shown. This study confirmed the absorption, migration, and excretion of 14C-labeled hyaluronic acid (14C-hyaluronic acid). 14C-hyaluronic acid was orally or intravenously administered to male SD rats aged 7 to 8 weeks. Plasma radioactivity after oral administration showed the highest level 8 hours after administration, and orally administered 14C-hyaluronic acid was found in the blood. Approximately 90% of 14C-hyaluronic acid was absorbed from the digestive tract and used as an energy source or a structural constituent of tissues based on tests of the urine, feces, expired air, and cadaver up to 168 hours (one week) after administration. The autoradiographic results suggested that radioactivity was distributed systematically and then reduced over time. The radioactivity was higher in the skin than in the blood at 24 and 96 hours after administration. The results show the possibility that orally administered hyaluronic acid migrated into the skin. No excessive accumulation was observed and more than 90% of the hyaluronic acid was excreted in expired air or urine. PMID:25383371
Dietary hyaluronic acid migrates into the skin of rats.

PubMed

Oe, Mariko; Mitsugi, Koichi; Odanaka, Wataru; Yoshida, Hideto; Matsuoka, Ryosuke; Seino, Satoshi; Kanemitsu, Tomoyuki; Masuda, Yasunobu

2014-01-01

Hyaluronic acid is a constituent of the skin and helps to maintain hydration. The oral intake of hyaluronic acid increases water in the horny layer as demonstrated by human trials, but in vivo kinetics has not been shown. This study confirmed the absorption, migration, and excretion of (14)C-labeled hyaluronic acid ((14)C-hyaluronic acid). (14)C-hyaluronic acid was orally or intravenously administered to male SD rats aged 7 to 8 weeks. Plasma radioactivity after oral administration showed the highest level 8 hours after administration, and orally administered (14)C-hyaluronic acid was found in the blood. Approximately 90% of (14)C-hyaluronic acid was absorbed from the digestive tract and used as an energy source or a structural constituent of tissues based on tests of the urine, feces, expired air, and cadaver up to 168 hours (one week) after administration. The autoradiographic results suggested that radioactivity was distributed systematically and then reduced over time. The radioactivity was higher in the skin than in the blood at 24 and 96 hours after administration. The results show the possibility that orally administered hyaluronic acid migrated into the skin. No excessive accumulation was observed and more than 90% of the hyaluronic acid was excreted in expired air or urine.
Glucocorticoid combined with hyaluronic acid enhance glucocorticoid receptor activity through inhibiting p-38MAPK signal pathway activation in treating acute lung injury in rats.

PubMed

Lv, Q

2016-09-01

In order to seek an effective strategy for clinical treatment of acute lung injury (ALI), we are committed to explore the effect of combination therapy of glucocorticoid and hyaluronic acid on acute lung injury caused by an endotoxin (LPS) and its mechanism. Adult male Sprague-Dawley (SD) rats were divided randomly into 5 groups: normal group (n=8); LPS group (n=8); dexamethasone +LPS group (DXMS group, n=8); hyaluronic acid+ LPS group (HA group, n=8); dexamethasone +hyaluronic acid +LPS group (DXMS+HA group, n=8). Firstly, SD rat model with acute lung injury induced by LPS was established, and injected corresponding drugs according to the plan. Then, the expression of TNF-a, IL-8, IL-10, ICAM-1 and total protein were measured by ELISA, and the HE staining was used for detected the pathological change in lung tissue. Subsequently, the water content, dry and wet ratio and permeability in lung tissues of SD rats was assayed. Finally, the expression level of the glucocorticoid receptor (GR) was detected by RT-PCR, and activation of p-p38MAPK was determined by Western blotting. The results showed that concentration of IL-8, IL-10 and ICAM-1 was significantly increased in BALF after LPS injection, and the results from HE staining showed it had widespread inflammation. However, lung structures in SD rats with inhalation lung injury were improved significantly after the injection of dexamethasone and hyaluronic acid, and the Pa02/Fi02, blood pressure and Cdyn were also increased. Moreover, lung water content, the ratio of wet and dry lung, and lung permeability index (LPI) was decreased after having treated the SD rats with a combination of dexamethasone and hyaluronic acid, and the apoptosis index was also decreased in the rats with LPS-induced ALI. Our data also suggested that TNF-α, IL-8, IL-10, intercellular cell adhesion molecule-1 (ICAM-1) and total protein was significantly declined in bronchoalveolar lavage fluid (BALF) of rats with LPS-induced acute lung injury

Hyaluronic acid as a potential boron carrier for BNCT: Preliminary evaluation.

PubMed

Zaboronok, A; Yamamoto, T; Nakai, K; Yoshida, F; Uspenskii, S; Selyanin, M; Zelenetskii, A; Matsumura, Akira

2015-12-01

Hyaluronic acid (HA), a nonimmunogenic, biocompatible polymer found in different biological tissues, has the potential to attach to CD44 receptors on the surface of certain cancer cells, where the receptor is overexpressed compared with normal cells. Boron-hyaluronic acid (BHA) was tested for its feasibility as a potential agent for BNCT. BHA with low-viscosity 30 kDa HA could be administered by intravenous injection. The compound showed a certain degree of cytotoxicity and accumulation in C6 rat glioma cells in vitro. Instability of the chelate bonds between boron and HA and/or insufficient specificity of CD44 receptors on C6 cells to BHA could account for the insufficient in vitro accumulation. To ensure the future eligibility of BHA for BNCT experiments, using alternative tumor cell lines and chemically securing the chelate bonds or synthesizing BHA with boron covalently attached to HA might be required. Copyright © 2015 Elsevier Ltd. All rights reserved.
The efficacy of intra-articular hyaluronan injection after the microfracture technique for the treatment of articular cartilage lesions.

PubMed

Strauss, Eric; Schachter, Aaron; Frenkel, Sally; Rosen, Jeffrey

2009-04-01

Although the exact mechanism of action has yet to be elucidated, recent animal studies have demonstrated chondroprotective and anti-inflammatory properties of hyaluronic acid viscosupplementation. Intra-articular hyaluronic acid after microfracture improves the quality of the repair leading to a more hyaline-like repair tissue with better defect fill and adjacent area integration. Controlled laboratory study. Full-thickness cartilage defects were created in the weightbearing area of the medial femoral condyle in 36 female New Zealand White rabbits. The defects were then treated with surgical microfracture. Eighteen rabbits formed the 3-month cohort and the other 18 formed the 6-month cohort. Within each cohort, 6 rabbits were randomly assigned to receive 3 weekly injections of hyaluronic acid (group A), 5 weekly injections (group B), or control injections of normal saline (group C). At 3 and 6 months postmicrofracture, the animals were sacrificed and the operative knee harvested. Repair tissue was assessed blinded- both grossly, using a modified component of the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment scoring scale, and histologically, using the modified O'Driscoll histological cartilage scoring system. Comparisons were made with respect to gross and histologic findings between treatment groups at each time point. Effects of each treatment type were also evaluated longitudinally by comparing the 3-month results with the 6-month results. Statistical analysis was performed using unpaired Student t tests with significance defined as P < .05. At 3 months, gross and histologic evaluation of the repair tissue demonstrated that the 3-injection group had significantly better fill of the defects and more normal appearing, hyaline-like tissue than controls (a mean ICRS score of 1.92 vs 1.26; P < .05 and a mean modified O'Driscoll score of 10.3 vs 7.6; P < .02). Specimens treated with 5 weekly injections were not significantly improved
Endoscopic injection therapy.

PubMed

Kim, Sang Woon; Lee, Yong Seung; Han, Sang Won

2017-06-01

Since the U.S. Food and Drug Administration approved dextranomer/hyaluronic acid copolymer (Deflux) for the treatment of vesicoureteral reflux, endoscopic injection therapy using Deflux has become a popular alternative to open surgery and continuous antibiotic prophylaxis. Endoscopic correction with Deflux is minimally invasive, well tolerated, and provides cure rates approaching those of open surgery (i.e., approximately 80% in several studies). However, in recent years a less stringent approach to evaluating urinary tract infections (UTIs) and concerns about long-term efficacy and complications associated with endoscopic injection have limited the use of this therapy. In addition, there is little evidence supporting the efficacy of endoscopic injection therapy in preventing UTIs and vesicoureteral reflux-related renal scarring. In this report, we reviewed the current literature regarding endoscopic injection therapy and provided an updated overview of this topic.
Hyaluronic Acid Hydrogels for Biomedical Applications

PubMed Central

Burdick, Jason A.; Prestwich, Glenn D.

2013-01-01

Hyaluronic acid (HA), an immunoneutral polysaccharide that is ubiquitous in the human body, is crucial for many cellular and tissue functions and has been in clinical use for over thirty years. When chemically modified, HA can be transformed into many physical forms -- viscoelastic solutions, soft or stiff hydrogels, electrospun fibers, non-woven meshes, macroporous and fibrillar sponges, flexible sheets, and nanoparticulate fluids -- for use in a range of preclinical and clinical settings. Many of these forms are derived from the chemical crosslinking of pendant reactive groups by addition/condensation chemistry or by radical polymerization. Clinical products for cell therapy and regenerative medicine require crosslinking chemistry that is compatible with the encapsulation of cells and injection into tissues. Moreover, an injectable clinical biomaterial must meet marketing, regulatory, and financial constraints to provide affordable products that can be approved, deployed to the clinic, and used by physicians. Many HA-derived hydrogels meet these criteria, and can deliver cells and therapeutic agents for tissue repair and regeneration. This progress report covers both basic concepts and recent advances in the development of HA-based hydrogels for biomedical applications. PMID:21394792
Efficacy of Temporomandibular Joint Arthrocentesis with Sodium Hyaluronate in the Management of Temporomandibular Joint Disorders: A Prospective Randomized Control Trial.

PubMed

Gorrela, Harsha; Prameela, J; Srinivas, G; Reddy, B Vijay Baskar; Sudhir, Mvs; Arakeri, Gururaj

2017-12-01

This study was designed to investigate the efficacy of the temporomandibular joint arthrocentesis with and without injection of sodium hyaluronate (SH) in the treatment of temporomandibular joint disorders. A total of sixty two TMJs in 34 males and 28 females aged 20-65 years comprised the study material. The patients' complaints were limited mouth opening, TMJ pain, and joint noises during function. Patients were randomly divided into 2 groups in which arthrocentesis plus intra-articular injection of sodium hyaluronate was performed in 1 group and only arthrocentesis was performed in the other group. Both groups contained patients with disc displacement with reduction and without reduction. Clinical evaluation of the patients was done before the procedure, immediately after the procedure, at 1 week and 1, 3 and 6 months postoperatively. Intensity of TMJ pain was assessed using visual analog scales. Maximal mouth opening and lateral jaw movements also were recorded at each follow-up visit. Both techniques increased maximal mouth opening, lateral movements, and function, while reducing TMJ pain and noise. Although patients benefitted from both techniques, arthrocentesis with injection of SH seemed to be superior to arthrocentesis alone.
Streptococcus pneumoniae Can Utilize Multiple Sources of Hyaluronic Acid for Growth

PubMed Central

Marion, Carolyn; Stewart, Jason M.; Tazi, Mia F.; Burnaugh, Amanda M.; Linke, Caroline M.; Woodiga, Shireen A.

2012-01-01

The mechanisms by which Streptococcus pneumoniae obtains carbohydrates for growth during airway colonization remain to be elucidated. The low concentration of free carbohydrates in the normal human airway suggests that pneumococci must utilize complex glycan structures for growth. The glycosaminoglycan hyaluronic acid is present on the apical surface of airway epithelial cells. As pneumococci express a hyaluronate lyase (Hyl) that cleaves hyaluronic acid into disaccharides, we hypothesized that during colonization pneumococci utilize the released carbohydrates for growth. Hyaluronic acid supported significant pneumococcal growth in an hyl-dependent manner. A phosphoenolpyruvate-dependent phosphotransferase system (PTS) and an unsaturated glucuronyl hydrolase (Ugl) encoded downstream of hyl are also essential for growth on hyaluronic acid. This genomic arrangement is present in several other organisms, suggesting conservation of the utilization mechanism between species. In vivo experiments support the hypothesis that S. pneumoniae utilizes hyaluronic acid as a carbon source during colonization. We also demonstrate that pneumococci can utilize the hyaluronic acid capsule of other bacterial species for growth, suggesting an alternative carbohydrate source for pneumococcal growth. Together, these data support a novel function for pneumococcal degradation of hyaluronic acid in vivo and provide mechanistic details of growth on this glycosaminoglycan. PMID:22311922
Periarticular locking plate vs intramedullary nail for tibiotalocalcaneal arthrodesis: a biomechanical investigation.

PubMed

Ohlson, Blake L; Shatby, Meena W; Parks, Brent G; White, Kacey L; Schon, Lew C

2011-02-01

Augmented retrograde intramedullary (IM) nail fixation was compared with augmented periarticular locking- plate fixation for tibiotalocalcaneal arthrodesis. Specimens in 10 matched pairs were randomly assigned to a fixation construct and loaded cyclically in dorsiflexion. The groups did not differ in initial or final stiffness, load to failure, or construct deformation. No correlation was found between bone mineral density and construct deformation for either group. A humeral locking plate may be a viable alternative to an IM nail for tibiotalocalcaneal fixation in cases not amenable to IM nailing.
Correction of Age-Related Midface Volume Loss With Low-Volume Hyaluronic Acid Filler.

PubMed

Wilson, Monique Vanaman; Fabi, Sabrina Guillen; Greene, Ryan

2017-03-01

The pivotal approval trial for a smooth, highly cohesive, viscous, 20-mg/mL hyaluronic acid filler demonstrated sustained aesthetic improvement, with a mean injection volume of 6.65 mL. In daily practice, however, it is not often practical or necessary to use large injection volumes to achieve the desired cosmetic outcome. To assess the efficacy, longevity, and patient satisfaction associated with correction of age-related midface volume loss using the low volumes of hyaluronic acid filler more commonly used in day-to-day practice. A 2-center, retrospective cohort study examined medical records of 61 healthy patients who underwent treatment for facial volume loss with hyaluronic acid filler from November 1, 2013, through April 31, 2014. Follow-up visits were conducted at 1, 3, 6, and 12 months after the procedure. Data were pooled from a private facial plastic surgery practice in Weston, Florida, and a private cosmetic dermatology practice in San Diego, California. Patients were treated with hyaluronic acid filler according to the investigator's usual practices. The main outcome measure was patient-graded Global Aesthetic Improvement Scale scores at 1, 3, 6, and 12 months after treatment. Scores range from 1 to 5; 1 indicates very much improved and 5, worse. A total of 61 consecutive, healthy adult patients (mean [SD] age, 57.4 [12.8] years) with mild to severe facial volume loss were enrolled in the study. A total of 46 patients (75%) were white, 3 (5%) were black/African American, 9 (15%) were Hispanic/Latino, 1 (2%) was Asian/Pacific Islander, and 2 (3%) were other. Three patients (5%) were male, and 58 (95%) were female. Mean initial treatment volume was 1.6 mL. At follow-up, 29 patients (48%) elected to have a touch-up treatment; mean total touch-up volume was 1.4 mL. The patient-graded Global Aesthetic Improvement Scale scores at 1, 3, 6, and 12 months after treatment demonstrated that 73% (41 of 56) to 89% (24 of 27) of the study patients reported being very
Adult periarticular locking plates for the treatment of pediatric and adolescent subtrochanteric hip fractures.

PubMed

Sanders, Samuel; Egol, Kenneth A

2009-01-01

Two cases are presented in which adult, precontoured, lower-extremity periarticular locking plates were utilized for fixation of subtrochanteric femur fractures in pediatric patients. Recognition of the fact that a distal tibial locking plate in a small child and a proximal tibial locking plate in an adolescent anatomically ft the proximal femur in each case may provide a surgeon treating subtrochanteric hip fractures in this population increased options for operative stabilization.
Evaluation of gelatin-hyaluronic acid composite hydrogels for accelerating wound healing.

PubMed

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

2017-05-01

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

PubMed

Wall, P D H; Parsons, N R; Parsons, H; Achten, J; Balasubramanian, S; Thompson, P; Costa, M L

2017-07-01

The aim of this study was to compare the effectiveness of a femoral nerve block and a periarticular infiltration in the management of early post-operative pain after total knee arthroplasty (TKA). A pragmatic, single centre, two arm parallel group, patient blinded, randomised controlled trial was undertaken. All patients due for TKA were eligible. Exclusion criteria included contraindications to the medications involved in the study and patients with a neurological abnormality of the lower limb. Patients received either a femoral nerve block with 75 mg of 0.25% levobupivacaine hydrochloride around the nerve, or periarticular infiltration with 150 mg of 0.25% levobupivacaine hydrochloride, 10 mg morphine sulphate, 30 mg ketorolac trometamol and 0.25 mg of adrenaline all diluted with 0.9% saline to make a volume of 150 ml. A total of 264 patients were recruited and data from 230 (88%) were available for the primary analysis. Intention-to-treat analysis of the primary outcome measure of a visual analogue score for pain on the first post-operative day, prior to physiotherapy, was similar in both groups. The mean difference was -0.7 (95% confidence interval (CI) -5.9 to 4.5; p = 0.834). The periarticular group used less morphine in the first post-operative day compared with the femoral nerve block group (74%, 95% CI 55 to 99). The femoral nerve block group reported 39 adverse events, of which 27 were serious, in 31 patients and the periarticular group reported 51 adverse events, of which 38 were serious, in 42 patients up to six weeks post-operatively. None of the adverse events were directly attributed to either of the interventions under investigation. Periarticular infiltration is a viable and safe alternative to femoral nerve block for the early post-operative relief of pain following TKA. Cite this article: Bone Joint J 2017;99-B:904-11. ©2017 The British Editorial Society of Bone & Joint Surgery.
Optimization of hyaluronic acid production and its cytotoxicity and degradability characteristics.

PubMed

Gedikli, Serap; Güngör, Gökhan; Toptaş, Yağmur; Sezgin, Dilber Ece; Demirbilek, Murat; Yazıhan, Nuray; Aytar Çelik, Pınar; Denkbaş, Emir Baki; Bütün, Vural; Çabuk, Ahmet

2018-06-14

In the present study, culture conditions of Streptococcus equi was optimized through Box-Behnken experimental design for hyaluronic acid production. About 0.87 gL -1 of hyaluronic acid was produced under the determined conditions and optimal conditions were found as 38.42 °C, 24 hr and 250 rpm. The validity and practicability of this statistical optimization strategy were confirmed relation between predicted and experimental values. The hyaluronic acid obtained under optimal conditions was characterized. The effects of different conditions such as ultraviolet light, temperature and enzymatic degradation on hyaluronic acid produced under optimal conditions were determined. 118 °C for 32 min of autoclaved HA sample included 63.09 µg mL -1 of d-glucuronic acid, which is about two-fold of enzymatic effect. Cytotoxicity of hyaluronic acid on human dermal cells (HUVEC, HaCaT), L929 and THP-1 cells was studied. In vitro effect on pro or anti-inflammatory cytokine release of THP-1 cells was determined. Although it varies depending on the concentration, cytotoxicity of hyaluronic acid is between 5 and 30%. However, it varies depending on the concentration of hyaluronic acid, TNF-α release was not much increased compared to control study. Consequently, purification procedure is necessary to develop and it is worth developing the bacterial hyaluronic acid.
Magnetic hyaluronate hydrogels: preparation and characterization

NASA Astrophysics Data System (ADS)

Tóth, Ildikó Y.; Veress, Gábor; Szekeres, Márta; Illés, Erzsébet; Tombácz, Etelka

2015-04-01

A novel soft way of hyaluronate (HyA) based magnetic hydrogel preparation was revealed. Magnetite nanoparticles (MNPs) were prepared by co-precipitation. Since the naked MNPs cannot be dispersed homogenously in HyA-gel, their surface was modified with natural and biocompatible chondroitin-sulfate-A (CSA) to obtain CSA-coated MNPs (CSA@MNPs). The aggregation state of MNPs and that loaded with increasing amount of CSA up to 1 mmol/g was measured by dynamic light scattering at pH~6. Only CSA@MNP with ≥0.2 mmol/g CSA content was suitable for magnetic HyA-gel preparation. Rheological studies showed that the presence of CSA@MNP with up to 2 g/L did not affect the hydrogel's rheological behavior significantly. The results suggest that the HyA-based magnetic hydrogels may be promising formulations for future biomedical applications, e.g. as intra-articular injections in the treatment of osteoarthritis.
[PREPARATION AND BIOCOMPATIBILITY OF IN SITU CROSSLINKING HYALURONIC ACID HYDROGEL].

PubMed

Liang, Jiabi; Li, Jun; Wang, Ting; Liang, Yuhong; Zou, Xuenong; Zhou, Guangqian; Zhou, Zhiyu

2016-06-08

To fabricate in situ crosslinking hyaluronic acid hydrogel and evaluate its biocompatibility in vitro. The acrylic acid chloride and polyethylene glycol were added to prepare crosslinking agent polyethylene glycol acrylate (PEGDA), and the molecular structure of PEGDA was analyzed by Flourier transformation infrared spectroscopy and 1H nuclear magnetic resonance spectroscopy. Hyaluronic acid hydrogel was chemically modified to prepare hyaluronic acid thiolation (HA-SH). And the degree of HA-SH was analyzed qualitatively and quantitatively by Ellman method. HA-SH solution in concentrations ( W/V ) of 0.5%, 1.0%, and 1.5% and PEGDA solution in concentrations ( W/V ) of 2%, 4%, and 6% were prepared with PBS. The two solutions were mixed in different ratios, and in situ crosslinking hyaluronic acid hydrogel was obtained; the crosslinking time was recorded. The cellular toxicity of in situ crosslinking hyaluronic acid hydrogel (1.5% HA-SH and 4% PEGDA mixed) was tested by L929 cells. Meanwhile, the biocompatibility of hydrogel was tested by co-cultured with human bone mesenchymal stem cells (hBMSCs). Flourier transformation infrared spectroscopy showed that most hydroxyl groups were replaced by acrylate groups; 1H nuclear magnetic resonance spectroscopy showed 3 characteristic peaks of hydrogen representing acrylate and olefinic bond at 5-7 ppm. The thiolation yield of HA-SH was 65.4%. In situ crosslinking time of hyaluronic acid hydrogel was 2 to 70 minutes in the PEGDA concentrations of 2%-6% and HA-SH concentrations of 0.5%-1.5%. The hyaluronic acid hydrogel appeared to be transparent. The toxicity grade of leaching solution of hydrogel was grade 1. hBMSCs grew well and distributed evenly in hydrogel with a very high viability. In situ crosslinking hyaluronic acid hydrogel has low cytotoxicity, good biocompatibility, and controllable crosslinking time, so it could be used as a potential tissue engineered scaffold or repairing material for tissue regeneration.
Intra-articular and soft tissue injections, a systematic review of relative efficacy of various corticosteroids.

PubMed

Garg, Neha; Perry, Lisa; Deodhar, Atul

2014-12-01

The comparative efficacy of various Corticosteroid (CS) injections commonly used to treat musculoskeletal conditions has not been systematically studied. Our objective is to synthesize data about comparative efficacy of various CS used for intra-articular and periarticular soft tissue injections. Online databases were searched including MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effectiveness, and bibliographies of studies till November 2013. We included all randomized controlled trials comparing two CS for intra-articular and periarticular injections, selected according to Preferred Reporting Items for Systematic reviews and Meta-Analyses methodology. Seven good quality trials were selected for qualitative data synthesis. Two trials comparing triamcinolone hexacetonide (TH) and methylprednisolone (MP) for knee arthritis suggested faster pain relief with TH for rheumatoid arthritis (RA) at day 7 (p < 0.05) and osteoarthritis (OA) at week 3 (visual analogue scale, 33 mm vs 14 mm, p < 0.01) but a similar long-term efficacy. One trial suggested faster pain relief with MP compared to triamcinolone acetonide (TA) for rotator cuff tendonitis at 2 weeks (percentage of patients improving 92 % vs. 50 %; p = 0.02) but similar long-term efficacy, while another trial suggested no difference between TA and MP for knee OA. Two trials for knee arthritis suggested a substantially better efficacy for TH than TA (response rate at 24 months 77 % vs 39 %; p = 0.001) and betamethasone (BM) at day 42 (p < 0.01). There is paucity of data regarding comparative efficacy of various CS injections. Limited number of studies favored TH over other CS (TA, MP, BM).
Liposomal Bupivacaine Injection Technique in Total Knee Arthroplasty.

PubMed

Meneghini, R Michael; Bagsby, Deren; Ireland, Philip H; Ziemba-Davis, Mary; Lovro, Luke R

2017-01-01

Liposomal bupivacaine has gained popularity for pain control after total knee arthroplasty (TKA), yet its true efficacy remains unproven. We compared the efficacy of two different periarticular injection (PAI) techniques for liposomal bupivacaine with a conventional PAI control group. This retrospective cohort study compared consecutive patients undergoing TKA with a manufacturer-recommended, optimized injection technique for liposomal bupivacaine, a traditional injection technique for liposomal bupivacaine, and a conventional PAI of ropivacaine, morphine, and epinephrine. The optimized technique utilized a smaller gauge needle and more injection sites. Self-reported pain scores, rescue opioids, and side effects were compared. There were 41 patients in the liposomal bupivacaine optimized injection group, 60 in the liposomal bupivacaine traditional injection group, and 184 in the conventional PAI control group. PAI liposomal bupivacaine delivered via manufacturer-recommended technique offered no benefit over PAI ropivacaine, morphine, and epinephrine. Mean pain scores and the proportions reporting no or mild pain, time to first opioid, and amount of opioids consumed were not better with PAI liposomal bupivacaine compared with PAI ropivacaine, morphine, and epinephrine. The use of the manufacturer-recommended technique for PAI of liposomal bupivacaine does not offer benefit over a conventional, less expensive PAI during TKA. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
A Randomized Clinical Trial of Comparing Monophasic Monodensified and Biphasic Nonanimal Stabilized Hyaluronic Acid Dermal Fillers in Treatment of Asian Nasolabial Folds.

PubMed

Zhou, Shuang-Bai; Xie, Yun; Chiang, Cheng-An; Liu, Kai; Li, Qing-Feng

2016-09-01

Cross-linked hyaluronic acids (HAs) with varying characteristics and formulations are available. Despite the popularity of HA, limited studies compared the effectiveness of monophasic monodensified hyaluronic acid (MMHA) and biphasic nonanimal stabilized hyaluronic acid (BHA) products in correcting nasolabial folds (NLFs) in the Asian population. This double-blinded, randomized research aimed at evaluating the outcomes of MMHA and BHA products in treating Asian NLFs. Subjects aged between 18 and 65 years with moderate-to-severe NLFs were randomized to receive MMHA or BHA treatment. A touch-up treatment with the same product was performed at the 4-week follow-up, if needed. The effectiveness was evaluated for 24 weeks by masked investigators. All adverse events were recorded for safety evaluation. Twenty-five subjects in the MMHA Group and twenty-four subjects in the BHA Group finished 24-week follow-up. Results showed that subjects from both groups obtained satisfactory outcome in NLF correction. A lower amount of MMHA was required to achieve a similar result as that of BHA (p < .01). Both HA products maintained the effectiveness at the end of the 24-week follow-up. Both MMHA and BHA are effective for correcting NLF in Asian patients, producing satisfactory results. Monophasic monodensified hyaluronic acid provides similar satisfaction to BHA while requiring less injection volume.
Hyaluronic Acid Conjugated Magnetic Prussian Blue@Quantum Dot Nanoparticles for Cancer Theranostics

PubMed Central

Yang, Yongbo; Jing, Lijia; Li, Xiaoda; Lin, Li; Yue, Xiuli; Dai, Zhifei

2017-01-01

A multifunctional nanotheranostic agent was developed by conjugating both hyaluronic acid and bovine serum albumin coated CuInS2-ZnS quantum dots onto the surface of magnetic Prussian blue nanoparticles. The obtained nanoagent could serve as an efficient contrast agent to simultaneously enhance near infrared (NIR) fluorescence and magnetic resonance (MR) imaging greatly. The coexistence of magnetic core and CD44 ligand hyaluronic acid was found to largely improve the specific uptake of the nanoagent by CD44 overexpressed HeLa cells upon applying an external magnetic field. Both NIR fluorescence and MR imaging in vivo proved high accumulation of the nanoagent at tumor site due to its excellent CD44 receptor/magnetic dual targeting capability. After intravenous injection of the nanoagent and treatment of external magnetic field, the tumor in nude mice was efficiently ablated upon NIR laser irradiation and the tumor growth inhibition was more than 89.95%. Such nanotheranostic agent is of crucial importance for accurately identifying the size and location of the tumor before therapy, monitoring the photothermal treatment procedure in real-time during therapy, assessing the effectiveness after therapy. PMID:28255343
Periarticular uptake of /sup 99m/technetium diphosphonate in psoriatics. Correlation with cutaneous activity

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

Namey, T.C.; Rosenthall, L.

1976-01-01

The periarticular uptake of /sup 99m/technetium-labeled diphosphonate (/sup 99m/TcDP) was compared in 12 patients hospitalized for psoriasis and in 12 hospitalized for other dermatoses not associated with arthropathy. The 12 patients with psoriasis had recent onset disease of less than 5 years duration; neither group had historical or clinical evidence of arthritis. All psoriatics had markedly abnormal scans with symmetrically increased periarticular uptake about the imaged joints. None of the controls had similar findings. In 4 patients scanned with /sup 99m/technetium-pertechnetate within 24 hours of their /sup 99m/TcDP scan, no evidence of inflammatory synovitis was found. Three of these patientsmore » were serially imaged with /sup 99m/TcDP at intervals of 2 weeks to 3 months after their initial study, when obvious clinical improvement in their psoriasis was apparent. Improvement in the radionuclide joint images was demonstrated in some of the patients, but none reverted to normal during the study period. In light of recent evidence for the preferential binding of /sup 99m/TcDP to immature collagen, it is suggested that psoriasis may represent a generalized, but uncharacterized, collagen disorder present in bone as well as skin, linking the cutaneous disease with the potential for arthropathy.« less
[The application of cross-linked hyaluronate hydrogel to trabeculectomy].

PubMed

Shoji, Nobuyuki; Shimizu, Kimiya; Takahashi, Katsuya; Nemoto, Rika; Kawai, Hiromi; Tomioka, Toshiya

2004-05-01

We investigated the possibility of applying cross-linked hyaluronate hydrogel (HA gel) during trabeculectomy in rabbit eyes. 1. We injected 0.9% salt solution (n = 3), Opegan-HI (n = 3), or HA gel (n = 3) into the subconjunctiva to make a follicle, and investigated its size. 2. After making a limbal-based conjunctival flap and a scleral flap, we injected HA gel or 0.9% salt solution into the subconjunctiva of rabbit eyes and sutured each flap (n = 4 each). Three weeks after the operation, we incised the conjunctiva and investigated the case of peeling away the conjunctival flap or the scleral flap. 3. We performed trabeculectomy with and without subconjunctival HA gel (n = 7 and 6, respectively), and compared the reduction of intraocular pressure between the two groups. The results showed that the formation of the follicle was excellent and it was easy to peel away the adhesion. The reduction of intraocular pressure was statistically significant 4 weeks after the operation in which the HA gel was used. It could be useful to apply HA gel in trabeculectomy to prevent adhesion.

Prognostic indicators of the outcome of arthrocentesis with and without sodium hyaluronate injection for the treatment of disc displacement without reduction: a magnetic resonance imaging study.

PubMed

Aktas, I; Yalcin, S; Sencer, S

2010-11-01

This study analysed the prognostic factors for successful arthrocentesis with and without sodium hyaluronate (SH) injection for the treatment of temporomandibular joint (TMJ) disc displacement without reduction (DDwoR) using clinical and radiological results. 29 TMJs in 25 patients with DDwoR were included. Patients were treated with arthrocentesis or arthrocentesis followed by intra-articular (i.a.) injection of SH. Treatment was evaluated for postoperative range of maximum mouth opening and the degree of postoperative pain on a VAS. Prognostic factors analysed were age, sex, duration of locking, trauma history, previous TMJ treatment, depression, bruxism, malocclusion and missing teeth. Degenerative changes were evaluated as probable prognostic factors. After treatment, 24 joints (83%) fulfilled the criteria for success. Duration of locking and present preoperative degenerative changes were the most significant factors for treatment outcome. The results suggest it is sufficient to use only arthrocentesis in patients without preoperative degenerative changes and arthrocentesis with SH in patients with degenerative changes on their preoperative MRIs, but because there were some significant differences between the two groups preventing the authors from comparing them statistically, they cannot come to that conclusion. To clarify the use of SH in such cases, standardized study groups are necessary for future studies. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.
Chitosan-co-Hyaluronic acid porous cryogels and their application in tissue engineering.

PubMed

Kutlusoy, Tuğçe; Oktay, Burcu; Apohan, Nilhan Kayaman; Süleymanoğlu, Mediha; Kuruca, Serap Erdem

2017-10-01

In this work, the usability of chitosan-co-hyaluronic acid cryogels as a tissue-engineering scaffold was investigated. Chitosan-co-hyaluronic acid cryogels were synthesized at subzero temperature. Cryogels which were composed of various compositions of chitosan and hyaluronic acid (0, 10, 20, 30 and 50wt% hyaluronic acid) was prepared. Morphological studies showed that the macroporous cryogels have been developed with 90-95% porosity. Particularly, the mechanical and biomaterial property of pure chitosan was improved by making copolymer with hyaluronic acid in different concentration. The MTT cell viability results demonstrated that the cryogels have no significant cytotoxicity effect on 3T3 fibroblast and SAOS-2 cells. Copyright © 2017 Elsevier B.V. All rights reserved.
Hyaluronic acid in dermatomyositis and polymyositis: relationship with disease and cutaneous lesions.

PubMed

Silva, Marilda Guimarães; Shinjo, Samuel Katsuyuki

2018-01-01

There are scarce studies in the literature about hyaluronic acid in systemic autoimmune myopathies. To analyze the serum level of hyaluronic acid in patients with dermatomyositis and polymyositis. Cross-sectional study, single-center, that evaluated hyaluronic acid in 18 dermatomyositis and 15 polymyositis (Bohan and Peter criteria), newly diagnosed, with clinical and laboratory activity, with no previous drug treatment. The patients were also age-, gender- and ethnicity-matched to 36 healthy individuals. The hyaluronic acid was analyzed by ELISA/EIA kit anti-hyaluronic acid. There was a higher serum level of hyaluronic acid in patients with autoimmune myopathies, in relation to control group (P<0.05). Moreover, the serum level of this glycosaminoglycan was higher in dermatomyositis, when compared to polymyositis. Both groups were comparable with regard to demographic, clinical and laboratory data, except for the presence of skin lesions in the first group. The presence of hyaluronic acid in cutaneous lesions, particularly of patients with dermatomyositis, was not analyzed neither quantified. In addition, due to disease rarity and the establishment of strict inclusion and exclusion criteria, there was a small sample in the present study. As an example of others systemic autoimmune diseases, it is possible that the hyaluronic acid is involved in the pathogenesis of autoimmune myopathies, and particularly when associated with cutaneous lesions.
[Lidocaine-containing hyaluronic acid filler on a CPM® basis for lip augmentation : Experience from clinical practice].

PubMed

Fischer, T; Sattler, G; Gauglitz, G

2016-06-01

Lip augmentation with hyaluronic acid fillers is an established procedure. As monophasic polydensified hyaluronic acid products with variable density CPM-HAL1 (Belotero® Balance Lidocaine) and CPM-HAL2 (Belotero® Intense Lidocaine) are qualified for beautification and particularly natural-looking rejuvenation, respectively. Assessment of handling and outcome of lip augmentation using the lidocaine-containing hyaluronic acid fillers CPM-HAL1 and CPM-HAL2. Data from patients who received lip augmentation by means of bautification and/or rejuvenation using CPM-HAL1 and/or CPM-HAL2 were documented. Observation period was 4 months, with assessment of natural outcome, evenness, handling, fluidity, distribution, malleability, tolerability, as well as patient satisfaction and pain. In total, 146 patients from 21 German centres participated. Physicians rated natural outcome and evenness as good or very good for > 95 % of patients. Handling, fluidity, distribution and malleability were assessed for both fillers as good or very good in > 91 % of patients. At every evaluation point, more than 93 % of patients were very or very much satisfied with the product. A total of 125 patients (85.6 %) experienced transient injection-related side effects. Pain intensity during the procedure was mild (2.72 ± 1.72 on the 0-10 pain assessment scale) and abated markedly within 30 min (0.42 ± 0.57). Lip augmentation with hyaluronic acid fillers produced a long-term cosmetic result. Due to the lidocaine content, procedural pain was low and transient. Accordingly, a high degree of patient satisfaction was achieved that was maintained throughout the observation period.
Hyaluronic acid for post sinus surgery care: systematic review and meta-analysis.

PubMed

Fong, E; Garcia, M; Woods, C M; Ooi, E

2017-01-01

Wound healing after endoscopic sinus surgery may result in adhesion formation. Hyaluronic acid may prevent synechiae development. A systematic review was performed to evaluate the current evidence on the clinical efficacy of hyaluronic acid applied to the nasal cavity after sinus surgery. Studies using hyaluronic acid as an adjunct treatment following endoscopic sinus surgery for chronic rhinosinusitis were identified. The primary outcome was adhesion formation rates. A meta-analysis was performed on adhesion event frequency. Secondary outcome measures included other endoscopic findings and patient-reported outcomes. Thirteen studies (501 patients) met the selection criteria. A meta-analysis of adhesion formation frequency on endoscopy demonstrated a lower risk ratio in the hyaluronic acid intervention group (42 out of 283 cases) compared to the control group (81 out of 282) of 0.52 (95 per cent confidence interval = 0.37-0.72). Hyaluronic acid use was not associated with any significant adverse events. Hyaluronic acid appears to be clinically safe and well tolerated, and may be useful in the early stages after sinus surgery to limit adhesion rate. Further research, including larger randomised controlled trials, is required to evaluate patient- and clinician-reported outcomes of hyaluronic acid post sinus surgery.
Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits.

PubMed

Chiang, En-Rung; Ma, Hsiao-Li; Wang, Jung-Pan; Liu, Chien-Lin; Chen, Tain-Hsiung; Hung, Shih-Chieh

2016-01-01

Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo.
Hyaluron Filler Containing Lidocaine on a CPM Basis for Lip Augmentation: Reports from Practical Experience.

PubMed

Fischer, Tanja C; Sattler, Gerhard; Gauglitz, Gerd G

2016-06-01

Lip augmentation with hyaluronic acid fillers is established. As monophasic polydensified hyaluronic acid products with variable density, CPM-HAL1 (Belotero Balance Lidocaine, Merz Aesthetics, Raleigh, NC) and CPM-HAL2 (Belotero Intense Lidocaine, Merz Aesthetics, Raleigh, NC) are qualified for beautification and particularly natural-looking rejuvenation, respectively. The aim of this article was to assess the handling and outcome of lip augmentation using the lidocaine-containing hyaluronic acid fillers, CPM-HAL1 and CPM-HAL2. Data were documented from patients who received lip augmentation by means of beautification and/or rejuvenation using CPM-HAL1 and/or CPM-HAL2. Observation period was 4 months, with assessment of natural outcome, evenness, distribution, fluidity, handling, malleability, tolerability, as well as patient satisfaction and pain. A total of 146 patients from 21 German centers participated. Physicians rated natural outcome and evenness as good or very good for more than 95% of patients. Distribution, fluidity, handling, and malleability were assessed for both fillers as good or very good in more than 91% of patients. At every evaluation point, more than 93% of patients were very or very much satisfied with the product. A total of 125 patients (85.6%) experienced transient injection-related side effects. Pain intensity during the procedure was mild (2.72 ± 1.72 on the 0-10 pain assessment scale) and abated markedly within 30 minutes (0.42 ± 0.57). Lip augmentation with hyaluronic acid fillers produced a long-term cosmetic result. Due to the lidocaine content, procedural pain was low and transient. Accordingly, a high degree of patient satisfaction was achieved that was maintained throughout the observation period. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Rooster comb hyaluronate-protein, a non-covalently linked complex.

PubMed Central

Tsiganos, C P; Vynios, D H; Kalpaxis, D L

1986-01-01

Hyaluronate from rooster comb was isolated by ion-exchange chromatography on DEAE-cellulose from tissue extracts and papain digests. The preparations were labelled with [14C]acetic anhydride and subjected to CsCl-density-gradient centrifugation in 4 M-guanidinium chloride in the presence and absence of 4% ZwittergentTM 3-12. A radioactive protein fraction was separated from the hyaluronate when the zwitterionic detergent was also present. The protein could also be separated from the glycosaminoglycan by chromatography on Sepharose CL-6B eluted with the same solvent mixture. The protein fraction contained three protein bands of Mr 15,000-17,000 as assessed by polyacrylamide-gel electrophoresis in 0.1% SDS, and seemed to lack lysozyme activity. No evidence of other protein or amino acid(s) covalently linked with the hyaluronate was obtained. The hyaluronate-protein complex may be re-formed upon mixing the components, the extent of its formation depending on the conditions used. The results show that, as in chondrosarcoma [Mason, d'Arville, Kimura & Hascall (1982) Biochem. J. 207, 445-457] and teratocarcinoma cells [Prehm (1983) Biochem. J. 211, 191-198] the rooster comb hyaluronate also is not linked covalently to a core protein. PMID:3741374
Urethral injection therapy for urinary incontinence in women.

PubMed

Kirchin, Vivienne; Page, Tobias; Keegan, Phil E; Atiemo, Kofi Om; Cody, June D; McClinton, Samuel; Aluko, Patricia

2017-07-25

statistical significance if an intention-to-treat analysis was used.Eight trials compared different agents and all results had wide confidence intervals. Silicone particles, calcium hydroxylapatite, ethylene vinyl alcohol, carbon spheres and dextranomer hyaluronic acid combination gave improvements which were not shown to be more or less efficacious than collagen. Dextranomer hyaluronic acid compound treated patients appeared to have significantly higher rates of injection site complications (16% with the hyaluronic acid compound versus none with collagen; RR 37.78, 95% CI 2.34 to 610.12) and this product has now been withdrawn from the market.A comparison of periurethral and transurethral methods of injection found similar outcomes but a higher (though not statistically significant) rate of early complications in the periurethral group. One trial of 30 women showed a weak (but not clinically significant) advantage for patient satisfaction (data not suitable for analysis in RevMan) after mid-urethral injection in comparison to bladder neck injection but with no demonstrable difference in continence levels. The available evidence base remains insufficient to guide practice. In addition, the finding that placebo saline injection was followed by a similar symptomatic improvement to bulking agent injection raises questions about the mechanism of any beneficial effects. One small trial comparing silicone particles with pelvic floor muscle training was suggestive of benefit at three months but it is not known if this was sustained, and the treatment was associated with high levels of postoperative retention and dysuria. Greater symptomatic improvement was observed with surgical treatments, though the advantages need to be set against likely higher risks. No clear-cut conclusions could be drawn from trials comparing alternative agents, although dextranomer hyaluronic acid was associated with more local side effects and is no longer commercially available for this indication. There
An In Vivo Study of Composite Microgels Based on Hyaluronic Acid and Gelatin for the Reconstruction of Surgically Injured Rat Vocal Folds

ERIC Educational Resources Information Center

Coppoolse, Jiska M. S.; Van Kooten, T. G.; Heris, Hossein K.; Mongeau, Luc; Li, Nicole Y. K.; Thibeault, Susan L.; Pitaro, Jacob; Akinpelu, Olubunm; Daniel, Sam J.

2014-01-01

Purpose: The objective of this study was to investigate local injection with a hierarchically microstructured hyaluronic acid-gelatin (HA-Ge) hydrogel for the treatment of acute vocal fold injury using a rat model. Method: Vocal fold stripping was performed unilaterally in 108 Sprague-Dawley rats. A volume of 25 µl saline (placebo controls),…
A Single Center, Prospective, Randomized, Sham-Controlled, Double-Blinded, Split-Face Trial Using Microinjections of Transparent Hyaluronic Acid Gel for Cheek Rejuvenation.

PubMed

Jones, Isabela T; Vanaman Wilson, Monique J; Bolton, Joanna; Zaleski-Larsen, Lisa; Wu, Douglas C; Goldman, Mitchel P

2018-06-01

"Skin boosting" with injections of hyaluronic acid has been demonstrated to improve aged skin. The aim of this study was to determine the efficacy and safety of small-particle hyaluronic acid with lidocaine (SP-HAL) microaliquots for the correction of fine lines of the cheeks. Twenty subjects with mild to moderate static mid to lower cheek rhytides were enrolled. The right or left cheek was randomized to receive 1 mL of SP-HAL using a microdroplet technique, with the contralateral cheek treated with sham injection of sterile normal saline. The degree of cheek wrinkling and elastosis based on the Fitzpatrick-Goldman Wrinkle and Elastosis Scale was assessed at baseline and 7, 14, 30, 90, and 180 days after treatment. Subjects rated their satisfaction at days 90 and 180. Fourteen patients completed the study. There were no statistically significant improvements in wrinkling or elastosis of the SP-HAL-treated cheek or control cheek at any time point. In addition, there were no significant differences in wrinkling, elastosis, or patient satisfaction between the treatment cheek and control cheek. One treatment of intradermal microdroplet injections of SP-HAL to the mid to lower cheek failed to show superiority over normal saline in improving clinical signs of skin wrinkling and elastosis.
Competitive Protein Adsorption on Polysaccharide and Hyaluronate Modified Surfaces

PubMed Central

Ombelli, Michela; Costello, Lauren; Postle, Corinne; Anantharaman, Vinod; Meng, Qing Cheng; Composto, Russell J.; Eckmann, David M.

2011-01-01

We measured adsorption of bovine serum albumin (BSA) and fibrinogen (Fg) onto six distinct bare and dextran- and hyaluronate-modified silicon surfaces created using two dextran grafting densities and three hyaluronic acid (HA) sodium salts derived from human umbilical cord, rooster comb and streptococcus zooepidemicus. Film thickness and surface morphology depended on HA molecular weight and concentration. BSA coverage was enhanced on surfaces upon competitive adsorption of BSA:Fg mixtures. Dextranization differentially reduced protein adsorption onto surfaces based on oxidation state. Hyaluronization was demonstrated to provide the greatest resistance to protein coverage, equivalent to that of the most resistant dextranized surface. Resistance to protein adsorption was independent of the type of hyaluronic acid utilized. With changing bulk protein concentration from 20 to 40 µg ml−1 for each species, Fg coverage on silicon increased by 4×, whereas both BSA and Fg adsorption on dextran and HA were far less dependent of protein bulk concentration. PMID:21623481
Lower Face Rejuvenation with Injections: Botox, Juvederm, and Kybella for Marionette Lines and Jowls.

PubMed

Mess, Sarah Ann

2017-11-01

A 55-year-old woman requesting noninvasive rejuvenation of the lower face received multimodal injections in a single office visit to rejuvenate the jowls. The patient experienced no adverse events other than self-limiting bruising at the hyaluronic acid injection site and minimal edema. The outcomes were evaluated as follows: (1) by the patient using the self-rated Face-Q assessment and (2) by 5 plastic surgeons (none of whom were the author of this study) based on the WAS scale and before and after photographs to evaluate the corners of the mouth and the marionette lines. This case study report suggests that the combined use of neuromodulator, hyaluronic acid dermal filler, and synthetic deoxycholic acid can rejuvenate the lower face as a minimally invasive alternative to surgery to the satisfaction of the patient and 6 plastic surgeons (including the author).
Clinical Application of Earlobe Augmentation with Hyaluronic Acid Filler in the Chinese Population.

PubMed

Qian, Wei; Zhang, Yan-Kun; Cao, Qian; Hou, Ying; Lv, Wei; Fan, Ju-Feng

2017-02-01

Larger earlobes, which are a symbol of "richness" in traditional Chinese culture, are favored by Chinese patients. The objective of this paper is to investigate the application of earlobe augmentation with hyaluronic acid (HA) filler injection and its clinical effects in the Chinese population. A total of 19 patients (38 ears) who received earlobe augmentation with HA filler injections between March 2013 and March 2015 were included. The clinical effects, duration, and complications of these cases were investigated. All patients who received earlobe HA injections showed immediate postoperative effects with obvious morphological improvement of their earlobes. The volume of HA filler injected into each ear was 0.3-0.5 ml. The duration of the effect was 6-9 months. Two of the 19 cases (3 ears) demonstrated mild bruising at the injection site, but the bruising completely disappeared within 7 days after the injection. No vascular embolism, infection, nodule, or granuloma complications were observed in the studied group. The application of earlobe augmentation with HA filler injection is a safe, effective, simple procedure for earlobe shaping. It has an easy clinical application with good clinical prospects. 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 .
Safety of radiofrequency treatment over human skin previously injected with medium-term injectable soft-tissue augmentation materials: a controlled pilot trial.

PubMed

Alam, Murad; Levy, Ross; Pajvani, Urvi; Pavjani, Urvi; Ramierez, James A; Guitart, Joan; Veen, Heather; Gladstone, Hayes B

2006-03-01

Several soft-tissue augmentation materials are now available for reduction of nasolabial fold creases and perioral rhytides. Nasolabial folds and perioral rhytides can also be improved by skin tightening delivered by non-ablative radiofrequency (RF) treatment. The purpose of this study was to assess the safety of RF treatment over skin areas recently injected with medium-term injectable soft-tissue augmentation materials. Five subjects were assigned to the experimental arm (augmentation materials plus RF) and one to the control arm (augmentation materials alone). Each subject received injections of 0.3 mL of hyaluronic acid derivative (Restylane) and calcium hydroxylapatite (Radiesse) 3 cm apart on the upper inner arm. Two weeks later, two non-overlapping passes of RF (Thermage ThermaCool TC) were delivered at 63.5 setting with medium-fast 1.5 cm2 tip over injected sites in all of the experimental subjects. Punch skin biopsies were obtained 3 days later from each of the two injection sites on each subject. Light microscopy and digital photomicrographs obtained at low, medium, and high power showed no difference between filler materials in experimental and control subjects. In both cases filler was evident at the deep dermal-subcutaneous junction. Nodule formation, foreign body extravasation, or hemorrhage/clot was not observed grossly or histologically. Subjects and physicians did not report any difference in signs and symptoms between the experimental and control arms. Slightly increased transitory pain was noted when RF was delivered over filler versus over normal skin. Applying RF treatment over the same area 2 weeks after deep dermal injection with hyaluronic acid derivatives or calcium hydroxylapatite does not appear to cause gross morphological changes in the filler material or surrounding skin. Further studies with different parameters are necessary to confirm these findings. 2006 Wiley-Liss, Inc.
Liquid Paraffin vs Hyaluronic Acid in Preventing Intraperitoneal Adhesions.

PubMed

Kataria, Hanish; Singh, Vinod Prem

2017-12-01

Adhesion formation after abdominal and pelvic operations remains a challenging problem. Role of adjuvant barriers have been studied but there is no comparative study between liquid paraffin and hyaluronic acid as a barrier method. Hence, we planned to compare the effectiveness of 0.4 % hyaluronic acid and liquid paraffin in the prevention of postoperative intraperitoneal adhesions in rats. This prospective, randomized and controlled study was conducted in 60 adult Wistar albino rats. Surgical trauma by caecal abrasion and 1 g talcum powder was used in the rat model to induce adhesion formation. After trauma, 3 ml normal saline was instilled in the peritoneal cavity in control group ( n = 20), 3 ml liquid paraffin was instilled in experimental group A ( n = 20) and 3 ml 0.4 % hyaluronic acid was instilled in experimental group B ( n = 20). Two weeks after laparotomy, repeat laparotomy was performed and the adhesions were scored according to Zuhlke classification. Liquid paraffin and hyaluronic acid both reduce the extent and grade of adhesions both macroscopically ( p = 0.018, p = 0.017) and microscopically ( p = 0.019, p = 0.019) respectively. Although there was significant reduction in adhesions by hyaluronic acid at certain specific sites as compared with liquid paraffin, its overall effectiveness in preventing postoperative intraperitoneal adhesions is not significantly different from liquid paraffin ( p = 0.092, p = 0.193) respectively. The presence of liquid paraffin and hyaluronic acid in the peritoneal cavity reduce postoperative intraperitoneal adhesions significantly in rats. However, there is no overall significant difference in the effectiveness of two groups. Dosage and safety of these chemicals in human beings remains to be established.
[A CASE OF DEXTRANOMER-HYALURONIC ACID COPOLYMER (Deflux®) IMPLANTS CALCIFICATION MIMICKING DISTAL URETERAL CALCULI].

PubMed

Matsumoto, Fumi; Matsui, Futoshi; Yazawa, Koji; Shimada, Kenji

2017-01-01

Since 2011, endoscopic correction of vesicoureteral reflux using dextranomer-hyaluronic acid copolymer (Deflux ® ) has been widely accepted in Japan due to its safety and minimally invasive nature. However, long-term complications are unknown. We present a case of Deflux ® implants calcification mimicking distal ureteral calculi in a 12-year-old boy with a history of Deflux ® injection performed at three years of age for primary VUR. We should be aware of this complication to avoid misdiagnosis and unnecessary invasive examination such as radiological imaging or endoscopy.
Lower Face Rejuvenation with Injections: Botox, Juvederm, and Kybella for Marionette Lines and Jowls

PubMed Central

2017-01-01

Summary: A 55-year-old woman requesting noninvasive rejuvenation of the lower face received multimodal injections in a single office visit to rejuvenate the jowls. The patient experienced no adverse events other than self-limiting bruising at the hyaluronic acid injection site and minimal edema. The outcomes were evaluated as follows: (1) by the patient using the self-rated Face-Q assessment and (2) by 5 plastic surgeons (none of whom were the author of this study) based on the WAS scale and before and after photographs to evaluate the corners of the mouth and the marionette lines. This case study report suggests that the combined use of neuromodulator, hyaluronic acid dermal filler, and synthetic deoxycholic acid can rejuvenate the lower face as a minimally invasive alternative to surgery to the satisfaction of the patient and 6 plastic surgeons (including the author). PMID:29263958
Retention of Human-Induced Pluripotent Stem Cells (hiPS) With Injectable HA Hydrogels for Vocal Fold Engineering.

PubMed

Imaizumi, Mitsuyoshi; Li-Jessen, Nicole Y K; Sato, Yuka; Yang, David T; Thibeault, Susan L

2017-04-01

One prospective treatment option for vocal fold scarring is regeneration with an engineered scaffold containing induced pluripotent stem cells (iPS). In the present study, we investigated the feasibility of utilizing an injectable hyaluronic acid (HA) scaffold encapsulated with human-iPS cell (hiPS) for regeneration of vocal folds. Thirty athymic nude rats underwent unilateral vocal fold injury. Contralateral vocal folds served as uninjured controls. Hyaluronic acid hydrogel scaffold, HA hydrogel scaffold containing hiPS, and HA hydrogel scaffold containing hiPS with epidermal growth factor (EGF) were injected in both vocal folds immediately after surgery. One and 2 weeks after injection, larynges were excised for histology, immunohistochemistry, and fluorescence in situ hybridization (FISH). Presence of HA hydrogel was confirmed in vocal folds 1 and 2 weeks post injection. The FISH analysis confirmed the presence and viability of hiPS in the injected vocal folds. Histological results demonstrated that vocal folds injected with HA hydrogel scaffold containing EGF demonstrated less fibrosis than those with HA hydrogel only. Human-iPS survived in injured rat vocal folds. The HA hydrogel with hiPS and EGF ameliorated the fibrotic response. Additional work is necessary to optimize hiPS differentiation and further confirm the safety of hiPS for clinical applications.
Age-related changes in cyclic phosphatidic acid-induced hyaluronic acid synthesis in human fibroblasts.

PubMed

Sano, Katsura; Gotoh, Mari; Dodo, Kyoko; Tajima, Noriaki; Shimizu, Yoshibumi; Murakami-Murofushi, Kimiko

2018-01-01

Hyaluronic acid is a major component of the extracellular matrix, which is important for skin hydration. As aging brings skin dehydration, we aimed to clarify the mRNA expression of hyaluronic acid-related proteins in human skin fibroblasts from donors of various ages (range 0.7-69 years). Previously, we reported that cyclic phosphatidic acid (cPA), a unique phospholipid mediator, stimulated the expression of HAS2 and increased hyaluronic acid synthesis in human skin fibroblasts (donor age: 3 days). In this study, we measured the mRNA expression of hyaluronic acid-related proteins: hyaluronan synthase (HAS) 1-3, hyaluronidase-1, -2, and hyaluronic acid-binding protein (versican). In addition, we tested whether cPA could increase hyaluronic acid synthesis in skin fibroblasts derived from donors of various ages. The expression of HAS1, 3, hyaluronidase-1, and -2 did not change with aging. However, the mRNA expression of versican decreased with aging. Although it is thought that the amount of hyaluronic acid in the dermis decreases with aging, the mRNA expression of HAS2 was increased. But the amount of hyaluronic acid secreted by fibroblasts did not increase with aging. This suggests that the activity and/or protein expression of HAS2 decrease with aging. Furthermore, we observed that cPA caused the increase of hyaluronic acid synthesis at any age, and this effect was increased with aging. These results suggest that aging made the fibroblasts more sensitive to cPA treatment. Therefore, cPA represents a suitable candidate for the health maintenance and improvement of the skin by increasing the level of hyaluronic acid in the dermis.

Comparison of the effects of sodium hyaluronate-chondroitin sulphate and corticosteroid in the treatment of lateral epicondylitis: a prospective randomized trial.

PubMed

Tosun, Haci Bayram; Gumustas, Seyitali; Agir, Ismail; Uludag, Abuzer; Serbest, Sancar; Pepele, Demet; Ertem, Kadir

2015-09-01

Hyaluronic acid and glycosaminoglycans have shown positive effects in improving lateral epicondylitis and other tendinosis conditions. Therefore, we designed a prospective, randomized study to compare the effects of a combined sodium hyaluronate and chondroitin sulfate (HA + CS) injection versus a triamcinolone injection in the treatment of lateral epicondylitis. In total, 57 consecutive patients with clinically diagnosed lateral epicondylitis were divided randomly into two groups. In the HA + CS group, 25 patients received a single injection of a solution containing an HA + CS combination and prilocaine HCl, while the 32 patients in the triamcinolone group received a single injection of a solution of triamcinolone and prilocaine HCl. We evaluated the pain and function outcome measures using the Patient-Rated Tennis Elbow Evaluation (PRTEE) questionnaire at the beginning of the study, and 3 and 6 months after the injection. Additionally, the Minimum Clinically Important Difference values and percentage changes in the PRTEE subscale scores between the assessments were calculated. No serious adverse events were reported throughout the study. The mean pain and function scores for the HA + CS and triamcinolone groups had significantly improved at 3 months, but the mean function scores in the HA + CS group were statistically significantly better when compared to the triamcinolone group. At 6 months, both groups had significantly improved mean pain and function scores, compared to the baseline scores; however, the mean pain and function scores in the 6-month HA + CS treatment group were better than in the 6-month triamcinolone group. The relative change for the mean total score in the HA + CS group was much better when compared with the triamcinolone group, and the HA + CS treatment group showed clinically significant improvement when compared with triamcinolone group at 3 and 6 months. This study supports the idea that for a single injection treatment of patients with
Physiochemical properties and application of hyaluronic acid: a systematic review.

PubMed

Salwowska, Natalia M; Bebenek, Katarzyna A; Żądło, Dominika A; Wcisło-Dziadecka, Dominika L

2016-12-01

Hyaluronic acid is a widely available, biocompatible, polysaccharide with distinguishing physiochemical properties which inspire its application throughout several fields of medicine. We aim to investigate the application of hyaluronic acid and its effectiveness throughout several fields of medicine, including several therapies administered and prescribed by general health practitioners. We conducted a systematic review on randomized controlled trials about the physiochemical properties of hyaluronic acid and its application through primary care. Studies included in this review were peer reviewed and met our inclusion criteria. Factors were clustered into the following: uses throughout several fields of medicine, physiochemical properties, bioavailability, tolerance, effectiveness, and adverse effects. Therapies with hyaluronic acid provided long-lasting, pain relieving, moisturizing, lubricating, and dermal filling effect. Tissue hydration, elasticity, and durability improved. Adjunct therapy with hyaluronic acid provides longer-lasting therapeutic effect when compared to the use of glucocorticosteroids and NSAIDs in osteoarthritic chronic diseases, is well-established in ophthalmology due to its lubricating properties for the corneal endothelium, and improves tissue hydration and cellular resistance to mechanical damage in aesthetic dermatology, and has marginal adverse effects. Several trials indicated its role in tumor markers, liver diseases, and in pharmaceuticals, but further research would be necessary to draw conclusive results in those fields. © 2016 Wiley Periodicals, Inc.
Effects of Hyaluronic Acid Conjugation on Anti-TNF-alpha Inhibition of Inflammation in Burns

DTIC Science & Technology

2014-05-01

Effects of hyaluronic acid conjugation on anti-TNF-α inhibition of inflammation in burns Emily E. Friedrich1, Liang Tso Sun1, Shanmugasundaram...alone, mixed with hyaluronic acid or conjugated to hyaluronic acid . We found that non-conjugated anti-TNF-α decreased macrophage infiltration to a...greater extent than that conjugated to hyaluronic acid ; however there was little effect on the degree of progression or IL-1β levels. A simple transport
Combined adductor canal block with periarticular infiltration versus periarticular infiltration for analgesia after total knee arthroplasty.

PubMed

Ma, Jinhui; Gao, Fuqiang; Sun, Wei; Guo, Wanshou; Li, Zirong; Wang, Weiguo

2016-12-01

Both adductor canal block (ACB) and periarticular infiltration (PI) have been shown to reduce pain after total knee arthroplasty (TKA) without the motor blockade. However, the efficacy and safety of combined ACB with PI (ACB + PI) as compared to PI alone for analgesia after TKA remains controversial. We therefore performed a meta-analysis to compare the effects of ACB + PI with PI alone on pain controll after TKA. PubMed, Medline, Embase, Web of Science, and the Cochrane Library were searched to identify studies comparing ACB + PI with PI alone for TKA patients. The primary outcomes included pain score with rest or activity and morphine consumption. Secondary outcomes were distance walked, length of hospital stay, and postoperative complications. Relevant data were analyzed using RevMan v5.3. Three studies involving 337 patients were included. Combined ACB with PI was associated with longer distances walked than PI alone (MD = 7.27, 95% CI: 0.43-14.12, P = 0.04) on postoperative day 1. The outcomes of pain, morphine consumption, length of hospital stay, and postoperative complications were not statistically different between the 2 groups (P > 0.05). Our meta-analysis suggests that combined ACB with PI may achieve earlier ambulation for patients after TKA without a reduction in analgesia when compared to PI alone in the early postoperative period. There were no significant differences in morphine consumption, length of hospital stay, and postoperative complications between the 2 groups. However, owing to the variation of included studies, no firm conclusions can be drawn.
The evolving role of hyaluronic acid fillers for facial volume restoration and contouring: a Canadian overview

PubMed Central

Muhn, Channy; Rosen, Nathan; Solish, Nowell; Bertucci, Vince; Lupin, Mark; Dansereau, Alain; Weksberg, Fred; Remington, B Kent; Swift, Arthur

2012-01-01

Recent advancements, including more versatile facial fillers, refined injection techniques and the adoption of a global facial approach, have contributed to improved patient outcome and increased patient satisfaction. Nine Canadian specialists (eight dermatologists, one plastic surgeon) collaborated to develop an overview on volume restoration and contouring based on published literature and their collective clinical experience. The specialists concurred that optimal results in volume restoration and contouring depend on correcting deficiencies at various layers of the facial envelope. This includes creating a foundation for deep structural support in the supraperiosteal or submuscular plane; volume repletion of subcutaneous fat compartments; and the reestablishment of dermal and subdermal support to minimize cutaneous rhytids, grooves and furrows. It was also agreed that volume restoration and contouring using a global facial approach is essential to create a natural, youthful appearance in facial aesthetics. A comprehensive non-surgical approach should therefore incorporate combining fillers such as high-viscosity, low-molecular-weight hyaluronic acid (LMWHA) for structural support and hyaluronic acid (HA) for lines, grooves and furrows with neuromodulators, lasers and energy devices. PMID:23071398
Hyaluronic acid (with fibronectin) as a bioimplant for the vocal fold mucosa.

PubMed

Chan, R W; Titze, I R

1999-07-01

To measure the viscoelastic shear properties of hyaluronic acid, with and without fibronectin, and to compare them with those of the human vocal fold mucosa and other phonosurgical biomaterials. Viscoelastic shear properties of various implantable biomaterials (Teflon, gelatin, collagen, fat, hyaluronic acid, and hyaluronic acid with fibronectin) were measured with a parallel-plate rotational rheometer. Elastic and viscous shear properties were quantified as a function of oscillation frequency (0.01-15 Hz) at 37 degrees C. The shear properties of hyaluronic acid were relatively close to those of human vocal fold mucosal tissues reported previously. Hyaluronic acid at specific concentrations (0.5%-1%), with or without fibronectin, was found to exhibit viscous shear properties (viscous shear modulus and dynamic viscosity) similar to those of the average male and female vocal fold mucosa. According to a theory that establishes the effects of tissue shear properties on vocal fold oscillation, phonation threshold pressure (a measure of the ease of phonation) is directly related to the viscous shear modulus of the vibrating vocal fold mucosa. Therefore, our findings suggest that hyaluronic acid, either by itself or mixed with fibronectin, may be a potentially optimal bioimplant for the surgical management of vocal fold mucosal defects and lamina propria deficiencies (e.g., scarring) from a biomechanical standpoint.
Topically administered hyaluronic acid in the upper airway: A narrative review.

PubMed

Pignataro, Lorenzo; Marchisio, Paola; Ibba, Tullio; Torretta, Sara

2018-01-01

Hyaluronic acid plays a role in controlling inflammatory airway processes and mucociliary clearance, and it is also involved in tissue healing and remodelling. Some studies have tested the effectiveness of topically administered hyaluronic acid in patients with upper airway diseases with positive preliminary results. This article describes the use of topically administered hyaluronic acid in patients with otolaryngological disorders. Pertinent studies published between January 2000 and October 2016 were selected by means of a MEDLINE search using the following terms: 'hyaluronic acid' and 'otolaryngology', 'otitis', 'pharyngitis', 'tonsillitis', 'rhinitis', 'rhinosinusitis' and 'nose'. Twelve of the 19 initially identified papers were selected, corresponding to 902 patients as a whole. There is some evidence that topically administered hyaluronic acid is effective or moderately effective in different otolaryngological conditions, as it improves the global subjective and clinical status of patients with inflammation of the nasopharyngeal and oto-tubaric complex, those with rhinitis or rhinosinusitis and those who have undergone nasal and sinonasal surgery. However, these findings should be viewed cautiously as they are based on a limited number of studies, some of which were probably under-powered because of their small patient samples.
Design of Cell-Matrix Interactions in Hyaluronic Acid Hydrogel Scaffolds

PubMed Central

Segura, Tatiana

2013-01-01

The design of hyaluronic acid-based hydrogel scaffolds to elicit highly controlled and tunable cell response and behavior is a major field of interest in developing tissue engineering and regenerative medicine applications. This review will begin with an overview of the biological context of hyaluronic acid, knowledge needed to better understand how to engineer cell-matrix interactions in the scaffolds via the incorporation of different types of signals in order to direct and control cell behavior. Specifically, recent methods of incorporating various bioactive, mechanical, and spatial signals are reviewed, as well as novel hyaluronic acid modifications and crosslinking schemes with a focus on specificity. PMID:23899481
Injection and adhesion palatoplasty: a preliminary study in a canine model.

PubMed

Martínez-Álvarez, Concepción; González-Meli, Beatriz; Berenguer-Froehner, Beatriz; Paradas-Lara, Irene; López-Gordillo, Yamila; Rodríguez-Bobada, Cruz; González, Pablo; Chamorro, Manuel; Arias, Pablo; Hilborn, Jöns; Casado-Gómez, Inmaculada; Martínez-Sanz, Elena

2013-08-01

Raising mucoperiosteal flaps in traditional palatoplasty impairs mid-facial growth. Hyaluronic acid-based hydrogels have been successfully tested for minimally invasive craniofacial bone generation in vivo as carriers of bone morphogenetic protein-2 (BMP-2). We aimed to develop a novel flapless technique for cleft palate repair by injecting a BMP-2 containing hydrogel. Dog pups with congenital cleft palate were either non-treated (n=4) or treated with two-flap palatoplasty (n=6) or with the proposed injection/adhesion technique (n=5). The experimental approach was to inject a hyaluronic acid-based hydrogel containing hydroxyapatite and BMP-2 subperiosteally at the cleft palate margins of pups aged six weeks. At week ten, a thin strip of the medial edge mucosa was removed and the margins were closed directly. Occlusal photographs and computed tomography (CT) scans were obtained up to week 20. Four weeks after the gel injection the cleft palate margins had reached the midline and engineered bone had enlarged the palatal bones. Removal of the medial edge mucosa and suturing allowed complete closure of the cleft. Compared to traditional palatoplasty, the injection/adhesion technique was easier, and the post-surgical recovery was faster. CT on week 20 revealed some overlapping or "bending" of palatal shelves in the two-flap repair group, which was not observed in the experimental nor control groups. A minimally invasive technique for cleft palate repair upon injectable scaffolds in a dog model of congenital cleft palate is feasible. Results suggest better growth of palatal bones. This represents an attractive clinical alternative to traditional palatoplasty for cleft palate patients. Copyright © 2013 Elsevier Inc. All rights reserved.
Production and characterization of bacterial cellulose membranes with hyaluronic acid from chicken comb.

PubMed

de Oliveira, Sabrina Alves; da Silva, Bruno Campos; Riegel-Vidotti, Izabel Cristina; Urbano, Alexandre; de Sousa Faria-Tischer, Paula Cristina; Tischer, Cesar Augusto

2017-04-01

The bacterial cellulose (BC), from Gluconacetobacter hansenii, is a biofilm with a high degree of crystallinity that can be used for therapeutic purposes and as a candidate for healing wounds. Hyaluronic acid (HA) is a constitutive polysaccharide found in the extracellular matrix and is a material used in tissue engineering and scaffolding for tissue regeneration. In this study, polymeric composites were produced in presence of hyaluronic acid isolated from chicken comb on different days of fermentation, specifically on the first (BCHA-SABT0) and third day (BCHA-SABT3) of fermentation. The structural characteristics, thermal stability and molar mass of hyaluronic acid from chicken comb were evaluated. Native membrane and polymeric composites were characterized with respect to their morphology and crystallinity. The optimized process of extraction and purification of hyaluronic acid resulted in low molar mass hyaluronic acid with structural characteristics similar to the standard commercial hyaluronic acid. The results demonstrate that the polymeric composites (BC/HA-SAB) can be produced in situ. The membranes produced on the third day presented better incorporation of HA-SAB between cellulose microfiber, resulting in membranes with higher thermal stability, higher roughness and lower crystallinity. The biocompatiblily of bacterial cellulose and the importance of hyaluronic acid as a component of extracellular matrix qualify the polymeric composites as promising biomaterials for tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.
Hylan G-F 20 Versus Low Molecular Weight Hyaluronic Acids for Knee Osteoarthritis: A Meta-Analysis.

PubMed

Zhao, Hongmou; Liu, Hongliang; Liang, Xiaojun; Li, Yi; Wang, Junhu; Liu, Cheng

2016-10-01

Hyaluronic acid injection has been reported to decrease pain compared with baseline levels in knee joint osteoarthritis. Hylan G-F 20 is distinguished from the other products by its chemical structure and relatively higher molecular weight. Many trials have compared hylan G-F 20 and low molecular weight hyaluronic acids (LMWHAs); however, their relative efficacy and safety are still debated. The aim was to compare the effectiveness and safety of intra-articular injection of hylan G-F 20 and LMWHA in the treatment of knee joint osteoarthritis. A comprehensive search of the literature up to February 2016 was performed; multiple databases were searched with 'Synvisc' or 'hylan' or 'hyaluronan' as free word terms. The pain-related outcomes and treatment-related adverse events from intent-to-treat analyzed studies were pooled for meta-analysis; other functional outcomes were included in the qualitative analysis. Twenty trials with a total of 3034 patients and 3153 knees were included, with a pooled dropout rate of 7.2 %. The pooled pain-related outcomes at 2 to 3 months reached a statistically significant difference in favor of hylan G-F 20 (I 2 = 88 %; random effects; P = 0.02), and the significance still existed with exclusion (in order to eliminate heterogeneity) of the three studies that most favored hylan G-F 20 (I 2 = 51 %; fixed effect; P = 0.03). No significant difference was reached for other group and subgroup analyses. No significant difference was reached in comparing the patients with treatment-related adverse events (seven trials; 2025 patients; P = 0.13) or the treatment-related adverse events (six trials; 1633 patients; P = 0.14). According to the current results, limited evidence showed a superior effect favoring hylan G-F 20 over LMWHA in the period from 2 to 3 months post-injection for pain-related outcomes. There was no evidence of increased risk of treatment-related adverse events for hylan G-F 20 injections.
Endoscopic treatment of vesicoureteral reflux with polyacrylate polyalcohol copolymer and dextranomer/hyaluronic acid in adults.

PubMed

Turk, Akif; Selimoglu, Ahmet; Demir, Kadir; Celik, Osman; Saglam, Erkin; Tarhan, Fatih

2014-01-01

Aim of this study is to examine the effectiveness of dextranomer/hyaluronic acid copolymer and polyacrylate polyalcohol copolymer in endoscopic treatment of vesicoureteral reflux disease in adult patients with and without chronic renal failure. Thirty two patients (12 female, 20 male) with a total of 50 renal units were treated for vesicoureteral reflux. There were 26 (81%) chronic renal failure patients. The success of treatment was evaluated by voiding cystouretrography at 3rd and 12th months after subureteric injection. The persistence of reflux was considered as failure. Patients were divided into two groups according to injected material. Age, sex, grade of reflux and treatment results were recorded and evaluated. Reflux was scored as grade 1 in seven (14%), grade 2 in 16 (32%), grade 3 in 21 (42%) and grade 4 in six (12%) renal units. There was not patient with grade 5 reflux. Fourteen renal units (28%) were treated with dextranomer/hyaluronic acid copolymer (group 1) and 36 renal units (72%) were treated with polyacrylate polyalcohol copolymer (group 2). The overall treatment success was achieved at 40 renal units (80%). The treatment was successful at 11 renal units (79%) in group 1 and 29 renal units (81%) in group 2 (p = 0.71). There was not statistically significant difference between two groups with patients with chronic renal failure in terms of treatment success (p = 1.00). The effectiveness of two bulking agents was similar in treatment of vesicoureteral reflux disease in adult patients and patients with chronic renal failure.
Fibroblast populated collagen lattices exhibit opposite biophysical conditions by fibrin or hyaluronic acid supplementation.

PubMed

Chopin-Doroteo, Mario; Salgado-Curiel, Rosa M; Pérez-González, José; Marín-Santibáñez, Benjamín M; Krötzsch, Edgar

2018-06-01

Fibrin and hyaluronic acid are important components of the provisional wound matrix. Through interactions with fibroblasts, they provide biophysical cues that regulate the viscoelastic properties of the extracellular matrix. To understand the roles of fibrin and hyaluronic acid in a collagenous environment, we used fibroblast populated collagen lattices (collagen, collagen-fibrin, and collagen-hyaluronic acid). Compared with collagen and collagen-hyaluronic acid cultures, collagen-fibrin cultures showed less contraction, which is correlated with increased elastic (G') and complex (|G*|) moduli, and reduced proportions of dendritic fibroblasts, despite increased αv integrin expression. Stiffness decreased during culture in collagen-fibrin environment, meanwhile phase shift (δ) values increased, clearly associated with the rise in fibrinolytic and gelatinolytic activities. These processes changed the viscoelastic properties of the system toward G' and |G*| values observed on day 5 in collagen cultures. Although less collagen turnover was observed in collagen-fibrin cultures than in collagen and collagen-hyaluronic acid cultures, collagen neosynthesis was apparently insufficient to contribute to the overall viscoelastic properties of the system. Collagen-hyaluronic acid cultures showed very limited changes during time. Firstly, they exhibited the highest δ values, suggesting an increase in the viscous behavior due to the hygroscopic properties of hyaluronic acid. These results showed that fibrin and hyaluronic acid not only affect differently the viscoelastic properties of the culture, they can tune fibroblastic activity by regulating cell attachment and extracellular matrix remodeling. Copyright © 2018 Elsevier Ltd. All rights reserved.
Physics of soft hyaluronic acid-collagen type II double network gels

NASA Astrophysics Data System (ADS)

Morozova, Svetlana; Muthukumar, Murugappan

2015-03-01

Many biological hydrogels are made up of multiple interpenetrating, charged components. We study the swelling, elastic diffusion, mechanical, and optical behaviors of 100 mol% ionizable hyaluronic acid (HA) and collagen type II fiber networks. Dilute, 0.05-0.5 wt% hyaluronic acid networks are extremely sensitive to solution salt concentration, but are stable at pH above 2. When swelled in 0.1M NaCl, single-network hyaluronic acid gels follow scaling laws relevant to high salt semidilute solutions; the elastic shear modulus G' and diffusion constant D scale with the volume fraction ϕ as G' ~ϕ 9 / 4 and D ~ϕ 3 / 4 , respectively. With the addition of a collagen fiber network, we find that the hyaluronic acid network swells to suspend the rigid collagen fibers, providing extra strength to the hydrogel. Results on swelling equilibria, elasticity, and collective diffusion on these double network hydrogels will be presented.
Hyaluronic Acid Graft Copolymers with Cleavable Arms as Potential Intravitreal Drug Delivery Vehicles.

PubMed

Borke, Tina; Najberg, Mathie; Ilina, Polina; Bhattacharya, Madhushree; Urtti, Arto; Tenhu, Heikki; Hietala, Sami

2018-01-01

Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2-diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer-from-polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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.
Is there a place for intra-articular hyaluronate in osteoarthritis of the knee?

PubMed

Kirwan, J

2001-06-01

Viscosupplementation refers to the intra-articular injection of hyaluronic acid (HA) as a hyaluronate to relieve pain and improve function, usually in patients with knee OA. HA is the major constituent of a 1-2-micron layer on the surface of articular cartilage as well as a major constituent of synovial fluid (SF). Solutions of HA can act as lubricants when movements are slow and as shock absorbers when movements are fast. In arthritis, the molecular weight of HA is reduced, and so are its properties. Viscosupplementation has been advocated as a way of reversing this, but intra-articular HA has other properties, such as an anti-inflammatory effect, which may also contribute to any therapeutic effect. There is a large placebo effect from intra-articular injections, and the benefits of intra-articular glucocorticoids may be only slightly better than this effect. In only one randomised, placebo-controlled trial was the difference in response significant. Studies of intra-articular HA also show a marked placebo response (where it has been measured), but some have suggested a measurable benefit, which may be more prolonged that that of glucocorticoids. There is only a single study in which the effects of intra-articular therapy with placebo, glucocorticoids and viscosupplementation can be compared. Here, HA may have had a slightly longer period of benefit than triamcinolone hexacetonide or placebo. The very large placebo response after aspiration of the knee may seriously mislead those engaged in uncontrolled therapeutic evaluation of intra-articular therapy. Current evidence suggests that viscosupplements probably provide a similar level of pain relief to glucocorticoids and do so for several months, but the onset is slower, and there is the potential for local adverse reactions.
Budesonide nanocrystal-loaded hyaluronic acid microparticles for inhalation: In vitro and in vivo evaluation.

PubMed

Liu, Tingting; Han, Meihua; Tian, Fang; Cun, Dongmei; Rantanen, Jukka; Yang, Mingshi

2018-02-01

Most inhaled pharmaceutical formulations on the market are intended to exert immediate pharmacological action, even although inhaled sustained-release formulations can be needed to reduce the frequency of dosing. The purpose of this study was to investigate the pulmonary retention and pharmacokinetics of a poorly water-soluble drug after loading its nanocrystal form into inhalable mucoadhesive microparticles composed of hyaluronic acid. It was intended to prolong the pharmacological effect without compromising the dissolution rate of the poorly water-soluble drug. In this study, budesonide, a corticosteroid anti-inflammatory drug, was used as a model poorly water-soluble drug. Submicron budesonide particles were prepared by wet ball milling, and subsequently loaded into hyaluronic acid microparticles by the spray drying process. The ball-milled budesonide particles and the spray-dried microparticles were characterized using dynamic light scattering (DLS), laser diffraction, Scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). Selected formulations were evaluated in terms of their dissolution/release rate, aerosol performance, muco-adhesion and pharmacokinetics in rats. As shown by XRD and DSC analysis, the nanonized budesonide particles in this study were mainly in crystalline form. The dissolution/release study showed that the in vitro release of budesonide from the microparticles was not significantly sustained compared with the dissolution rate of budesonide nanocrystals (BUD-NC). However, the budesonide in the microparticles exhibited prolonged retention on the surface of porcine tracheal tube owing to the muco-adhesion ability of hyaluronic acid. After intratracheal administration to rats, the BUD-NC exhibited a similar pharmacokinetic profile to that of budesonide solution via i.v. injection. In contrast, budesonide loaded in the mucoadhesive microparticles exhibited a significantly prolonged T max
Protein Expression Level of Skin Wrinkle-Related Factors in Hairless Mice Fed Hyaluronic Acid.

PubMed

Yun, Min-Kyu; Lee, Sung-Jin; Song, Hye-Jin; Yu, Heui-Jong; Rha, Chan Su; Kim, Dae-Ok; Choe, Soo-Young; Sohn, Johann

2017-04-01

The aim of this study was to evaluate the wrinkle improving effect of hyaluronic acid intakes. Wrinkles were induced by exposing the skin of hairless mice to ultraviolet B (UVB) irradiation for 14 weeks. Hyaluronic acid was administered to the mice for 14 weeks including 4 weeks before experiments. Skin tissue was assayed by enzyme-linked immunosorbent assay to determine protein expression of wrinkle-related markers. The group supplemented with high concentrations of hyaluronic acid appeared significantly better than control group for collagen, matrix metalloproteinase 1, interleukin (IL)-1β, and IL-6 assay. Transforming growth factor-β1 (TGF-β1) and hyaluronic acid synthase 2 (HAS-2) were not shown to be significantly different. In conclusion, hyaluronic acid administration regulated expression levels of proteins associated with skin integrity, and improved the wrinkle level in skin subjected to UVB irradiation.
Analysis of hyaluronic acid concentration in rat vocal folds during estral and gravidic puerperal cycles.

PubMed

Pedroso, José Eduardo de Sá; Brasil, Osíris Camponês do; Martins, João Roberto Maciel; Nader, Helena Bociane; Simões, Manuel de Jesus

2009-01-01

Hormone plays an important role in the larynx. Among other substances, vocal folds contain hyaluronic acid, which tissue concentration may vary according to hormone action. the objective of this study is to analyze hyaluronic acid concentration in the vocal folds during estral and gravidic-puerperal cycles. Experimental study. 40 adult rats were divided into two groups. In the first group we used 20 rats to establish the concentration of hyaluronic acid during the estral cycle and in the second group, 20 animals were submitted to the same procedure but during the gravidic-puerperal cycle. Variations in hyaluronic acid concentration was not observed during the estral cycle. In the gravidic puerperal cycle group, an increase in hyaluronic acid concentration was observed in the puerperal subgroup. Comparing the two groups of estral and gravidic-puerperal cycles, no difference was observed. In comparing all subgroups of estral and gravidic-puerperal cycles, an increase in hyaluronic acid concentration was noticed only in the puerperal phase.

Hyaluronidase: Understanding Its Properties and Clinical Application for Cosmetic Injection Adverse Events.

PubMed

Harrison, Jeanine; Rhodes, Oriol

The recent global consensus on the management of cosmetic aesthetic injectable complications from hyaluronic acid (HA) has increased the focus on the use of hyaluronidase more than ever before (M. Signorini et al., 2016). A comprehensive knowledge of facial anatomy, including structural positioning of facial arteries and veins, and an extensive knowledge of HA products available for injection procedures, combined with best practice protocols, will assist to prevent adverse events. Despite the growing number of patients using cosmetic fillers for facial restoration, the incidents incidence of adverse events remains low. Indeed, the avoidance of complications through safe and effective injection practice remains the key to preventing the need to use hyaluronidase.
High and low molecular weight hyaluronic acid differentially influence macrophage activation

PubMed Central

Rayahin, Jamie E.; Buhrman, Jason S.; Zhang, Yu; Koh, Timothy J.; Gemeinhart, Richard A.

2015-01-01

Macrophages exhibit phenotypic diversity permitting wide-ranging roles in maintaining physiologic homeostasis. Hyaluronic acid, a major glycosaminoglycan of the extracellular matrix, has been shown to have differential signaling based on its molecular weight. With this in mind, the main objective of this study was to elucidate the role of hyaluronic acid molecular weight on macrophage activation and reprogramming. Changes in macrophage activation were assessed by activation state selective marker measurement, specifically quantitative real time polymerase chain reaction, and cytokine enzyme-linked immunoassays, after macrophage treatment with differing molecular weights of hyaluronic acid under four conditions: the resting state, concurrent with classical activation, and following inflammation involving either classically or alternatively activated macrophages. Regardless of initial polarization state, low molecular weight hyaluronic acid induced a classically activated-like state, confirmed by up-regulation of pro-inflammatory genes, including nos2, tnf, il12b, and cd80, and enhanced secretion of nitric oxide and TNF-α. High molecular weight hyaluronic acid promoted an alternatively activated-like state, confirmed by up regulation of pro-resolving gene transcription, including arg1, il10, and mrc1, and enhanced arginase activity. Overall, our observations suggest that macrophages undergo phenotypic changes dependent on molecular weight of hyaluronan that correspond to either (1) pro-inflammatory response for low molecular weight HA or (2) pro-resolving response for high molecular weight HA. These observations bring significant further understanding of the influence of extracellular matrix polymers, hyaluronic acid in particular, on regulating the inflammatory response of macrophages. This knowledge can be used to guide the design of HA-containing biomaterials to better utilize the natural response to HAs. PMID:26280020
Periarticular Fractures of the Knee in Polytrauma Patients

PubMed Central

Bertrand, M.L.; Andrés-Cano, P.; Pascual-López, F.J.

2015-01-01

Periarticular fractures around the knee are a challenge for the orthopaedic surgeon. When these fractures are presented in the context of a multiple trauma patient, they are even more difficult to manage because the treatment approach depends not only on the fracture itself, but also on the patient’s general condition. These fractures, caused by high-energy trauma, present complex fracture patterns with severe comminution and major loss of articular congruity, and are often associated with vascular and nerve complications, particularly in the proximal tibia, due to its anatomical features with poor myocutaneous coverage. They are almost always accompanied by soft tissue injury. The management of polytrauma patients requires a multidisciplinary team and accurate systemic stabilization of the patient before undertaking orthopaedic treatment. These fractures are usually addressed sequentially, either according to the general condition of the patient or to the local characteristics of the lesions. In recent decades, various fixation methods have been proposed, but there is still no consensus as to the ideal method for stabilizing these fractures. In this paper, we describe the general characteristics of these fractures, the stabilization methods traditionally used and those that have been developed in recent years, and discuss the treatment sequences proposed as most suitable for the management of these injuries. PMID:26312118
Exploring reasons for the observed inconsistent trial reports on intra-articular injections with hyaluronic acid in the treatment of osteoarthritis: Meta-regression analyses of randomized trials.

PubMed

Johansen, Mette; Bahrt, Henriette; Altman, Roy D; Bartels, Else M; Juhl, Carsten B; Bliddal, Henning; Lund, Hans; Christensen, Robin

2016-08-01

The aim was to identify factors explaining inconsistent observations concerning the efficacy of intra-articular hyaluronic acid compared to intra-articular sham/control, or non-intervention control, in patients with symptomatic osteoarthritis, based on randomized clinical trials (RCTs). A systematic review and meta-regression analyses of available randomized trials were conducted. The outcome, pain, was assessed according to a pre-specified hierarchy of potentially available outcomes. Hedges׳s standardized mean difference [SMD (95% CI)] served as effect size. REstricted Maximum Likelihood (REML) mixed-effects models were used to combine study results, and heterogeneity was calculated and interpreted as Tau-squared and I-squared, respectively. Overall, 99 studies (14,804 patients) met the inclusion criteria: Of these, only 71 studies (72%), including 85 comparisons (11,216 patients), had adequate data available for inclusion in the primary meta-analysis. Overall, compared with placebo, intra-articular hyaluronic acid reduced pain with an effect size of -0.39 [-0.47 to -0.31; P < 0.001], combining very heterogeneous trial findings (I(2) = 73%). The three most important covariates in reducing heterogeneity were overall risk of bias, blinding of personnel and trial size, reducing heterogeneity with 26%, 26%, and 25%, respectively (Interaction: P ≤ 0.001). Adjusting for publication/selective outcome reporting bias (by imputing "null effects") in 24 of the comparisons with no data available reduced the combined estimate to -0.30 [-0.36 to -0.23; P < 0.001] still in favor of hyaluronic acid. Based on available trial data, intra-articular hyaluronic acid showed a better effect than intra-articular saline on pain reduction in osteoarthritis. Publication bias and the risk of selective outcome reporting suggest only small clinical effect compared to saline. Copyright © 2016 Elsevier Inc. All rights reserved.
Evaluation of magnetic resonance signal modification induced by hyaluronic acid therapy in chondromalacia patellae: a preliminary study.

PubMed

Magarelli, N; Palmieri, D; Ottaviano, L; Savastano, M; Barbato, M; Leone, A; Maggialetti, A; Ciampa, F P; Bonomo, L

2008-01-01

Hyaluronic Acid (HA) is an alternative method for the treatment of osteoarthritis (OA), which acts on pain through a double action: anti-inflammatory and synovial fluid (SF) visco-supplementation. Magnetic Resonance Imaging (MRI), utilizing specific sequences, is a valid method for studying the initial phase of chondral damage. The analysis of the data, obtained through the intensity of values taken by positioning Region of Interest (ROIs) within the lesion, determining the differences before and after treatment with HA injected into the knee. The results obtained after six months and one year from the injection were statistically different in respect to those taken before, immediately and after three months of treatment. MRI represents a valid tool to evaluate the grade of chondromalacia patellae and also to follow the cartilage modification induced by HA therapy.
The role of serum hyaluronic acid determination in the diagnosis of liver fibrosis.

PubMed

Gudowska, Monika; Cylwik, Bogdan; Chrostek, Lech

2017-01-01

The common pathway leading to liver fibrosis and cirrhosis is growing deposition of extracellular matrix (ECM). It results from molecular and histological rearrangement of collagens, glycoproteins and hyaluronans. Hyaluronic acid is a chief component of the extracellular matrix of connective tissues and plays the main structural role in the formation of ECM. The most important organ involved in the synthesis of hyaluronic acid is the liver. In this paper the meaning of hyaluronic acid in the diagnostics of liver diseases is discussed. Here, we focus on the described changes of hyaluronic acid concentration in the pathological processes of the liver, including alcoholic and non-alcoholic liver diseases. The results of published clinical studies have shown its high diagnostic sensitivity, which probably enables its application in laboratory diagnosis.
[Anti-wrinkle creams with hyaluronic acid: how effective are they?].

PubMed

Poetschke, Julian; Schwaiger, Hannah; Steckmeier, Stephanie; Ruzicka, Thomas; Gauglitz, Gerd G

2016-05-25

Anti-wrinkle creams containing hyaluronic-acid are often advertised as an efficacious option for the treatment of wrinkles and have even been presented as an option equal to some medical procedures in this regard. Evidence from conclusive and systematic research supporting those claims, however, is widely lacking. During this trial we examined whether the daily use of anti-wrinkle creams containing hyaluronic-acid has an influence on the depth of wrinkles as well as skin tightness and elasticity. We split up 20 patients into four groups, each of which were assigned an anti-wrinkle cream containing hyaluronic acid for daily use. Four different creams within different price ranges were chosen (Balea, Nivea, Lancôme, Chanel). Before and after the 3 month trial, wrinkle depth was assessed using the PRIMOS(pico) (GFMesstechnik, Teltow, Germany) and skin-tightness and elasticity were evaluated using the Cutometer MP580 (Courage+Khazaka, Cologne, Germany). Additionally, after the trial, questionnaire data on patient satisfaction with their individual product was collected. The depth of perioral and orbital wrinkles decreased significantly in all groups, with depth reduction ranging between 10% and 20%. Skin-tightness increased significantly in all groups, rising by 13 to 30%. Minimal significant changes in skin-elasticity could only be shown in individual groups. The regular use of hyaluronic-acid containing anti-wrinkle creams for over 3 months showed clear and positive effects on wrinkle-depth and skin-tightness. Due to the design of the study, however, no clear indication on the efficacy of hyaluronic acid could be shown.
Effect of intra-articular injection of intermediate-weight hyaluronic acid on hip and knee cartilage: in-vivo evaluation using T2 mapping.

PubMed

Ferrero, Giulio; Sconfienza, Luca Maria; Fiz, Francesco; Fabbro, Emanuele; Corazza, Angelo; Dettore, Daniele; Orlandi, Davide; Castellazzo, Carlo; Tornago, Stefano; Serafini, Giovanni

2018-06-01

We used T2 mapping to quantify the effect of intra-articular hyaluronic acid administration (IAHAA) on cartilage with correlation to clinical symptoms. One hundred two patients with clinical and MRI diagnosis of hip or knee grade I-III chondropathy were prospectively included. All patients received a standard MRI examination of the affected hip/knee (one joint/patient) and T2-mapping multiecho sequence for cartilage evaluation. T2 values of all slices were averaged and used for analysis. One month after MR evaluation 72 patients (38 males; mean age 51±10 years) underwent IAHAA. As a control group, 30 subjects (15 males; 51 ± 9 years) were not treated. MR and WOMAC evaluation was performed at baseline and after 3, 9, and 15 months in all patients. T2 mapping in hyaluronic acid (HA) patients showed a significant increase in T2 relaxation times from baseline to the first time point after therapy in knees (40.7 ± 9.8 ms vs. 45.8 ± 8.6 ms) and hips (40.9 ± 9.7 ms; 45.9 ± 9.5 ms) (p < 0.001). At the 9- and 15-month evaluations, T2 relaxation dropped to values similar to the baseline ones (p < 0.001 vs. 3 month). The correlation between T2 increase and pain reduction after IAHAA was statistically significant (r = 0.54, p < 0.01) in patients with grade III chondropathy. T2 mapping can be used to evaluate the effect over time of IAHAA in patients with hip and knee chondropathy. • T2 relaxation times change over time after hyaluronic acid intra-articular administration • T2 relaxation times of the medial femoral condyle correlate with WOMAC variation • T2 relaxation times are different between Outerbridge I and II-III.
Oral delivery of exenatide via microspheres prepared by cross-linking of alginate and hyaluronate.

PubMed

Zhang, Baojie; He, Dongyang; Fan, Yu; Liu, Nan; Chen, Yijun

2014-01-01

Exenatide is an FDA-approved glucose-lowering peptide drug for the treatment of type 2 diabetes by subcutaneous injection. To address the issues on the inconvenience for patient use and the difficulty of oral administration of peptide drugs, chemical cross-linking of two pH-responsive biomaterials, alginate and hyaluronate, was carried out to prepare a new material for the encapsulation of exenatide as a form of microspheres. The exenatide-loaded microspheres exhibited spherical structures with excellent loading and release behaviors in the simulated gastrointestinal tract environments. After oral administration of the microspheres in db/db mice, maximum plasma concentration of exenatide appeared at 4 hours, and blood glucose was effectively reduced to a normal level within 2 hours and maintained for another 4 hours. The bioavailability of the exenatide-loaded microspheres, relative to subcutaneous injection of exenatide, reached 10.2%. Collectively, the present study demonstrated the feasibility of orally delivering exenatide with the new cross-linked biomaterial and formulation, and showed therapeutic potential for clinical applications.
High and Low Molecular Weight Hyaluronic Acid Differentially Regulate Human Fibrocyte Differentiation

PubMed Central

Maharjan, Anu S.; Pilling, Darrell; Gomer, Richard H.

2011-01-01

Background Following tissue injury, monocytes can enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but little is known about what regulates this differentiation. Extracellular matrix contains high molecular weight hyaluronic acid (HMWHA; ∼2×106 Da). During injury, HMWHA breaks down to low molecular weight hyaluronic acid (LMWHA; ∼0.8–8×105 Da). Methods and Findings In this report, we show that HMWHA potentiates the differentiation of human monocytes into fibrocytes, while LMWHA inhibits fibrocyte differentiation. Digestion of HMWHA with hyaluronidase produces small hyaluronic acid fragments, and these fragments inhibit fibrocyte differentiation. Monocytes internalize HMWHA and LMWHA equally well, suggesting that the opposing effects on fibrocyte differentiation are not due to differential internalization of HMWHA or LMWHA. Adding HMWHA to PBMC does not appear to affect the levels of the hyaluronic acid receptor CD44, whereas adding LMWHA decreases CD44 levels. The addition of anti-CD44 antibodies potentiates fibrocyte differentiation, suggesting that CD44 mediates at least some of the effect of hyaluronic acid on fibrocyte differentiation. The fibrocyte differentiation-inhibiting factor serum amyloid P (SAP) inhibits HMWHA-induced fibrocyte differentiation and potentiates LMWHA-induced inhibition. Conversely, LMWHA inhibits the ability of HMWHA, interleukin-4 (IL-4), or interleukin-13 (IL-13) to promote fibrocyte differentiation. Conclusions We hypothesize that hyaluronic acid signals at least in part through CD44 to regulate fibrocyte differentiation, with a dominance hierarchy of SAP>LMWHA≥HMWHA>IL-4 or IL-13. PMID:22022512
The effects of hyaluronic acid incorporated as a wetting agent on lysozyme denaturation in model contact lens materials.

PubMed

Weeks, Andrea; Boone, Adrienne; Luensmann, Doerte; Jones, Lyndon; Sheardown, Heather

2013-09-01

Conventional and silicone hydrogels as models for contact lenses were prepared to determine the effect of the presence of hyaluronic acid on lysozyme sorption and denaturation. Hyaluronic acid was loaded into poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate)/TRIS--methacryloxypropyltris (trimethylsiloxy silane) hydrogels, which served as models for conventional and silicone hydrogel contact lens materials. The hyaluronic acid was cross-linked using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide in the presence of dendrimers. Active lysozyme was quantified using a Micrococcus lysodeikticus assay while total lysozyme was determined using 125-I radiolabeled protein. To examine the location of hyaluronic acid in the gels, 6-aminofluorescein labeled hyaluronic acid was incorporated into the gels using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide chemistry and the gels were examined using confocal laser scanning microscopy. Hyaluronic acid incorporation significantly reduced lysozyme sorption in poly(2-hydroxyethyl methacrylate) (p < 0.00001) and poly(2-hydroxyethyl methacrylate)/TRIS--methacryloxypropyltris (trimethylsiloxy silane) (p < 0.001) hydrogels, with the modified materials sorbing only 20% and 16% that of the control, respectively. More importantly, hyaluronic acid also decreased lysozyme denaturation in poly(2-hydroxyethyl methacrylate) (p < 0.005) and poly(2-hydroxyethyl methacrylate)/TRIS--methacryloxypropyltris (trimethylsiloxy silane) (p < 0.02) hydrogels. The confocal laser scanning microscopy results showed that the hyaluronic acid distribution was dependent on both the material type and the molecular weight of hyaluronic acid. This study demonstrates that hyaluronic acid incorporated as a wetting agent has the potential to reduce lysozyme sorption and denaturation in contact lens applications. The distribution of hyaluronic acid within hydrogels appears to affect denaturation, with more surface mobile, lower
Accurate, safe, and rapid method of intraoperative tumor identification for totally laparoscopic distal gastrectomy: injection of mixed fluid of sodium hyaluronate and patent blue.

PubMed

Nakagawa, Masatoshi; Ehara, Kazuhisa; Ueno, Masaki; Tanaka, Tsuyoshi; Kaida, Sachiko; Udagawa, Harushi

2014-04-01

In totally laparoscopic distal gastrectomy, determining the resection line with safe proximal margins is often difficult, particularly for tumors located in a relatively upper area. This is because, in contrast to open surgery, identifying lesions by palpating or opening the stomach is essentially impossible. This study introduces a useful method of tumor identification that is accurate, safe, and rapid. On the operation day, after inducing general anesthesia, a mixture of sodium hyaluronate and patent blue is injected into the submucosal layer of the proximal margin. When resecting stomach, all marker spots should be on the resected side. In all cases, the proximal margin is examined histologically by using frozen sections during the operation. From October 2009 to September 2011, a prospective study that evaluated this method was performed. A total of 34 patients who underwent totally laparoscopic distal gastrectomy were enrolled in this study. Approximately 5 min was required to complete the procedure. Proximal margins were negative in all cases, and the mean ± standard deviation length of the proximal margin was 23.5 ± 12.8 mm. No side effects, such as allergy, were encountered. As a method of tumor identification for totally laparoscopic distal gastrectomy, this procedure appears accurate, safe, and rapid.
Determination of the presence of hyaluronic acid in preparations containing amino acids: the molecular weight characterization.

PubMed

Bellomaria, A; Nepravishta, R; Mazzanti, U; Marchetti, M; Piccioli, P; Paci, M

2014-10-15

Several pharmaceutical preparations contain hyaluronic acid in the presence of a large variety of low molecular weight charged molecules like amino acids. In these mixtures, it is particularly difficult to determine the concentration and the molecular weight of the hyaluronic acid fragments. In fact zwitterionic compounds in high concentration behave by masking the hyaluronic acid due to the electrostatic interactions between amino acids and hyaluronic acid. In such conditions the common colorimetric test of the hyaluronic acid determination appears ineffective and in the (1)H NMR spectra the peaks of the polymer disappear completely. By a simple separation procedure the presence of hyaluronic acid was revealed by the DMAB test and (1)H NMR while its average molecular weight in the final product was determined by DOSY NMR spectroscopy alone. The latter determination is very important due to the healthy effects of some sizes of this polymer's fragments. Copyright © 2014 Elsevier B.V. All rights reserved.
Alpha-2-macroglobulin and hyaluronic acid as fibromarkers in patients with chronic hepatitis C.

PubMed

Pitekova, B; Kupcova, V; Uhlikova, E; Mojto, V; Turecky, L

2017-01-01

Liver fibrosis is the final common pathway of chronic liver diseases of various etiology. From the practical standpoint, it would be ideal to have a noninvasive fibromarker. The aim of our study was to investigate the levels of alpha-2-macroglobulin, potential fibromarker, in correlation to histological staging and another potential fibromarker, hyaluronic acid, in patients with chronic hepatitis C. Population groups in this study consisted of 51 healthy volunteers and 54 patients with chronic hepatitis C. Liver biopsies were obtained under ultrasound guidance. Alpha-2-macroglobulin was determined by electroimmunodiffusion and hyaluronic acid with enzyme-linked binding protein assay. Both potential fibromarkers, alpha-2-macroglobulin and hyaluronic acid, were increased in patients with chronic hepatitis C. The alpha-2-macroglobulin levels were not significantly increased in the groups F0-F1. In the groups F2-F4, alpha-2-macroglobulin levels were significantly higher than in the control group. The changes of hyaluronic acid were similar to changes of alpha-2-macroglobulin. Regression analysis showed a significant correlation between hyaluronic acid and alpha-2-macroglobulin levels. According to the results of our study, it can be concluded that alpha-2-macroglobulin and hyaluronic acid might be useful markers of liver fibrosis (Tab. 2, Ref. 15).
The use of hyaluronic and aminocaproic acid in the treatment of alveolar osteitis.

PubMed

Dubovina, Dejan; Mihailović, Branko; Bukumirić, Zoran; Vlahović, Zoran; Miladinović, Milan; Miković, Nikola; Lazić, Zoran

2016-11-01

Alveolar osteitis (AO), also known as “dry socket”, is relatively common post-extraction complication. It probably occurs due to excessive fibrinolytic activity in the coagulum and is characterized by intense pain sensations. The aim of this clinical study was to examine the role of hyaluronic acid and aminocaproic acid in the treatment of AO. The study included 60 patients with the clinical diagnosis of AO. All the patients were divided into two groups of 30 patients each according to the applied non-pharmacological measure: irrigation – irrigation of dry socket with sterile saline; curettage – careful curettage. Both of these groups were further divided into three subgroups regarding the applied treatment (hyaluronic acid; hyaluronic acid + aminocaproic acid; Alvogyl ®, an anesthetic and antiseptic paste), each with 10 patients, according to the following protocol: 0.2 mL of hyaluronic acid in the form of a 0.8% gel; 2 mL of aminocaproic acid and hyaluronic acid; Alvogyl®. During each visit, scheduled for every two days until complete absence of painful sensations, the patients had the therapeutic method repeated as at the first examination. At each control visit the number of present symptoms and signs of AO was recorded, as well as the level of pain (measured with a visual analogue scale). With the use of hyaluronic acid, with or without aminocaproic one, a statistically significantly faster reduction in pain sensations was achieved, along with the reduction in the number of symptoms and signs of AO compared to the use of Alvogyl®. Hyaluronic acid, applied alone or in combination with aminocaproic acid significantly reduces pain sensation, thus it can be successfully used in the treatment of AO.
Cashew apple juice as microbial cultivation medium for non-immunogenic hyaluronic acid production.

PubMed

Oliveira, Adriano H; Ogrodowski, Cristiane C; de Macedo, André C; Santana, Maria Helena A; Gonçalves, Luciana R B

2013-12-01

In this work, natural cashew apple juice was used as cultivation medium as an alternative to substitute brain heart infusion medium. The effect of aeration and juice supplementation with yeast extract on the production of hyaluronic acid in batch fermentation was also investigated. Similar levels of cell mass were obtained in inoculum using cashew apple juice supplemented with yeast extract or the conventional brain heart infusion medium. Fermentation in Erlenmeyer flasks produced low biomass and hyaluronic acid concentrations. The hyaluronic acid concentration and viscosity increased from 0.15 g/L and 3.87 cP (no aeration or medium supplementation) to 1.76 g/L and 107 cP, when aeration (2 vvm) and 60 g/L of yeast extract were used. The results suggest the production of low-molecular weight hyaluronic acid oligomers instead of the high molecular weight polymer.
Cashew apple juice as microbial cultivation medium for non-immunogenic hyaluronic acid production

PubMed Central

Oliveira, Adriano H.; Ogrodowski, Cristiane C.; de Macedo, André C.; Santana, Maria Helena A.; Gonçalves, Luciana R.B.

2013-01-01

In this work, natural cashew apple juice was used as cultivation medium as an alternative to substitute brain heart infusion medium. The effect of aeration and juice supplementation with yeast extract on the production of hyaluronic acid in batch fermentation was also investigated. Similar levels of cell mass were obtained in inoculum using cashew apple juice supplemented with yeast extract or the conventional brain heart infusion medium. Fermentation in Erlenmeyer flasks produced low biomass and hyaluronic acid concentrations. The hyaluronic acid concentration and viscosity increased from 0.15 g/L and 3.87 cP (no aeration or medium supplementation) to 1.76 g/L and 107 cP, when aeration (2 vvm) and 60 g/L of yeast extract were used. The results suggest the production of low-molecular weight hyaluronic acid oligomers instead of the high molecular weight polymer. PMID:24688498
Comparison of two ultrasound-guided injection techniques targeting the sacroiliac joint region in equine cadavers.

PubMed

Stack, John David; Bergamino, Chiara; Sanders, Ruth; Fogarty, Ursula; Puggioni, Antonella; Kearney, Clodagh; David, Florent

2016-09-20

To compare the accuracy and distribution of injectate for cranial (CR) and caudomedial (CM) ultrasound-guided injections of equine sacroiliac joints. Both sacroiliac joints from 10 lumbosacropelvic specimens were injected using cranial parasagittal (CR; curved 18 gauge, 25 cm spinal needles) and caudomedial (CM; straight 18 gauge, 15 cm spinal needles) ultrasound-guided approaches. Injectate consisted of 4 ml iodinated contrast and 2 ml methylene blue. Computed tomographical (CT) scans were performed before and after injections. Time for needle guidance and repositioning attempts were recorded. The CT sequences were analysed for accuracy and distribution of contrast. Intra-articular contrast was detected in sacroiliac joints following 15/40 injections. The CR and CM approaches deposited injectate ≤2 cm from sacroiliac joint margins following 17/20 and 20/20 injections, respectively. Median distance of closest contrast to the sacroiliac joint was 0.4 cm (interquartile range [IQR]: 1.5 cm) for CR approaches and 0.6 cm (IQR: 0.95 cm) for CM approaches. Cranial injections resulted in injectate contacting lumbosacral intertransverse joints 15/20 times. Caudomedial injections were perivascular 16/20 times. Safety and efficacy could not be established. Cranial and CM ultrasound-guided injections targeting sacroiliac joints were very accurate for periarticular injection, but accuracy was poor for intra-articular injection. Injectate was frequently found in contact with interosseous sacroiliac ligaments, as well as neurovascular and synovial structures in close vicinity of sacroiliac joints.
Microvascular complications associated with injection of cosmetic facelift dermal fillers

NASA Astrophysics Data System (ADS)

Yousefi, Siavash; Prendes, Mark; Chang, Shu-Hong; Wang, Ruikang K.

2015-02-01

Minimally-invasive cosmetic surgeries such as injection of subdermal fillers have become very popular in the past decade. Although rare, some complications may follow injections such as tissue necrosis and even blindness. There exist two hypothesis regarding source of these complications both of which include microvasculature. The first hypothesis is that fillers in between the tissue structures and compress microvasculature that causes blockage of tissue neutrition and oxygen exchange in the tissue. In another theory, it is hypothesized that fillers move inside major arteries and block the arteries/veins. In this paper, we study these hypotheses using optical coherence tomography and optical microangiography technologies with different hyaluronic-acid fillers in a mouse ear model. Based on our observations, the fillers eventually block arteries/veins if injected directly into them that eventually causes tissue necrosis.
Comparison of intra-articular hyaluronic acid injections with transcutaneous electric nerve stimulation for the management of knee osteoarthritis: a randomized controlled trial.

PubMed

Chen, Wen-Ling; Hsu, Wei-Chun; Lin, Yi-Jia; Hsieh, Lin-Fen

2013-08-01

To compare the effects of intra-articular hyaluronic acid (HA; ARTZ) and transcutaneous electric nerve stimulation (TENS) in the treatment of patients with knee osteoarthritis. A prospective, randomized controlled trial. Rehabilitation clinic of a teaching hospital. Patients with knee osteoarthritis (N=50; aged 51-80y) were randomly assigned to the HA group (n=27) or the TENS group (n=23). The HA group received intra-articular HA injection into the affected knee once a week for 5 consecutive weeks, and the TENS group received a 20- minute session of TENS 3 times a week for 4 consecutive weeks. The primary outcome measures used were the visual analog scale (VAS) for pain and the Lequesne index. The secondary outcome measures were range of motion of the knee, walking time, pain threshold, patient global assessment, and disability in activities of daily living. All subjects were assessed at baseline, and at 2 weeks, 2 months, and 3 months after the treatments were completed. The TENS group exhibited a significantly greater improvement in VAS than the HA group at 2 weeks' follow-up (4.17 ± 1.98 vs 5.31 ± 1.78, respectively; P=.03). In addition, the TENS group also exhibited a significantly greater improvement in the Lequesne index than the HA group at 2 weeks' follow-up (7.78 ± 2.08 vs 9.85 ± 3.54, respectively; P=.01) and at 3 months' follow-up (7.07 ± 2.85 vs 9.24 ± 4.04, respectively; P=.03). TENS with silver spike point electrodes was observed to be more effective than intra-articular HA injection for patients with knee osteoarthritis in improving the VAS for pain at 2 weeks' follow-up as well as the Lequesne index at 2 weeks' and 3 months' follow-up. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial.

PubMed

Raeissadat, Seyed Ahmad; Rayegani, Seyed Mansoor; Ahangar, Azadeh Gharooee; Abadi, Porya Hassan; Mojgani, Parviz; Ahangar, Omid Gharooi

2017-01-01

Knee osteoarthritis is the most common joint disease. We aimed to compare the efficacy and safety of intra-articular injection of a newly developed plasma rich in growth factor (PRGF) versus hyaluronic acid (HA) on pain and function of patients with knee osteoarthritis. In this single-blinded randomized clinical trial, patients with symptomatic osteoarthritis of knee were assigned to receive 2 intra-articular injections of our newly developed PRGF in 3 weeks or 3 weekly injections of HA. Our primary outcome was the mean change from baseline until 2 and 6 months post intervention in scores of visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. We used analysis of variance for repeated-measures statistical test. A total of 69 patients entered final analysis. The mean age of patients was 58.2 ± 7.41 years and 81.2% were women. In particular, total WOMAC index decreased from 42.9 ± 13.51 to 26.8 ± 13.45 and 24.4 ± 16.54 at 2 and 6 months in the newly developed PRGF group (within subjects P = .001), and from 38.8 ± 12.62 to 27.8 ± 11.01 and 27.4 ± 11.38 at 2 and 6 months in the HA group (within subjects P = .001), respectively (between subjects P = .631). There was no significant difference between PRGF and HA groups in patients' satisfaction and minor complications of injection, whereas patients in HA group reported significantly lower injection-induced pain. In 6 months follow up, our newly developed PRGF and HA, both are effective options to decrease pain and improvement of function in patients with symptomatic mild to moderate knee osteoarthritis.
Single-arm open-label study of Durolane (NASHA nonanimal hyaluronic acid) for the treatment of osteoarthritis of the thumb

PubMed Central

Velasco, Eloisa; Ribera, Mª Victoria; Pi, Joan

2017-01-01

Introduction Osteoarthritis of the trapeziometacarpal (TMC) joint of the thumb – also known as rhizarthrosis – is painful and has a significant impact on quality of life. Intra-articular injection of hyaluronic acid may potentially meet the need for effective, minimally invasive intervention in patients not responding adequately to initial treatment. We aimed to confirm the safety and effectiveness of viscosupplementation with Durolane (NASHA nonanimal hyaluronic acid) in rhizarthrosis. Patients and methods This was a prospective, single-arm, multicenter, open-label study with a 6-month follow-up period. Eligible patients had Eaton–Littler grade II–III rhizarthrosis in one TMC joint with pain and visual analog scale (VAS) pain score ≥4 (scale: 0–10). A single injection of NASHA was administered to the affected TMC joint. The primary effectiveness variable was change from baseline in VAS pain score. Results Thirty-five patients (mean age 60.8 years; 85.7% female) received NASHA and completed the study. The least-squares mean change from baseline in VAS pain score over 6 months was −2.00, a reduction of 27.8% (p<0.001). The reduction in pain exceeded 25% as early as month 1 (26.5%), and gradual improvement was observed throughout the 6-month follow-up period. Secondary effectiveness parameters included QuickDASH (shortened version of Disabilities of the Arm, Shoulder, and Hand [DASH]), Kapandji thumb opposition test, radial abduction, metacarpophalangeal (MCP) joint flexion, and pinch (clamp) strength. Most of these measurements showed statistically significant improvements from baseline over 6 months. Five adverse events (injection site reactions) were reported in four patients (11.4%), and there were no serious or allergic reactions. Conclusion This study suggests that viscosupplementation using NASHA is effective and well tolerated in treating the symptoms of rhizarthrosis. PMID:28392718
Single-arm open-label study of Durolane (NASHA nonanimal hyaluronic acid) for the treatment of osteoarthritis of the thumb.

PubMed

Velasco, Eloisa; Ribera, Mª Victoria; Pi, Joan

2017-01-01

Osteoarthritis of the trapeziometacarpal (TMC) joint of the thumb - also known as rhizarthrosis - is painful and has a significant impact on quality of life. Intra-articular injection of hyaluronic acid may potentially meet the need for effective, minimally invasive intervention in patients not responding adequately to initial treatment. We aimed to confirm the safety and effectiveness of viscosupplementation with Durolane (NASHA nonanimal hyaluronic acid) in rhizarthrosis. This was a prospective, single-arm, multicenter, open-label study with a 6-month follow-up period. Eligible patients had Eaton-Littler grade II-III rhizarthrosis in one TMC joint with pain and visual analog scale (VAS) pain score ≥4 (scale: 0-10). A single injection of NASHA was administered to the affected TMC joint. The primary effectiveness variable was change from baseline in VAS pain score. Thirty-five patients (mean age 60.8 years; 85.7% female) received NASHA and completed the study. The least-squares mean change from baseline in VAS pain score over 6 months was -2.00, a reduction of 27.8% ( p <0.001). The reduction in pain exceeded 25% as early as month 1 (26.5%), and gradual improvement was observed throughout the 6-month follow-up period. Secondary effectiveness parameters included QuickDASH (shortened version of Disabilities of the Arm, Shoulder, and Hand [DASH]), Kapandji thumb opposition test, radial abduction, metacarpophalangeal (MCP) joint flexion, and pinch (clamp) strength. Most of these measurements showed statistically significant improvements from baseline over 6 months. Five adverse events (injection site reactions) were reported in four patients (11.4%), and there were no serious or allergic reactions. This study suggests that viscosupplementation using NASHA is effective and well tolerated in treating the symptoms of rhizarthrosis.
Characterization of hyaluronate binding proteins isolated from 3T3 and murine sarcoma virus transformed 3T3 cells

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

Turley, E.A.; Moore, D.; Hayden, L.J.

1987-06-02

A hyaluronic acid binding fraction was purified from the supernatant media of both 3T3 and murine sarcoma virus (MSV) transformed 3T3 cultures by hyaluronate and immunoaffinity chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved the hyaluronate affinity-purified fraction into three major protein bands of estimated molecular weight (M/sub r,e/) 70K, 66K, and 56K which contained hyaluronate binding activity and which were termed hyaluronate binding proteins (HABP). Hyaluronate affinity chromatography combined with immunoaffinity chromatography, using antibody directed against the larger HABP, allowed a 20-fold purification of HABP. Fractions isolated from 3T3 supernatant medium also contained additional binding molecules in the molecular weightmore » range of 20K. This material was present in vanishingly small amounts and was not detected with a silver stain or with (/sup 35/S)methionine label. The three protein species isolated by hyaluronate affinity chromatography (M/sub r,e/ 70K, 66K, and 56K) were related to one another since they shared antigenic determinants and exhibited similar pI values. In isocratic conditions, HABP occurred as aggregates of up to 580 kilodaltons. Their glycoprotein nature was indicated by their incorporation of /sup 3/H-sugars. Enzyme-linked immunoadsorbent assay showed they were antigenically distinct from other hyaluronate binding proteins such as fibronectin, cartilage link protein, and the hyaluronate binding region of chondroitin sulfate proteoglycan. The results are discussed with regard both to the functional significance of hyaluronate-cell surface interactions in transformed as well as normal cells and to the relationship of HABP to other reported hyaluronate binding proteins.« less
Effects of hyaluronic acid on bleeding following third molar extraction.

PubMed

Gocmen, Gokhan; Aktop, Sertac; Tüzüner, Burcin; Goker, Bahar; Yarat, Aysen

2017-01-01

To explore the effects of hyaluronic acid (HA) on bleeding and associated outcomes after third molar extraction. Forty patients who had undergone molar extraction were randomly divided into two groups; 0.8% (w/v) HA was applied to the HA group (n=20) whereas a control group (n=20) was not treated. Salivary and gingival tissue factor (TF) levels, bleeding time, maximum interincisal opening (MIO), pain scored on a visual analog scale (VAS), and the swelling extent were compared between the two groups. HA did not significantly affect gingival TF levels. Salivary TF levels increased significantly 1 week after HA application but not in the control group. Neither the VAS pain level nor MIO differed significantly between the two groups. The swelling extent on day 3 and the bleeding time were greater in the HA group than in the control group. Local injection of HA at 0.8% prolonged the bleeding time, and increased hemorrhage and swelling in the early postoperative period after third molar extractions.
Risk factors for decreased range of motion and poor outcomes in open periarticular elbow fractures.

PubMed

Dickens, Jonathan F; Wilson, Kevin W; Tintle, Scott M; Heckert, Reed; Gordon, Wade T; D'Alleyrand, Jean-Claude G; Potter, Benjamin K

2015-04-01

The purpose of this study was to identify risk factors present at the time of injury that predict poor functional outcomes and heterotopic ossification (HO) in open periarticular elbow fractures. We performed a retrospective review of 136 combat-related open elbow fractures from 2003 to 2010. Patient demographics, injury characteristics, treatment variables, and complications were recorded. Functional outcomes were analyzed to determine range of motion (ROM) and Mayo Elbow Performance Score (MEPS). Secondary outcome measures included the development of HO, return to duty, and revision operation. At a median 2.7 years from injury the median MEPS was 67.8 (range 30-100) with an average ulnohumeral arc motion of 89°. Bipolar fractures, with periarticular fractures on both sides of the elbow and at least one side containing intra-articular extension, were independently associated with decreased ulnohumeral motion (p=0.02) and decreased MEPS (p<0.004). Additional independent risk factors for decreased ROM included more severe osseous comminution (p=0.001), and increased time to definitive fixation (p=0.03) and HO (p=0.02). More severe soft tissue injury (Gustilo and Anderson fracture type, p=0.02), peripheral nerve injury (p=0.04), and HO (p=0.03) were independently associated with decreased MEPS. HO developed in 65% (89/136) of extremities and was associated with more severe Orthopaedic Trauma Association (OTA) fracture type (p=0.01) and escalating Gustilo and Anderson fracture classification (p=0.049). In the largest series of open elbow fractures, we identified risk factors that portend a poor clinical outcome and decreased ROM. Bipolar elbow fractures, which have not previously been associated with worse results, are particularly prone to decreased ROM and worse outcomes. Prognostic level IV. Published by Elsevier Ltd.
Sedimentation properties in density gradients correspond with levels of sperm DNA fragmentation, chromatin compaction and binding affinity to hyaluronic acid.

PubMed

Torabi, Forough; Binduraihem, Adel; Miller, David

2017-03-01

Mature spermatozoa bind hyaluronic acid in the extracellular matrix via hyaladherins. Immature spermatozoa may be unable to interact because they do not express the appropriate hyaladherins on their surface. Fresh human semen samples were fractionated using differential density gradient centrifugation (DDGC) and the ability of these fractions to bind hyaluronic acid was evaluated. The presence of sperm hyaladherins was also assessed. CD44 was located mainly on the acrosome and equatorial segment and became more restricted to the equatorial segment in capacitated spermatozoa. Hyaluronic acid-TRITC (hyaluronic acid conjugated with tetramethylrhodamine isothiocyanante), a generic hyaluronic-acid-binding reagent, labelled the membrane and the neck region, particularly after capacitation. Sperm populations obtained after DDGC or after interaction with hyaluronic acid were assessed for DNA fragmentation and chromatin maturity. Strong relationships between both measures and sperm sedimentation and hyaluronic-acid-binding profiles were revealed. Capacitation enhanced hyaluronic acid binding of both DDGC-pelleted sperm and sperm washed free of seminal fluid. In conclusion, hyaladherins were detected on human sperm and a higher capacity for sperm hyaluronic-acid-binding was shown to correspond with their DDGC sedimentation profiles and with lower levels of DNA fragmentation and better chromatin maturity. Capacitation induced changes in the distribution and presence of hyaladherins may enhance hyaluronic-acid-binding. Copyright Â© 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Radiographic followup of joints injected with triamcinolone hexacetonide for the management of childhood arthritis.

PubMed

Sparling, M; Malleson, P; Wood, B; Petty, R

1990-06-01

Evidence of deleterious effects following intraarticular injection of triamcinolone hexacetonide was sought through a review of radiographs of 145 joints of 55 children with chronic arthritis. Possible deleterious effects were noted in 16 joints of 11 patients. These effects included: small patella (2 joints), patellar osteochondritis dissecans (1 joint), periarticular calcification (9 joints), intraarticular tibial bony spur (1 joint), avascular necrosis of the distal radial epiphysis (2 joints), and avascular necrosis of the proximal femoral epiphysis (1 joint). Only the latter possible complication was symptomatic. Serial radiographs of 76 joints of 30 children showed mild progressive changes compatible with the underlying disease, except in the hip joint, where changes were more severe. The intraarticular injection of triamcinolone hexacetonide is a procedure that appears to be associated with an acceptably low frequency of radiologic abnormalities for many joints in children with chronic arthritis, but its effects on the hip joint remain uncertain.
Study of FibroTest and hyaluronic acid biological variation in healthy volunteers and comparison of serum hyaluronic acid biological variation between chronic liver diseases of different etiology and fibrotic stage using confidence intervals.

PubMed

Istaces, Nicolas; Gulbis, Béatrice

2015-07-01

Personalized ranges of liver fibrosis serum biomarkers such as FibroTest or hyaluronic acid could be used for early detection of fibrotic changes in patients with progressive chronic liver disease. Our aim was to generate reliable biological variation estimates for these two biomarkers with confidence intervals for within-subject biological variation and reference change value. Nine fasting healthy volunteers and 66 chronic liver disease patients were included. Biological variation estimates were calculated for FibroTest in healthy volunteers, and for hyaluronic acid in healthy volunteers and chronic liver disease patients stratified by etiology and liver fibrosis stage. In healthy volunteers, within-subject biological coefficient of variation (with 95% confidence intervals) and index of individuality were 20% (16%-28%) and 0.6 for FibroTest and 34% (27%-47%) and 0.79 for hyaluronic acid, respectively. Overall hyaluronic acid within-subject biological coefficient of variation was similar among non-alcoholic fatty liver disease and chronic hepatitis C with 41% (34%-52%) and 45% (39%-55%), respectively, in contrast to chronic hepatitis B with 170% (140%-215%). Hyaluronic acid within-subject biological coefficients of variation were similar between F0-F1, F2 and F3 liver fibrosis stages in non-alcoholic fatty liver disease with 34% (25%-49%), 41% (31%-59%) and 34% (23%-62%), respectively, and in chronic hepatitis C with 34% (27%-47%), 33% (26%-45%) and 38% (27%-65%), respectively. However, corresponding hyaluronic acid indexes of individuality were lower in the higher fibrosis stages. Non-overlapping confidence intervals of biological variation estimates allowed us to detect significant differences regarding hyaluronic acid biological variation between chronic liver disease subgroups. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Oral Delivery of Exenatide via Microspheres Prepared by Cross-Linking of Alginate and Hyaluronate

PubMed Central

Zhang, Baojie; He, Dongyang; Fan, Yu; Liu, Nan; Chen, Yijun

2014-01-01

Exenatide is an FDA-approved glucose-lowering peptide drug for the treatment of type 2 diabetes by subcutaneous injection. To address the issues on the inconvenience for patient use and the difficulty of oral administration of peptide drugs, chemical cross-linking of two pH-responsive biomaterials, alginate and hyaluronate, was carried out to prepare a new material for the encapsulation of exenatide as a form of microspheres. The exenatide-loaded microspheres exhibited spherical structures with excellent loading and release behaviors in the simulated gastrointestinal tract environments. After oral administration of the microspheres in db/db mice, maximum plasma concentration of exenatide appeared at 4 hours, and blood glucose was effectively reduced to a normal level within 2 hours and maintained for another 4 hours. The bioavailability of the exenatide-loaded microspheres, relative to subcutaneous injection of exenatide, reached 10.2%. Collectively, the present study demonstrated the feasibility of orally delivering exenatide with the new cross-linked biomaterial and formulation, and showed therapeutic potential for clinical applications. PMID:24465870
Improving the accuracy of hyaluronic acid molecular weight estimation by conventional size exclusion chromatography.

PubMed

Shanmuga Doss, Sreeja; Bhatt, Nirav Pravinbhai; Jayaraman, Guhan

2017-08-15

There is an unreasonably high variation in the literature reports on molecular weight of hyaluronic acid (HA) estimated using conventional size exclusion chromatography (SEC). This variation is most likely due to errors in estimation. Working with commercially available HA molecular weight standards, this work examines the extent of error in molecular weight estimation due to two factors: use of non-HA based calibration and concentration of sample injected into the SEC column. We develop a multivariate regression correlation to correct for concentration effect. Our analysis showed that, SEC calibration based on non-HA standards like polyethylene oxide and pullulan led to approximately 2 and 10 times overestimation, respectively, when compared to HA-based calibration. Further, we found that injected sample concentration has an effect on molecular weight estimation. Even at 1g/l injected sample concentration, HA molecular weight standards of 0.7 and 1.64MDa showed appreciable underestimation of 11-24%. The multivariate correlation developed was found to reduce error in estimations at 1g/l to <4%. The correlation was also successfully applied to accurately estimate the molecular weight of HA produced by a recombinant Lactococcus lactis fermentation. Copyright © 2017 Elsevier B.V. All rights reserved.
Preservation of viscoelastic properties of rabbit vocal folds after implantation of hyaluronic Acid-based biomaterials.

PubMed

Choi, Jeong-Seok; Kim, Nahn Ju; Klemuk, Sarah; Jang, Yun Ho; Park, In Suh; Ahn, Kyung Hyun; Lim, Jae-Yol; Kim, Young-Mo

2012-09-01

To compare the rheological characteristics of structurally different hyaluronic acid (HA)-based biomaterials that are presently used for phonosurgery and to investigate their influence on the viscoelastic properties of vocal folds after implantation in an in vivo rabbit model. In vitro and in vivo rheometric investigation. Experimental laboratory, Inha and Seoul National Universities. Viscoelastic shear properties of 3 HA-based biomaterials (Rofilan, Restylane, and Reviderm) were measured with a strain-controlled rheometer. These biomaterials were injected into the deep layers of rabbit vocal folds, and viscoelastic moduli of the injected vocal folds were determined 2 months after the injection. The vocal fold specimens were observed using a light microscope and a transmission electron microscope. All HA-based biomaterials showed similar levels of shear viscosity, which were slightly higher than that of human vocal folds reported in previous studies. Compared with noninjected control vocal folds, there were no significant differences in the magnitudes of both elastic shear modulus (G') and viscous modulus (G") of injected vocal folds among all of the materials. Light microscopic images showed that all materials were observed in the deep layers of vocal folds and electron scanning images revealed that injected HA particles were homogeneously distributed in regions of collagenous fibers. HA-based biomaterials could preserve the viscoelastic properties of the vocal folds, when they were injected into vocal folds in an in vivo rabbit model. However, further studies on the influence of the biomaterials on the viscoelasticity of human vocal folds in ECM surroundings are still needed.
Production and characterization of hyaluronic acid microparticles for the controlled delivery of growth factors using a spray/dehydration method.

PubMed

Babo, Pedro S; Reis, Rui L; Gomes, Manuela E

2016-11-01

Hyaluronic acid is the main polysaccharide present in the connective tissue. Besides its structural function as backbone of the extracellular matrix, hyaluronic acid plays staple roles in several biological processes including the modulation of inflammation and wound healing processes. The application of hyaluronic acid in regenerative medicine, either as cells and/or drug/growth factors delivery vehicles, relies on its ability to be cross-linked using a plethora of reactions, producing stable hydrogels. In this work, we propose a novel method for the production of hyaluronic acid microparticles that presents several advantages over others that have been used. Basically, droplets of hyaluronic acid solution produced with a nozzle are collected in an isopropanol dehydration bath, and stabilized after crosslinking with adipic acid dihydrazide, using a cabodiimide-based chemistry. The size and morphology of the hyaluronic acid microparticles produced by this method varied with the molecular weight and concentration of the hyaluronic acid solution, the nozzle chamber pressure, the distance between the nozzle and the crosslinking solution, and the number of crosslinking steps. The degree of crosslinking of the hyaluronic acid microparticles produced was tunable and allowed to control the rate of the degradation promoted by hyaluronidase. Moreover, the particles were loaded with platelet lysate, a hemoderivative rich in cytokines with interest for regenerative medicine applications. The hyaluronic acid microparticles showed potential to bind selectively to positively charged molecules, as the factors present in the platelet lysate. It is envisioned that these can be further released in a sustained manner by ion exchange or by the degradation of the hyaluronic acid microparticles matrix promoted by extracellular matrix remodeling. © The Author(s) 2016.
Chitosan solutions as injectable systems for dermal filler applications: Rheological characterization and biological evidence.

PubMed

Halimi, C; Montembault, A; Guerry, A; Delair, T; Viguier, E; Fulchiron, R; David, L

2015-01-01

A new generation of dermal filler for wrinkle filler based on chitosan was compared to current hyaluronic acid-based dermal fillers by using a new rheological performance criterion based on viscosity during injection related to Newtonian viscosity. In addition an in vivo evaluation was performed for preclinical evidence of chitosan use as dermal filler. In this way, biocompatibility and dermis reconstruction was evaluated on a pig model.
Injectable hydrogels for treatment of osteoarthritis - A rheological study.

PubMed

von Lospichl, Benjamin; Hemmati-Sadeghi, Shabnam; Dey, Pradip; Dehne, Tilo; Haag, Rainer; Sittinger, Michael; Ringe, Jochen; Gradzielski, Michael

2017-11-01

Osteoarthritis (OA) is a disabling condition especially in the elderly population. The current therapeutic approaches do not halt the OA progression or reverse joint damage. In order to overcome the problem of rapid clearance of hyaluronic acid (HA), a standard viscosupplement for OA, we investigated the rheological properties of a relatively non-degradable dendritic polyglycerol sulfate (dPGS) hydrogel to determine a suitable concentration for intra articular injections that mimics HA in terms of its viscoelastic and mechanical properties. To do so, the concentration range from 3.6 to 4.8wt% of dPGS and, as a reference, blends of commercially available HAs (Ostenil ® , GO-ON ® , Synocrom ® Forte and Synvisc ® ), were investigated by means of oscillating and flow rheology, thereby yielding storage (G') and loss modulus (G"), as well as yield stress and shear viscosity. In our rheological experiments we observe a pronounced coupling of the molecular weight and the rheological properties for the HAs. Furthermore, we find the dPGS hydrogel to form more compact networks with increasing concentration. From a broader comparison the current findings suggest that an overall polymer concentration of 4.0wt% dPGS has viscoelastic properties that are comparable to hyaluronic acid in the medically relevant frequency range, where for medical application the dPGS hydrogel has the advantage of being much less easily displaced from its injection place than HA. Copyright © 2017 Elsevier B.V. All rights reserved.
Effectiveness of hyaluronic acid in post-tonsillectomy pain relief and wound healing: a prospective, double-blind, controlled clinical study.

PubMed

Hancı, Deniz; Altun, Huseyin

2015-09-01

To find the effectiveness of hyaluronic acid in post-tonsillectomy pain relief and wound healing. Fifty patients were included in this prospective, double-blind, controlled clinical study (20 males, 30 females mean age of 13.56 years). Hyaluronic acid was applied to one side and the other side was used as a control during tonsillectomy. Therefore, the same patient evaluated and scored the post-tonsillectomy pain, excluding individual bias. Results indicated that patients had significantly lower pain scores for hyaluronic acid treated side (p<0.001). At the end of two weeks follow-up period, the wound in the hyaluronic acid side was almost completely healed, indicating that the healing was faster with hyaluronic acid compared to control side (p<0.001). Hyaluronic acid could be recommended as an effective treatment for the management of post-tonsillectomy pain and wound healing. Copyright © 2015. Published by Elsevier Ireland Ltd.
Hyaluronic acid gel distribution pattern in periocular area with high-resolution ultrasound imaging.

PubMed

Goh, Alice S; Kohn, Jocelyne C; Rootman, Daniel B; Lin, Joseph L; Goldberg, Robert A

2014-05-01

High-resolution ultrasound (HRUS) is a useful tool in defining anatomic and dynamic soft tissue relationships in the periocular area. It also allows visualization of hyaluronic acid (HA) gel within the soft tissue. The authors investigate the difference in the distribution pattern between 2 HA fillers in the periocular tissue using HRUS. The charts of 10 patients who underwent periocular injection using HA gel filler and were subsequently examined with HRUS were reviewed. Half of the patients (n = 5) were treated with Restylane-L (Medicis Aesthetics, Inc, Scottsdale, Arizona) and the remaining 5 with Belotero Balance (Merz Aesthetics, Inc, San Mateo, California). Ultrasonographic evaluation (Logiq p6; GE Healthcare, Waukesha, Washington) was performed before and immediately after HA filler injection. The HA appears as a hypoechoic image within the soft tissue plane on HRUS. Restylane-L filler formed a localized hypoechoic image within the tissue, with some spread into bubbles or pearl-like configuration. Belotero Balance spread more widely into the tissue plane and diffused into an elongated or spindle-shaped hypoechoic image. Our preliminary data suggest that HA gel fillers with differing production technologies show distinct spread and distribution patterns in the periocular tissues on HRUS examination.
Alginate Microcapsules Incorporating Hyaluronic Acid Recreate Closer in Vivo Environment for Mesenchymal Stem Cells.

PubMed

Cañibano-Hernández, Alberto; Saenz Del Burgo, Laura; Espona-Noguera, Albert; Orive, Gorka; Hernández, Rosa M; Ciriza, Jesús; Pedraz, Jose Luis

2017-07-03

The potential clinical application of alginate cell microencapsulation has advanced enormously during the past decade. However, the 3D environment created by alginate beads does not mimic the natural extracellular matrix surrounding cells in vivo, responsible of cell survival and functionality. As one of the most frequent macromolecules present in the extracellular matrix is hyaluronic acid, we have formed hybrid beads with alginate and hyaluronic acid recreating a closer in vivo cell environment. Our results show that 1% alginate-0.25% hyaluronic acid microcapsules retain 1.5% alginate physicochemical properties. Moreover, mesenchymal stem cells encapsulated in these hybrid beads show enhanced viability therapeutic protein release and mesenchymal stem cells' potential to differentiate into chondrogenic lineage. Although future studies with additional proteins need to be done in order to approach even more the extracellular matrix features, we have shown that hyaluronic acid protects alginate encapsulated mesenchymal stem cells by providing a niche-like environment and remaining them competent as a sustainable drug delivery system.
Blindness following cosmetic injections of the face.

PubMed

Lazzeri, Davide; Agostini, Tommaso; Figus, Michele; Nardi, Marco; Pantaloni, Marcello; Lazzeri, Stefano

2012-04-01

Complications following facial cosmetic injections have recently heightened awareness of the possibility of iatrogenic blindness. The authors conducted a systematic review of the available literature to provide the best evidence for the prevention and treatment of this serious eye injury. The authors included in the study only the cases in which blindness was a direct consequence of a cosmetic injection procedure of the face. Twenty-nine articles describing 32 patients were identified. In 15 patients, blindness occurred after injections of adipose tissue; in the other 17, it followed injections of various materials, including corticosteroids, paraffin, silicone oil, bovine collagen, polymethylmethacrylate, hyaluronic acid, and calcium hydroxyapatite. Some precautions may minimize the risk of embolization of filler into the ophthalmic artery following facial cosmetic injections. Intravascular placement of the needle or cannula should be demonstrated by aspiration before injection and should be further prevented by application of local vasoconstrictor. Needles, syringes, and cannulas of small size should be preferred to larger ones and be replaced with blunt flexible needles and microcannulas when possible. Low-pressure injections with the release of the least amount of substance possible should be considered safer than bolus injections. The total volume of filler injected during the entire treatment session should be limited, and injections into pretraumatized tissues should be avoided. Actually, no safe, feasible, and reliable treatment exists for iatrogenic retinal embolism. Nonetheless, therapy should theoretically be directed to lowering intraocular pressure to dislodge the embolus into more peripheral vessels of the retinal circulation, increasing retinal perfusion and oxygen delivery to hypoxic tissues. Risk, V.
Clinical comparison between two hyaluronic acid-derived fillers in the treatment of nasolabial folds in Chinese subjects: BioHyalux versus Restylane.

PubMed

Wu, Yan; Sun, Nan; Xu, Yue; Liu, Huixian; Zhong, Shaomin; Chen, Liyang; Li, Dong

2016-04-01

Hyaluronic acid fillers are used to improve the appearance of nasolabial folds (NLF). This study aimed to compare the efficacy, safety, and durability of a new hyaluronic acid gel (BioHyalux) versus Restylane for the correction of NLF. This was a multicenter, double-blinded, randomized, controlled, non-inferiority clinical trial involving 88 subjects with moderate to severe NLF. Subjects were randomized to BioHyalux and Restylane on either sides of the NLF. NLF was assessed before and right after injection, and at 1 week, 1, 3, and 6 months. Patients were followed up for 13-15 months to evaluate the durability and long-term safety. A clinically meaningful response was predefined as at least one-point improvement on the Wrinkle Severity Rating Scale, which is a five-point scale. At 6 months, the response rate of BioHyalux was not inferior to that of Restylane (P < 0.05). At the 13-15 months follow-up, the response rate by investigators was 58.0 % on the BioHyalux side versus 63.8 % on the Restylane side. The response rate by subjects showed similar results, which was 56.5 % on the BioHyalux side versus 60.9 % on the Restylane side at 13-15 months. The subjects' Global Aesthetic Improvement Scale (GAIS) showed that most subjects felt improvements on both sides of NLF (P > 0.05) at all time points. At 6 months, 100 % reported improvements on both side; at 13-15 months, 60 % of subjects reported improvements with BioHyalux versus 64 % with Restylane. Adverse events were transient and predominantly mild or moderate in severity including injection site swelling, pain, itching, bruising, and tenderness. BioHyalux had reliable safety and tolerance, and could be an effective injectable filler for correcting NLF.

Utilizing hyaluronic acid as a versatile platform for fluorescence resonance energy transfer-based glucose sensing.

PubMed

Ge, Minghao; Bai, Pengli; Chen, Mingli; Tian, Jingjing; Hu, Jun; Zhi, Xu; Yin, Huancai; Yin, Jian

2018-03-01

Here, we utilized the ultrasonic emulsification technique to generate hyaluronic acid microspheres incorporating a fluorescence-based glucose biosensor. We synthesized a novel lanthanide ion luminophore based on Eu 3+ . Eu sulfosuccinimidyl dextran (Eu-dextran) and Alexa Fluor 647 sulfosuccinimidyl-ConA (Alexa Fluor 647-ConA) were encapsulated in hyaluronic acid hydrogel to generate microspheres. Glucose sensing was carried out using a fluorescence resonance energy transfer (FRET)-based assay principle. A proportional fluorescence intensity increase was found within a 0.5-10-mM glucose concentration range. The glucose-sensing strategy showed an excellent tolerance for potential interferents. Meanwhile, the fluorescent signal of hyaluronic acid microspheres was very stable after testing for 72 h in glucose solution. Overall, hyaluronic acid microspheres encapsulating sensing biomolecules offer a stable and biocompatible biosensor for a variety of applications including cell culture systems, tissue engineering, detection of blood glucose, etc. Graphical abstract We report an ingenious biosensor encapsulated in hyaluronic acid microspheres for monitoring of glucose. Glucose sensing is carried out using a fluorescence resonance energy transfer-based assay principle with a novel lanthanide ions luminophore. The glucose detection system has excellent biocompatibility and stability for monitoring of glucose.
Four-point injection technique for lip augmentation.

PubMed

Sahan, Ali; Funda, Tamer

2018-06-01

Lip augmentation procedures with hyaluronic acid dermal fillers have become increasingly popular worldwide because full lips are often considered beautiful and youthful. The goal of a lip augmentation procedure is to create smooth lips with adequate volume and a natural appearance. Various techniques for lip augmentation have been utilized and described. In the four-point injection technique, the lips were divided equally into right side and left side. Four entry points were made above the vermilion border for the upper lip and below the vermilion border for the lower lip. The filler was administered with a fanning technique through each entry point. Between January 2017 and November 2017, 50 female patients underwent a nonsurgical lip augmentation procedure with injectable fillers using this technique. Forty-five patients (90%) reported that they were satisfied or extremely satisfied with their lip enhancement procedure. No serious complications were observed. The advantages of this technique are reducing the risk of complications like erythema, edema, and vascular injuries, and providing easy access to injection sites.
Use of Intra-Articular Hyaluronic Acid in the Management of Knee Osteoarthritis in Clinical Practice

PubMed Central

Cooper, Cyrus; Rannou, François; Richette, Pascal; Bruyère, Olivier; Al-Daghri, Nasser; Altman, Roy D.; Brandi, Maria Luisa; Basset, Sabine Collaud; Herrero-Beaumont, Gabriel; Migliore, Alberto; Pavelka, Karel; Uebelhart, Daniel; Reginster, Jean-Yves

2017-01-01

This review emphasizes the safety profile of intra-articular hyaluronic acid treatment of knee osteoarthritis, as well as its moderate but real efficacy on symptoms, which is in the same range than other pharmacological modalities used in this indication. Effectiveness of intra-articular hyaluronic acid has also been highlighted based on ‘real-life’ data, together with the clinical benefit of systematic repeated treatment cycles, and the influence of the molecular weight of hyaluronic acid on treatment outcome. These aspects should be particularly helpful to clinicians when making personalized care decisions. PMID:28118523
Influence of D-Penicillamine on the Viscosity of Hyaluronic Acid Solutions

NASA Astrophysics Data System (ADS)

Liang, Jing; Krause, Wendy E.; Colby, Ralph H.

2006-03-01

Polyelectrolyte hyaluronic acid (HA, hyaluronan) is an important component in synovial fluid. Its presence results in highly viscoelastic solutions with excellent lubricating and shock-absorbing properties. In comparison to healthy synovial fluid, diseased fluid has a reduced viscosity. In osteoarthritis this reduction in viscosity results from a decline in both the molecular weight and concentration of hyaluronic acid HA. Initial results indicate that D-penicillamine affects the rheology of bovine synovial fluid, a model synovial fluid solution, and its components, including HA. In order to understand how D-penicillamine modifies the viscosity of these solutions, the rheological properties of sodium hyaluronate (NaHA) in phosphate-buffered saline (PBS) with D-penicillamine were studied as function of time, D-penicillamine concentration (0 -- 0.01 M), and storage conditions. Penicillamine has a complex, time dependent effect on the viscosity of NaHA solutions---reducing the zero shear rate viscosity of a 3 mg/mL NaHA in PBS by ca. 40% after 44 days.
Measurement of ulnar subtrochlear sclerosis using a percentage scale in labrador retrievers with minimal radiographic signs of periarticular osteophytosis.

PubMed

Smith, Thomas J; Fitzpatrick, Noel; Evans, Richard B; Pead, Mathew J

2009-02-01

To report the development of a measurement method for quantifying ulnar subtrochlear sclerosis (STS) in Labrador Retrievers. Prospective blinded study. Radiographs of Labrador Retrievers elbows (n=30) with minimal radiographic signs of periarticular osteophytosis. Measurement of STS as a % of the distance between 2 standardized radiographic landmarks (%STS) was developed. Mediolateral radiographic projections of flexed elbows were collected from 2 cohorts termed diseased (n=15; confirmed disease of the medial coronoid process) and control (n=15; free from clinically evident disease). Five observers blindly assessed each radiograph for radiographic technique, elbow positioning, periarticular osteophytosis, and STS, which, if present, was measured and assigned a %STS score. Intraobserver and interobserver variations in measuring STS and the ability to differentiate study cohorts were assessed using receiver operator curve (ROC) characteristics. A P-value of <.05 was considered significant. Median %STS for diseased elbows was 47% (range, 0-74%) and 0% (range, 0-62%) for control elbows. Correlations were not significantly different between each observer's assessments of %STS, with a median Spearman's P-value of .75 (range, .67-.86). All observers differentiated the 2 cohorts with "fair-good" accuracy, with a median ROC value of 0.81 (range, 0.75-0.88). Measurement of %STS in Labrador Retrievers was repeatable for each observer and repeatable between observers. A method for measuring STS allows comparison of Labrador Retrievers of different sizes, is easy to perform, and could be used to investigate the clinical significance of STS in this breed.
A New Sacroiliac Joint Injection Technique and Its Short-Term Effect on Chronic Sacroiliac Region Pain.

PubMed

Do, Kyung Hee; Ahn, Sang Ho; Jones, Rodney; Jang, Sung Ho; Son, Su Min; Lee, Dong Gyu; Cho, Hee Kyung; Choi, Gyu Sik; Cho, Yun-Woo

2016-10-01

Sacroiliac joint (SIJ) injections have been used to provide short-term relief of SIJ pain. In this study, the authors investigated a new technique using a superior approach. Twenty four patients with chronic SI joint paint were recruited. Each patient was treated with a single SIJ intra-articular injection plus a periarticular injection of local anesthetic and corticosteroid in one procedure. Technical accuracy of the intra-articular procedure was determined by having 2 independent observers review and rate the quality of arthrograms obtained. Treatment effects were evaluated using a numerical rating scale, the Oswestry disability index (ODI) and global perceived effect (GPE). Both independent observers agreed that satisfactory arthrograms were obtained in all patients. Pain scores and disability were significantly reduced at 2 weeks and 4 weeks after treatment. Nineteen patients (79%) reported satisfaction with treatment. No serious adverse effects were encountered. The superior approach consistently achieves good access to the SI joint, and achieves outcomes that are compatible with those of other techniques. The superior approach constitutes an alternative to other techniques for injections into the SI joint. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Effects of molecular weight of hyaluronic acid on its viscosity and enzymatic activities of lysozyme and peroxidase.

PubMed

Kim, Jihoon; Chang, Ji-Youn; Kim, Yoon-Young; Kim, Moon-Jong; Kho, Hong-Seop

2018-05-01

To investigate the effects of the molecular weight of hyaluronic acid on its viscosity and enzymatic activities of lysozyme and peroxidase in solution and on the hydroxyapatite surface. Hyaluronic acids of four different molecular weights (10 kDa, 100 kDa, 1 MDa, and 2 MDa), hen egg-white lysozyme, bovine lactoperoxidase, and human whole saliva were used. Viscosity values of hyaluronic acids were measured using a cone-and-plate viscometer at six different concentrations (0.1-5.0 mg/mL). Enzymatic activities of lysozyme and peroxidase were examined by hydrolysis of fluorescein-labeled Micrococcus lysodeikticus and oxidation of fluorogenic 2',7'-dichlorofluorescein to fluorescing 2',7'-dichlorofluorescein, respectively. In solution assays, only 2 MDa-hyaluronic acid significantly inhibited lysozyme activities in saliva. In surface assays, hyaluronic acids inhibited lysozyme and peroxidase activities; the inhibitory activities were more apparent with high-molecular-weight ones in saliva than in purified enzymes. The 100 kDa-hyaluronic acid at 5.0 mg/mL, 1 MDa-one at 0.5 mg/mL, and 2 MDa-one at 0.2 mg/mL showed viscosity values similar to those of human whole saliva at a shear rate range required for normal oral functions. The differences among the influences of the three conditions on the enzymatic activities were not statistically significant. High-molecular-weight hyaluronic acids at low concentration and low-molecular-weight ones at high concentration showed viscosity values similar to those of human whole saliva. Inhibitory effects of hyaluronic acids on lysozyme and peroxidase activities were more significant with high-molecular-weight ones on the surface and in saliva compared with in solution and on purified enzymes. Copyright © 2018 Elsevier Ltd. All rights reserved.
Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial

PubMed Central

Raeissadat, Seyed Ahmad; Rayegani, Seyed Mansoor; Ahangar, Azadeh Gharooee; Abadi, Porya Hassan; Mojgani, Parviz; Ahangar, Omid Gharooi

2017-01-01

Background and objectives: Knee osteoarthritis is the most common joint disease. We aimed to compare the efficacy and safety of intra-articular injection of a newly developed plasma rich in growth factor (PRGF) versus hyaluronic acid (HA) on pain and function of patients with knee osteoarthritis. Methods: In this single-blinded randomized clinical trial, patients with symptomatic osteoarthritis of knee were assigned to receive 2 intra-articular injections of our newly developed PRGF in 3 weeks or 3 weekly injections of HA. Our primary outcome was the mean change from baseline until 2 and 6 months post intervention in scores of visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. We used analysis of variance for repeated-measures statistical test. Results: A total of 69 patients entered final analysis. The mean age of patients was 58.2 ± 7.41 years and 81.2% were women. In particular, total WOMAC index decreased from 42.9 ± 13.51 to 26.8 ± 13.45 and 24.4 ± 16.54 at 2 and 6 months in the newly developed PRGF group (within subjects P = .001), and from 38.8 ± 12.62 to 27.8 ± 11.01 and 27.4 ± 11.38 at 2 and 6 months in the HA group (within subjects P = .001), respectively (between subjects P = .631). There was no significant difference between PRGF and HA groups in patients’ satisfaction and minor complications of injection, whereas patients in HA group reported significantly lower injection-induced pain. Conclusions: In 6 months follow up, our newly developed PRGF and HA, both are effective options to decrease pain and improvement of function in patients with symptomatic mild to moderate knee osteoarthritis. PMID:29051707
Optimal conjugation of catechol group onto hyaluronic acid in coronary stent substrate coating for the prevention of restenosis.

PubMed

Lih, Eugene; Choi, Seul Gi; Ahn, Dong June; Joung, Yoon Ki; Han, Dong Keun

2016-01-01

Although endovascular stenting has been used as an interventional therapy to treat cardio- and cerebro-vascular diseases, it is associated with recurrent vascular diseases following stent thrombosis and in-stent restenosis. In this study, a metallic stent was coated with dopamine-conjugated hyaluronic acid with different ratios of catechol group to improve hemocompatibility and re-endothelialization. Especially, we were interested in how much amount of catechol group is appropriate for the above-mentioned purposes. Therefore, a series of dopamine-conjugated hyaluronic acid conjugates with different ratios of catechol group were synthesized via a carbodiimide coupling reaction. Dopamine-conjugated hyaluronic acid conjugates were characterized with 1 H-nuclear magnetic resonance and Fourier transform infrared spectroscopy, and the amount of catechol group in dopamine-conjugated hyaluronic acid was measured by ultraviolet spectrometer. Co-Cr substrates were polished and coated with various dopamine-conjugated hyaluronic acid conjugates under pH 8.5. Dopamine-conjugated hyaluronic acid amounts on the substrate were quantified by micro-bicinchoninic acid assay. Surface characteristics of dopamine-conjugated hyaluronic-acid-coated Co-Cr were evaluated by water contact angle, scanning electron microscopy, and atomic force microscopy. The hemocompatibility of the surface-modified substrates was assessed by protein adsorption and platelet adhesion tests. Adhesion and activation of platelets were confirmed with scanning electron microscopy and lactate dehydrogenase assay. Human umbilical vein endothelial cells were cultured on the substrates, and the viability, adhesion, and proliferation were investigated through cell counting kit-8 assay and fluorescent images. Obtained results demonstrated that optimal amounts of catechol group (100 µmol) in the dopamine-conjugated hyaluronic acid existed in terms of various properties such as hemocompatibility and cellular responses.
Treatment of facial atrophic scars with Esthélis, a hyaluronic acid filler with polydense cohesive matrix (CPM).

PubMed

Hasson, Ariel; Romero, William A

2010-12-01

The treatment of atrophic scars is difficult and dermal filler materials provide a simple alternative with immediate results. Esthélis® is an injectable non-animal crosslinked hyaluronic acid of Swiss origin characterized by a polydense cohesive matrix (CPM®) which produces a gel of uniform consistency with better biointegration to the tissues and a longer duration. To evaluate Esthélis in the treatment of atrophic scars. Twelve patients aged 18-56 years with facial atrophic scars caused by acne vulgaris, dog bite, piercing, basal cell carcinoma and leishmaniasis were treated with Esthélis. The injection technique was linear threading, serial puncture or a combination of both. Clinical efficacy was assessed independently by the authors and by patients immediately, one week and one month after the injection. Adverse events were registered. Authors described the results as moderate (27%), good (57%) and excellent (17%), immediately, one week and one month after the injection. Patients evaluated the cosmetic improvement as good (42%) or excellent (58%) one month after the treatment. Pain during the injection was described as slight or moderate. Only mild erythema was observed immediately after injection, which spontaneously resolved within few hours. Esthélis showed good or excellent results in most patients with atrophic scars, and these were perceived as even better when patients evaluated the cosmetic improvement. The best results were observed in patients with more deforming scars such as surgical scars or trauma.
Hyaluronic Acid Enhances Gene Delivery into the Cochlea

PubMed Central

Shibata, Seiji B.; Cortez, Sarah R.; Wiler, James A.; Swiderski, Donald L.

2012-01-01

Abstract Cochlear gene therapy can be a new avenue for the treatment of severe hearing loss by inducing regeneration or phenotypic rescue. One necessary step to establish this therapy is the development of a safe and feasible inoculation surgery, ideally without drilling the bony cochlear wall. The round window membrane (RWM) is accessible in the middle-ear space, but viral vectors placed on this membrane do not readily cross the membrane to the cochlear tissues. In an attempt to enhance permeability of the RWM, we applied hyaluronic acid (HA), a nontoxic and biodegradable reagent, onto the RWM of guinea pigs, prior to delivering an adenovirus carrying enhanced green fluorescent protein (eGFP) reporter gene (Ad-eGFP) at the same site. We examined distribution of eGFP in the cochlea 1 week after treatment, comparing delivery of the vector via the RWM, with or without HA, to delivery by a cochleostomy into the perilymph. We found that cochlear tissue treated with HA-assisted delivery of Ad-eGFP demonstrated wider expression of transgenes in cochlear cells than did tissue treated by cochleostomy injection. HA-assisted vector delivery facilitated expression in cells lining the scala media, which are less accessible and not transduced after perilymphatic injection. We assessed auditory function by measuring auditory brainstem responses and determined that thresholds were significantly better in the ears treated with HA-assisted Ad-eGFP placement on the RWM as compared with cochleostomy. Together, these data demonstrate that HA-assisted delivery of viral vectors provides an atraumatic and clinically feasible method to introduce transgenes into cochlear cells, thereby enhancing both research methods and future clinical application. PMID:22074321
Hyaluronic acid enhances gene delivery into the cochlea.

PubMed

Shibata, Seiji B; Cortez, Sarah R; Wiler, James A; Swiderski, Donald L; Raphael, Yehoash

2012-03-01

Cochlear gene therapy can be a new avenue for the treatment of severe hearing loss by inducing regeneration or phenotypic rescue. One necessary step to establish this therapy is the development of a safe and feasible inoculation surgery, ideally without drilling the bony cochlear wall. The round window membrane (RWM) is accessible in the middle-ear space, but viral vectors placed on this membrane do not readily cross the membrane to the cochlear tissues. In an attempt to enhance permeability of the RWM, we applied hyaluronic acid (HA), a nontoxic and biodegradable reagent, onto the RWM of guinea pigs, prior to delivering an adenovirus carrying enhanced green fluorescent protein (eGFP) reporter gene (Ad-eGFP) at the same site. We examined distribution of eGFP in the cochlea 1 week after treatment, comparing delivery of the vector via the RWM, with or without HA, to delivery by a cochleostomy into the perilymph. We found that cochlear tissue treated with HA-assisted delivery of Ad-eGFP demonstrated wider expression of transgenes in cochlear cells than did tissue treated by cochleostomy injection. HA-assisted vector delivery facilitated expression in cells lining the scala media, which are less accessible and not transduced after perilymphatic injection. We assessed auditory function by measuring auditory brainstem responses and determined that thresholds were significantly better in the ears treated with HA-assisted Ad-eGFP placement on the RWM as compared with cochleostomy. Together, these data demonstrate that HA-assisted delivery of viral vectors provides an atraumatic and clinically feasible method to introduce transgenes into cochlear cells, thereby enhancing both research methods and future clinical application.
Viscosupplementation of the knee: Three cases of acute Pseudoseptic Arthritis with painful and irritating complications and a literature review

PubMed Central

Aydın, Murat; Arıkan, Murat; Toğral, Güray; Varış, Onur; Aydın, Güle

2017-01-01

Acute pseudoseptic arthritis is a very rare complication that is associated with intra-articular hyaluronic acid injections, which normally involve minimal risk. The most common adverse events that are caused by hyaluronic acid injections are inflammatory reactions or flares at the injection site. In this study, we described three cases of acute pseudoseptic arthritis that was caused by hyaluronic acid; the symptoms in these cases were reminiscent of acute septic arthritis. Moreover, we performed a literature review on pseudoseptic arthritis following hyaluronic acid injections to determine the manner in which this condition can be described, diagnosed, and treated. PMID:28293455
Comparison of intra-articular injections of plasma rich in growth factors (PRGF-Endoret) versus Durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: a randomized controlled trial.

PubMed

Vaquerizo, Víctor; Plasencia, Miguel Ángel; Arribas, Ignacio; Seijas, Roberto; Padilla, Sabino; Orive, Gorka; Anitua, Eduardo

2013-10-01

The purpose of this study was to compare the efficacy and safety in a randomized, clinical trial of 3 injections of PRGF-Endoret (BTI Biotechnology Institute, Vitoria, Spain) versus one single intra-articular injection of Durolane hyaluronic acid (HA) (Q-MED AB, Uppsala, Sweden) as a treatment for reducing symptoms in patients with knee osteoarthritis (OA). Ninety-six patients with symptomatic knee OA were randomly assigned to receive PRGF-Endoret (3 injections on a weekly basis) or one infiltration with Durolane HA. The primary outcome measures were a 30% decrease and a 50% decrease in the summed score for the pain, physical function, and stiffness subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne scores from baseline to weeks 24 and 48. The percentage of OMERACT-OARSI (Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative) responders was also documented. As secondary outcomes, pain, stiffness, and physical function by use of the WOMAC and the Lequesne score were considered and overall safety of the injection themselves. The mean age of the patients was 63.6 years. Treatment with PRGF-Endoret was significantly more efficient than treatment with Durolane HA in reducing knee pain and stiffness and improving physical function in patients with knee OA. The rate of response to PRGF-Endoret was significantly higher than the rate of response to HA for all the scores including pain, stiffness, and physical function on the WOMAC, Lequesne index, and OMERACT-OARSI responders at 24 and 48 weeks. Adverse events were mild and evenly distributed between the groups. Our findings show that PRGF-Endoret is safe and significantly superior to Durolane HA in primary and secondary efficacy analysis both at 24 and 48 weeks; provides a significant clinical improvement, reducing patients' pain and improving joint stiffness and
Design of aqueous two-phase systems for purification of hyaluronic acid produced by metabolically engineered Lactococcus lactis.

PubMed

Rajendran, Vivek; Puvendran, Kirubhakaran; Guru, Bharath Raja; Jayaraman, Guhan

2016-02-01

Hyaluronic acid has a wide range of biomedical applications and its commercial value is highly dependent on its purity and molecular weight. This study highlights the utility of aqueous two-phase separation as a primary recovery step for hyaluronic acid and for removal of major protein impurities from fermentation broths. Metabolically engineered cultures of a lactate dehydrogenase mutant strain of Lactococcus lactis (L. lactis NZ9020) were used to produce high-molecular-weight hyaluronic acid. The cell-free fermentation broth was partially purified using a polyethylene glycol/potassium phosphate system, resulting in nearly 100% recovery of hyaluronic acid in the salt-rich bottom phase in all the aqueous two-phase separation experiments. These experiments were optimized for maximum removal of protein impurities in the polyethylene glycol rich top phase. The removal of protein impurities resulted in substantial reduction of membrane fouling in the subsequent diafiltration process, carried out with a 300 kDa polyether sulfone membrane. This step resulted in considerable purification of hyaluronic acid, without any loss in recovery and molecular weight. Diafiltration was followed by an adsorption step to remove minor impurities and achieve nearly 100% purity. The final hyaluronic acid product was characterized by Fourier-transform IR and NMR spectroscopy, confirming its purity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Injectable fillers: review of material and properties.

PubMed

Attenello, Natalie Huang; Maas, Corey S

2015-02-01

With an increasing understanding of the aging process and the rapidly growing interest in minimally invasive treatments, injectable facial fillers have changed the perspective for the treatment and rejuvenation of the aging face. Other than autologous fat and certain preformed implants, the collagen family products were the only Food and Drug Administration approved soft tissue fillers. But the overwhelming interest in soft tissue fillers had led to the increase in research and development of other products including bioengineered nonpermanent implants and permanent alloplastic implants. As multiple injectable soft tissue fillers and biostimulators are continuously becoming available, it is important to understand the biophysical properties inherent in each, as these constitute the clinical characteristics of the product. This article will review the materials and properties of the currently available soft tissue fillers: hyaluronic acid, calcium hydroxylapatite, poly-l-lactic acid, polymethylmethacrylate, and autologous fat (and aspirated tissue including stem cells). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Molecular Dynamic Analysis of Hyaluronic Acid and Phospholipid Interaction in Tribological Surgical Adjuvant Design for Osteoarthritis.

PubMed

Siódmiak, Jacek; Bełdowski, Piotr; Augé, Wayne K; Ledziński, Damian; Śmigiel, Sandra; Gadomski, Adam

2017-09-04

Tribological surgical adjuvants constitute a therapeutic discipline made possible by surgical advances in the treatment of damaged articular cartilage beyond palliative care. The purpose of this study is to analyze interactions between hyaluronic acid and phospholipid molecules, and the formation of geometric forms, that play a role in the facilitated lubrication of synovial joint organ systems. The analysis includes an evaluation of the pathologic state to detail conditions that may be encountered by adjuvants during surgical convalescence. The synovial fluid changes in pH, hyaluronic acid polydispersity, and phospholipid concentration associated with osteoarthritis are presented as features that influence the lubricating properties of adjuvant candidates. Molecular dynamic simulation studies are presented, and the Rouse model is deployed, to rationalize low molecular weight hyaluronic acid behavior in an osteoarthritic environment of increased pH and phospholipid concentration. The results indicate that the hyaluronic acid radius of gyration time evolution is both pH- and phospholipid concentration-dependent. Specifically, dipalmitoylphosphatidylcholine induces hydrophobic interactions in the system, causing low molecular weight hyaluronic acid to shrink and at high concentration be absorbed into phospholipid vesicles. Low molecular weight hyaluronic acid appears to be insufficient for use as a tribological surgical adjuvant because an increased pH and phospholipid concentration induces decreased crosslinking that prevents the formation of supramolecular lubricating forms. Dipalmitoylphosphatidylcholine remains an adjuvant candidate for certain clinical situations. The need to reconcile osteoarthritic phenotypes is a prerequisite that should serve as a framework for future adjuvant design and subsequent tribological testing.
The Efficacy, Longevity, and Safety of Combined Radiofrequency Treatment and Hyaluronic Acid Filler for Skin Rejuvenation

PubMed Central

Kim, Hyuk; Park, Kui Young; Choi, Sun Young; Koh, Hyun-Ju; Park, Sun-Young; Park, Won-Seok; Bae, Il-Hong

2014-01-01

Background Recent advances in hyaluronic acid (HA) fillers and radiofrequency (RF) devices have been made in the context of skin rejuvenation and cosmetic surgery. Moreover, combination regimens with both techniques are currently being developed. Objective The present study was designed to examine the clinical and histologic effects of a new needle that incorporates an RF device for HA injections. Methods A new intradermal needle RF device (INNOfill; Pacific Pharma, Korea) was assessed in the present study. In the animal arm, procollagen production was measured by using enzyme-linked immunosorbent assay, the filler volume was quantified by incorporating a dye with filler, and the filler distribution was assessed through the changes in tissue structure. In the human arm, the efficacy of the combination regimen was assessed by using the wrinkle severity rating scale (WSRS). Results In the animal study, RF treatment increased procollagen production in a time-dependent fashion. The total volume was significantly increased with the RF treatment when compared with the filler injections alone, and lasted for up to 7 weeks after treatment. Additionally, the filler distribution was reduced in animals treated with RF when compared with the untreated group. In the human study, the nasolabial folds of subjects treated with RF before filler injections exhibited a significantly greater change in the WSRS score from baseline when compared with the nasolabial folds treated with filler injections alone. Conclusion A new device incorporating RF treatment before HA filler injection may represent a biocompatible and long-lasting advance in skin rejuvenation. PMID:25143672
Hyaluronic Acid Decreases Lipid Synthesis in Sebaceous Glands.

PubMed

Jung, Yu Ra; Hwang, Chul; Ha, Jeong-Min; Choi, Dae-Kyoung; Sohn, Kyung-Cheol; Lee, Young; Seo, Young-Joon; Lee, Young-Ho; Kim, Chang-Deok; Lee, Jeung-Hoon; Im, Myung

2017-06-01

Hyaluronic acid (HA) is the major glycosaminoglycan in the extracellular matrix and has been implicated in several functions in skin cells. However, evidence is lacking regarding the HA signaling in sebaceous glands, and its potential role needs to be clarified. We investigated the role of HA in lipid production in sebaceous glands in an experimental study of human sebocytes followed by a clinical study. We first examined the effects of HA on sebaceous glands in hamsters and intradermal injection of HA into hamster auricles decreased both the size of sebaceous glands and the level of lipid production. We demonstrated that human skin sebaceous glands in vivo and sebocytes in vitro express CD44 (HA binding receptor) and that HA downregulates lipid synthesis in a dose-dependent manner. To evaluate the clinical relevance of HA in human skin, 20 oily participants were included in a double-blind, placebo-controlled, split-face study, and the HA-treated side showed a significant decrease in sebum production. The results of this study indicate that HA plays a functional role in human sebaceous gland biology and HA signaling is an effective candidate in the management of disorders in which sebum production is increased. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Synthesis and Characterization of Hyaluronic Acid Modified Colloidal Mesoporous Silica Nanoparticles

NASA Astrophysics Data System (ADS)

Zhang, Wenbiao; Wang, Yu; Li, Zhen; Wang, Wanxia; Sun, Honghao; Liu, Mingxing

2017-12-01

The colloidal mesoporous silica nanoparticles functionalized with hyaluronic acid (CMS-HA) were successfully synthesized by grafting hyaluronic acid onto the external surface of the amino-functionalized mesoporous silica nanoparticles (CMS-NH2). Moreover, the paticle properties of CMS-HA were characterized by fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS) and transmission electron microscopy (TEM). The nanomaterials were negatively charged and had a relatively uniform spherical morphology with about 100 nm in diameter, which could make it more compatible with blood. So the results suggested that the CMS-HA might be a critical nanomaterial for applying in target drug delivery system.

Efficacy of two different thiol-modified crosslinked hyaluronate formulations as vitreous replacement compared to silicone oil in a model of retinal detachment

PubMed Central

Schnichels, Sven; Schneider, Nele; Hohenadl, Christine; Hurst, José; Schatz, Andreas; Januschowski, Kai; Spitzer, Martin S.

2017-01-01

The efficacy of two novel artificial vitreous body substitutes (VBS) consisting of highly biocompatible thiolated cross-linked hyaluronic acid (HA)-based hydrogels in comparison to silicone oil in a model of retinal detachment was investigated. Pars plana vitrectomy (23G) was performed in the right eye of 24 pigmented rabbits. Retinal detachment of two quadrants was induced by creating a small retinotomy near the vascular arcade and injecting balanced salt solution (BSS) subretinally. The retina was reattached by injecting air, which was followed by increasing the infusion pressure, and the retinal tear was treated by endolaser photocoagulation. At the end of the procedure, the eye was filled either with 5000-cs silicone oil (after fluid air exchange) or the respective hydrogel (with two different viscosities). Follow-up examination included slit lamp examination, funduscopy, intraocular pressure measurements (IOP), optical coherence tomography (OCT) and electroretinogram (ERG) measurements. After a maximum follow-up of four weeks both eyes were removed, examined macroscopically, photographed, and prepared for histology. Of the eight rabbits that received silicone oil, seven (87.5%) developed a recurrent retinal detachment with pronounced proliferative vitreoretinopathy within the first two weeks after surgery. In contrast, in the hydrogel treated eyes, the retina stayed attached in the majority of the cases (73.3%). IOP and retinal morphology were normal as long as the retina remained re-attached. In conclusions, this model of retinal detachment, both thiolated crosslinked hyaluronate hydrogels showed superior efficacy when compared to silicone oil. These hydrogels have a promising potential as novel vitreous body substitutes. PMID:28248989
Global Aesthetics Consensus: Hyaluronic Acid Fillers and Botulinum Toxin Type A—Recommendations for Combined Treatment and Optimizing Outcomes in Diverse Patient Populations

PubMed Central

Liew, Steven; Signorini, Massimo; Vieira Braz, André; Fagien, Steven; Swift, Arthur; De Boulle, Koenraad L.; Raspaldo, Hervé; Trindade de Almeida, Ada R.; Monheit, Gary

2016-01-01

Background: Combination of fillers and botulinum toxin for aesthetic applications is increasingly popular. Patient demographics continue to diversify, and include an expanding population receiving maintenance treatments over decades. Methods: A multinational panel of plastic surgeons and dermatologists convened the Global Aesthetics Consensus Group to develop updated guidelines with a worldwide perspective for hyaluronic acid fillers and botulinum toxin. This publication considers strategies for combined treatments, and how patient diversity influences treatment planning and outcomes. Results: Global Aesthetics Consensus Group recommendations reflect increased use of combined treatments in the lower and upper face, and some midface regions. A fully patient-tailored approach considers physiologic and chronologic age, ethnically associated facial morphotypes, and aesthetic ideals based on sex and culture. Lower toxin dosing, to modulate rather than paralyze muscles, is indicated where volume deficits influence muscular activity. Combination of toxin with fillers is appropriate for several indications addressed previously with toxin alone. New scientific data regarding hyaluronic acid fillers foster an evidence-based approach to selection of products and injection techniques. Focus on aesthetic units, rather than isolated rhytides, optimizes results from toxin and fillers. It also informs longitudinal treatment planning, and analysis of toxin nonresponders. Conclusions: The emerging objective of injectable treatment is facial harmonization rather than rejuvenation. Combined treatment is now a standard of care. Its use will increase further as we refine the concept that aspects of aging are intimately related, and that successful treatment entails identifying and addressing the primary causes of each. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID:27119917
A membrane-associated adenylate cyclase modulates lactate dehydrogenase and creatine kinase activities required for bull sperm capacitation induced by hyaluronic acid.

PubMed

Fernández, Silvina; Córdoba, Mariana

2017-04-01

Hyaluronic acid, as well as heparin, is a glycosaminoglycan present in the female genital tract of cattle. The aim of this study was to evaluate oxidative metabolism and intracellular signals mediated by a membrane-associated adenylate cyclase (mAC), in sperm capacitation with hyaluronic acid and heparin, in cryopreserved bull sperm. The mAC inhibitor, 2',5'-dideoxyadenosine, was used in the present study. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities and lactate concentration were determined spectrophotometrically in the incubation medium. Capacitation and acrosome reaction were evaluated by chlortetracycline technique, while plasma membrane and acrosome integrity were determined by trypan blue stain/differential interference contrast microscopy. Heparin capacitated samples had a significant decrease in LDH and CK activities, while in hyaluronic acid capacitated samples LDH and CK activities both increased compared to control samples, in heparin and hyaluronic acid capacitation conditions, respectively. A significant increase in lactate concentration in the incubation medium occurred in hyaluronic acid-treated sperm samples compared to heparin treatment, indicating this energetic metabolite is produced during capacitation. The LDH and CK enzyme activities and lactate concentrations in the incubation medium were decreased with 2',5'-dideoxyadenosine treatment in hyaluronic acid samples. The mAC inhibitor significantly inhibited heparin-induced capacitation of sperm cells, but did not completely inhibit hyaluronic acid capacitation. Therefore, hyaluronic acid and heparin are physiological glycosaminoglycans capable of inducing in vitro capacitation in cryopreserved bull sperm, stimulating different enzymatic pathways and intracellular signals modulated by a mAC. Hyaluronic acid induces sperm capacitation involving LDH and CK activities, thereby reducing oxidative metabolism, and this process is mediated by mAC. Copyright © 2017 Elsevier B.V. All
CD44 and TLR4 mediate hyaluronic acid regulation of Lgr5+ stem cell proliferation, crypt fission, and intestinal growth in postnatal and adult mice.

PubMed

Riehl, Terrence E; Santhanam, Srikanth; Foster, Lynne; Ciorba, Matthew; Stenson, William F

2015-12-01

Hyaluronic acid, a glycosaminoglycan in the extracellular matrix, binds to CD44 and Toll-like receptor 4 (TLR4). We previously addressed the role of hyaluronic acid in small intestinal and colonic growth in mice. We addressed the role of exogenous hyaluronic acid by giving hyaluronic acid intraperitoneally and the role of endogenous hyaluronic acid by giving PEP-1, a peptide that blocks hyaluronic acid binding to its receptors. Exogenous hyaluronic acid increased epithelial proliferation but had no effect on intestinal length. PEP-1 resulted in a shortened small intestine and colon and diminished epithelial proliferation. In the current study, we sought to determine whether the effects of hyaluronic acid on growth were mediated by signaling through CD44 or TLR4 by giving exogenous hyaluronic acid or PEP-1 twice a week from 3-8 wk of age to wild-type, CD44(-/-), and TLR4(-/-) mice. These studies demonstrated that signaling through both CD44 and TLR4 were important in mediating the effects of hyaluronic acid on growth in the small intestine and colon. Extending our studies to early postnatal life, we assessed the effects of exogenous hyaluronic acid and PEP-1 on Lgr5(+) stem cell proliferation and crypt fission. Administration of PEP-1 to Lgr5(+) reporter mice from postnatal day 7 to day 14 decreased Lgr5(+) cell proliferation and decreased crypt fission. These studies indicate that endogenous hyaluronic acid increases Lgr5(+) stem cell proliferation, crypt fission, and intestinal lengthening and that these effects are dependent on signaling through CD44 and TLR4. Copyright © 2015 the American Physiological Society.
Efficacy of injecting platelet concentrate combined with hyaluronic acid for the treatment of vulvovaginal atrophy in postmenopausal women with history of breast cancer: a phase 2 pilot study.

PubMed

Hersant, Barbara; SidAhmed-Mezi, Mounia; Belkacemi, Yazid; Darmon, Franklin; Bastuji-Garin, Sylvie; Werkoff, Gabrielle; Bosc, Romain; Niddam, Jeremy; Hermeziu, Oana; La Padula, Simone; Meningaud, Jean Paul

2018-05-07

Approximately 50% to 70% of breast cancer survivors are affected by one or more symptoms of vulvovaginal atrophy (VVA). For those who cannot take hormone therapy, autologous platelet-rich plasma combined with hyaluronic acid (A-PRP-HA) may provide a new alternative therapy for the treatment of VVA in postmenopausal women with history of breast cancer. We enrolled 20 postmenopausal breast cancers survivors with VVA and a score of <15 on the Gloria Bachman Vaginal Health Index (VHI) comprised of five items including: vaginal pH, elasticity, fluid volume (secretions), epithelial integrity, and moisture.We administered intramucosal injections of A-PRP combined with HA (Regenkit) and performed clinical evaluations at 0, 1, 3, and 6 months. Primary endpoint: evaluation of vulvovaginal mucosa changes using the VHI; secondary endpoint: evaluation of dyspareunia and sexual dysfunction based on the Female Sexual Distress (FSD) score. All participants (20 women) showed improvement in the clinical symptoms of vaginal dryness and dyspareunia. The VHI score showed a significant increase at 6 months, going from a total baseline score (pretreatment) of 10.7 ± 2.12 to 20.75 ± 4.8 (P < 0.0001) at 6 months. Improvement in hydration and vaginal epithelial integrity was reported. A VHI score of > 15 showed a successful treatment outcome. The FSD score decreased significantly during the study, from a baseline score of 36.35 ± 2.53 pretreatment to 30.15 ± 2.47 6 months after treatment, representing improvement of 17% (P < 0.0001, respectively). No adverse events were reported. The injection of A-PRP-HA appeared to be a promising method to improve the trophicity and hydration of vaginal mucosa for the treatment of VVA in postmenopausal breast cancer survivors with contraindications to hormone therapy.
Cross-linked hyaluronic acid in pressure ulcer prevention.

PubMed

Beniamino, P; Vadalà, M; Laurino, C

2016-07-02

Long-term bedridden patients are at high risk of acquring pressure ulcers (PUs). In this group of patients, prevention is necessary to cut the health costs, improve quality of life and reduce the mortality. Here, we evaluated the effectiveness of a cross-linked hyaluronic acid (HA) as plastic bulking-agent filling and remodelling the deep dermis and subcutaneous space of the skin areas exposed to the risk of necrosis. Our work hypothesis has been to inflate a sub-dermal elastic cushion, filled with a natural ECM component, with the aim to induce a stronger tissue background resistant to the ulcerative process. All the patients had an increased risk of PUs, at the sacral, ileum or heel skin. Patients were being nursed accordingly to the standard orthopaedic ward management with a pressure relieveing air mattress. The standard protocol consisted in body mobilisation every 3 hours, 24 hours a day and accurate cleaning of the skin with liquid soap and water without any towel friction and without adding any cream or lotion for the skin protection. Our filling protocol enclosed: accurate disinfection of the skin to be injected with povidone-iodine solution, followed by a local anaesthesia with 28G 13 mm needle, injecting 1.5 ml of 1% xylocaine. Then slow, deep, subcutaneous injection of cross-linked HA was performed with a 18G long needle, in order to deliver a homogeneous, soft gel layer underneath and around the whitish erythematous skin edges at risk of ulceration. Patients' tolerability of the compound and adverse events were also recorded. There were 15 patients (78-94 years old) who participated in the study. All tolerated the procedure very well and no serious side effects were declared. No skin pressure ulceration was detected in the four weeks follow-up Conclusion: We have demonstrated the safety and tolerability of a cross-linked HA subdermal injection in PUs prevention. The compound stratifies in a soft, elastic, interstitial bulk into the deep dermis, thus
Chemical Sintering Generates Uniform Porous Hyaluronic Acid Hydrogels

PubMed Central

Cam, Cynthia; Segura, Tatiana

2014-01-01

Implantation of scaffolds for tissue repair has been met with limited success primarily due to the inability to achieve vascularization within the construct. Many strategies have shifted to incorporate pores into these scaffolds to encourage rapid cellular infiltration and subsequent vascular ingrowth. We utilized an efficient chemical sintering technique to create a uniform network of polymethyl methacrylate (PMMA) microspheres for porous hyaluronic acid hydrogel formation. The porous hydrogels generated from chemical sintering possessed comparable pore uniformity and interconnectivity as the commonly used non- and heat sintering techniques. Moreover, similar cell response to the porous hydrogels generated from each sintering approach was observed in cell viability, spreading, proliferation in vitro, as well as, cellular invasion in vivo. We propose chemical sintering of PMMA microspheres using a dilute acetone solution as an alternative method to generating porous hyaluronic acid hydrogels since it requires equal or ten-fold less processing time as the currently used non-sintering or heat sintering technique, respectively. PMID:24120847
1- and 2-particle Microrheology of Hyaluronic Acid

NASA Astrophysics Data System (ADS)

Sagan, Austin; Kearns, Sarah; Ross, David; Das, Moumita; Thurston, George; Franklin, Scott

2015-03-01

Hyaluronic acid (also called HA or Hyaluronan) is a high molecular weight polysaccaride ubiquitous in the extracellular matrix of soft tissue such as cartilage, skin, the eye's vitreous gel and synovial fluid. It has been shown to play an important role in mechanotransduction, cell migration and proliferation, and in tissue morphodynamics. We present a confocal microrheology study of hyaluronic acid of varying concentrations. The mean squared displacement (MSD) of sub-micron colloidal tracer particles is tracked in two dimensions and shows a transition from diffusive motion at low concentrations to small-time trapping by the protein network as the concentration increases. Correlations between particle motion can be used to determine an effective mean-squared displacement which deviates from the single-particle MSD as the fluid becomes less homogeneous. The real and effective mean-squared displacements are used to probe the local and space-averaged frequency dependent rheological properties of the fluid as the concentration changes.
Evaluation of the efficacy and safety of a lidocaine and tetracaine (7%/7%) cream for induction of local dermal anesthesia for facial soft tissue augmentation with hyaluronic Acid.

PubMed

Cohen, Joel L; Gold, Michael H

2014-10-01

Injection of dermal fillers for soft tissue augmentation is a minimally invasive cosmetic procedure with growing popularity. However, patients often express concern about pain with such procedures. A topical anesthetic cream formulated with lidocaine/tetracaine 7%7% was approved by the United States Food and Drug Administration in 2006 and recently reintroduced to the market for use during superficial dermatological procedures. A Phase 3 study was conducted to assess the efficacy and safety of lidocaine/tetracaine 7%7% cream versus placebo cream when used to induce local dermal anesthesia during injections with hyaluronic acid. Mean visual analog scale scores significantly favored lidocaine/tetracaine 7%7% cream. A significant percent of subjects also indicated that lidocaine/tetracaine 7%7% cream provided adequate pain relief and that they would use lidocaine/tetracaine 7%7% cream again. Investigators also rated lidocaine/tetracaine 7%7% cream significantly better than placebo cream for providing adequate pain relief and on the assessment of pain scale. Lidocaine/tetracaine 7%7% cream was safe and well tolerated with most subjects reporting no erythema, edema, or blanching. No related adverse events were reported with lidocaine/tetracaine 7%7% cream; one related adverse event of erythema was reported with placebo cream. The results of this study indicate that lidocaine/tetracaine 7%7% cream is efficacious and safe at providing pain relief for soft tissue augmentation with hyaluronic acid.
Evaluation of the Efficacy and Safety of a Lidocaine and Tetracaine (7%/7%) Cream for Induction of Local Dermal Anesthesia for Facial Soft Tissue Augmentation with Hyaluronic Acid

PubMed Central

Gold, Michael H.

2014-01-01

Injection of dermal fillers for soft tissue augmentation is a minimally invasive cosmetic procedure with growing popularity. However, patients often express concern about pain with such procedures. A topical anesthetic cream formulated with lidocaine/tetracaine 7%7% was approved by the United States Food and Drug Administration in 2006 and recently reintroduced to the market for use during superficial dermatological procedures. A Phase 3 study was conducted to assess the efficacy and safety of lidocaine/tetracaine 7%7% cream versus placebo cream when used to induce local dermal anesthesia during injections with hyaluronic acid. Mean visual analog scale scores significantly favored lidocaine/tetracaine 7%7% cream. A significant percent of subjects also indicated that lidocaine/tetracaine 7%7% cream provided adequate pain relief and that they would use lidocaine/tetracaine 7%7% cream again. Investigators also rated lidocaine/tetracaine 7%7% cream significantly better than placebo cream for providing adequate pain relief and on the assessment of pain scale. Lidocaine/tetracaine 7%7% cream was safe and well tolerated with most subjects reporting no erythema, edema, or blanching. No related adverse events were reported with lidocaine/tetracaine 7%7% cream; one related adverse event of erythema was reported with placebo cream. The results of this study indicate that lidocaine/tetracaine 7%7% cream is efficacious and safe at providing pain relief for soft tissue augmentation with hyaluronic acid. PMID:25371769
The saline load test of the knee redefined: a test to detect traumatic arthrotomies and rule out periarticular wounds not requiring surgical intervention.

PubMed

Konda, Sanjit R; Howard, Daniel; Davidovitch, Roy I; Egol, Kenneth A

2013-09-01

To describe the use of the saline load test (SLT) using a new definition that more adequately characterizes its use in the emergency department (ED) setting. Retrospective review. Level I trauma center. Fifty consecutive patients who underwent an SLT of the knee in the ED and had a minimum of 14 days follow-up. Saline Load Test. Positive traumatic arthrotomy of the knee (+TAK) defined as operating room (OR) confirmation of an arthrotomy (assumed to develop a septic knee) or -SLT with follow-up revealing a septic knee. Periarticular wound equivalent to no traumatic arthrotomy of the knee [pw = (-TAK)] defined as OR evaluation revealing no arthrotomy (assumed not to develop a septic knee) or -SLT whose follow-up revealed no septic knee. Development of a septic knee was considered the gold standard for determining true positives/negatives and false positives/negatives. The mean wound size was 3.9 ± 4.3 cm and the mean saline load volume was 74.9 ± 28.2 cm. There were 19 +SLTs of which there were 16 +TAK and 3 pw = (-TAK). The 3 pw = (-TAK) in the +SLT group were evaluated in the OR where inspection of the joint capsule revealed the absence of a traumatic arthrotomy. There were 31 -SLTs of which there were 1 +TAK and 30 pw = (-TAK). The SLT has a sensitivity of 94% and a specificity of 91% for detecting +TAKs and ruling out periarticular wounds not requiring surgical intervention [pw = (-TAK)]. The false-positive rate of the SLT to detect +TAK is 9%. Using +TAK and pw = (-TAK) as the newly defined measures of the SLT, we report the sensitivity (94%) and specificity (91%) of the SLT in the ED setting while still maintaining the clinical relevancy of the test. Based on a small sample size, knees with small periarticular wounds and a -SLT and no other radiographic or clinical evidence of an arthrotomy appear to have an infection rate of 0% with nonoperative management. Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Role of Periarticular Liposomal Bupivacaine Infiltration in Patients Undergoing Total Knee Arthroplasty-A Meta-analysis of Comparative Trials.

PubMed

Singh, Preet Mohinder; Borle, Anuradha; Trikha, Anjan; Michos, Lia; Sinha, Ashish; Goudra, Basavana

2017-02-01

Over last 2 years, many trials have evaluated newly approved liposomal bupivacaine for periarticular infiltration in total knee arthroplasty (TKA) with mixed results. Our meta-analysis attempts to consolidate the results and make evidence-based conclusions. Trails comparing periarticular infiltration of liposomal bupivacaine to conventional analgesic regimens for total knee arthroplasty published till June 2016 were searched in medical database. Comparisons were made for length of stay (LOS), postoperative pain scores, range of motion, and opioid consumption. Meta-regression was performed for LOS to evaluate various analgesic control subgroups. Sixteen trials were included in the final analysis. Liposomal bupivacaine group showed a shorter LOS (reported in 13 subgroups) than control group by 0.17 ± 0.04 days (random effects, P < .001, I 2 = 84.66%). Meta-regression for various types of control showed a predictability (R 2 ) of 73%, τ 2 = 0.013 (random effects, P < .001, I 2 = 45.16). Only femoral block subgroup attained statistically significant shorter LOS on splitting the control group. Numeric pain scores were lower for pooled control group and local anesthetic infiltration subgroup in immediate postoperative phase. Second postoperative day analgesia was statistically superior to overall clubbed controls and femoral block subgroup. Superiority and/or inferiority of liposomal bupivacaine could not be proven for opioid consumption and range of motion because of a small pooled sample size. Publication bias is likely for LOS (Egger test, X intercept = 2.42, P < .001). Liposomal bupivacaine infiltration has questionable clinical advantage, as it marginally shortens patient's hospital stay especially in comparison with patients receiving analgesic femoral nerve block. Compared with conventional regimens, it can provide slightly superior yet sustained (till second postoperative day) perioperative analgesia. High heterogeneity suggests need for standardization
A hybrid composite system of biphasic calcium phosphate granules loaded with hyaluronic acid-gelatin hydrogel for bone regeneration.

PubMed

Faruq, Omar; Kim, Boram; Padalhin, Andrew R; Lee, Gun Hee; Lee, Byong-Taek

2017-10-01

An ideal bone substitute should be made of biocompatible materials that mimic the structure, characteristics, and functions of natural bone. Many researchers have worked on the fabrication of different bone scaffold systems including ceramic-polymer hybrid system. In the present study, we incorporated hyaluronic acid-gelatin hydrogel to micro-channeled biphasic calcium phosphate granules as a carrier to improve cell attachment and proliferation through highly interconnected porous structure. This hybrid system is composed of ceramic biphasic calcium phosphate granules measuring 1 mm in diameter with seven holes and hyaluronic acid-gelatin hydrogel. This combination of biphasic calcium phosphate and hyaluronic acid-gelatin retained suitable characteristics for bone regeneration. The resulting scaffold had a porosity of 56% with a suitable pore sizes. The mechanical strength of biphasic calcium phosphate granule increased after loading hyaluronic acid-gelatin from 4.26 ± 0.43 to 6.57 ± 0.25 MPa, which is highly recommended for cancellous bone substitution. Swelling and degradation rates decreased in the hybrid scaffold compared to hydrogel due to the presence of granules in hybrid scaffold. In vitro cytocompatibility studies were observed by preosteoblasts (MC3T3-E1) cell line and the result revealed that biphasic calcium phosphate/hyaluronic acid-gelatin significantly increased cell growth and proliferation compared to biphasic calcium phosphate granules. Analysis of micro-computed tomography data and stained tissue sections from the implanted samples showed that the hybrid scaffold had good osseointegration and better bone formation in the scaffold one and two months postimplantation. Histological section confirmed the formation of dense collagenous tissue and new bone in biphasic calcium phosphate/hyaluronic acid-gelatin scaffolds at two months. Our study demonstrated that such hybrid biphasic calcium phosphate/hyaluronic acid-gelatin scaffold is a
3D composites based on the blends of chitosan and collagen with the addition of hyaluronic acid.

PubMed

Sionkowska, Alina; Kaczmarek, Beata; Lewandowska, Katarzyna; Grabska, Sylwia; Pokrywczyńska, Marta; Kloskowski, Tomasz; Drewa, Tomasz

2016-08-01

3D porous composites based on blends of chitosan, collagen and hyaluronic acid were obtained through the lyophilization process. Mechanical properties, swelling behavior and thermal stability of the blends were studied. Moreover, SEM images were taken and the structure of the blends was studied. Biological properties of the materials obtained were investigated by analyzing of proliferation rate of fibroblast cells incubated with biomaterial extract using MTT assay (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide). The results showed that the properties of 3D composites based on the blends of chitosan and collagen were altered after the addition 1%, 2% and 5% of hyaluronic acid. Mechanical properties and thermal stability of chitosan/collagen blends were improved in the presence of hyaluronic acid in the composite. New 3D materials based on the blends of chitosan, collagen and hyaluronic acid were non-toxic and did not significantly affect cell morphology. Copyright © 2016 Elsevier B.V. All rights reserved.
Treatment strategy for sacroiliac joint-related pain at or around the posterior superior iliac spine.

PubMed

Murakami, Eiichi; Kurosawa, Daisuke; Aizawa, Toshimi

2018-02-01

Pain at or around the posterior superior iliac spine (PSIS) is characteristic of sacroiliac joint (SIJ) -related pain. This pain can be treated by either a peri- or intra-articular injection into the joint, with the former being much easier to perform. We investigated whether peri- or intra-articular injections were more frequently effective in patients with SIJ-related pain, and aimed to create an efficient treatment strategy for SIJ-related pain at or around the PSIS. Prospective case-control study. We evaluated 85 patients with pain at or around the posterior superior iliac spine as indicated by the one finger test. First, we performed a peri-articular sacroiliac joint injection. If it was ineffective, an intra-articular injection was later given. Groin pain, sitting pain, sacroiliac joint shear test results, and posterior superior iliac spine and sacro-tuberous ligament tenderness were also compared between patients for whom a peri- or intra-articular injection was effective. Seventy-two (85%) of 85 patients had an effective injection. Out of these 72 patients, 58 (81%) had a positive peri-articular injection and 14 (19%) had a positive intra-articular injection. Four items, excluding tenderness of the sacro-tuberous ligament had no significant difference between these two injection types. To treat sacroiliac joint-related pain at or around the posterior superior iliac spine, a peri-articular injection should be performed first, and only if it is not effective should an intra-articular injection be administered. Using this strategy, we expect that most patients with sacroiliac joint-related pain will be efficiently diagnosed and treated. Copyright © 2017 Elsevier B.V. All rights reserved.
Effect of stiffness of chitosan-hyaluronic acid dialdehyde hydrogels on the viability and growth of encapsulated chondrocytes.

PubMed

V Thomas, Lynda; Vg, Rahul; D Nair, Prabha

2017-11-01

Substrate elasticity or stiffness can influence the phenotypic and functional characteristics of chondrocytes. This work aimed to study the effect of varying stiffness compositions of a two-component injectable hydrogel based on chitosan (CH) and oxidized hyaluronic acid (HDA) on the growth and functionality of encapsulated chondrocytes. Three different ratios of the gel were prepared (10:1,10:3 and 10:5 CH-HDA) and characterized. The stiffness of the gels was evaluated from the force displacement curves using force spectroscopy AFM analysis. Rabbit articular chondrocytes were harvested and the cells from Passage 2 to 4 were used for the encapsulation study. The viability and ECM production of encapsulated chondrocytes were assessed at 7day, 14day and 28day post culture. The results of the study show that as the ratio of hyaluronic acid dialdehyde component was increased, the stiffness of the gels increased from 130.78±19.83kPa to 181.47±19.77kPa which was also evidenced from the decrease in gelling time. Although there was an increase in the percentage of viable encapsulated cells which also maintained the spherical phenotype in the less stiff gels, decreased expression of ECM markers- Collagen type II and Glycosaminoglycans was observed compared to the stiffer gels. These findings indicate that gel stiffness strongly impacts the chondrocyte microenvironment both in maintenance of phenotypic integrity and ECM production. Copyright © 2017. Published by Elsevier B.V.
Elastin-like protein-hyaluronic acid (ELP-HA) hydrogels with decoupled mechanical and biochemical cues for cartilage regeneration.

PubMed

Zhu, Danqing; Wang, Huiyuan; Trinh, Pavin; Heilshorn, Sarah C; Yang, Fan

2017-05-01

Hyaluronic acid (HA) is a major component of cartilage extracellular matrix and is an attractive material for use as 3D injectable matrices for cartilage regeneration. While previous studies have shown the promise of HA-based hydrogels to support cell-based cartilage formation, varying HA concentration generally led to simultaneous changes in both biochemical cues and stiffness. How cells respond to the change of biochemical content of HA remains largely unknown. Here we report an adaptable elastin-like protein-hyaluronic acid (ELP-HA) hydrogel platform using dynamic covalent chemistry, which allows variation of HA concentration without affecting matrix stiffness. ELP-HA hydrogels were created through dynamic hydrazone bonds via the reaction between hydrazine-modified ELP (ELP-HYD) and aldehyde-modified HA (HA-ALD). By tuning the stoichiometric ratio of aldehyde groups to hydrazine groups while maintaining ELP-HYD concentration constant, hydrogels with variable HA concentration (1.5%, 3%, or 5%) (w/v) were fabricated with comparable stiffness. To evaluate the effects of HA concentration on cell-based cartilage regeneration, chondrocytes were encapsulated within ELP-HA hydrogels with varying HA concentration. Increasing HA concentration led to a dose-dependent increase in cartilage-marker gene expression and enhanced sGAG deposition while minimizing undesirable fibrocartilage phenotype. The use of adaptable protein hydrogels formed via dynamic covalent chemistry may be broadly applicable as 3D scaffolds with decoupled niche properties to guide other desirable cell fates and tissue repair. Copyright © 2017 Elsevier Ltd. All rights reserved.
Elastin-like Protein-Hyaluronic acid (ELP-HA) Hydrogels with Decoupled Mechanical and Biochemical cues for Cartilage Regeneration

PubMed Central

Zhu, Danqing; Wang, Huiyuan; Trinh, Pavin; Heilshorn, Sarah C.; Yang, Fan

2018-01-01

Hyaluronic acid (HA) is a major component of cartilage extracellular matrix and is an attractive material for use as 3D injectable matrices for cartilage regeneration. While previous studies have shown the promise of HA-based hydrogels to support cell-based cartilage formation, varying HA concentration generally led to simultaneous changes in both biochemical cues and stiffness. How cells respond to the change of biochemical content of HA remains largely unknown. Here we report an adaptable elastin-like protein-hyaluronic acid (ELP-HA) hydrogel platform using dynamic covalent chemistry, which allows varyiation of HA concentration without affecting matrix stiffness. ELP-HA hydrogels were created through dynamic hydrazone bonds via the reaction between hydrazine-modified ELP (ELP-HYD) and aldehyde-modified HA (HA-ALD). By tuning the stoichiometric ratio of aldehyde groups to hydrazine groups while maintaining ELP-HYD concentration constant, hydrogels with variable HA concentration (1.5%, 3%, or 5%) (w/v) were fabricated with comparable stiffness. To evaluate the effects of HA concentration on cell-based cartilage regeneration, chondrocytes were encapsulated within ELP-HA hydrogels with varying HA concentration. Increasing HA concentration led to a dose-dependent increase in cartilage-marker gene expression and enhanced sGAG deposition while minimizing undesirable fibrocartilage phenotype. The use of adaptable protein hydrogels formed via dynamic covalent chemistry may be broadly applicable as 3D scaffolds with decoupled niche properties to guide other desirable cell fates and tissue repair. PMID:28268018
Protective therapeutic effects of peptide nanofiber and hyaluronic acid hybrid membrane in in vivo osteoarthritis model.

PubMed

Arslan, Elif; Sardan Ekiz, Melis; Eren Cimenci, Cagla; Can, Nuray; Gemci, M Hanifi; Ozkan, Huseyin; Guler, Mustafa O; Tekinay, Ayse B

2018-06-01

Osteoarthritis (OA) is a condition where tissue function is lost through a combination of secondary inflammation and deterioration in articular cartilage. One of the most common causes of OA is age-related tissue impairment because of wear and tear due to mechanical erosion. Hyaluronic acid-based viscoelastic supplements have been widely used for the treatment of knee injuries. However, the current formulations of hyaluronic acid are unable to provide efficient healing and recovery. Here, a nanofiber-hyaluronic acid membrane system that was prepared by using a quarter of the concentration of commercially available hyaluronic acid supplement, Hyalgan®, was used for the treatment of an osteoarthritis model, and Synvisc®, which is another commercially available hyaluronic acid containing viscoelastic supplement, was used as a control. The results show that this system provides efficient protection of arthritic cartilage tissue through the preservation of cartilage morphology with reduced osteophyte formation, protection of the subchondral region from deterioration, and maintenance of cartilage specific matrix proteins in vivo. In addition, the hybrid nanofiber membrane enabled chondrocyte encapsulation and provided a suitable culturing environment for stem cell growth in vitro. Overall, our results suggest that this hybrid nanofibrous scaffold provides a potential platform the treatment of OA. Osteoarthritis is a debilitating joint disease affecting millions of people worldwide. It occurs especially in knees due to aging, sport injuries or obesity. Although hyaluronic acid-based viscoelastic supplements are widely used, there is still no effective treatment method for osteoarthritis, which necessitates surgical operation as an only choice for severe cases. Therefore, there is an urgent need for efficient therapeutics. In this study, a nanofiber-HA membrane system was developed for the efficient protection of arthritic cartilage tissue from degeneration. This hybrid
Systematic clinical evidence review of NASHA (Durolane hyaluronic acid) for the treatment of knee osteoarthritis.

PubMed

Leighton, Ross; Fitzpatrick, Jane; Smith, Helen; Crandall, Daniela; Flannery, Carl R; Conrozier, Thierry

2018-01-01

Pain and limitations in joint mobility associated with knee osteoarthritis (OA) are clinically challenging to manage, and advanced progression of disease can often lead to total knee arthroplasty. Intra-articular injection of hyaluronic acid (HA), also referred to as viscosupplementation, is a non-surgical treatment approach for OA, the effectiveness of which may depend on the HA composition, and the length of time over which it resides in the joint. One of the available options for such therapies includes NASHA (Durolane HA), a non-animal, biofermentation-derived product, which is manufactured using a process that stabilizes the HA molecules to slow down their rate of degradation and produce a unique formulation with a terminal half-life of ~1 month. The objectives of the current review were to assess, in patients with OA of the knee, the efficacy and safety of intra-articular treatment with NASHA relative to control (saline) injections, other HA products, and other injectables (corticosteroids, platelet-rich plasma, mesenchymal stem cells). This systematic evidence review examines patient outcomes following NASHA treatment as described in published data from studies conducted in subjects with knee OA. A Preferred Reporting Items for Systematic Reviews and Meta-analyses-compliant literature search strategy yielded 11 eligible clinical studies with a variety of comparator arms. Outcomes assessed at various time points following intra-articular treatment included measures of pain, function, quality of life, and incidence of treatment-related adverse events (AEs). The available evidence reported for the clinical studies assessed demonstrates sustained and effective relief of knee OA symptoms following a single injection of NASHA. In addition, an excellent biocompatibility profile is observed for NASHA as an intra-articular therapy for OA, as reflected by the low rate of AEs associated with treatment. Treatment with NASHA is an effective and safe single-injection

Suppression of glycosaminoglycan synthesis by articular cartilage, but not of hyaluronic acid synthesis by synovium, after exposure to radiation

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

Hugenberg, S.T.; Myers, S.L.; Brandt, K.D.

1989-04-01

We recently found that injection of 2 mCi of yttrium 90 (90Y; approximately 23,000 rads) into normal canine knees stimulated glycosaminoglycan (GAG) synthesis by femoral condylar cartilage. The present investigation was conducted to determine whether radiation affects cartilage metabolism directly. Rates of GAG synthesis and degradation in normal canine articular cartilage were studied following irradiation. Cultured synovium from the same knees was treated similarly, to determine the effects of irradiation on hyaluronic acid synthesis. Twenty-four hours after exposure to 1,000 rads, 10,000 rads, or 50,000 rads, 35S-GAG synthesis by the cartilage was 93%, 69%, and 37%, respectively, of that inmore » control, nonirradiated cartilage. The effect was not rapidly reversible: 120 hours after exposure to 50,000 rads, GAG synthesis remained at only 28% of the control level. Autoradiography showed marked suppression of 35S uptake by chondrocytes after irradiation. Cartilage GAG degradation was also increased following irradiation: 4 hours and 8 hours after exposure to 50,000 rads, the cartilage GAG concentration was only 66% and 54%, respectively, of that at time 0, while corresponding values for control, nonirradiated cartilage were 90% and 87%. In contrast to its effects on cartilage GAG metabolism, radiation at these levels had no effect on synovial hyaluronic acid synthesis.« less
Hyaluronic acid intra-articular injection and exercise therapy: effects on pain and disability in subjects affected by lower limb joints osteoarthritis. A systematic review by the Italian Society of Physical and Rehabilitation Medicine (SIMFER).

PubMed

Monticone, Marco; Frizziero, Antonio; Rovere, Giancarlo; Vittadini, Filippo; Uliano, Domenico; LA Bruna, Silvano; Gatto, Renato; Nava, Claudia; Leggero, Vittorio; Masiero, Stefano

2016-06-01

It is debated whether intra-articular viscosupplementation with hyaluronic acid (HA) can lead to improvements in subjects with osteoarthritis (OA) undergoing physical and rehabilitative interventions. To assess the effects of intra-articular viscosupplementation on disability in subjects with OA undergoing physical and rehabilitative interventions. Information on pain and quality of life were also collected. The databases of PubMed, Medline, EMbase and CINAHL were searched for English language full-text randomized controlled trials comparing intra-articular viscosupplementation alone or associated with physical and rehabilitative interventions to viscosupplementation alone, shame treatment, waiting lists, and any type of rehabilitative interventions. Methodological quality of each study was assessed by using the Physiotherapy Evidence Database (PEDro) Scale. A total of 115 references were retrieved, and 8 studies were selected. Three trials compared HA injection and physical therapy in knee OA, with disability and pain improvements in all studies, and between-group differences in favor of physical therapy in two studies; two trials compared HA injection and home exercises in knee OA, with improvements in pain, disability and quality of life in all studies, without between-group differences; two trials compared HA injection plus physical therapy agents and exercises to exercises plus physical therapy agents in knee OA, with improvements in disability and pain in both studies, and between-group differences in favor of the inclusion HA in one study; one trial compared HA injection and home exercises in ankle OA, with improvements in disability and pain in both arms without between-group differences. Physical therapy agents seemed to have greater effects than intra-articular viscosupplementation on disability and pain. In the other cases both intra-articular viscosupplementation and physical and rehabilitative interventions seemed to be equally effective in improving
Injection therapy for subacute and chronic low back pain: an updated Cochrane review.

PubMed

Staal, J Bart; de Bie, Rob A; de Vet, Henrica C W; Hildebrandt, Jan; Nelemans, Patty

2009-01-01

A systematic review of randomized controlled trials (RCTs). To determine if injection therapy is more effective than placebo or other treatments for patients with subacute or chronic low back pain. The effectiveness of injection therapy for low back pain is still debatable. Heterogeneity of target tissue, pharmacological agent, and dosage, generally found in RCTs, point to the need for clinically valid comparisons in a literature synthesis. We updated the search of the earlier systematic review and searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases up to March 2007 for relevant trials reported in English, French, German, Dutch, and Nordic languages. We also screened references from trials identified. RCTs on the effects of injection therapy involving epidural, facet, or local sites for subacute or chronic low back pain were included. Studies that compared the effects of intradiscal injections, prolotherapy, or ozone therapy with other treatments were excluded unless injection therapy with another pharmaceutical agent (no placebo treatment) was part of one of the treatment arms. Studies about injections in sacroiliac joints and studies evaluating the effects of epidural steroids for radicular pain were also excluded. Eighteen trials (1179 participants) were included in this review. The injection sites varied from epidural sites and facet joints (i.e. intra-articular injections, peri-articular injections and nerve blocks) to local sites (i.e. tender-and trigger points). The drugs that were studied consisted of corticosteroids, local anesthetics, and a variety of other drugs. The methodologic quality of the trials was limited with 10 of 18 trials rated as having a high methodologic quality. Statistical pooling was not possible because of clinical heterogeneity in the trials. Overall, the results indicated that there is no strong evidence for or against the use of any type of injection therapy. There is insufficient evidence to
Combination therapy with diquafosol tetrasodium and sodium hyaluronate in patients with dry eye after laser in situ keratomileusis.

PubMed

Toda, Ikuko; Ide, Takeshi; Fukumoto, Teruki; Ichihashi, Yoshiyuki; Tsubota, Kazuo

2014-03-01

To evaluate the possible advantages of combination therapy with diquafosol tetrasodium and sodium hyaluronate for dry eye after laser in situ keratomileusis (LASIK). Prospective randomized comparative trial. A total of 206 eyes of 105 patients who underwent LASIK were enrolled in this study. Patients were randomly assigned to 1 of 4 treatment groups according to the postoperative treatment: artificial tears, sodium hyaluronate, diquafosol tetrasodium, and a combination of hyaluronate and diquafosol. Questionnaire responses reflecting subjective dry eye symptoms, uncorrected and corrected visual acuity, functional visual acuity, manifest refraction, tear break-up time, fluorescein corneal staining, Schirmer test, and corneal sensitivity were examined before and 1 week and 1 month after LASIK. Distance uncorrected visual acuity was significantly better in the combination group than in the hyaluronate group 1 week and 1 month after LASIK. Near uncorrected visual acuity was significantly better in the combination group than in the artificial tear and diquafosol groups 1 week and 1 month after LASIK. Distance functional visual acuity improved significantly only in the combination group 1 month after LASIK. The Schirmer value in the combination group was significantly higher than that in the hyaluronate group at 1 month after LASIK. Subjective dry eye symptoms in the combination group improved significantly compared with those in the other groups 1 week after surgery. Our results suggest that hyaluronate and diquafosol combination therapy is beneficial for early stabilization of visual performance and improvement of subjective dry eye symptoms in patients after LASIK. Copyright © 2014 Elsevier Inc. All rights reserved.
Polymer microneedles fabricated from alginate and hyaluronate for transdermal delivery of insulin.

PubMed

Yu, Weijiang; Jiang, Guohua; Zhang, Yang; Liu, Depeng; Xu, Bin; Zhou, Junyi

2017-11-01

To reduce the inconvenient and painful of subcutaneous needle injection, the polymer microneedle patches that fabricated from modified alginate and hyaluronate were prepared for transdermal delivery of insulin. The as-prepared microneedles (MNs) exhibited excellent mechanical strength to penetrate the skin and good degradability to release loaded insulin. In vitro skin insertion capability was determined by staining with tissue-marking dye after insertion, and the real-time penetration depth was monitored using optical coherence tomography. Confocal microscopy images revealed that the rhodamine B and fluorescein isothiocyanate-labeled insulin (FITC-insulin) can gradually diffuse from the puncture sites to deeper tissue. In vivo and pharmacodynamic studies were then conducted to estimate the feasibility of the administration of insulin-loaded microneedle patches on diabetic mice for glucose regulation. The relative pharmacologic availability (RPA) and relative bioavailability (RBA) of insulin from microneedle patches were 90.5±6.8% and 92.9±7%, respectively. These results suggests the MNs developed in this study have a promising application in diabetes treatment via transdermal delivery. Copyright © 2017 Elsevier B.V. All rights reserved.
Postoperative Pain Management After Primary Total Knee Arthroplasty: The Value of Liposomal Bupivacaine.

PubMed

Sporer, Scott M; Rogers, Thea

2016-11-01

Multimodal pain protocols have been proposed to achieve improved long-acting postoperative analgesia. Controlling postoperative pain after joint arthroplasty is especially important as it relates to patient satisfaction and outcomes. The purpose of this study was to compare the postoperative pain, time to ambulation, and overall narcotic usage between patients who received either a femoral nerve block with a periarticular bupivacaine injection or a periarticular bupivacaine and extended-release liposomal bupivacaine injection after primary total knee arthroplasty. A total of 597 consecutive primary total knee arthroplasties performed between September 1, 2012 and August 31, 2014 received preoperative celecoxib, oxycodone, and transdermal scopolamine. Intraoperatively, patients either received a single-dose bupivacaine femoral nerve block along with 30-mL 0.25% bupivacaine periarticular injection (group A) or a 60-mL periarticular injection alone (20-mL liposomal bupivacaine, 30-mL 0.25% bupivacaine, and 10-mL saline; group B). The postoperative pain scores, narcotic usage, and time to ambulation were retrospectively collected from the electronic medical record. These outcomes were compared between treatment groups. There were 325 patients in group A compared with 272 in group B during the time frame. There was no difference among age, gender, race, and body mass index between the groups. Group B demonstrated a decreased need for breakthrough pain medication (16.9% vs 36.3% P < .001), decreased pain 12 hours postoperatively (3.2 vs 3.6 P < .003), and an earlier time to ambulation (29.5 hours vs 32.2 hours, P < .017). There was no difference in hospital length of stay (2.8 vs 2.6 days, P = .123). On controlling for demographic factors, patients in group B were able to ambulate 2.3 hours earlier than those in group A (coefficient = -2.3, P = .049). Liposomal bupivacaine resulted in a decrease need for breakthrough pain medication, improved pain scores at 12�
Hyaluronic Acid as a Protein Polymeric Carrier: An Overview and a Report on Human Growth Hormone.

PubMed

Mero, Anna; Campisi, Monica; Caputo, Michele; Cuppari, Christian; Rosato, Antonio; Schiavon, Oddone; Pasut, Gianfranco

2015-01-01

Hyaluronic acid (HA) is a natural polysaccharide primarily present in the vitreous humor and in cartilages where it plays a key structural role in organizing the cartilage extracellular matrix. HA is used in a wide range of applications including treatment of arthritis (as a viscosupplementation agent for joints) and in a variety of cosmetic injectable products. Its safety profile is thus well established. Thanks to its high biocompatibility and targeting properties, HA has also been investigated for use as a carrier of anticancer drugs and, recently, also of proteins. Its role in the last case is a particularly challenging one as dedicated coupling chemistries are required to preserve the protein's conformation and activity. This study focuses on the state of the art on protein HAylation. New data from our laboratory on the local delivery of specific biologics to joints will also be outlined.
Cyclic phosphatidic acid and lysophosphatidic acid induce hyaluronic acid synthesis via CREB transcription factor regulation in human skin fibroblasts.

PubMed

Maeda-Sano, Katsura; Gotoh, Mari; Morohoshi, Toshiro; Someya, Takao; Murofushi, Hiromu; Murakami-Murofushi, Kimiko

2014-09-01

Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator and an analog of the growth factor-like phospholipid lysophosphatidic acid (LPA). cPA has a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. We showed before that a metabolically stabilized cPA derivative, 2-carba-cPA, relieved osteoarthritis pathogenesis in vivo and induced hyaluronic acid synthesis in human osteoarthritis synoviocytes in vitro. This study focused on hyaluronic acid synthesis in human fibroblasts, which retain moisture and maintain health in the dermis. We investigated the effects of cPA and LPA on hyaluronic acid synthesis in human fibroblasts (NB1RGB cells). Using particle exclusion and enzyme-linked immunosorbent assays, we found that both cPA and LPA dose-dependently induced hyaluronic acid synthesis. We revealed that the expression of hyaluronan synthase 2 messenger RNA and protein is up-regulated by cPA and LPA treatment time dependently. We then characterized the signaling pathways up-regulating hyaluronic acid synthesis mediated by cPA and LPA in NB1RGB cells. Pharmacological inhibition and reporter gene assays revealed that the activation of the LPA receptor LPAR1, Gi/o protein, phosphatidylinositol-3 kinase (PI3K), extracellular-signal-regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding protein (CREB) but not nuclear factor κB induced hyaluronic acid synthesis by the treatment with cPA and LPA in NB1RGB cells. These results demonstrate for the first time that cPA and LPA induce hyaluronic acid synthesis in human skin fibroblasts mainly through the activation of LPAR1-Gi/o followed by the PI3K, ERK, and CREB signaling pathway. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
Hyaluronic acid enhances the effect of the PAMPS/PDMAAm double-network hydrogel on chondrogenic differentiation of ATDC5 cells

PubMed Central

2014-01-01

Background A double-network (DN) gel, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid) and poly-(N,N’-dimethyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. The present study investigated whether DN gel induced chondrogenic differentiation of ATDC5 cells in a maintenance medium without insulin, and whether supplementation of hyaluronic acid enhanced the chondrogenic differentiation effect of DN gel. Methods ATDC5 cells were cultured on the DN gel and the polystyrene (PS) dish in maintenance media without insulin for 21 days. Hyaluronic acid having a molecular weight of approximately 800 kDa was supplemented into the medium so that the concentration became 0.01, 0.1, or 1.0 mg/mL. The cultured cells were evaluated using immunocytochemistry for type-2 collagen and real time PCR for gene expression of type-2 collagen, aggrecan, and Sox9 at 7 and 21 days of culture. Results The cells cultured on the DN gel formed nodules and were stained with an anti-type-2 collagen antibody, and expression of type-2 collagen and aggrecan mRNA was significantly greater on the DN gel than on the PS dish surface (p < 0.05) in the hyaluronic acid-free maintenance medium. Hyaluronic acid supplementation of a high concentration (1.0 mg/mL) significantly enhanced expression of type-2 collagen and aggrecan mRNA in comparison with culture without hyaluronic acid at 21 days (p < 0.05). Conclusions The DN gel induced chondrogenic differentiation of ATDC5 cells without insulin. This effect was significantly affected by hyaluronic acid, depending on the level of concentration. There is a high possibility that hyaluronic acid plays an important role in the in vivo hyaline cartilage regeneration phenomenon induced by the DN gel. PMID:24997593
Hyaluronic acid enhances the effect of the PAMPS/PDMAAm double-network hydrogel on chondrogenic differentiation of ATDC5 cells.

PubMed

Kitamura, Nobuto; Kurokawa, Takayuki; Fukui, Takaaki; Gong, Jian P; Yasuda, Kazunori

2014-07-06

A double-network (DN) gel, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid) and poly-(N,N'-dimethyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. The present study investigated whether DN gel induced chondrogenic differentiation of ATDC5 cells in a maintenance medium without insulin, and whether supplementation of hyaluronic acid enhanced the chondrogenic differentiation effect of DN gel. ATDC5 cells were cultured on the DN gel and the polystyrene (PS) dish in maintenance media without insulin for 21 days. Hyaluronic acid having a molecular weight of approximately 800 kDa was supplemented into the medium so that the concentration became 0.01, 0.1, or 1.0 mg/mL. The cultured cells were evaluated using immunocytochemistry for type-2 collagen and real time PCR for gene expression of type-2 collagen, aggrecan, and Sox9 at 7 and 21 days of culture. The cells cultured on the DN gel formed nodules and were stained with an anti-type-2 collagen antibody, and expression of type-2 collagen and aggrecan mRNA was significantly greater on the DN gel than on the PS dish surface (p < 0.05) in the hyaluronic acid-free maintenance medium. Hyaluronic acid supplementation of a high concentration (1.0 mg/mL) significantly enhanced expression of type-2 collagen and aggrecan mRNA in comparison with culture without hyaluronic acid at 21 days (p < 0.05). The DN gel induced chondrogenic differentiation of ATDC5 cells without insulin. This effect was significantly affected by hyaluronic acid, depending on the level of concentration. There is a high possibility that hyaluronic acid plays an important role in the in vivo hyaline cartilage regeneration phenomenon induced by the DN gel.
Injection therapy for subacute and chronic low-back pain.

PubMed

Staal, J Bart; de Bie, Rob; de Vet, Henrica Cw; Hildebrandt, Jan; Nelemans, Patty

2008-07-16

The effectiveness of injection therapy for low-back pain is still debatable. Heterogeneity of target tissue, pharmacological agent and dosage generally found in randomized controlled trials (RCTs) points to the need for clinically valid comparisons in a literature synthesis. To determine if injection therapy is more effective than placebo or other treatments for patients with subacute or chronic low-back pain. We updated the search of the earlier systematic review and searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE databases from January 1999 to March 2007 for relevant trials reported in English, French, German, Dutch and Nordic languages. We also screened references from trials identified. RCTs on the effects of injection therapy involving epidural, facet or local sites for subacute or chronic low-back pain were included. Studies which compared the effects of intradiscal injections, prolotherapy or Ozone therapy with other treatments, were excluded unless injection therapy with another pharmaceutical agent (no placebo treatment) was part of one of the treatment arms. Studies about injections in sacroiliac joints and studies evaluating the effects of epidural steroids for radicular pain were also excluded. Two review authors independently assessed the quality of the trials. If study data were clinically and statistically too heterogeneous to perform a meta-analysis, we used a best evidence synthesis to summarize the results. The evidence was classified into five levels (strong, moderate, limited, conflicting or no evidence), taking into account the methodological quality of the studies. 18 trials (1179 participants) were included in this updated review. The injection sites varied from epidural sites and facet joints (i.e. intra-articular injections, peri-articular injections and nerve blocks) to local sites (i.e. tender- and trigger points). The drugs that were studied consisted of corticosteroids, local anesthetics and a variety of
Classification of Foreign Body Reactions due to Industrial Silicone Injection.

PubMed

Harlim, Ago; Kanoko, Mpu; Aisah, Siti

2018-05-02

A foreign body reaction (FBR) is a typical tissue response to a biomaterial that has been injected or implanted in human body tissue. There has been a lack of data on the classification of foreign body reaction to silicone injection, which can describe the pattern of body tissue responses to silicone. Determine the foreign body reaction to silicone injection. We modified the classification proposed by Duranti and colleagues, which has categorized a FBR to hyaluronic acid injection into a new classification of an FBR to silicone injection. A cohort study of 31 women suffering from silicone-induced granulomas on their chin was conducted. Granulomatous tissue and submental skin were stained with hematoxylin-eosin and evaluated. Our data revealed that there were at least 7 categories of FBRs to silicone injection that could be developed. Categories 1 to 4 showed inflammatory activity, and categories 5 to 8 showed tissue repair by fibrosis. Using histopathological staining, we are able to sequence the steps of body reactions to silicone injection. Initial inflammatory reaction is then replaced by fibrosis process repairing the damaged tissues. The process depends on the host immune tolerance.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Synthesis and characterization of a novel hyaluronic acid hydrogel.

PubMed

Zhao, X

2006-01-01

Hyaluronic acid (hyaluronan, HA) has many medical applications as a biomaterial. To enhance its biostability, a novel hydrogel of cross-linked hyaluronic acid was prepared using a double cross-linking process, which involves building cross-linkages between hydroxyl group pairs and carboxyl group pairs. The present study explored a number of cross-linking processes in order to obtain different degrees of cross-linking, which were evaluated by the measurement of water absorption capacity as an index of the gel network density. To gain a better understanding of the stability of the gel, the chemical structure and particularly the rheological behaviour of the cross-linked HA, which included the influences of factors, such as degree of cross-linking, HA concentration and gel particle size, were investigated. The in vitro biostability against hyaluronidase and free radical degradation was tested to show that the cross-linked hydrogel had improved resistance to in vitro hyaluronidase and free radical degradation.
Free radical scavenging properties of mannitol and its role as a constituent of hyaluronic acid fillers: a literature review.

PubMed

André, P; Villain, F

2017-08-01

Mannitol has both hydrating and antioxidant properties that make it an ideal excipient for use with hyaluronic acid (HA) fillers. This review examines the role of reactive oxygen species in the ageing process and their effects on both endogenous HA and HA products developed for aesthetic use. Evidence is presented to show that the free radical scavenging properties of mannitol provide it with a two-fold mechanism of action when combined with HA fillers: reducing the inflammation and swelling associated with the injection procedure itself, and preventing the degradation of the injected HA by free radicals. Mannitol also has a long- and well-established safety profile in both the food and pharmaceutical industry. Having established the rationale for using mannitol in combination with an HA filler, the products using this strategy are then reviewed. The addition of mannitol to HA fillers is a viable and safe option for improving both short- and long-term HA aesthetic effects. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.
Safety and effectiveness of hyaluronic acid fillers in skin of color.

PubMed

Grimes, Pearl E; Thomas, Jane A; Murphy, Diane K

2009-09-01

To assess the safety and effectiveness of hyaluronic acid (HA) fillers in skin of color. Two prospective studies followed up subjects with Fitzpatrick skin phototypes of IV, V, or VI for 24 weeks after dermal filler injections. In a double-blind, randomized study, subjects were injected with one of three high concentration (24 mg/mL) HA fillers (Juvéderm Ultra, Ultra Plus, and 30) in one nasolabial fold and Zyplast collagen in the other. In an open-label, randomized study, subjects received one of three low concentration (5.5 mg/mL) HA fillers (Hylaform, Hylaform Plus, and Captique) in both nasolabial folds. A total of 160 subjects (a subset of 439 study subjects) were randomized and treated with one of the three high concentration fillers, and 119 subjects were randomized and treated with one of the three low concentration fillers. For subjects treated with the high concentration fillers there were no occurrences of hypersensitivity or hypertrophic scarring, and no increased incidence of hyperpigmentation or hypopigmentation in non-Caucasian vs. Caucasian subjects. For subjects treated with the low concentration fillers there were no occurrences of keloid formation, hypertrophic scarring, hypopigmentation, hypersensitivity, and three instances of mild hyperpigmentation. For all of the fillers the majority of subjects maintained >/=1 point improvement in nasolabial fold severity scores through 24 weeks. All of the HA fillers were well tolerated in individuals with skin of color and demonstrated effectiveness throughout the 24 week period. Furthermore, the fillers provided smooth, natural-looking wrinkle correction in darker skin types.
Marker retention in the cochlea following injections through the round window membrane

PubMed Central

Salt, Alec N.; Sirjani, Davud B.; Hartsock, Jared J.; Gill, Ruth M.; Plontke, Stefan K.

2007-01-01

Local delivery of drugs to the inner ear is increasingly being used in both clinical and experimental studies. Although direct injection of drugs into perilymph appears to be the most promising way of administering drugs quantitatively, no studies have yet demonstrated the pharmacokinetics in perilymph following direct injections. In this study, we have investigated the retention of substance in perilymph following a single injection into the basal turn of scala tympani (ST). The substance injected was a marker, trimethylphenylammonium (TMPA) that can be detected in low concentrations with ion-selective microelectrodes. Perilymph pharmacokinetics of TMPA was assessed using sequential apical sampling to obtain perilymph for analysis. The amount of TMPA retained in perilymph was compared for different injection and sampling protocols. TMPA concentrations measured in fluid samples were close to those predicted by simulations when the injection pipette was sealed into the bony wall of ST but were systematically lower when the injection pipette was inserted through the round window membrane (RWM). In the latter condition it was estimated that over 60% of the injected TMPA was lost due to leakage of perilymph around the injection pipette at a rate estimated to be 0.09 μL/min. The effects of leakage during and after injections through the RWM were dramatically reduced when the round window niche was filled with 1% sodium hyaluronate gel before penetrating the RWM with the injection pipette. The findings demonstrate that in order to perform quantitative drug injections into perilymph, even small rates of fluid leakage at the injection site must be controlled. PMID:17662546
Three-dimensional remodeling of young Asian women's faces using 20-mg/ml smooth, highly cohesive, viscous hyaluronic acid fillers: a retrospective study of 320 patients.

PubMed

Bae, Jung Min; Lee, Dong Won

2013-09-01

Because Asian faces are generally flatter than Caucasian faces, Asian women are increasingly requesting facial volume enhancement. To clarify the effectiveness and safety of a volumizing treatment using 20-mg/mL smooth, highly cohesive, viscous hyaluronic acid fillers in young Asian women. We retrospectively reviewed 320 patients who had been treated with this filler from March 2010 to February 2012. The filler was injected in the shape of a diamond to the glabella, both malar eminences, and chin. Overall, 4 to 6 mL of filler was sufficient to enhance the volume of a face in young Asian women. Both the physicians and patients rated effectiveness on the Global Aesthetic Improvement Scale at week 4. Need for touch-up and any adverse events were also evaluated. Most patients were very satisfied with this volumizing procedure, and there were no major complications. The 20-mg/mL smooth, highly cohesive, viscous hyaluronic acid filler is an effective, well-tolerated treatment option in young Asian women wishing for a more-three-dimensional profile. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.
Development of an Injectable Calcium Phosphate/Hyaluronic Acid Microparticles System for Platelet Lysate Sustained Delivery Aiming Bone Regeneration.

PubMed

Babo, Pedro S; Santo, Vítor E; Gomes, Manuela E; Reis, Rui L

2016-11-01

Despite the biocompatibility and osteoinductive properties of calcium phosphate (CaP) cements their low biodegradability hampers full bone regeneration. Herein the incorporation of CaP cement with hyaluronic acid (HAc) microparticles loaded with platelet lysate (PL) to improve the degradability and biological performance of the cements is proposed. Cement formulations incorporating increasing weight ratios of either empty HAc microparticles or microparticles loaded with PL (10 and 20 wt%) are developed as well as cements directly incorporating PL. The direct incorporation of PL improves the mechanical properties of the plain cement, reaching values similar to native bone. Morphological analysis shows homogeneous particle distribution and high interconnectivity between the HAc microparticles. The cements incorporating PL (with or without the HAc microparticles) present a sustained release of PL proteins for up to 8 d. The sustained release of PL modulates the expression of osteogenic markers in seeded human adipose tissue derived stem cells, thus suggesting the stimulatory role of this hybrid system toward osteogenic commitment and bone regeneration applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Hyaluronic acid injection therapy for osteoarthritis of the knee: concordant efficacy and conflicting serious adverse events in two systematic reviews.

PubMed

O'Hanlon, Claire E; Newberry, Sydne J; Booth, Marika; Grant, Sean; Motala, Aneesa; Maglione, Margaret A; FitzGerald, John D; Shekelle, Paul G

2016-11-04

The prevalence of knee osteoarthritis (OA)/degenerative joint disease (DJD) is increasing in the USA. Systematic reviews of treatment efficacy and adverse events (AEs) of hyaluronic acid (HA) injections report conflicting evidence about the balance of benefits and harms. We review evidence on efficacy and AEs of intraarticular viscosupplementation with HA in older individuals with knee osteoarthritis and account for differences in these conclusions from another systematic review. We searched PubMed and eight other databases and gray literature sources from 1990 to December 12, 2014. Double-blind placebo-controlled randomized controlled trials (RCTs) reporting functional outcomes or quality-of-life; RCTs and observational studies on delay/avoidance of arthroplasty; RCTs, case reports, and large cohort studies and case series assessing safety; and systematic reviews reporting on knee pain were considered for inclusion. A standardized, pre-defined protocol was applied by two independent reviewers to screen titles and abstracts, review full text, and extract details on study design, interventions, outcomes, and quality. We compared our results with those of a prior systematic review and found them to be discrepant; our analysis of why this discrepancy occurred is the focus of this manuscript. Eighteen RCTs reported functional outcomes: pooled analysis of ten placebo-controlled, blinded trials showed a standardized mean difference of -0.23 (95 % confidence interval (CI) -0.45 to -0.01) favoring HA at 6 months. Studies reported few serious adverse events (SAEs) and no significant differences in non-serious adverse events (NSAEs) (relative risk (RR) [95 % CI] 1.03 [0.93-1.15] or SAEs (RR [95 % CI] 1.39 [0.78-2.47]). A recent prior systematic review reported similar functional outcomes, but significant SAE risk. Differences in SAE inclusion and synthesis accounted for the disparate conclusions. Trials show a small but significant effect of HA on function on which recent
Evidence based knee injections for the management of arthritis

PubMed Central

Cheng, Olivia T.; Souzdalnitski, Dmitri; Vrooman, Bruce; Cheng, Jianguo

2012-01-01

Objective Arthritis of the knee affects 46 million Americans. We aimed to determine the level of evidence of intraarticular knee injections in the management of arthritic knee pain. Methods We systematically searched PUBMED/MEDLINE and the Cochrane databases for articles published on knee injections and evaluated their level of evidence and recommendations according to established criteria. Results The evidence supports the use of intraarticular corticosteroid injections for rheumatoid arthritis (1A+ level), osteoarthritis (1A+ level), and juvenile idiopathic arthritis (2C+ level). Pain relief and functional improvement are significant for months up to one year after the injection. Triamcinolone hexacetonide offers an advantage over triamcinolone acetonide and should be the intraarticular steroid of choice (2B+ level). Intraarticular injection of hyaluronate may provide longer pain relief than steroid injection in osteoarthritis (2B+ level). It can also be effective for rheumatoid arthritis knee pain (1A+ level). However, it is only recommended for patients with significant surgical risk factors and for patients with mild radiographic disease in whom conservative treatment has failed (2B± level). Botulinum toxin Type A injection is effective in reducing arthritic knee pain (2B+ level) and so is tropisetron (2B+ level) and tanezumab (2B+ level). The new agents, such as rAAV2-TNFR:Fc, SB-210396/CE 9.1, and various radioisotopes have provided various degrees of success, but their long-term safety and efficacy remains to be determined. Conclusions We conclude that strong evidence supports the use of intraarticular knee injection as a valuable intervention in the continuum of management of arthritis between conservative treatment and knee surgeries. PMID:22621287

Clinical comparision of intravesical hyaluronic acid and hyaluronic acid-chondroitin sulphate therapy for patients with bladder pain syndrome/interstitital cystitis.

PubMed

Gülpınar, Omer; Kayış, Aytaç; Süer, Evren; Gökçe, Mehmet İlker; Güçlü, Adil Güçal; Arıkan, Nihat

2014-09-01

Patients with a history of bladder pain syndrome/interstitial cystitis (BPS/IC) and who responded poorly or unsatisfactorily with previous treatment were compared taking intravesical hyaluronic acid (HA) or hyaluronic acid-chondroitin sulphate (HA-CS). Patients were treated with intravesical instillation with 50 mL sterile sodium hyalurinic acid (Hyacyst, Syner-Med, Surrey, UK) (n = 32) and sodium hyaluronate 1.6% sodium chondroitin sulphate 2% (Ialuril, Aspire Pharma, UK) (n = 33). Intravesical instillations were performed weekly in first month, every 15 days in the second month and monthly in third and fourth months, for a total of 8 doses. Patients were evaluated using a visual analog pain scale (VAS), interstitial cystitis symptom index (ICSI), interstitial cystitis problem index (ICPI), voiding diary for frequency/nocturia, cystometric bladder capacity and voided volume at the beginning and at 6 months. All patients had a potassium sensitivity test (PST) initially. Wilcoxon and Mann-Whitney U tests were used for statistical analysis. In total, 53 patients met the study criteria. There were 30 patients in the HA-CS group (mean age: 48.47) and 23 patients in the HA group (mean age: 49.61) (p > 0.05). The initial PST was positive in 71.7% patients (38/53) overall with no difference between groups (p > 0.05). Responses for VAS, ICCS, ICPS, 24-hour frequency/nocturia statistically improved in both groups at 6 months. There was no significant difference in symptomatic improvement (p > 0.05). Eight patients had mild adverse events. HA and HA/CS instillation can be effective in BPS/IC patients who do not respond to conservative treatment. An important limitation of our study is that the HA dosage of the 2 treatment arms were different. It would be more appropriate with same HA dosage in both groups; however, there was no commercially available glycosaminoglycan (GAG) substance with same HA dosage for single and combination therapy. Large, long-term randomized studies
Comparison of peri-articular liposomal bupivacaine and standard bupivacaine for postsurgical analgesia in total knee arthroplasty: A systematic review and meta-analysis.

PubMed

Wang, Xi; Xiao, Lin; Wang, Zhiyuan; Zhao, Guanghui; Ma, Jianbing

2017-03-01

This meta-analysis aimed to compare the efficacy and safety of intraoperative peri-articular liposomal bupivacaine and standard bupivacaine in patients undergoing total knee arthroplasty. A systematic search was performed in Medline (1966-2016.9), PubMed (1966-2016.9), Embase (1980-2016.9), ScienceDirect (1985-2016.9) and the Cochrane Library. Only high-quality studies were selected. Meta-analysis was performed using Stata 11.0 software. Three randomized controlled trials (RCTs) and two non-randomized controlled trials (Non-RCTs), including 1214 patients met the inclusion criteria. The present meta-analysis indicated that there were significant differences between groups in terms of visual analogue scale (VAS) score at 24 h (SMD = -0.241, 95% CI: -0.374 to -0.108, P = 0.000), VAS score at 48 h (SMD = -0.124, 95% CI: -0.256 to 0.009, P = 0.0068), morphine equivalent consumption on POD 1 (SMD = -0.275, 95% CI: -0.398 to -0.153, P = 0.000) and incidence of nausea (RD = 0.038, 95% CI: 0.001 to 0.074, P = 0.042) and vomiting (RD = 0.38, 95% CI: 0.003 to 0.072, P = 0.032). Compared to standard bupivacaine, intraoperative peri-articular liposomal bupivacaine infiltration promotes superior pain relief and less morphine consumption after total knee arthroplasty. In addition, there were fewer side effects associated with liposomal bupivacaine infiltration. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
Hyaluronic Acid (HA) Scaffolds and Multipotent Stromal Cells (MSCs) in Regenerative Medicine.

PubMed

Prè, Elena Dai; Conti, Giamaica; Sbarbati, Andrea

2016-12-01

Traditional methods for tissue regeneration commonly used synthetic scaffolds to regenerate human tissues. However, they had several limitations, such as foreign body reactions and short time duration. In order to overcome these problems, scaffolds made of natural polymers are preferred. One of the most suitable and widely used materials to fabricate these scaffolds is hyaluronic acid. Hyaluronic acid is the primary component of the extracellular matrix of the human connective tissue. It is an ideal material for scaffolds used in tissue regeneration, thanks to its properties of biocompatibility, ease of chemical functionalization and degradability. In the last few years, especially from 2010, scientists have seen that the cell-based engineering of these natural scaffolds allows obtaining even better results in terms of tissue regeneration and the research started to grow in this direction. Multipotent stromal cells, also known as mesenchymal stem cells, plastic-adherent cells isolated from bone marrow and other mesenchymal tissues, with self-renew and multi-potency properties are ideal candidates for this aim. Normally, they are pre-seeded onto these scaffolds before their implantation in vivo. This review discusses the use of hyaluronic acid-based scaffolds together with multipotent stromal cells, as a very promising tool in regenerative medicine.
Contralateral structural femoral autograft use in treatment of an open periarticular knee fracture to perform knee arthrodesis.

PubMed

Mack, Andrew W; Helgeson, Melvin D; Tis, John E

2008-09-01

Combat-related blast injuries often cause devastating extremity trauma. We report a case of a 21-year-old male service member who sustained massive bilateral lower extremity trauma secondary to a blast injury. His orthopaedic injuries included a near traumatic disarticulation of the right knee and a left open type IIIB periarticular knee fracture with traumatic patellectomy, loss of the extensor mechanism, and segmental loss of the distal 11 cm of his femur. Definitive treatment of his injuries included a contralateral structural cortical femoral autograft which was implanted into the left knee segmental defect to facilitate knee fusion with an intramedullary knee fusion nail and a right transfemoral amputation. Radiographic evidence of solid fusion was obtained 8 months postoperatively. Currently, the patient is a community ambulator with the aid of his right lower extremity prosthetic limb and cane.
Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology.

PubMed

Saw, Khay-Yong; Anz, Adam; Merican, Shahrin; Tay, Yong-Guan; Ragavanaidu, Kunaseegaran; Jee, Caroline S Y; McGuire, David A

2011-04-01

The purpose of this study was to evaluate the quality of articular cartilage regeneration after arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous peripheral blood progenitor cells (PBPCs) in combination with hyaluronic acid (HA). Five patients underwent second-look arthroscopy with chondral core biopsy. These 5 patients are part of a larger pilot study in which 180 patients with International Cartilage Repair Society grade III and IV lesions of the knee joint underwent arthroscopic subchondral drilling followed by postoperative intra-articular injections. Continuous passive motion was used on the operated knee 2 hours per day for 4 weeks. Partial weight bearing was observed for the first 6 to 8 weeks. Autologous PBPCs were harvested 1 week after surgery. One week after surgery, 8 mL of the harvested PBPCs in combination with 2 mL of HA was injected intra-articularly into the operated knee. The remaining PBPCs were divided into vials and cryopreserved. A total of 5 weekly intra-articular injections were given. Second-look arthroscopy confirmed articular cartilage regeneration, and histologic sections showed features of hyaline cartilage. Apart from the minimal discomfort of PBPC harvesting and localized pain associated with the intra-articular injections, there were no other notable adverse reactions. Articular hyaline cartilage regeneration is possible with arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous PBPCs in combination with HA. Level IV, therapeutic case series. Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.
Predictors of the postoperative range of finger motion for comminuted periarticular metacarpal and phalangeal fractures treated with a titanium plate.

PubMed

Shimizu, Takamasa; Omokawa, Shohei; Akahane, Manabu; Murata, Keiichi; Nakano, Kenichi; Kawamura, Kenji; Tanaka, Yasuhito

2012-06-01

Plate and screw fixation was introduced for complex fractures of the hand. Several risk factors for a poor functional outcome have been identified, but there is a paucity of evidence regarding predictors of finger stiffness in difficult hand fractures. The purpose of this prospective cohort study was to identify independent prognostic factors of the postoperative total active motion (%TAM) in the treatment of metacarpal and phalangeal fractures. Seventy-two patients (62 males, 10 females; 37±15 years) with periarticular fractures involving metaphyseal comminution and displacement were evaluated at a minimum of 1 year following surgery. There were 49 phalangeal bone fractures, 30 intra-articular fractures and 20 associated soft-tissue injuries. The locations of plate placement were lateral in 42 patients and dorsal in 30. The mean duration from injury to surgery was 7.6 days (range, 0-40 days). There were eight examined variables related to patient characteristics (age, gender and hand dominance), fracture characteristics (fracture location, joint involvement and associated soft-tissue injury) and surgical variables (location of plate placement and duration from injury to surgery). Univariate and multivariate linear regression analysis were used to identify the degree to which variables affect %TAM at the final follow-up. Univariate analysis indicated moderate correlations of %TAM with fracture location, associated soft-tissue injury and age. Multiple linear regression modelling including fracture location, age and associated soft-tissue injury resulted in formulae that could account for 46.3% of the variability in %TAM: fracture location (β=-0.388, p<0.001), age (β=-0.339, p<0.001) and associated soft-tissue injury (β=-0.296, p=0.002). Phalangeal fracture, increasing age and associated soft-tissue injury were important risk factors to identify the postoperative %TAM in the treatment of comminuted periarticular metacarpal or phalangeal fracture with a titanium
The Classification and Prognosis of Periocular Complications Related to Blindness following Cosmetic Filler Injection.

PubMed

Myung, Yujin; Yim, Sangjun; Jeong, Jae Hoon; Kim, Baek-Kyu; Heo, Chan-Yeong; Baek, Rong-Min; Pak, Chang-Sik

2017-07-01

Common side effects during hyaluronic acid filler injections are typically mild and reversible, but several reports of blindness have received attention. The present study focused on orbital symptoms combined with blindness, aiming to classify affected patients and predict their disease course and prognosis. From September of 2012 to August of 2015, nine patients with vision loss after filler injection were retrospectively reviewed. Ptosis, ophthalmoplegia, and enophthalmos were recorded over a 6-month follow-up, and patients were classified into four types according to periocular symptom manifestation. Two patients were categorized as type I (blindness without ptosis or ophthalmoplegia), two patients as type II (blindness and ptosis without ophthalmoplegia), two patients as type III (blindness and ophthalmoplegia without ptosis), and three patients as type IV (blindness with ptosis and ophthalmoplegia). The present study includes previously unpublished information about orbital symptom manifestations and prognosis combined with blindness caused by retinal artery occlusion after cosmetic filler injection. Therapeutic, V.
Effects of corticosteroids and hyaluronic acid on torn rotator cuff tendons in vitro and in rats.

PubMed

Nakamura, Hidehiro; Gotoh, Masafumi; Kanazawa, Tomonoshin; Ohta, Keisuke; Nakamura, Keiichirou; Honda, Hirokazu; Ohzono, Hiroki; Shimokobe, Hisao; Mitsui, Yasuhiro; Shirachi, Isao; Okawa, Takahiro; Higuchi, Fujio; Shirahama, Masahiro; Shiba, Naoto; Matsueda, Satoko

2015-10-01

Corticosteroids (CS) or hyaluronic acid (HA) is used in subacromial injection for the conservative treatment of rotator cuff tears (RCT); this study addresses the question of how CS and HA affect the tendon tissue and fibroblasts in vitro and in rats. Cell proliferation assays were performed in human tendon fibroblasts from RCT. Rats underwent surgery to create RCT, and the surgical sites were injected with CS or HA. The rotator cuff tendons were subjected to biomechanical testing, microscopic and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), and ultrastructural analysis. Cell proliferation was significantly decreased with CS in vitro (p < 0.05). Maximal load of CS-treated tendons was significantly decreased compared with that of HA-treated tendons (p < 0.05), as well as PCNA(+) cells at 2 weeks (p < 0.05). Ultrastructural observations of the CS-treated rats detected apoptosis of tendon fibroblasts 24 h after surgery. Histological and biomechanical data 4 weeks after surgery were not significant among the three groups. Unlike HA, CS caused cell death, and inhibition of the proliferation of tendon fibroblasts, leading to a delay of tendon healing involved and a subsequent decrease of biomechanical strength at the surgical site. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Improvement in skin wrinkles using a preparation containing human growth factors and hyaluronic acid serum.

PubMed

Lee, Do Hyun; Oh, In Young; Koo, Kyo Tan; Suk, Jang Mi; Jung, Sang Wook; Park, Jin Oh; Kim, Beom Joon; Choi, Yoo Mi

2015-02-01

Skin aging is accompanied by wrinkle formation. At some sites, such as the periorbital skin, this is a relatively early phenomenon. We evaluated the anti-wrinkle effect of a preparation containing human growth factor and hyaluronic acid serum on periorbital wrinkles (crow's feet). In total, 23 Korean women (age range: 39-59 years), who were not pregnant, nursing, or undergoing any concurrent therapy, were enrolled in this study. All the patients completed an 8-week trial of twice-daily application of human growth factor and hyaluronic acid serum on the entire face. Efficacy was based on a global photodamage score, photographs, and image analysis using replicas and visiometer analysis every 4 weeks. The standard wrinkle and roughness parameters used in assessing skin by visiometer were calculated and statistically analyzed. Periorbital wrinkles were significantly improved after treatment, with improvements noted both by physician's assessment and visiometer analysis. Topical application of human growth factor and hyaluronic acid was beneficial in reducing periorbital wrinkles.
Intraarticular Injection of a Cross-Linked Sodium Hyaluronate Combined with Triamcinolone Hexacetonide (Cingal) to Provide Symptomatic Relief of Osteoarthritis of the Knee: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Trial.

PubMed

Hangody, Laszlo; Szody, Robert; Lukasik, Piotr; Zgadzaj, Wojciech; Lénárt, Endre; Dokoupilova, Eva; Bichovsk, Daniela; Berta, Agnes; Vasarhelyi, Gabor; Ficzere, Andrea; Hangody, György; Stevens, Gary; Szendroi, Miklos

2017-05-01

To evaluate the efficacy and safety of an intraarticular injection of Cingal (Anika Therapeutics, Inc., Bedford, MA) compared with Monovisc (Anika Therapeutics, Inc., Bedford, MA) or saline for the treatment of knee osteoarthritis. This multicenter, double-blind, saline-controlled clinical trial randomized subjects with knee osteoarthritis (Kellgren-Lawrence grades I-III) to a single injection of Cingal (4 mL, 88 mg hyaluronic acid [HA] plus 18 mg triamcinolone hexacetonide [TH]), Monovisc (4 mL, 88 mg HA), or saline (4 mL, 0.9%). The primary efficacy outcome was change in WOMAC (Western Ontario and McMaster Universities Arthritis Index) Pain Score through 12 weeks with Cingal versus saline. Secondary outcomes included Patient and Evaluator Global Assessments, OMERACT-OARSI Responder index, and WOMAC Total, Stiffness, and Physical Function scores through 26 weeks. A total of 368 patients were treated (Cingal, n = 149; Monovisc, n = 150; saline, n = 69). Cingal improvement from baseline was significantly greater than saline through 12 weeks ( P = 0.0099) and 26 weeks ( P = 0.0072). WOMAC Pain was reduced by 70% at 12 weeks and by 72% at 26 weeks with Cingal. Significant improvements were found in most secondary endpoints for pain and function at most time points through 26 weeks. At 1 and 3 weeks, Cingal was significantly better than Monovisc for most endpoints; Cingal and Monovisc were similar from 6 weeks through 26 weeks. A low incidence of related adverse events was reported. Cingal provides immediate and long-term relief of osteoarthritis-related pain, stiffness, and function, significant through 26 weeks compared to saline. Cingal had similar immediate advantages compared with HA alone, while showing benefit comparable to HA at 6 weeks and beyond.
Endoscopic treatment of grades IV and V vesicoureteral reflux with two bulking substances: Dextranomer hyaluronic acid copolymer versus polyacrylate polyalcohol copolymer in children.

PubMed

Kocaoglu, Canan

2016-10-01

We aimed at evaluating the efficacy and complications of two bulking substances: dextranomer/hyaluronic acid copolymer(Dx/Ha;Dexell®) versus polyacrylate polyalcohol copolymer(PPC;Vantris®) in subureteric injection treatment of children with high grades (grades IV-V) vesicoureteral reflux(VUR). Data of patients undergoing endoscopic treatment of high grade VUR (January 2009-August 2015) were retrospectively investigated. Patients with high grade VUR caused by posterior urethral valve, duplex system, paraureteral diverticula and neurogenic bladder were excluded. Classical subureteric injection method (STING) was used. Seventy-three children (45 girls and 28 boys) who had 88 refluxing renal units (RRUs) with grades IV-V VUR (n=64/n=24) underwent endoscopic treatment using Dx/Ha (n=63 RRUs) and PPC (n=25 RRUs). Mean age of patients in Dx/Ha and PPC groups were 6 (3) and 6 (3.75) year (p=0.81), and volumes of these substances given were 1.3 (1) and 1 (0.5) mL (p=0.003), respectively. Overall, for the first endoscopic injection, success rate of grades IV-V VUR per RRU was 53.9% with Dx/Ha, compared to 80% in PPC-injected group, (p=0.024). Late ureterovesical junction obstruction developed only in one patient in PPC-injected group. No ureteral obstruction was observed in Dx/Ha-injected group. Endoscopic injection of PPC resulted in significantly higher success rate, compared to Dx/Ha in subureteric injection treatment of children with high grade VUR. However, the development of late ureterovesical junction obstruction should also be taken into account in PPC injection. Copyright © 2016 Elsevier Inc. All rights reserved.
Assessment of clinical practice guideline methodology for the treatment of knee osteoarthritis with intra-articular hyaluronic acid.

PubMed

Altman, Roy D; Schemitsch, Emil; Bedi, Asheesh

2015-10-01

Clinical practice guidelines are of increasing importance in the decision making for the treatment of knee osteoarthritis. Inconsistent recommendations regarding the use of intra-articular hyaluronic acid for the treatment of knee osteoarthritis have led to confusion among treating physicians. Literature search to identify clinical practice guidelines that provide recommendations regarding the use of intra-articular hyaluronic acid treatment for knee osteoarthritis was conducted. Included guidelines were appraised using the AGREE II instrument. Guideline development methodologies, how the results were assessed, the recommendation formation, and work group composition were summarized. Overall, 10 clinical practice guidelines were identified that met our inclusion criteria. AGREE II domain scores were variable across the included guidelines. The methodology utilized across the guidelines was heterogeneous regarding the evidence inclusion criteria, analysis of evidence results, formulation of clinical practice recommendations, and work group composition. The recommendations provided by the guidelines for intra-articular hyaluronic acid treatment for knee osteoarthritis are highly inconsistent as a result of the variability in guideline methodology. Overall, 30% of the included guidelines recommended against the use of intra-articular hyaluronic acid in the treatment of knee osteoarthritis, while 30% deemed the treatment an appropriate intervention under certain scenarios. The remaining 40% of the guidelines provided either an uncertain recommendation or no recommendation at all, based on the high variability in reviewed evidence regarding efficacy and trial quality. There is a need for a standard "appropriate methodology" that is agreed upon for osteoarthritis clinical practice guidelines in order to prevent the development of conflicting recommendations for intra-articular hyaluronic acid treatment for knee osteoarthritis, and to assure that treating physicians who
Effects of topical hyaluronic acid on corneal wound healing in dogs: a pilot study.

PubMed

Gronkiewicz, Kristina M; Giuliano, Elizabeth A; Sharma, Ajay; Mohan, Rajiv R

2017-03-01

To investigate the efficacy of topical 0.2% hyaluronic acid in canine corneal ulcers in vivo. Six purpose-bred beagles were randomly assigned into two groups (three dogs/group): group A received experimental product (Optimend ™ , containing 0.2% hyaluronic acid, KineticVet ™ ); group B received control product (Optimend ™ without 0.2% hyaluronic acid and supplemented with carboxymethylcellulose). The clinical scorer was masked to product content and subject assignment. Under sedation and topical anesthesia, 6-mm axial corneal epithelial debridements were performed in the left eye. Wounded corneas received standard ulcer treatment and topical product (group A) or control product (group B) three times a day (TID) until ulcers were healed. Slit-lamp biomicroscopy was performed 6 h after wounding and then every 12 h; findings were graded according to modified McDonald-Shadduck scoring system; extraocular photography was performed after fluorescein stain application at all examination time points. Images were analyzed using NIH image j software to quantify rate of corneal epithelialization. Gelatin zymography was used to analyze matrix metalloproteinase (MMP) 2 and 9 protein expression in tears collected at set time points during the study period. No statistical differences in clinical ophthalmic examination scores, rate of corneal epithelialization, or MMP2 or MMP9 protein expression were found between groups at any tested time point. The application of 0.2% hyaluronic acid to standard ulcer medical management is well tolerated. Topical addition of the viscoelastic did not accelerate corneal wound healing compared to a topical control with similar viscosity in this study. © 2016 American College of Veterinary Ophthalmologists.
Development and characterization of crosslinked hyaluronic acid polymeric films for use in coating processes.

PubMed

Sgorla, Débora; Almeida, Andreia; Azevedo, Claudia; Bunhak, Ÿlcio Jose; Sarmento, Bruno; Cavalcanti, Osvaldo Albuquerque

2016-09-10

The aim of this work was to develop and characterize new hyaluronic acid-based responsive materials for film coating of solid dosage forms. Crosslinking of hyaluronic acid with trisodium trimetaphosphate was performed under controlled alkaline aqueous environment. The films were produced through casting process by mixing crosslinked or bare biopolymer in aqueous dispersion of ethylcellulose, at different proportions. Films were further characterized regarding morphology by scanning electron microscopy, robustness by permeation to water vapor transmission, and ability to hydrate in simulated gastric and intestinal physiological fluids. The safety and biocompatibility of films were assessed against Caco-2 and HT29-MTX intestinal cells. The permeation to water vapor transmission was favored by increasing hyaluronic acid content in the final formulation. When in simulated gastric fluid, films exhibited lower hydration ability compared to more extensive hydration in simulated intestinal fluids. Simultaneously, in simulated intestinal fluids, films partially lost weight, revealing ability for preventing drug release at gastric pH, but tailoring the release at higher intestinal pH. The physiochemical characterization suggests thermal stability of films and physical interaction between compounds of formulation. Lastly, cytotoxicity tests demonstrated that films and individual components of the formulations, when incubated for 4h, were safe for intestinal cells Overall, these evidences suggest that hyaluronic acid-based responsive films, applied as coating material of oral solid dosage forms, can prevent the premature release of drugs in harsh stomach conditions, but control the release it in gastrointestinal tract distal portion, assuring safety to intestinal mucosa. Copyright © 2016 Elsevier B.V. All rights reserved.
Systematic clinical evidence review of NASHA (Durolane hyaluronic acid) for the treatment of knee osteoarthritis

PubMed Central

Leighton, Ross; Fitzpatrick, Jane; Smith, Helen; Crandall, Daniela; Flannery, Carl R; Conrozier, Thierry

2018-01-01

Background Pain and limitations in joint mobility associated with knee osteoarthritis (OA) are clinically challenging to manage, and advanced progression of disease can often lead to total knee arthroplasty. Intra-articular injection of hyaluronic acid (HA), also referred to as viscosupplementation, is a non-surgical treatment approach for OA, the effectiveness of which may depend on the HA composition, and the length of time over which it resides in the joint. One of the available options for such therapies includes NASHA (Durolane HA), a non-animal, biofermentation-derived product, which is manufactured using a process that stabilizes the HA molecules to slow down their rate of degradation and produce a unique formulation with a terminal half-life of ~1 month. The objectives of the current review were to assess, in patients with OA of the knee, the efficacy and safety of intra-articular treatment with NASHA relative to control (saline) injections, other HA products, and other injectables (corticosteroids, platelet-rich plasma, mesenchymal stem cells). Methods This systematic evidence review examines patient outcomes following NASHA treatment as described in published data from studies conducted in subjects with knee OA. A Preferred Reporting Items for Systematic Reviews and Meta-analyses-compliant literature search strategy yielded 11 eligible clinical studies with a variety of comparator arms. Outcomes assessed at various time points following intra-articular treatment included measures of pain, function, quality of life, and incidence of treatment-related adverse events (AEs). Results The available evidence reported for the clinical studies assessed demonstrates sustained and effective relief of knee OA symptoms following a single injection of NASHA. In addition, an excellent biocompatibility profile is observed for NASHA as an intra-articular therapy for OA, as reflected by the low rate of AEs associated with treatment. Conclusion Treatment with NASHA is an
Intravenous Acetaminophen in Multimodal Pain Management for Patients Undergoing Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Murata-Ooiwa, Minako; Tsukada, Sachiyuki; Wakui, Motohiro

2017-10-01

Although multimodal pain management including periarticular multidrug injection can provide excellent pain relief in the early postoperative period after total knee arthroplasty (TKA), rebounding pain remains an important challenge. A randomized, double-blind, placebo-controlled trial was performed to investigate the efficacy of adding intravenous acetaminophen to multimodal pain management for TKA. We enrolled 67 patients scheduled for unilateral TKA. Patients were randomly assigned to receive either 1000 mg of intravenous acetaminophen at 6-hour intervals or normal saline at the same intervals. All patients were treated with intraoperative periarticular multidrug injection and intravenous and oral nonsteroidal anti-inflammatory drugs. The primary outcome was the postoperative 100-mm visual analog pain scale at the time of administration of study drugs. In the intention-to-treat analysis, the pain score was significantly better in the intravenous acetaminophen group than the placebo group at 17:00 one day after TKA (15.3 ± 17.0 mm vs 26.8 ± 19.0 mm; P = .013). There were no significant differences in terms of the rate of complications between groups. Even in the setting of multimodal pain management including periarticular multidrug injection, intravenous acetaminophen provided better pain relief for patients undergoing unilateral TKA. Copyright © 2017 Elsevier Inc. All rights reserved.
The effects of penile girth enhancement using injectable hyaluronic acid gel, a filler.

PubMed

Kwak, Tae Il; Oh, MiMi; Kim, Je Jong; Moon, Du Geon

2011-12-01

Despites the debates on penile girth enhancement (PGE), demands for enhancement are increasing. Recently, various fillers have been widely used for soft tissue augmentation with proven efficacy and safety. To identify the feasibility and efficacy of PGE by injection of filler. Fifty patients with subjective small penis who visited Korea University Guro outpatient clinic were enrolled and prospectively followed. Restylane Sub-Q (Q-med, Upssala, Sweden) was injected into the fascial layer of penile body via 21G cannula with "Back & Forth Technique" and homogenized with a roller. From April 2006 to February 2008, 50 patients were enrolled and 41 patients were followed until 18 months after PGE. Changes in penile girth at midshaft were measured by tapeline at 1 and 18 months. Patient's visual estimation of residual volume (Gr 0-4), patient's satisfaction (Gr 0-4), and any adverse reactions were also evaluated. Mean injected volume was 20.56 cc (18-22). Compared with basal girth of 7.48 ± 0.35 cm, maximal circumference was significantly increased to 11.41 ± 0.34 cm at 1 month (P < 0.0001) and maintained as 11.26 ± 0.33 cm until 18 months. In patient's visual estimation, two patients complained the decrease as Gr 3 with focal depression at 1 month. At 18 months, all patients answered as Gr 4 without asymmetry. Patient's and partner's satisfaction score was 3.71 ± 0.46 and 3.65 ± 0.48 at 1 month and 3.34 ± 0.53 and 3.38 ± 0.49 at 18 months. There were no inflammatory signs or serious adverse reactions in all cases. Considering the property of material, methods, and follow-up results of 18 months, PGE using filler is a very effective and safe technique for penile augmentation. © 2010 International Society for Sexual Medicine.
Surface modification of model hydrogel contact lenses with hyaluronic acid via thiol-ene "click" chemistry for enhancing surface characteristics.

PubMed

Korogiannaki, Myrto; Zhang, Jianfeng; Sheardown, Heather

2017-10-01

Discontinuation of contact lens wear as a result of ocular dryness and discomfort is extremely common; as many as 26% of contact lens wearers discontinue use within the first year. While patients are generally satisfied with conventional hydrogel lenses, improving on-eye comfort continues to remain a goal. Surface modification with a biomimetic, ocular friendly hydrophilic layer of a wetting agent is hypothesized to improve the interfacial interactions of the contact lens with the ocular surface. In this work, the synthesis and characterization of poly(2-hydroxyethyl methacrylate) surfaces grafted with a hydrophilic layer of hyaluronic acid are described. The immobilization reaction involved the covalent attachment of thiolated hyaluronic acid (20 kDa) on acrylated poly(2-hydroxyethyl methacrylate) via nucleophile-initiated Michael addition thiol-ene "click" chemistry. The surface chemistry of the modified surfaces was analyzed by Fourier transform infrared spectroscopy-attenuated total reflectance and X-ray photoelectron spectroscopy. The appearance of N (1s) and S (2p) peaks on the low resolution X-ray photoelectron spectroscopy spectra confirmed successful immobilization of hyaluronic acid. Grafting hyaluronic acid to the poly(2-hydroxyethyl methacrylate) surfaces decreased the contact angle, the dehydration rate, and the amount of nonspecific sorption of lysozyme and albumin in comparison to pristine hydrogel materials, suggesting the development of more wettable surfaces with improved water-retentive and antifouling properties, while maintaining optical transparency (>92%). In vitro testing also showed excellent viability of human corneal epithelial cells with the hyaluronic acid-grafted poly(2-hydroxyethyl methacrylate) surfaces. Hence, surface modification with hyaluronic acid via thiol-ene "click" chemistry could be useful in improving contact lens surface properties, potentially alleviating symptoms of contact lens related dryness and discomfort during
Appropriate Use Criteria for Hyaluronic Acid in the Treatment of Knee Osteoarthritis in the United States

PubMed Central

Bhadra, Arup K.; Altman, Roy; Dasa, Vinod; Myrick, Karen; Rosen, Jeffrey; Vad, Vijay; Vitanzo, Peter; Bruno, Michelle; Kleiner, Hillary; Just, Caryn

2016-01-01

Objective: A workgroup of clinical experts has developed an Appropriate Use Criteria (AUC) for the use of hyaluronic acid (HA) in the treatment of osteoarthritis (OA) of the knee. The increasingly broad and varied use of HA injections, lack of published clinical guidance, and limited coverage for their use has created the imperative to establish appropriateness criteria. Methods: The experts of this workgroup represent rheumatology, orthopedic surgery, physiatry, sports medicine, and nursing clinicians with substantive knowledge of intra-articular HA therapy. This workgroup utilized the results of a systematic review of evidence, expert clinical opinion, and current evidence-based clinical practice guidelines to develop appropriateness criteria for the use of intra-articular HA for knee OA in 17 real-world clinical scenarios. Results: The workgroup scored the appropriateness of treatment of each patient scenario using a 9-point scale to designate a treatment as appropriate (7-9), uncertain (4-6), or inappropriate (1-3). Six scenarios were scored as appropriate, 10 scenarios were scored as uncertain, and 1 scenario was scored as inappropriate. Conclusion: This article can assist clinicians in shared decision-making by providing best practices in considering HA injections for knee OA treatment. Moreover, this AUC article can aid payers and policy makers in determining reimbursement and preauthorization policies and more appropriately managing health care resources. It is clear that further research is still necessary—particularly in patient populations differentiated by OA severity—that may benefit the greatest from the use of HA injections for the treatment of knee OA. PMID:28618868
In vitro and in vivo gene delivery using chitosan/hyaluronic acid nanoparticles: Influences of molecular mass of hyaluronic acid and lyophilization on transfection efficiency.

PubMed

Sato, Toshinori; Nakata, Mitsuhiro; Yang, Zhihong; Torizuka, Yu; Kishimoto, Satoko; Ishihara, Masayuki

2017-08-01

Lyophilization is an effective method for preserving nonviral gene vectors. To improve the stability and transgene expression of lyophilized plasmid DNA (pDNA) complexes, we coated the surfaces of pDNA/chitosan complexes with hyaluronic acid (HA) of varying molecular masses. The transgene expression of pDNA/chitosan/HA ternary complexes was characterized in vitro and in vivo. pDNA complexes were lyophilized overnight and the resultant products with spongy, porous consistencies were stored at -30, 4 or 25°C for 2 weeks. Rehydrated complexes were characterized using gel retardation assays, aiming to confirm complex formation, measure particle size and evaluate zeta potential, as well as conduct luciferase gene reporter assays. The anti-tumor effects of pDNA ternary complexes were evaluated using suicide gene (pTK) coding thymidine kinase in Huh7-implanted mice. Transfection efficiencies of pDNA/chitosan/HA ternary complexes were dependent on the average molecular masses of HA. The coating of pDNA/chitosan complexes with HA maintained the cellular transfection efficiencies of lyophilized pDNA ternary complexes. Furthermore, intratumoral injection of lyophilized, rehydrated pDNA ternary complexes into tumor-bearing mice showed a significant suppression of tumor growth. The coating of pDNA/chitosan complexes with high-molecular-weight HA augmented the stability and cellular transfection ability of the complexes after lyophilization-rehydration. Copyright © 2017 John Wiley & Sons, Ltd.

Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys

PubMed Central

Olson, Erik J.; Lindgren, Bruce R.; Carlson, Cathy S.

2008-01-01

The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight-matched treatment groups for a 36-month treatment period. Group 1 (OVX control) received no treatment, Group 2 (SPE) received soy phytoestrogens, and Group 3 (ERT) received conjugated equine estrogens in the diet; all monkeys were labeled with calcein before necropsy. A midcoronal, plastic-embedded section of the right proximal tibia from 20 randomly selected animals per treatment group was examined histologically. Forty-nine of the sections (OVX control, n=16; SPE, n=16; ERT, n=17) contained lateral abaxial osteophytes, and static and dynamic histomorphometry measurements were taken from osteophyte bone, SCB from the lateral tibial plateau, and EMC bone. Data were analyzed using the ANOVA and Kruskal-Wallis test, correlation and regression methods, and the Friedman and Wilcoxon signed rank test. There was no significant effect of long-term ERT on osteophyte area or on any static or dynamic histomorphometry parameters. The bone volume, trabecular number, and trabecular thickness in osteophyte bone were considerably higher than in EMC bone; whereas, trabecular separation was considerably lower in osteophyte bone. In all three treatment groups, BS/BV was significantly lower in osteophyte bone vs. EMC bone and significantly higher in osteophyte bone vs. lateral SCB. We conclude that osteophyte area and static and dynamic histomorphometry parameters within periarticular tibial osteophytes in ovariectomized cynomolgus monkeys are not significantly influenced by long-term ERT, but
Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys.

PubMed

Olson, Erik J; Lindgren, Bruce R; Carlson, Cathy S

2008-05-01

The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight-matched treatment groups for a 36-month treatment period. Group 1 (OVX control) received no treatment, Group 2 (SPE) received soy phytoestrogens, and Group 3 (ERT) received conjugated equine estrogens in the diet; all monkeys were labeled with calcein before necropsy. A midcoronal, plastic-embedded section of the right proximal tibia from 20 randomly selected animals per treatment group was examined histologically. Forty-nine of the sections (OVX control, n=16; SPE, n=16; ERT, n=17) contained lateral abaxial osteophytes, and static and dynamic histomorphometry measurements were taken from osteophyte bone, SCB from the lateral tibial plateau, and EMC bone. Data were analyzed using the ANOVA and Kruskal-Wallis test, correlation and regression methods, and the Friedman and Wilcoxon signed rank test. There was no significant effect of long-term ERT on osteophyte area or on any static or dynamic histomorphometry parameters. The bone volume, trabecular number, and trabecular thickness in osteophyte bone were considerably higher than in EMC bone; whereas, trabecular separation was considerably lower in osteophyte bone. In all three treatment groups, BS/BV was significantly lower in osteophyte bone vs. EMC bone and significantly higher in osteophyte bone vs. lateral SCB. We conclude that osteophyte area and static and dynamic histomorphometry parameters within periarticular tibial osteophytes in ovariectomized cynomolgus monkeys are not significantly influenced by long-term ERT, but
Hyaluronic acid improves "pleasantness" and tolerability of nebulized hypertonic saline in a cohort of patients with cystic fibrosis.

PubMed

Buonpensiero, Paolo; De Gregorio, Fabiola; Sepe, Angela; Di Pasqua, Antonio; Ferri, Pasqualina; Siano, Maria; Terlizzi, Vito; Raia, Valeria

2010-11-01

Inhaled hypertonic saline improves lung function and decreases pulmonary exacerbations in people with cystic fibrosis. However, side effects such as cough, narrowing of airways and saltiness cause intolerance of the therapy in 8% of patients. The aim of our study was to compare the effect of an inhaled solution of hyaluronic acid and hypertonic saline with hypertonic solution alone on safety and tolerability. A total of 20 patients with cystic fibrosis aged 6 years and over received a single treatment regimen of 7% hypertonic saline solution or hypertonic solution with 0.1% hyaluronate for 2 days nonconsecutively after a washout period in an open crossover study. Cough, throat irritation, and salty taste were evaluated by a modified ordinal score for assessing tolerability; "pleasantness" was evaluated by a five-level, Likert-type scale. Forced expiratory volume in 1 second was registered before and after the end of the saline inhalations. All 20 patients (nine males, 11 females, mean age 13 years, range 8.9-17.7) completed the study. The inhaled solution of 0.1% hyaluronic acid and hypertonic saline significantly improved tolerability and pleasantness compared to hypertonic saline alone. No major adverse effects were observed. No difference was documented in pulmonary function tests between the two treatments. Hyaluronic acid combined with hypertonic saline solution may contribute to improved adherence to hypertonic saline therapy. Further clinical trials are needed to confirm our findings. Considering the extraordinary versatility of hyaluronic acid in biological reactions, perspective studies could define its applicability to halting progression of lung disease in cystic fibrosis.
Inhibition of hyaluronic acid formation sensitizes chronic myelogenous leukemia to treatment with doxorubicin.

PubMed

Uchakina, Olga N; Ban, Hao; Hostetler, Bryan J; McKallip, Robert J

2016-11-01

In the current study we examined the ability of 4-methylumbelliferone (4-MU), which can inhibit hyaluronic acid synthesis, to sensitize K562 chronic myelogenous leukemia (CML) cells to doxorubicin therapy. Exposure of K562 cells to doxorubicin led to increased hyaluronic acid synthase (HAS) gene expression and increased levels of cell surface hyaluronic acid. Furthermore, exposure of K562 cells to exogenous HA caused resistance to doxorubicin-induced cell death. The combination of low dose 4-MU and doxorubicin led to increased apoptosis when compared to higher doses of any agent alone. Additionally, treatment with 4-MU led to a significant reduction in doxorubicin-induced increase in HA cell surface expression. Mechanistically, 4-MU treatment led to an increase in p38 activation and PARP cleavage. The role of p38 in 4-MU/doxorubicin-treated K562 cells was confirmed when p38 inhibitors led to protection from 4-MU/doxorubicin-induced apoptosis. Together, results from this study suggest that treatment with 4-MU increases the sensitivity of CML to chemotherapeutics by decreasing their HA-mediated resistance to apoptosis. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
A serum-free medium for colony growth and hyaluronic acid production by Streptococcus zooepidemicus NJUST01.

PubMed

Zhang, Jianfa; Ding, Xia; Yang, Liuyan; Kong, Zhiming

2006-08-01

A hyaluronic acid (HA)-producing strain, Streptococcus zooepidemicus NJUST01, can grow in a serum-free agar medium, with starch as exclusive carbon source, but not glucose, sucrose, dextrine, xylose, or lactose. In this starch medium, the strain NJUST01 reproduced successively at 37 degrees C for 60 generations, with no obvious variation on morphology and physiology, but colonies of the strain after 60th generation could not produce a clear hemolytic zone on sheep blood agar plates. Hyaluronic acid production by the strain NJUST01 was analyzed relative to the starch medium. Employing a multifactor cross experiment, an optimum medium revealed for hyaluronic acid production was composed of 5% starch, 0.3% glucose, 0.5% peptone, 0.15% MgSO4, and 2.0% K2HPO4. The amount of HA 6.7 g/l was obtained in batch fermentation on a rotary shaker at 37 degrees C, 220 rpm for 36 h.
Temperature and magnetic field responsive hyaluronic acid particles with tunable physical and chemical properties

NASA Astrophysics Data System (ADS)

Ekici, Sema; Ilgin, Pinar; Yilmaz, Selahattin; Aktas, Nahit; Sahiner, Nurettin

2011-01-01

We report the preparation and characterization of thiolated-temperature-responsive hyaluronic acid-cysteamine-N-isopropyl acrylamide (HA-CYs-NIPAm) particles and thiolated-magnetic-responsive hyaluronic acid (HA-Fe-CYs) particles. Linear hyaluronic acid (HA) crosslinked with divinyl sulfone as HA particles was prepared using a water-in-oil micro emulsion system which were then oxidized HA-O with NaIO4 to develop aldehyde groups on the particle surface. HA-O hydrogel particles were then reacted with cysteamine (CYs) which interacted with aldehydes on the HA surface to form HA particles with cysteamine (HA-CYs) functionality on the surface. HA-CYs particles were further exposed to radical polymerization with NIPAm to obtain temperature responsive HA-CYs-NIPAm hydrogel particles. To acquire magnetic field responsive HA composites, magnetic iron particles were included in HA to form HA-Fe during HA particle preparation. HA-Fe hydrogel particles were also chemically modified. The prepared HA-CYs-NIPAm demonstrated temperature dependent size variations and phase transition temperature. HA-CYs-NIPAm and HA-Fe-CYs particles can be used as drug delivery vehicles. Sulfamethoxazole (SMZ), an antibacterial drug, was used as a model drug for temperature-induced release studies from these particles.
The equilibrium sedimentation of hyaluronic acid and of two synthetic polymers

PubMed Central

Nichol, L. W.; Ogston, A. G.; Preston, B. N.

1967-01-01

1. The method of equilibrium sedimentation has been investigated as an alternative to osmotic-pressure measurement for determining thermodynamic properties of polymer solutions at relatively high concentrations. 2. The simplifications that must be made in the theoretical treatment are discussed. 3. Measurements have been made on samples of polyethylene glycol, neutralized polymethacrylic acid and hyaluronic acid. With the first and third, values of the `non-ideality coefficients' have been obtained that agree with those obtained from osmotic measurements on the same materials. 4. Evidence has been obtained of the presence in hyaluronic acid preparations of a fraction that has either a lower degree of thermodynamic non-ideality or a higher density increment than the bulk of the sample. This fraction is not protein. ImagesFig. 3.Fig. 4.Fig. 5.Fig. 7.Fig. 8.Fig. 9.Fig. 11.Fig. 12.Fig. 13.Fig. 14. PMID:6029600
Bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels for targeted X-ray computed tomography imaging and chemotherapy of breast tumors.

PubMed

Zhu, Yaqin; Wang, Xiuxiu; Chen, Jing; Zhang, Jian; Meng, Fenghua; Deng, Chao; Cheng, Ru; Feijen, Jan; Zhong, Zhiyuan

2016-12-28

Nanotheranostics is a rapidly growing field combining disease diagnosis and therapy, which ultimately may add in the development of 'personalized medicine'. Here, we designed and developed bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted X-ray computed tomography (CT) imaging and chemotherapy of MCF-7 human breast tumors. HAI-NGs were obtained with a small size of ca. 90nm, bright green fluoresence and high serum stability from hyaluronic acid-cystamine-tetrazole and reductively degradable polyiodixanol-methacrylate via nanoprecipitation and a photo-click crosslinking reaction. Notably, paclitaxel (PTX)-loaded HAI-NGs showed a fast glutathione-responsive drug release. Confocal microscopy displayed efficient uptake of HAI-NGs by CD44 overexpressing MCF-7 cells via a receptor-mediated mechanism. MTT assays revealed that HAI-NGs were nontoxic to MCF-7 cells even at a high concentration of 1mg/mL whereas PTX-loaded HAI-NGs exhibited strong inhibition of MCF-7 cells. The in vivo pharmcokinetics, near-infrared imaging and biodistribution studies revealed that HAI-NGs significantly prolonged the blood circulation time and enhanced tumor accumulation of PTX. Interestingly, significantly enhanced CT imaging was observed for MCF-7 breast tumors in nude mice via either intratumoral or intravenous injection of HAI-NGs as compared to iodixanol. HAI-NGs fluoresence was distributed thoughout the whole tumor indicating deep tumor penetration. PTX-loaded HAI-NGs showed effective suppression of tumor growth with little systemic toxicity. HAI-NGs appear as a "smart" theranostic nanoplatform for the treatment of CD44 positive tumors. Copyright © 2016 Elsevier B.V. All rights reserved.
Hyaluronic acid fillers with cohesive polydensified matrix for soft-tissue augmentation and rejuvenation: a literature review

PubMed Central

Prasetyo, Adri D; Prager, Welf; Rubin, Mark G; Moretti, Ernesto A; Nikolis, Andreas

2016-01-01

Background Cohesive monophasic polydensified fillers show unique viscoelastic properties and variable density of hyaluronic acid, allowing for a homogeneous tissue integration and distribution of the material. Objective The aim of this paper was to review the clinical data regarding the performance, tolerability, and safety of the Belotero® fillers for soft-tissue augmentation and rejuvenation. Methods A literature search was performed up until May 31, 2015 to identify all relevant articles on Belotero® fillers (Basic/Balance, Hydro, Soft, Intense, Volume) and equivalent products (Esthélis®, Mesolis®, Fortélis®, Modélis®). Results This comprehensive review included 26 papers. Findings from three randomized controlled trials showed a greater reduction in nasolabial fold severity with Belotero® Basic/Balance than with collagen (at 8, 12, 16, and 24 weeks, n=118) and Restylane® (at 4 weeks, n=40), and higher patient satisfaction with Belotero® Intense than with Perlane® (at 2 weeks, n=20). With Belotero® Basic/Balance, an improvement of at least 1 point on the severity scale can be expected in ~80% of patients 1–6 months after injection, with an effect still visible at 8–12 months. Positive findings were also reported with Belotero® Volume (no reduction in hyaluronic acid volume at 12 months, as demonstrated by magnetic resonance imaging), Soft (improvement in the esthetic outcomes when used in a sequential approach), and Hydro (improvement in skin appearance in all patients). The most common adverse effects were mild-to-moderate erythema, edema, and hematoma, most of which were temporary. There were no reports of Tyndall effect, nodules, granulomas, or tissue necrosis. Conclusion Clinical evidence indicates sustainable esthetic effects, good safety profile, and long-term tolerability of the Belotero® fillers, particularly Belotero® Basic/Balance and Intense. PMID:27660479
Evaluation of Hyaluronic Acid Dilutions at Different Concentrations Using a Quartz Crystal Resonator (QCR) for the Potential Diagnosis of Arthritic Diseases

PubMed Central

Ahumada, Luis Armando Carvajal; González, Marco Xavier Rivera; Sandoval, Oscar Leonardo Herrera; Olmedo, José Javier Serrano

2016-01-01

The main objective of this article is to demonstrate through experimental means the capacity of the quartz crystal resonator (QCR) to characterize biological samples of aqueous dilutions of hyaluronic acid according to their viscosity and how this capacity may be useful in the potential diagnosis of arthritic diseases. The synovial fluid is viscous due to the presence of hyaluronic acid, synthesized by synovial lining cells (type B), and secreted into the synovial fluid thus making the fluid viscous. In consequence, aqueous dilutions of hyaluronic acid may be used as samples to emulate the synovial fluid. Due to the viscoelastic and pseudo-plastic behavior of hyaluronic acid, it is necessary to use the Rouse model in order to obtain viscosity values comparable with viscometer measures. A Fungilab viscometer (rheometer) was used to obtain reference measures of the viscosity in each sample in order to compare them with the QCR prototype measures. PMID:27879675
Antibody loaded collapsible hyaluronic acid hydrogels for intraocular delivery.

PubMed

Egbu, Raphael; Brocchini, Steve; Khaw, Peng T; Awwad, Sahar

2018-03-01

Injectable gels have the potential to encapsulate drugs for sustained release of protein therapeutics for use in the eye. Hyaluronic acid (HA) is a biodegradable clinically used material and poly N-isopropylacrylamide (pNIPAAM) is a stimuli responsive polymer that can display a lower critical solution temperature (LCST) at physiological conditions. Two gel systems incorporating HA were prepared in the presence of the antibody infliximab (INF): i) 1% and 5% tyramine-substituted HA (HA-Tyr) was enzymatically crosslinked in the presence of INF to form HA-Tyr-INF and ii) NIPAAM was chemically crosslinked in the presence of HA and INF with 1 and 3% poly(ethylene glycol) diacrylate (PEGDA) to form PEGDA-pNIPAAM-HA-INF. The PEGDA-pNIPAAM-HA-INF hydrogels displayed LCSTs at temperatures ranging from 31.4 ± 0.2 to 35.7 ± 0.3 °C. Although all the gels prepared were injectable, INF-loaded gels with lower crosslinking density (1% PEGDA-pNIPAAM-HA and 1% HA-Tyr) showed lower elastic (G') and viscous (G″) moduli compared to higher crosslinked gels (3% PEGDA-pNIPAAM-HA-INF and 5% HA-Tyr-INF) resulting in differences in swelling ratio (SR). Moduli may be correlated with overall stiffness of the gel. All hydrogels demonstrated sustained release of INF in a two-compartment in vitro outflow model of the human eye called the PK-Eye. The 1% PEGDA-pNIPAAM-HA-INF hydrogel displayed the slowest release (24.9 ± 0.4% INF release by day 9) in phosphate buffered saline (PBS, pH 7.4), which is a better release profile than the free drug alone (tested under the same conditions). These results suggest that PEGDA-pNIPAAM-HA has potential for the continued development of formulations to prolong the intraocular release of proteins. Copyright © 2017 Elsevier B.V. All rights reserved.
Hyaluronic acid effect on adipose-derived stem cells. Biological in vitro evaluation.

PubMed

Moreno, A; Martínez, A; Olmedillas, S; Bello, S; de Miguel, F

2015-01-01

To evaluate the in vitro effects of hyaluronic acid (HA) on adipose-derived stem cells (ASC) in order to consider the possibility of their combined used in the treatment of knee arthrosis. The ASC cells were grown both in the presence and absence of AH, and several studies were carried out: proliferation (WST8) and cell viability studies (Alamar Blue® and Trypan Blue), possible chondrogenic differentiation (collagen type 2 expression) by RT-PCR, AH receptor expression (CD44) by flow cytometry and RT-QPCR, and expression of inflammatory and anti-inflammatory factors (IL-6, TGFß, IL-10) by RT-QPCR. The number of ASC significantly increased after 7 days with HA (158±39%, p <0.05). Additionally, the cell viability of the ASC treated with HA after 1, 3, 5 and 7 days was similar to that of the control cells, being considered non-toxic. There were no changes observed in the expression of CD44 and chondrogenic differentiation. TGFß expression was not modified after AH treatment, but there was a 4-fold decrease in IL-6 expression and IL-10 expression increased up to 2-fold compared to control cells. Hyaluronic acid favours ASC proliferation without causing cellular toxicity, and inducing an anti-inflammatory profile in these cells. Hyaluronic acid appears to be a suitable vehicle for the intra-articular administration of mesenchymal stem cells. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.
Tissue Expansion Using Hyaluronic Acid Filler for Single-Stage Ear Reconstruction: A Novel Concept for Difficult Areas.

PubMed

Inbal, Amir; Lemelman, Benjamin T; Millet, Eran; Greensmith, Andrew

2017-10-16

Auricular reconstruction is one of the most challenging procedures in plastic surgery. An adequate skin envelope is essential for cartilage framework coverage, yet few good options exist without additional surgery. We propose a novel method for minimally invasive tissue expansion, using hyaluronic acid (HA) filler to allow for single-stage ear reconstruction. To introduce the novel concept of HA filler for tissue expansion in ear reconstruction, and as an alternative to traditional expansion techniques. Macrolane is a large particle HA gel developed for large volume restoration. Expansion of the non-hair-bearing mastoid skin was performed in our clinic weekly or every other week. Final expansion was completed one week prior to reconstructive surgery. Tissue from one patient's expanded pocket was sent for histological analysis. Ten patients underwent single-stage auricular reconstruction with preoperative expansion. Injection sessions ranged from 7 to 13 (mean, 9.7). Mean injected volume per session was 2.03 mL per patient, for an average total of 19.8 mL (range, 14.5-30 mL). There were no major complications. One minor complication required removal of exposed wire from the antihelix in the office. Hematoxylin and eosin stain revealed similar histology to that seen with traditional expanders. This novel expansion technique using serial HA injections allowed for optimized skin coverage in single-stage ear reconstruction. The concept of tissue expansion using HA filler is a new frontier for research that may be applicable to other arenas of reconstruction. 4. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com
Noninvasive penetration of 5 nm hyaluronic acid molecules across the epidermal barrier (in vitro) and its interaction with human skin cells.

PubMed

Nashchekina, Yu A; Raydan, M

2018-02-01

Hyaluronic acid represents one of the major components of the extracellular environment. The main challenge remains in the ability to deliver these molecules noninvasively across the skin barrier, which can be overcome by the reduction in size to an extent that allows these molecules to pass across the skin barrier. The aim of this study was to measure the penetration and bioavailability of low molecular weight hyaluronic acid to cross an epidermal barrier model. Determining the quantity of hyaluronic acid in the test solutions was carried with method of photocolorimetry analysis. Investigation of the interaction of cells with LMWHA was studied with a confocal microscope. The study showed that LMWHA is able to cross the epidermis. Most effective penetration level is during the first 6 hours reaching 75%, and then the concentration started to decline and reached the equilibrium state within the following 2 hours. Confocal laser microscopy demonstrated different distribution and behavior of these molecules among the keratinocytes and fibroblasts. Reducing the size of hyaluronic acid to 5 nm enhance their transport across the epidermal layer. The concentration of hyaluronic acid molecules was higher on the fibroblast surface in comparison to their extracellular environment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Usefulness of intra-articular botulinum toxin injections. A systematic review.

PubMed

Khenioui, Hichem; Houvenagel, Eric; Catanzariti, Jean François; Guyot, Marc Alexandre; Agnani, Olivier; Donze, Cécile

2016-03-01

Botulinum toxin is a proven and widely used treatment for numerous conditions characterized by excessive muscular contractions. Recent studies have assessed the analgesic effect of botulinum toxin in joint pain and started to unravel its mechanisms. We searched the international literature via the Medline database using the term "intraarticular botulinum toxin injection" combined with any of the following terms: "knee", "ankle", "shoulder", "osteoarthritis", "adhesive capsulitis of the shoulder". Of 16 selected articles about intraarticular botulinum toxin injections, 7 were randomized controlled trials done in patients with osteoarthritis, adhesive capsulitis of the shoulder, or chronic pain after joint replacement surgery. Proof of anti-nociceptive effects was obtained in some of these indications and the safety and tolerance profile was satisfactory. The studies are heterogeneous. The comparator was usually a glucocorticoid or a placebo; a single study used hyaluronic acid. Pain intensity was the primary outcome measure. The number of randomized trials and sample sizes are too small to provide a satisfactory level of scientific evidence or statistical power. Unanswered issues include the effective dosage and the optimal dilution and injection modalities of botulinum toxin. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.
Development and Characterization of Sodium Hyaluronate Microparticle-Based Sustained Release Formulation of Recombinant Human Growth Hormone Prepared by Spray-Drying.

PubMed

Kim, Sun J; Kim, Chan W

2016-02-01

The purpose of this study was to develop and characterize a sodium hyaluronate microparticle-based sustained release formulation of recombinant human growth hormone (SR-rhGH) prepared by spray-drying. Compared to freeze-drying, spray-dried SR-rhGH showed not only prolonged release profiles but also better particle property and injectability. The results of size-exclusion high-performance liquid chromatography showed that no aggregate was detected, and dimer was just about 2% and also did not increase with increase of inlet temperature up to 150 °C. Meanwhile, the results of reversed-phase high-performance liquid chromatography revealed that related proteins increased slightly from 4.6% at 100 °C to 6.3% at 150 °C. Thermal mapping test proved that product temperature did not become high to cause protein degradation during spray-drying because thermal energy was used for the evaporation of surface moisture of droplets. The structural characterization by peptide mapping, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and circular dichroism revealed that the primary, secondary, and tertiary structures of rhGH in SR-rhGH were highly comparable to those of reference somatropin materials. The biological characterization by rat weight gain and cell proliferation assays provided that bioactivity of SR-rhGH was equivalent to that of native hGH. These data establish that spray-dried SR-rhGH is highly stable by preserving intact rhGH and hyaluronate microparticle-based formulation by spray-drying can be an alternative delivery system for proteins. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Oil-free hyaluronic acid matrix for serial femtosecond crystallography

NASA Astrophysics Data System (ADS)

Sugahara, Michihiro; Song, Changyong; Suzuki, Mamoru; Masuda, Tetsuya; Inoue, Shigeyuki; Nakane, Takanori; Yumoto, Fumiaki; Nango, Eriko; Tanaka, Rie; Tono, Kensuke; Joti, Yasumasa; Kameshima, Takashi; Hatsui, Takaki; Yabashi, Makina; Nureki, Osamu; Numata, Keiji; Iwata, So

2016-04-01

The grease matrix was originally introduced as a microcrystal-carrier for serial femtosecond crystallography and has been expanded to applications for various types of proteins, including membrane proteins. However, the grease-based matrix has limited application for oil-sensitive proteins. Here we introduce a grease-free, water-based hyaluronic acid matrix. Applications for proteinase K and lysozyme proteins were able to produce electron density maps at 2.3-Å resolution.
Reversible Alopecia with Localized Scalp Necrosis After Accidental Embolization of the Parietal Artery with Hyaluronic Acid.

PubMed

Yang, Qing; Qiu, Lihong; Yi, Chenggang; Xue, Ping; Yu, Zhou; Ma, Xianjie; Su, Yingjun; Guo, Shuzhong

2017-06-01

Hyaluronic acid (HA) filler injection is widely used for soft-tissue augmentation. Complications associated with HA filling are not uncommon; however, HA-induced alopecia is a rarely reported complication that could result in severe secondary psychological trauma. The etiology, clinical traits, treatment strategies, outcomes, and possible reversibility of HA-induced alopecia have not been characterized. Here, we report a case in which bilateral temple injections of 6.5 mL of HA led to persistent pain over the left scalp for several days. Although the pain was relieved at day 9 after 600 U of hyaluronidase were injected in the left temple, the patient developed localized alopecia at the left temporoparietal region with central skin necrosis at day 15. After topical applications of recombinant bovine basic fibroblast growth factor gel and 2% minoxidil spay, the necrotic skin wound was healed at day 42. Hair regrowth and normal hair density were restored at day 74. Analyses of Doppler ultrasound examinations and histopathology of the skin biopsy suggested that mild ischemia of the left temporoparietal region led to reversible alopecia, while the permanent hair loss in the left parietal area was associated with severe skin ischemia. Therefore, the key to treatment would be to focus on the effective correction of severe ischemia-induced skin necrosis to prevent permanent hair loss. Level of Evidence V 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 .
Preliminary study of efficacy of hyaluronic acid on caustic esophageal burns in an experimental rat model.

PubMed

Cevik, Muazez; Demir, Tuncer; Karadag, Cetin Ali; Ketani, Muzaffer Aydin; Celik, Hakim; Kaplan, Davut Sinan; Boleken, Mehmet Emin

2013-04-01

The aim of this study was to investigate the effectiveness of hyaluronic acid on the prevention of esophageal damage and stricture formation after experimental caustic (alkaline) esophageal injury in rats. Twenty-one Wistar albino rats were randomly divided into three groups. A caustic esophageal burn was created following the Gehanno model: Group l (n=7) underwent operation, but no injury; Group 2 (n=7) was injured and left untreated; and Group 3 (n=7) was injured and treated with hyaluronic acid, first topically and then orally by gavage (2×0.3mL; 12.5mg/mL for 7days). The caustic esophageal burn was created by instilling 25% NaOH into the distal esophagus. All rats were euthanized on day 22 for evaluation. The efficacy of hyaluronic acid treatment was assessed histopathologically and biochemically via blood determination of the total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and sulfhydryl group (SH) and lipid hydroperoxidase (LOOH) levels. Statistical analyses were performed. Weight gain was significantly lower in Group 2 than in the other two groups (P<0.05). The mean stenosis index, histopathologic damage score, TAS, TOS, OSI, and SH and LOOH levels were higher in Group 2 than in the other two groups. The mean stenosis index, inflammation, TAS, SH and OSI in Group 2 were significantly different than those in the other two groups (P<0.05). Hyaluronic acid treatment is effective in treating damage and preventing strictures after caustic esophageal burn in rats. Copyright © 2013 Elsevier Inc. All rights reserved.
An Investigation on the Influence of Hyaluronic Acid on Polidocanol Foam Stability.

PubMed

Chen, An-Wei; Liu, Yi-Ran; Li, Kai; Liu, Shao-Hua

2016-01-01

Foam sclerotherapy is an effective treatment strategy for varicose veins and venous malformations. Foam stability varies according to foam composition, volume, and injection technique. To evaluate the stability of polidocanol (POL) foam with the addition of hyaluronic acid (HA). Group A: 2 mL of 1% POL + 0 mL of 1% HA + 8 mL of air; Group B: 2 mL of 1% POL + 0.05 mL of 1% HA + 8 mL of air; Group C: 2 mL of 1% POL + 0.1 mL of 1% HA + 8 mL of air. Tessari's method was used for foam generation. The half-life, or the time for a volume of foam to be reduced to half of its original volume, was used to evaluate foam stability. Five recordings were made for each group. The half-life was 142.8 (±4.32) seconds for 1% POL without the addition of HA, 310.6 (±7.53) seconds with the addition of 0.05 mL of 1% HA, and 390.4 (±13.06) seconds with the addition of 0.1 mL of 1% HA. The stability of POL foam was highly increased by the addition of small amounts of HA.

Viscosity of materials for laryngeal injection: a review of current knowledge and clinical implications.

PubMed

Lisi, Christopher; Hawkshaw, Mary J; Sataloff, Robert T

2013-01-01

Over the past several decades, researchers have sought the ideal substances for use in injection laryngoplasty. This search has inspired several basic science studies centering on the viscoelastic properties of popularly used injectables as well as of experimental substances. Unfortunately, these studies have used various techniques and different units for measuring viscosity. For clinical purposes, there has been a need for a concise compilation of these data, converted into consistent units, to permit easy comparison of the reported viscosities of various substances. The literature has been reviewed to address this need. Scholarly review. Comparable data are available for various substances, including vocal fold mucosa, subcutaneous fat, bovine dermal collagen, glutaraldehyde cross-linked collagen, polytetrafluoroethylene, and hyaluronic acid products. The values for difference substances vary widely. There appears to be a growing body of useful knowledge about viscosity of substances used for medial (vibratory margin) injection. However, decisions regarding viscosity of substances for lateral injection medialization appear to have been made without the benefit of evidence-based research. It is possible that the trend toward relatively low viscosity materials for lateral injection is based on ease of surgical use through a small needle, but that the low viscosity may adversely affect the control over the position of the injected substance. Research is needed comparing viscosity with predictability of surgical deposition of injected substances. Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.
Hyaluronic Acid Hydrogel Functionalized with Self-Assembled Micelles of Amphiphilic PEGylated Kartogenin for the Treatment of Osteoarthritis.

PubMed

Kang, Mi-Lan; Jeong, Se-Young; Im, Gun-Il

2017-07-01

Synthetic hyaluronic acid (HA) containing a covalently integrated drug is capable of releasing therapeutic molecules and is an attractive candidate for the intra-articular treatment of osteoarthritis (OA). Herein, self-assembled PEGylated kartogenin (PEG/KGN) micelles consisting of hydrophilic polyethylene glycol (PEG) and hydrophobic KGN, which has been shown to induce chondrogenesis in human mesenchymal stem cells, were prepared by covalent crosslinking. HA hydrogels containing PEG/KGN micelles (HA/PEG/KGN) were prepared by covalently bonding PEG chains to HA. The physicochemical properties of the HA/PEG/KGN conjugate gels were investigated using Fourier transform infrared spectroscopy, 1 H NMR, dynamic light scattering (DLS), and scanning electron microscopy (SEM). HA/PEG/KGN gels exhibited larger micelles in aqueous solution than PEG/KGN. SEM images of PEG/KGN micelles showed a dark core and a bright shell, whereas PEG/KGN micelles covalently integrated into HA had an irregular oval shape. Covalent integration of PEG/KGN micelles in HA hydrogels significantly reduced drug release rates and provided sustained release over a prolonged period of time. HA/PEG/KGN hydrogels were degradable enzymatically by collagenase and hyaluronidase in vitro. Injection of HA/PEG/KGN hydrogels into articular cartilage significantly suppressed the progression of OA in rats compared with free-HA hydrogel injection. These results suggest that the HA/PEG/KGN hydrogels have greater potency than free-HA hydrogels against OA as biodegradable synthetic therapeutics.
Additive Effect of preservative-free sodium hyaluronate 0.1% in treatment of dry eye syndrome with diquafosol 3% eye drops.

PubMed

Hwang, Ho Sik; Sung, Yoon-Mi; Lee, Weon Sun; Kim, Eun Chul

2014-09-01

The aim of this study was to evaluate the treatment effect of diquafosol 3% with preservative-free sodium hyaluronate 0.1% eye drops in dry eye syndrome. In total, 150 patients with dry eye syndrome were divided randomly into 3 groups. Group 1 (50 patients) was treated 4 times daily with preserved sodium hyaluronate 0.1%, group 2 (50 patients) was treated 4 times daily with diquafosol 3%, and group 3 (50 patients) was treated 4 times daily with diquafosol 3% and preservative-free sodium hyaluronate 0.1% eye drops for 3 months. Ocular surface disease index (OSDI) score, tear film break-up time, Schirmer I test, corneal fluorescein staining, and impression cytology were evaluated. There were significant improvements in the OSDI score, tear film break-up time, Schirmer I score, fluorescein and Rose Bengal staining, goblet cell density, and impression cytological findings in groups 2 and 3 compared with those for group 1 in patients with dry eye syndrome at 1, 2, and 3 months (P < 0.05). There were statistically significant improvements in the OSDI score (-8.48 ± 0.97, -5.69 ± 0.78; P = 0.02), fluorescein (-1.43 ± 0.21, -1.02 ± 0.18; P = 0.03), and Rose Bengal staining (-1.12 ± 0.26, -0.75 ± 0.12; P = 0.03), goblet cell density (89.65 ± 14.39, 70.36 ± 16.75; P = 0.03), and impression cytological findings (-0.53 ± 0.12, -0.34 ± 0.90; P = 0.01) in group 3 compared with those in group 2 at 3 months. Treatment with diquafosol 3% with preservative-free sodium hyaluronate 0.1% was more effective than diquafosol 3% monotherapy or treatment with preserved sodium hyaluronate 0.1% in dry eye syndrome. Preservative-free sodium hyaluronate 0.1% eye drops can increase the effect of diquafosol 3% in dry eye syndrome.
Hyaluronic acid: its role in voice.

PubMed

Ward, P Daniel; Thibeault, Susan L; Gray, Steven D

2002-09-01

The extracellular matrix (ECM), once regarded simply as a structural scaffold, is now recognized as an important modulator of cellular behavior and function. One component that plays a prominent role in this process is hyaluronic acid (HA)--a molecule found in many different tissues. Research into the roles of HA indicates that it plays a key role in tissue viscosity, shock absorption, and space filling. Specifically, research into the role of HA in laryngology indicates that it has profound effects on the structure and viscosity of vocal folds. This article provides an introduction to the structure and biological functions of HA and its importance in voice. In addition, an overview of the pharmaceutical applications of HA is discussed.
Product Differences in Intra-articular Hyaluronic Acids for Osteoarthritis of the Knee.

PubMed

Altman, Roy D; Bedi, Asheesh; Karlsson, Jon; Sancheti, Parag; Schemitsch, Emil

2016-08-01

Knee osteoarthritis (OA) is a common and often disabling joint disorder among adults that may result in impaired activity and daily function. A variety of treatment options are currently available and prescribed for knee OA depending on the severity of the disorder and physician preference. Intra-articular hyaluronic acid (IA-HA) injection is a treatment for knee OA that reportedly provides numerous biochemical and biological benefits, including shock absorption, chondroprotection, and anti-inflammatory effects within the knee. Clarity is needed as to whether the available IA-HA products should be considered for therapy as a group or whether there are significant differences in the products that need to be considered in treatment of OA of the knee. To determine whether there are differences in efficacy and safety with respect to intrinsic properties of available IA-HA injections for knee OA. Meta-analysis. A comprehensive literature search of the Medline, EMBASE, and PubMed databases was conducted for all existing randomized trials of IA-HA. The primary outcome measure analyzed was the mean pain score at the reported follow-up nearest to 26 weeks after injection. Pooled efficacy and safety results were recorded for subgroupings of HA product characteristics. A total of 68 studies were included for analysis. Products with an average molecular weight ≥3000 kDa provided favorable efficacy results when compared with products of an average molecular weight <3000 kDa. Products with a molecular weight ≥3000 kDa demonstrated significantly fewer discontinuations due to treatment-related adverse events than did ≤1500 kDa counterparts, while trial discontinuation rates were similar between biological fermentation-derived HA products and avian-derived HA. The results did not demonstrate a significant difference in the occurrence of effusion across molecular weight subgroups. Additionally, biological fermentation-derived HA had a significantly smaller incidence of
Safety and efficacy of bi-annual intra-articular LBSA0103 injections in patients with knee osteoarthritis.

PubMed

Lee, Jin Kyu; Choi, Chong-Hyuk; Oh, Kwang-Jun; Kyung, Hee-Soo; Yoo, Ju-Hyung; Ha, Chul-Won; Bin, Seong-Il; Kang, Seung-Baik; Kim, Myung Ku; Lee, Ju-Hong; Lee, Myung Chul

2017-11-01

The objective of this study is to assess the safety and efficacy of repeated intra-articular injection of high molecular weight hyaluronic acid (LBSA0103) at a 26-week interval, in patients with osteoarthritis of the knee. The study was an open-label, single arm, multicentre prospective trial conducted in patients with symptomatic knee osteoarthritis. The intervention consisted of two intra-articular injections of LBSA0103, with the second injection performed 26 weeks after the first injection. The primary outcome was the incidence of adverse drug reactions related to each injection. Assessment of efficacy of repeated injections in terms of maintenance of pain relief was a secondary objective of this study. Of the 185 patients screened, 174 patients received the first injection and 153 patients received both injections of LBSA0103. Nine adverse drug reactions occurred in seven patients (4.02%) after the first injection, while only one adverse drug reaction occurred (0.65%) after the second injection. As a secondary outcome measure, the improvements in the efficacy parameters including total WOMAC score and weight-bearing pain were all significant at both week 13 and 39 compared to the baseline value (P < 0.001), and improvements after the second injection were consistent with those after the initial injection of LBSA0103 (between week 26 and week 39, P < 0.001). Repeated intra-articular injection of LBSA0103 at a 26-week interval is safe without increased risk of adverse drug reactions. Additionally, LBSA0103 is effective in reduction of osteoarthritis knee pain and in maintenance of pain reduction for a 39-week period when a second injection is administered.
Histopathology of Lyme arthritis in LSH hamsters

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

Hejka, A.; Schmitz, J.L.; England, D.M.

1989-05-01

The authors studied the histopathologic evolution of arthritis in nonirradiated and irradiated hamsters infected with Borrelia burgdorferi. Nonirradiated hamsters injected in the hind paws with B. burgdorferi developed an acute inflammatory reaction involving the synovium, periarticular soft tissues, and dermis. This acute inflammatory reaction was short-lived and was replaced by a mild chronic synovitis as the number of detectable spirochetes in the synovium, periarticular soft tissues, and perineurovascular areas diminished. Exposing hamsters to radiation before inoculation with B. burgdorferi exacerbated and prolonged the acute inflammatory phase. Spirochetes also persisted longer in the periarticular soft tissues. A major histopathologic finding wasmore » destructive and erosive bone changes of the hind paws, which resulted in deformation of the joints. These studies should be helpful in defining the immune mechanism participating in the onset, progression, and resolution of Lyme arthritis.« less
Current Concepts in the Use of Small-Particle Hyaluronic Acid.

PubMed

Bertucci, Vince; Lynde, Carrie B

2015-11-01

Soft-tissue augmentation with hyaluronic acid (HA) fillers has become one of the most popular cosmetic procedures performed. HA fillers represent safe and commonly used fillers. Several different HA fillers are available. The differences lie in the manufacturing process, allowing for tailored uses. A small-particle HA with lidocaine (SP-HAL; Restylane Silk; Galderma, Uppsala, Sweden) was approved by the US Food and Drug Administration in June 2014 but has been available for many years in Canada as Restylane Fine Lines and in Europe as Restylane Vital. Relevant articles were reviewed relating to the composition, effectiveness, and safety of SP-HAL. We also discuss the author's extensive clinical experience in the use of this product in Canada. SP-HAL has demonstrated proven benefits for lip fullness, augmentation, and treatment of perioral rhytides. Although off-label in the United States, SP-HAL is also well suited for the treatment of superficial fine lines, including periorbital, forehead, marionette, and smile lines. In addition, it has also been used in the tear trough region. A novel application for SP-HAL includes use as a skinbooster with intradermal micropuncture. In this technique, small aliquots of product are injected so as to gradually rejuvenate the skin in areas such as the face and hands. Side effects of SP-HAL were generally transient and mild. The most common side effects were swelling, tenderness, bruising, pain, and redness. SP-HAL is an effective and safe HA filler with varied clinical uses.
Human Growth Factor Cream and Hyaluronic Acid Serum in Conjunction with Micro Laser Peel

PubMed Central

Katz, Bruce E.; Cohen, Joel L.; Biron, Julie

2010-01-01

The present study investigated the use of a novel hyaluronic acid serum in combination with a cream comprising a mixture of human growth factors in conjunction with the micro laser peel procedure for skin rejuvenation. After preconditioning the face with the hyaluronic acid serum followed by the cream twice daily for one month, 15 female volunteers between 35 to 65 years of age with demonstrable facial wrinkling received a micro laser peel on the entire face using an erbium-doped yttrium aluminium garnet laser. Immediately following the laser procedure, the subjects applied the test products twice daily until the second laser peel one month later. Immediately following the second procedure, the subjects reapplied the test products for another month. In the large majority of subjects, erythema or edema, crusts or erosions, and transitory stinging or burning sensations after the micro laser peel were minimal or mild when the skin was treated with the serum followed by the cream. The micro laser peel in conjunction with the test products helped to significantly improve hyperpigmentation, wrinkles, and texture as compared to before treatment. This study with the micro laser peel device demonstrated that a novel hyaluronic acid serum combined with the human growth factor cream can be successfully used for skin rejuvenation in conjunction with light-to-medium invasive laser skin treatments. PMID:21203354
Diclofenac in hyaluronic acid gel: an alternative treatment for actinic cheilitis

PubMed Central

LIMA, Giana da Silveira; da SILVA, Gabriela Ferrari; GOMES, Ana Paula Neutzling; de ARAÚJO, Lenita Maria Aver; SALUM, Fernanda Gonçalves

2010-01-01

Objective Actinic cheilitis (AC) is a precancerous lesion of the lip vermillion caused by prolonged exposure to ultraviolet light. The aim of this study was to evaluate the effect of 3% diclofenac in 2.5% hyaluronic acid gel in the treatment of AC. Methods Thirty-four patients with chronic AC were treated twice a day with topical diclofenac during a period of 30 to 180 days. The individuals were followed up every 15 days by means of clinical examination and digital photographic documentation. Results Of the 27 patients that completed the study, 12 (44%) showed complete remission of the whitish plaques and exfoliative areas, and 15 (56%) had partial remission of the clinical picture of cheilitis. The latter group was submitted to excision of the leukoplakic areas which diagnosis varied from mild to moderate epithelial dysplasia. Conclusion The results suggest a promising role for diclofenac in hyaluronic acid gel in the treatment of AC. This treatment has the advantages of not being invasive and showing few side effects. PMID:21085813
Collagen and hyaluronic acid hydrogel in water-in-oil microemulsion delivery systems.

PubMed

Kupper, Sylwia; Kłosowska-Chomiczewska, Ilona; Szumała, Patrycja

2017-11-01

The increase in skin related health issues has promoted interest in research on the efficacy of microemulsion in dermal and transdermal delivery of active ingredients. Here, we assessed the water-in-oil microemulsion capacity to incorporate two natural polymers, i.e. collagen and hyaluronic acid with low and high molecular weight. Systems were extensively characterized in terms of conductivity, phase inversion studies, droplet diameter, polydispersity index and rheological properties. The results of this research indicate that the structure and extent of water phase in microemulsions is governed by ratio and amount of surfactant mixture (sorbitan ester derivatives). However, results have also shown that collagen, depending upon the weight of the molecule and its surface activity, influence the droplet size of the microemulsions. While the hyaluronic acid, especially with high molecular weight, due to the water-binding ability and hydrogel formation alters the rheological properties of the microemulsion, thus providing viscous consistency of the formulation. Copyright © 2017 Elsevier Ltd. All rights reserved.
Co-delivery of evodiamine and rutaecarpine in a microemulsion-based hyaluronic acid hydrogel for enhanced analgesic effects on mouse pain models.

PubMed

Zhang, Yong-Tai; Li, Zhe; Zhang, Kai; Zhang, Hong-Yu; He, Ze-Hui; Xia, Qing; Zhao, Ji-Hui; Feng, Nian-Ping

2017-08-07

The aim of this study was to improve the analgesic effect of evodiamine and rutaecarpine, using a microemulsion-based hydrogel (ME-Gel) as the transdermal co-delivery vehicle, and to assess hyaluronic acid as a hydrogel matrix for microemulsion entrapment. A microemulsion was formulated with ethyl oleate as the oil core to improve the solubility of the alkaloids and was loaded into a hyaluronic acid-structured hydrogel. Permeation-enhancing effects of the microemulsion enabled evodiamine and rutaecarpine in ME-Gel to achieve 2.60- and 2.59-fold higher transdermal fluxes compared with hydrogel control (p<0.01). The hyaluronic acid hydrogel-containing microemulsion exhibited good skin biocompatibility, whereas effective ME-Gel co-delivery of evodiamine and rutaecarpine through the skin enhanced the analgesic effect in mouse pain models compared with hydrogel. Notably, evodiamine and rutaecarpine administered using ME-Gel effectively down-regulated serum levels of prostaglandin E 2 , interleukin 6, and tumor necrosis factor α in formaldehyde-induced mouse pain models, possibly reflecting the improved transdermal permeability of ME-Gel co-delivered evodiamine and rutaecarpine, particularly with hyaluronic acid as the hydrogel matrix. Copyright © 2017 Elsevier B.V. All rights reserved.
Clinical evaluation of the additive effect of diquafosol tetrasodium on sodium hyaluronate monotherapy in patients with dry eye syndrome: a prospective, randomized, multicenter study.

PubMed

Kamiya, K; Nakanishi, M; Ishii, R; Kobashi, H; Igarashi, A; Sato, N; Shimizu, K

2012-10-01

To assess the additive effect of diquafosol tetrasodium on sodium hyaluronate monotherapy in patients with dry eye syndrome. This study evaluated 64 eyes of 32 patients (age: 62.6±12.8 years (mean±SD)) in whom treatment with 0.1% sodium hyaluronate was insufficiently responsive. The eyes were randomly assigned to one of the two regimens in each patient: topical administration of sodium hyaluronate and diquafosol tetrasodium in one eye, and that of sodium hyaluronate in the other. Before treatment, and 2 and 4 weeks after treatment, we determined tear volume, tear film break-up time (BUT), fluorescein and rose bengal vital staining scores, subjective symptoms, and adverse events. We found a significant improvement in BUT (P=0.049, Dunnett test), fluorescein and rose bengal staining scores (P=0.02), and in subjective symptoms (P=0.004 for dry eye sensation, P=0.02 for pain, and P=0.02 for foreign body sensation) 4 weeks after treatment in the diquafosol eyes. On the other hand, we found no significant change in these parameters after treatment in the control eyes. In dry eyes, where sodium hyaluronate monotherapy was insufficient, diquafosol tetrasodium was effective in improving objective and subjective symptoms, suggesting its viability as an option for the additive treatment of such eyes.
Rapamycin and a hyaluronic acid-carboxymethylcellulose membrane did not lead to reduced adhesion formations in a rat abdominal adhesion model.

PubMed

Dietrich, Arne; Bouzidi, Maria; Hartwig, Thomas; Schütz, Alexander; Jonas, Sven

2012-06-01

Rapamycin, an immunosuppressive in transplant surgery, has an additional antiproliferative effect. The aim of this study was to investigate the potential protective effects of rapamycin on postoperative adhesion development. Ten rats per group underwent midline incision laparotomy and adhesion induction including bowel sutures. Therapy groups received daily intraperitoneal rapamycin injections (1.5 mg/kg body weight) for 3 weeks postoperatively. Controls were rats without any postoperative treatment, rats receiving the rapamycin solvent or a hyaluronic acid-carboxymethylcellulose membrane (Seprafilm(™)). Postoperative rapamycin application led to enhanced adhesion development and there was a higher rate of wound infections. In addition, Seprafilm(™) did not reduce adhesions, in subgroups there were even more. Rapamycin is not recommendable for perioperative immunosuppression, it enhances adhesion development and leads to a higher rate of wound infections. Surprisingly, the established Seprafilm(™) membrane led to more adhesions in our experimental setting.
Electrophoretic deposition and electrochemical behavior of novel graphene oxide-hyaluronic acid-hydroxyapatite nanocomposite coatings

NASA Astrophysics Data System (ADS)

Li, Ming; Liu, Qian; Jia, Zhaojun; Xu, Xuchen; Shi, Yuying; Cheng, Yan; Zheng, Yufeng; Xi, Tingfei; Wei, Shicheng

2013-11-01

Novel ternary graphene oxide-hyaluronic acid-hydroxyapatite (GO-HY-HA) nanocomposite coatings were prepared on Ti substrate using anodic electrophoretic deposition (EPD). Hyaluronic acid was employed as charging additive and dispersion agent during EPD. The kinetics and mechanism of the deposition, and the microstructure of the coated samples were investigated using scanning electron microscopy, X-ray diffraction, Raman spectrum, thermo-gravimetric analysis, and microscopic Fourier transform infrared analysis. The results showed that the addition of GO sheets into the HY-HA suspensions could increase the deposition rate and inhibit cracks creation and propagation in the coatings. The corrosion resistant of the resulting samples were evaluated using potentiodynamic polarization method in simulated body fluid, and the GO-HY-HA coatings could effectively improve the anti-corrosion property of the Ti substrate.
Platelet rich plasma versus hyaluronic acid in patients with hip osteoarthritis: A meta-analysis of randomized controlled trials.

PubMed

Ye, Ye; Zhou, Xiang; Mao, Shuiwei; Zhang, Jun; Lin, Bingmin

2018-05-01

This study aims to compare the efficacy of intra-articular injection of hyaluronic acid (HA) and platelet-rich plasma (PRP) for treating hip osteoarthritis (OA). We performed systematic searches in PubMed, EmBase, ScienceDirect Web of science and the Cochrane Library for relevant literature published in or before February 2018. Only randomized controlled trials (RCTs) were included. The risk of bias assessment was performed using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). We used STATA 14.0 (College Station, TX, USA) to analyze the data. A total of 287 records were identified by the initial database search. Finally, 4 RCTs were included in our study. The present meta-analysis indicated that PRP was associated with a significant reduction of VAS score at 2 months compared with HA. However, it did not show significantly better outcomes at 6 and 12 months. There was no significant difference regarding the WOMAC and HHS at a 12-month follow up. No increased risk of adverse effects were observed. Intra-articular injection of PRP was associated with a significant reduction of VAS at 2 months. Both of them showed comparable results in terms of functional recovery. Further studies were still necessary. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
Comparison of the Hyaluronic Acid Vaginal Cream and Conjugated Estrogen Used in Treatment of Vaginal Atrophy of Menopause Women: A Randomized Controlled Clinical Trial

PubMed Central

Jokar, Azam; Davari, Tayebe; Asadi, Nasrin; Ahmadi, Fateme; Foruhari, Sedighe

2016-01-01

Background: Vaginal atrophy is a common complication in menopause which does not improve with time and, if untreated, can affect the quality of life for women. The aim of this study was to compare the effectiveness of the vaginal cream of hyaluronic acid and conjugated estrogen (Premarin) in treatment of vaginal atrophy. Methods: This study was a randomized controlled clinical trial on 56 menopausal women with symptoms of vaginal atrophy; they were randomly allocated to two groups (recipient conjugated estrogen and hyaluronic acid). The severity of each sign of atrophy was evaluated by visual analog signals (VAS) and on the basis of a four point scale. Also to recognize the cellular maturation with pap smear and the maturation degree were calculated according to the formula and scores 0-100. As to the vaginal PH, we used PH marker band, the rate of which was divided into 4 degrees. Data were analyzed using SPSS, version 20, and P≤0.05 was considered as significant. Results: The results of this study showed that the symptoms of vaginal atrophy compared with the baseline level were relieved significantly in both groups. Dryness, itching, maturation index, PH and composite score of the vaginal symptoms were relieved significantly in both groups (P<0.001). Dyspareunia in Premarin (P<0.05) and hyaluronic acid (P<0.001) decreased compared with pre-treatment. Urinary incontinence only showed improvement in the hyaluronic acid group (P<0.05). Improvement in urinary incontinence, dryness, maturation index (P<0.05) and composite score of vaginal symptoms (P<0.001) in the hyaluronic acid group was better than those in the Premarin group. Conclusion: According to the results of the present study, hyaluronic acid and conjugated estrogen improved the symptoms of vaginal atrophy. But hyaluronic acid was more effective and this drug is suggested for those who do not want to or cannot take local hormone treatment. Trial Registration Number: IRCT2013022712644N1 PMID:26793732
Comparison of the Hyaluronic Acid Vaginal Cream and Conjugated Estrogen Used in Treatment of Vaginal Atrophy of Menopause Women: A Randomized Controlled Clinical Trial.

PubMed

Jokar, Azam; Davari, Tayebe; Asadi, Nasrin; Ahmadi, Fateme; Foruhari, Sedighe

2016-01-01

Vaginal atrophy is a common complication in menopause which does not improve with time and, if untreated, can affect the quality of life for women. The aim of this study was to compare the effectiveness of the vaginal cream of hyaluronic acid and conjugated estrogen (Premarin) in treatment of vaginal atrophy. This study was a randomized controlled clinical trial on 56 menopausal women with symptoms of vaginal atrophy; they were randomly allocated to two groups (recipient conjugated estrogen and hyaluronic acid). The severity of each sign of atrophy was evaluated by visual analog signals (VAS) and on the basis of a four point scale. Also to recognize the cellular maturation with pap smear and the maturation degree were calculated according to the formula and scores 0-100. As to the vaginal PH, we used PH marker band, the rate of which was divided into 4 degrees. Data were analyzed using SPSS, version 20, and P≤0.05 was considered as significant. The results of this study showed that the symptoms of vaginal atrophy compared with the baseline level were relieved significantly in both groups. Dryness, itching, maturation index, PH and composite score of the vaginal symptoms were relieved significantly in both groups (P<0.001). Dyspareunia in Premarin (P<0.05) and hyaluronic acid (P<0.001) decreased compared with pre-treatment. Urinary incontinence only showed improvement in the hyaluronic acid group (P<0.05). Improvement in urinary incontinence, dryness, maturation index (P<0.05) and composite score of vaginal symptoms (P<0.001) in the hyaluronic acid group was better than those in the Premarin group. According to the results of the present study, hyaluronic acid and conjugated estrogen improved the symptoms of vaginal atrophy. But hyaluronic acid was more effective and this drug is suggested for those who do not want to or cannot take local hormone treatment. IRCT2013022712644N1.
Novel hyaluronic acid dermal filler: dermal gel extra physical properties and clinical outcomes.

PubMed

Monheit, Gary D; Baumann, Leslie S; Gold, Michael H; Goldberg, David J; Goldman, Mitchel P; Narins, Rhoda S; Bachtell, Nathan; Garcia, Emily; Kablik, Jeffrey; Gershkovich, Julia; Burkholder, David

2010-11-01

Dermal gel extra (DGE) is a new, tightly cross-linked hyaluronic acid (HA)-based dermal filler containing lidocaine engineered to resist gel deformation and degradation. To develop a firmer gel product (DGE) and compare the efficacy and safety of DGE with nonanimal stabilized HA (NASHA) for correction of nasolabial folds (NLFs). DGE physical properties were characterized, and 140 subjects with moderate to deep NLFs were treated with DGE and NASHA in a randomized, multicenter, split-face design study. Efficacy, pain, and satisfaction were measured using appropriate standard instruments. Adverse events were monitored throughout the study. DGE has a higher modulus and a higher gel:fluid ratio than other HA fillers. Similar optimal correction was observed with DGE and NASHA through 36 weeks (9 months). Study subjects required less volume (p<.001) and fewer touch-ups (p=.005) and reported less injection pain (p<.001) with DGE treatment. Most adverse events were mild to moderate skin reactions. DGE is a firm HA gel that required significantly less volume and fewer touch-ups to provide equivalent efficacy to NASHA for NLF correction; both dermal gels were well tolerated. DGE will provide a comfortable and cost-effective dermal filler option for clinicians and patients. © 2010 by the American Society for Dermatologic Surgery, Inc.
A nonfouling voltammetric immunosensor for the carcinoembryonic antigen based on the use of polyaniline nanowires wrapped with hyaluronic acid.

PubMed

Wang, Jiasheng; Hui, Ni

2018-06-16

A non-fouling electrochemical immunosensor is described for determination of the tumor biomarker carcinoembryonic antigen (CEA). It is based on the use of composite wires made by chemical grafting of hyaluronic acid onto polyaniline nanowires. The modified nanowires possess excellent antifouling property both in single protein solutions and in dilute serum samples. The current of immunoelectrode exhibits a linear response in the 0.01 pg mL -1 to 10,000 pg mL -1 CEA concentration range and 0.0075 pg mL -1 detection limit. This work demonstrates that coating an electrode with hyaluronic acid can largely reduce unspecific adsorption of proteins on the electrode surface. Graphical abstract Schematic of a nonfouling electrochemical immunosensor for the carcinoembryonic antigen. It is based on novel composite wires made through the chemical grafting of easily available hyaluronic acid (HA) onto polyaniline (PANI) nanowires. The HA/PANI demonstrated excellent antifouling property both in single protein solutions and human serum samples.

Ultrasound-mediated nanoparticle delivery across ex vivo bovine retina after intravitreal injection.

PubMed

Huang, Di; Chen, Ying-Shan; Thakur, Sachin S; Rupenthal, Ilva D

2017-10-01

Intravitreal injection is the most common administration route for the treatment of retinal diseases. However, the vitreous and some of the retinal layers themselves act as significant barriers to efficient delivery of drugs administered intravitreally. This study aimed to improve the diffusive mobility of nanoparticles (NPs) in the vitreous and enhance their permeation across the retina after intravitreal injection by application of ultrasound (US). Ex vivo posterior bovine eye cups were used and the vitreous was either left intact or removed gently from the neural retina. Hyaluronic acid coated human serum albumin NPs were administered into the eye cups and continuous US with a frequency of 1MHz, an intensity of 0.5W/cm 2 , and a duration of 30s was applied once or repeatedly via the transscleral route. After pre-determined time points, fluorescence intensities in the vitreous and the retina were analyzed. Short pulses of US significantly improved the diffusive mobility of NPs through the vitreous as well as their penetration across the neural retina into the retinal pigment epithelium and choroid without causing any detectable damage to the ocular tissues. Therefore, transscleral US could be a powerful and safe tool to enhance retinal delivery of intravitreally injected NPs. Copyright © 2017 Elsevier B.V. All rights reserved.
The effect of actinoquinol with hyaluronic acid in eye drops on the optical properties and oxidative damage of the rabbit cornea irradiated with UVB rays.

PubMed

Čejka, Čestmír; Luyckx, Jacques; Ardan, Taras; Pláteník, Jan; Širc, Jakub; Michálek, Jiří; Čejková, Jitka

2010-01-01

Irradiation of the cornea with UVB rays leads to its oxidative damage, swelling and increased light absorption. We investigated changes in the corneal optics (evaluated by changes of corneal hydration and light absorption) and microscopical disturbances of corneas irradiated with UVB rays as influenced by eye drops containing actinoquinol with hyaluronic acid. Rabbit corneas were irradiated with a daily dose of 0.5 or 1.01 J cm(-2) of UVB rays (312 nm) for 4 days. During irradiation, the eye drops were applied on the right eye and buffered saline (or hyaluronic acid) on the left eye. On day 5 the rabbits were sacrificed and the corneas examined spectrophotometrically for light absorption. The corneal thickness (hydration) was measured using a pachymeter. Corneas of some other rabbits were examined immunohistochemically. After buffered saline treatment UVB rays evoked changes in the corneal optics and induced oxidative damage of the corneas. After actinoquinol-hyaluronic acid application, these changes were diminished. Hyaluronic acid alone was less effective. In conclusion, actinoquinol-hyaluronic acid eye drops decreased changes in corneal optics and suppressed oxidative damage in the UVB-irradiated cornea. However, the effective corneal protection by these eye drops was limited to the lower UVB dose. © 2010 The Authors. Journal Compilation. The American Society of Photobiology.
APRI test and hyaluronic acid as non-invasive diagnostic tools for post HCV liver fibrosis: Systematic review and meta-analysis.

PubMed

El Serafy, Magdy Amin; Kassem, Abdel Meguid; Omar, Heba; Mahfouz, Mohammad Shaaban; El Said El Raziky, Maissa

2017-06-01

Hepatitis C virus (HCV) accounts for a sizable proportion of chronic liver disease cases and represents the most common indication for liver transplantation. Precise diagnosis of hepatic fibrosis stage is considered a funnel-neck in proper management and follow-up of HCV-infected patients. Given the possible complications of liver biopsy, a non-invasive method for assessing hepatic fibrosis is needed. This study aimed to evaluate the diagnostic accuracy of APRI and hyaluronic acid as non-invasive diagnostic assessment tools for post HCV liver fibrosis. Systematic literature searching identified studies performed on Egyptian territory to evaluate APRI and hyaluronic acid as non-invasive tests of fibrosis and using liver biopsy as the reference standard. Meta-analysis was performed for areas with an adequate number of publications. Validation of meta- analysis on APRI was done on a subset of 150 treatment-naïve post-hepatitis C patients. Both APRI and hyaluronic acid have superior predictive power for hepatic cirrhosis (F4) than for significant fibrosis (F2-F3). The pooled estimate for sensitivities and specificities of APRI and hyaluronic acid to diagnose F4 were (84% and 82%) and (83% and 89%) respectively. In the subgroup of treatment naïve post-hepatitis C patients, APRI had higher diagnostic performance to diagnose liver cirrhosis with 93.8% sensitivity and 72.4% specificity (AUC; 0.908, 95%CI; 0.851-0.965, p-value; <0.001) compared to its accuracy to diagnose significant hepatic fibrosis with 65.1% sensitivity and 77.8% (AUC; 0.685, 95% CI; 0.59-0.78, p-value; 0.001). APRI score and hyaluronic acid levels are simple and reliable non-invasive markers to detect advanced fibrosis among post-hepatitis C patients. Copyright © 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Hyaluronic acid, an efficient biomacromolecule for treatment of inflammatory skin and joint diseases: A review of recent developments and critical appraisal of preclinical and clinical investigations.

PubMed

Chen, Li Hui; Xue, Jian Feng; Zheng, Zhi Yong; Shuhaidi, Muhammad; Thu, Hnin Ei; Hussain, Zahid

2018-05-18

Hyaluronic acid (HA) plays multifaceted role in regulating various biological processes and maintaining homeostasis into the body. Numerous researches evidenced the biomedical implications of HA in skin repairmen, cancer prognosis, wound healing, tissue regeneration, anti-inflammatory, immunomodulation. The present review was aimed to summarize and critically appraise the recent developments and efficacy of HA for treatment of inflammatory skin and joint diseases. A thorough analysis of the literature revealed that HA based formulations (i.e., gels, creams, autologous graft, thin sheets, soaked gauze, gauze pad, tincture, injection) have shown remarkable efficacy in treating a wide range of inflammatory skin diseases. The safety, tolerability, and efficacy of HA (as intra-articular injection) have also been well-documented for treatment of various types of joint disease including knee osteoarthritic, joint osteoarthritis, canine osteoarthritis, and meniscal swelling. Intra-articular injection of HA produces remarkable reduction in joint pain, synovial inflammation, and articular swelling. A remarkable improvement in chondrocyte density, territorial matrix appearance, reconstitution of superficial amorphous layer of the cartilage, collagen remodelling, and regeneration of meniscus have also been evident in patients treated with HA. Conclusively, we validate that the application/administration of HA is a promising pharmacotherapeutic regimen for treatment of inflammatory skin and joint diseases. Copyright © 2018. Published by Elsevier B.V.
Computed tomography scan to detect traumatic arthrotomies and identify periarticular wounds not requiring surgical intervention: an improvement over the saline load test.

PubMed

Konda, Sanjit R; Davidovitch, Roy I; Egol, Kenneth A

2013-09-01

To report our experience with computed tomography (CT) scans to detect traumatic arthrotomies of the knee (TAK) joint based on the presence of intra-articular air. Retrospective review. Level I trauma center. Sixty-two consecutive patients (63 knees) underwent a CT scan of the knee in the emergency department and had a minimum of 14 days follow-up. Cohort of 37 patients (37 knees) from the original 62 patients who underwent a saline load test (SLT). CT scan and SLT. Positive traumatic arthrotomy of the knee (+TAK) was defined as operating room (OR) confirmation of an arthrotomy or no intra-articular air on CT scan (-iaCT) (and -SLT if performed) with follow-up revealing a septic knee. Periarticular wound equivalent to no traumatic arthrotomy (pw = (-TAK)) was defined as OR evaluation revealing no arthrotomy or -iaCT (and -SLT if performed) with follow-up revealing no septic knee. All 32 knees with intra-articular air on CT scan (+iaCT) had OR confirmation of a TAK and none of these patients had a knee infection at a mean follow-up of 140.0 ± 279.6 days. None of the 31 patients with -iaCT had a knee infection at a mean follow-up of 291.0 ± 548.1 days. Based on these results, the sensitivity and specificity of the CT scan to detect +TAK and pw = (-TAK) was 100%. In a subgroup of 37 patients that received both a CT scan and the conventional SLT, the sensitivity and specificity of the CT scan was 100% compared with 92% for the SLT (P < 0.001). CT scan performs better than the conventional SLT to detect traumatic knee arthrotomies and identify periarticular knee wounds that do not require surgical intervention and should be considered a valid diagnostic test in the appropriate clinical setting. Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Hyaluronic Acid Surface Modified Liposomes Prepared via Orthogonal Aminoxy Coupling: Synthesis of Nontoxic Aminoxylipids Based on Symmetrically α-Branched Fatty Acids, Preparation of Liposomes by Microfluidic Mixing, and Targeting to Cancer Cells Expressing CD44.

PubMed

Bartheldyová, Eliška; Effenberg, Roman; Mašek, Josef; Procházka, Lubomír; Knötigová, Pavlína Turánek; Kulich, Pavel; Hubatka, František; Velínská, Kamila; Zelníčková, Jaroslava; Zouharová, Darina; Fojtíková, Martina; Hrebík, Dominik; Plevka, Pavel; Mikulík, Robert; Miller, Andrew D; Macaulay, Stuart; Zyka, Daniel; Drož, Ladislav; Raška, Milan; Ledvina, Miroslav; Turánek, Jaroslav

2018-06-25

New synthetic aminoxy lipids are designed and synthesized as building blocks for the formulation of functionalized nanoliposomes by microfluidization using a NanoAssemblr. Orthogonal binding of hyaluronic acid onto the outer surface of functionalized nanoliposomes via aminoxy coupling ( N-oxy ligation) is achieved at hemiacetal function of hyaluronic acid and the structure of hyaluronic acid-liposomes is visualized by transmission electron microscopy and cryotransmission electron microscopy. Observed structures are in a good correlation with data obtained by dynamic light scattering (size and ζ-potential). In vitro experiments on cell lines expressing CD44 receptors demonstrate selective internalization of fluorochrome-labeled hyaluronic acid-liposomes, while cells with down regulated CD44 receptor levels exhibit very low internalization of hyaluronic acid-liposomes. A method based on microfluidization mixing was developed for preparation of monodispersive unilamellar liposomes containing aminoxy lipids and orthogonal binding of hyaluronic acid onto the liposomal surface was demonstrated. These hyaluronic acid-liposomes represent a potentially new drug delivery platform for CD44-targeted anticancer drugs as well as for immunotherapeutics and vaccines.
Engineering S. equi subsp. zooepidemicus towards concurrent production of hyaluronic acid and chondroitin biopolymers of biomedical interest.

PubMed

Cimini, Donatella; Iacono, Ileana Dello; Carlino, Elisabetta; Finamore, Rosario; Restaino, Odile F; Diana, Paola; Bedini, Emiliano; Schiraldi, Chiara

2017-12-01

Glycosaminoglycans, such as hyaluronic acid and chondroitin sulphate, are not only more and more required as main ingredients in cosmeceutical and nutraceutical preparations, but also as active principles in medical devices and pharmaceutical products. However, while biotechnological production of hyaluronic acid is industrially established through fermentation of Streptococcus spp. and recently Bacillus subtilis, biotechnological chondroitin is not yet on the market. A non-hemolytic and hyaluronidase negative S. equi subsp. zooepidemicus mutant strain was engineered in this work by the addition of two E. coli K4 genes, namely kfoA and kfoC, involved in the biosynthesis of chondroitin-like polysaccharide. Chondroitin is the precursor of chondroitin sulphate, a nutraceutical present on the market as anti-arthritic drug, that is lately being studied for its intrinsic bioactivity. In small scale bioreactor batch experiments the production of about 1.46 ± 0.38 g/L hyaluronic acid and 300 ± 28 mg/L of chondroitin with an average molecular weight of 1750 and 25 kDa, respectively, was demonstrated, providing an approach to the concurrent production of both biopolymers in a single fermentation.
Hyaluronic Acid and Its Composites as a Local Antimicrobial/Antiadhesive Barrier

PubMed Central

Romanò, C.L.; De Vecchi, E.; Bortolin, M.; Morelli, I.; Drago, L.

2017-01-01

Living in biofilms is probably the most common condition for bacteria and fungi and biofilm-related infections account for the majority of bacterial infectious diseases worldwide. Among others biofilm-related infections, those associated with implanted biomaterials have an enormous and still largely underestimated impact in orthopaedics and trauma, cardio-surgery and several other surgical disciplines. Given the limited efficacy of existing antibiotics in the prevention and treatment of bacterial biofilms, new strategies are needed to protect implants and host tissues, overcoming the striking ability of the microorganisms to adhere on different surfaces and to immediately protect themselves by forming the biofilm matrix. Adhesion is a necessary first step in microbial colonization and pathogenesis and provides a potential target for new preventive and treatment approach. Among various polymers, tested as antibacterial coatings, hyaluronic acid and some of its composites do offer a well-established long-term safety profile and a proven ability to reduce bacterial adhesion and biofilm formation. Aim of the present review is to summarize the available evidence concerning the antiadhesion/antibiofilm activity of hyaluronic acid and some of its derivatives to reduce/prevent bacterial adhesion and biofilm formation in various experimental and clinical settings. PMID:28529865
An In Vivo Study of Composite Microgels Based on Hyaluronic Acid and Gelatin for the Reconstruction of Surgically Injured Rat Vocal Folds

PubMed Central

Coppoolse, Jiska M. S.; Van Kooten, T. G.; Heris, Hossein K.; Mongeau, Luc; Li, Nicole Y. K.; Thibeault, Susan L.; Pitaro, Jacob; Akinpelu, Olubunmi; Daniel, Sam J.

2016-01-01

Purpose The objective of this study was to investigate local injection with a hierarchically microstructured hyaluronic acid–gelatin (HA-Ge) hydrogel for the treatment of acute vocal fold injury using a rat model. Method Vocal fold stripping was performed unilaterally in 108 Sprague-Dawley rats. A volume of 25 ml saline (placebo controls), HA-bulk, or HA-Ge hydrogel was injected into the lamina propria (LP) 5 days after surgery. The vocal folds were harvested at 3, 14, and 28 days after injection and analyzed using hematoxylin and eosin staining and immunohistochemistry staining for macrophages, myofibroblasts, elastin, collagen type I, and collagen type III. Results The macrophage count was statistically significantly lower in the HA-Ge group than in the saline group (p < .05) at Day 28. Results suggested that the HA-Ge injection did not induce inflammatory or rejection response. Myofibroblast counts and elastin were statistically insignificant across treatment groups at all time points. Increased elastin deposition was qualitatively observed in both HA groups from Day 3 to Day 28, and not in the saline group. Significantly more elastin was observed in the HA-bulk group than in the uninjured group at Day 28. Significantly more collagen type I was observed in the HA-bulk and HA-Ge groups than in the saline group (p < .05) at Day 28. The collagen type I concentration in the HA-Ge and saline groups was found to be comparable to that in the uninjured controls at Day 28. The concentration of collagen type III in all treatment groups was similar to that in uninjured controls at Day 28. Conclusion Local HA-Ge and HA-bulk injections for acute injured vocal folds were biocompatible and did not induce adverse response. PMID:24687141
A randomized controlled experimental study of the efficacy of platelet-rich plasma and hyaluronic acid for the prevention of adhesion formation in a rat uterine horn model.

PubMed

Oz, Murat; Cetinkaya, Nilufer; Bas, Sevda; Korkmaz, Elmas; Ozgu, Emre; Terzioglu, Gokay Serdar; Buyukkagnici, Umran; Akbay, Serap; Caydere, Muzaffer; Gungor, Tayfun

2016-09-01

Platelet-rich plasma (PRP) has been known to possess an efficacy in tissue regeneration. The aim of this study was to determine the role of PRP on post-operative adhesion formation in an experimental rat study. Thirty Sprague-Dawley rats were randomly divided into control, hyaluronic acid, and PRP treatment groups and operated on for uterine horn adhesion modeling. Blood was collected to produce a PRP with platelet counts of 688 × 10(3)/μL, and 1 ml of either hyaluronic acid gel or PRP was administered over the standard lesions, while the control group received no medication. The evaluation of post-operative adhesions was done on the 30th post-operative day. The location, extent, type, and tenacity of adhesions as well as total adhesion scores, tissue inflammation, fibrosis and transforming growth factor-1beta (TGF-1β) expressions were evaluated. The total adhesion score was significantly lower in the PRP group (3.2 ± 1.5) compared with the hyaluronic acid (5.0 ± 1.3) and control (8.1 ± 1.7) groups. The extent of the adhesions was significantly lower in the PRP group. There was no significant difference in the type and tenacity of adhesions between the hyaluronic acid and the PRP group. The level of inflammation was significantly higher in the control group than the others, while there was no difference between the PRP and hyaluronic acid groups. TGF-1β expression was significantly lesser in the PRP group than the control and hyaluronic acid groups. PRP is more effective than hyaluronic acid treatment in preventing post-operative adhesion formation in an experimental rat uterine horn adhesion model.
Clinical Improvement of Subacute and Chronic Otitis Media With Effusion Treated With Hyaluronic Acid Plus Hypertonic Solution via Nasal Lavage: A Randomized Controlled Trial.

PubMed

Cioffi, Luigi; Gallo, Patrizia; D'Avino, Antonio; Carlomagno, Francesco; Aloi, Giuseppe; D'Onofrio, Antonietta; Del Gaizo, Donatella; Giuliano, Maria; De Franchis, Raffaella; Sandomenico, Maria L; Pecoraro, Anna

2017-01-01

Background . This study, a randomized controlled trial, aims to demonstrate a clinically significant improvement in subacute and chronic otitis media with effusion through the administration of hyaluronic acid associated with hypertonic solution compared with the administration of hypertonic solution alone. The setting was an outpatient clinic of 20 primary care pediatrician offices affiliated with the 3 Local Health Units (Azienda Sanitaria Locale) of Naples. Materials and Methods . The study was conducted for 6 months, from October 2014 to the end of March 2015. The study saw the participation of 20 pediatricians who were experts in pneumatic otoscopy, each of whom enrolled 15 children. Each investigator was randomized to carry out the treatment with 3% hypertonic solution or high-molecular-weight hyaluronic acid + 3% hypertonic solution. Results . A total of 275 children were enrolled, of whom 11(equal to 4% ) were lost to follow-up. A total of 264 children completed the trial according to the protocol, 120 in the hyaluronic acid + hypertonic solution group and 144 in the hypertonic solution group. Hyaluronic acid associated with hypertonic solution and hypertonic solution alone administered by nasal lavage have proven to be safe and effective in the treatment of prolonged otitis media with effusion (initial score of -0.5, final score of 0.9, P < 001, for the hypertonic + hyaluronic acid group; initial score of -0.3, final score of 0.2, P < .001, for the hypertonic solution group). Though starting from a less favorable initial clinical score (-0.5 vs -0.3, P < .016), hyaluronic acid associated with hypertonic solution resulted in a significant increase in clinical healing (0.9 vs 0.2, P < .001). One interesting outcome was the significant reduction in the consumption of drugs (cortisone and antibiotics) during the follow-up.
Thermoresponsive hyaluronic acid nanogels as hydrophobic drug carrier to macrophages.

PubMed

Fernandes Stefanello, Talitha; Szarpak-Jankowska, Anna; Appaix, Florence; Louage, Benoit; Hamard, Lauriane; De Geest, Bruno G; van der Sanden, Boudewijn; Nakamura, Celso Vataru; Auzély-Velty, Rachel

2014-11-01

Delivery systems for macrophages are particularly attractive since these phagocytic cells play a important role in immunological and inflammatory responses, also acting as host cells for microorganisms that are involved in deadly infectious diseases, such as leishmaniasis. Hyaluronic acid (HA) is specifically recognized by macrophages that are known to express HA receptors. Therefore, in this study, we focused on HA-based nanogels as drug carriers for these cells. The drug delivery was validated in an in vivo study on mice using intravital two-photon laser scanning microscopy. HA derivatives were modified with a biocompatible oligo(ethylene glycol)-based thermoresponsive polymer to form nanogels. These HA conjugates were readily prepared by varying the molar mass of initial HA and the degree of substitution via radical-mediated thiol-ene chemistry in aqueous solution. The derivatives were shown to self-assemble into spherical gel particles with diameters ranging from 150 to 214 nm above 37 °C. A poorly water-soluble two-photon dye was successfully loaded into the nanogels during this self-assembly process. In vitro cellular uptake tests using a RAW 264.7 murine macrophage cell line showed successful intracellular delivery of the hydrophobic dye. After intravenous injection in mice, the nanogels circulated freely in the blood but were rapidly phagocytized within 13 min by circulating macrophages and stored in the liver and spleen, as observed by two-photon microscopy. Benefit can be thus expected in using such a delivery system for the liver and spleen macrophage-associated diseases. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Single-Molecule Studies of Hyaluronic Acid Conformation

NASA Astrophysics Data System (ADS)

Innes-Gold, Sarah; Berezney, John; Saleh, Omar

Hyaluronic acid (HA) is a charged linear polysaccharide abundant in extracellular spaces. Its solution conformation and mechanical properties help define the environment outside of cells, play key roles in cell motility and adhesion processes, and are of interest for the development of HA biomaterials. Intra-chain hydrogen bonds and electrostatic repulsion contribute to HAs physical structure, but the nature of this structure, as well as its dependence on solution electrostatics, are not well-understood. To address this problem, we have investigated HA conformation and mechanical properties under a range of solution conditions systematically designed to affect charge screening or hydrogen bonding. We used magnetic tweezers to apply biological-scale stretching forces to individual HA chains under varying solution conditions.
Topical Hyaluronic Acid vs. Standard of Care for the Prevention of Radiation Dermatitis After Adjuvant Radiotherapy for Breast Cancer: Single-Blind Randomized Phase III Clinical Trial

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

Pinnix, Chelsea; Perkins, George H.; Strom, Eric A.

2012-07-15

Purpose: To determine the efficacy of an emulsion containing hyaluronic acid to reduce the development of {>=}Grade 2 radiation dermatitis after adjuvant breast radiation compared with best supportive care. Methods and Materials: Women with breast cancer who had undergone lumpectomy and were to receive whole-breast radiotherapy to 50 Gy with a 10- to 16-Gy surgical bed boost were enrolled in a prospective randomized trial to compare the effectiveness of a hyaluronic acid-based gel (RadiaPlex) and a petrolatum-based gel (Aquaphor) for preventing the development of dermatitis. Each patient was randomly assigned to use hyaluronic acid gel on the medial half ormore » the lateral half of the irradiated breast and to use the control gel on the other half. Dermatitis was graded weekly according to the Common Terminology Criteria v3.0 by the treating physician, who was blinded as to which gel was used on which area of the breast. The primary endpoint was development of {>=}Grade 2 dermatitis. Results: The study closed early on the basis of a recommendation from the Data and Safety Monitoring Board after 74 of the planned 92 patients were enrolled. Breast skin treated with the hyaluronic acid gel developed a significantly higher rate of {>=}Grade 2 dermatitis than did skin treated with petrolatum gel: 61.5% (40/65) vs. 47.7% (31/65) (p = 0.027). Only 1ne patient developed Grade 3 dermatitis using either gel. A higher proportion of patients had worse dermatitis in the breast segment treated with hyaluronic acid gel than in that treated with petrolatum gel at the end of radiotherapy (42% vs. 14%, p = 0.003). Conclusion: We found no benefit from the use of a topical hyaluronic acid-based gel for reducing the development of {>=}Grade 2 dermatitis after adjuvant radiotherapy for breast cancer. Additional studies are needed to determine the efficacy of hyaluronic acid-based gel in controlling radiation dermatitis symptoms after they develop.« less
Topical hyaluronic acid vs. standard of care for the prevention of radiation dermatitis after adjuvant radiotherapy for breast cancer: single-blind randomized phase III clinical trial.

PubMed

Pinnix, Chelsea; Perkins, George H; Strom, Eric A; Tereffe, Welela; Woodward, Wendy; Oh, Julia L; Arriaga, Lisa; Munsell, Mark F; Kelly, Patrick; Hoffman, Karen E; Smith, Benjamin D; Buchholz, Thomas A; Yu, T Kuan

2012-07-15

To determine the efficacy of an emulsion containing hyaluronic acid to reduce the development of ≥ Grade 2 radiation dermatitis after adjuvant breast radiation compared with best supportive care. Women with breast cancer who had undergone lumpectomy and were to receive whole-breast radiotherapy to 50 Gy with a 10- to 16-Gy surgical bed boost were enrolled in a prospective randomized trial to compare the effectiveness of a hyaluronic acid-based gel (RadiaPlex) and a petrolatum-based gel (Aquaphor) for preventing the development of dermatitis. Each patient was randomly assigned to use hyaluronic acid gel on the medial half or the lateral half of the irradiated breast and to use the control gel on the other half. Dermatitis was graded weekly according to the Common Terminology Criteria v3.0 by the treating physician, who was blinded as to which gel was used on which area of the breast. The primary endpoint was development of ≥ Grade 2 dermatitis. The study closed early on the basis of a recommendation from the Data and Safety Monitoring Board after 74 of the planned 92 patients were enrolled. Breast skin treated with the hyaluronic acid gel developed a significantly higher rate of ≥ Grade 2 dermatitis than did skin treated with petrolatum gel: 61.5% (40/65) vs. 47.7% (31/65) (p = 0.027). Only one patient developed Grade 3 dermatitis using either gel. A higher proportion of patients had worse dermatitis in the breast segment treated with hyaluronic acid gel than in that treated with petrolatum gel at the end of radiotherapy (42% vs. 14%, p = 0.003). We found no benefit from the use of a topical hyaluronic acid-based gel for reducing the development of ≥ Grade 2 dermatitis after adjuvant radiotherapy for breast cancer. Additional studies are needed to determine the efficacy of hyaluronic acid-based gel in controlling radiation dermatitis symptoms after they develop. Copyright © 2012 Elsevier Inc. All rights reserved.
Topical Hyaluronic acid vs. Standard of Care for the Prevention of Radiation Dermatitis after Adjuvant Radiotherapy for Breast Cancer: Single-Blind Randomized Phase III Clinical Trial

PubMed Central

Pinnix, Chelsea; Perkins, George H.; Strom, Eric A.; Tereffe, Welela; Woodward, Wendy; Oh, Julia L.; Arriaga, Lisa; Munsell, Mark F.; Kelly, Patrick; Hoffman, Karen E.; Smith, Benjamin D.; Buchholz, Thomas A.; Yu, T. Kuan

2014-01-01

Purpose To determine the efficacy of an emulsion containing hyaluronic acid to reduce the development of ≥ grade 2 radiation dermatitis after adjuvant breast radiation (RT) compared with best supportive care. Materials and Methods Women with breast cancer who had undergone lumpectomy and were to receive whole-breast RT to 50 Gy with a 10- to 16-Gy surgical bed boost were enrolled in a prospective randomized trial to compare the effectiveness of a hyaluronic acid-based gel (RadiaPlex) and a petrolatum-based gel (Aquaphor) for preventing the development of dermatitis. Each patient was randomly assigned to use hyaluronic acid gel, on the medial half or the lateral half of the irradiated breast, and the control gel to the other half. Dermatitis was graded weekly according to the Common Terminology Criteria v3.0 by the treating physician, who was blinded as to which gel was used on which area of the breast. The primary endpoint was development of ≥grade 2 dermatitis. Results The study closed early based on a recommendation from the Data and Safety Monitoring Board after 74 of the planned 92 patients were enrolled. Breast skin treated with the hyaluronic acid gel developed significantly higher rate of ≥grade 2 dermatitis than did skin treated with petrolatum gel (61.5% [40/65] vs. 47.7% [31/65], P = 0.027). Only one patient developed grade 3 dermatitis using either gel. A higher proportion of patients had worse dermatitis in the breast segment treated with hyaluronic acid gel than petrolatum gel at the end of RT (42% vs. 14%, P = 0.003). Conclusion We found no benefit from use of a topical hyaluronic acid-based gel for reducing the development of grade ≥2 dermatitis after adjuvant RT for breast cancer. Additional studies are needed to determine the efficacy of hyaluronic acid-based gel in controlling radiation dermatitis symptoms after they develop. PMID:22172912
Effect of sodium hyaluronate/carboxymethyl cellulose (Guardix-sol) on retear rate and postoperative stiffness in arthroscopic rotator cuff repair patients: A prospective cohort study.

PubMed

Jeong, Jeung Yeol; Chung, Pill Ku; Yoo, Jae Chul

2017-01-01

Hyaluronate-based anti-adhesive agents are expected to enhance rotator cuff healing; however, their effect on the incidence and extent of postoperative complications such as stiffness and retears has not been investigated. From July 2012 to February 2013, 80 patients undergoing arthroscopic rotator cuff repair surgery were prospectively enrolled. Forty patients were assigned to the control group, while the other 40 were assigned to the injection group and received a Guardix-sol injection immediately after surgery. Passive range of motion, pain visual analog scale, and functional score were assessed at 8 weeks, 6 months, and 24 months postoperatively. Gliding motion between the deltoid muscle and the greater tuberosity of the proximal humerus was evaluated using ultrasonography at 2 and 8 weeks postoperatively, and tendon integrity was evaluated using magnetic resonance imaging at 6 months postoperatively. We found no significant difference between the groups regarding gliding motion at 2 weeks postoperatively. However, at 8 weeks, the incidence of poor gliding motion was 2.5% and 15% for the injected patients and control group, respectively, which was statistically significant. At 6 months after surgery, the retear rate between the two groups was not statistically significant. We found no statistically significant difference between the two groups regarding retear rate and clinical score throughout the follow-up period. We noted no complications related to the use of Guardix-sol. Patients who received the Guardix-sol injection showed improved gliding motion between the deltoid muscle and the greater tuberosity in the early postoperative period.
Ocular Pain and Impending Blindness During Facial Cosmetic Injections: Is Your Office Prepared?

PubMed

Prado, Giselle; Rodríguez-Feliz, Jose

2017-02-01

Soft tissue filler injections are the second most common non-surgical procedure performed by the plastic surgeon. Embolization of intravascular material after facial injection is a rare but terrifying outcome due to the high likelihood of long-term sequela such as blindness and cerebrovascular accident. The literature is replete with examples of permanent blindness caused by injection with autologous fat, soft tissue fillers such as hyaluronic acid, PLLA, calcium hydroxyl-apatite, and even corticosteroid suspensions. However, missing from the discussion is an effective treatment algorithm that can be quickly and safely followed by injecting physicians in the case of an intravascular injection with impending blindness. In this report, we present the case of a 64-year-old woman who suffered from blindness and hemiparesis after facial cosmetic injections performed by a family physician. We use this case to create awareness that this complication has become more common as the number of injectors and patients seeking these treatments have increased exponentially over the past few years. We share in this study our experience with the incorporation of a "blindness safety kit" in each of our offices to promptly initiate treatment in someone with embolization and impending blindness. The kit contains a step-by-step protocol to follow in the event of arterial embolization of filler material associated with ocular pain and impending loss of vision. 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 .
Results of endovesical hyaluronic acid/chondroitin sulfate in the treatment of Interstitial Cystitis/Painful Bladder Syndrome.

PubMed

Porru, D; Cervigni, M; Nasta, L; Natale, F; Lo Voi, R; Tinelli, C; Gardella, B; Anghileri, A; Spinillo, A; Rovereto, B

2008-05-01

The aim of our study was to test the effect of a more viscous compound than existent hyaluronic acid formulation in helping to restore a defective glycosaminoglycan layer, and therefore in improving Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) symptoms when administered intravesically in IC/PBS patients. A total of 23 female patients completed the study. Patients received endovesical administration of hyaluronic acid and chondroitin sulfate in normal saline, 40 ml, weekly for 12 weeks and then bi-weekly for 6 months, if there was initial response. After 12 weeks treatment both Interstitial Cystitis Symptom and Problem Index (ICSI/ICPI), pelvic pain and Urgency/Frequency Symptom Scale (PUF) showed a mean significant improvement, which was maintained thereafter. The average number of voidings and mean voiding volumes revealed significant improvement after the 12 weeks' treatment period, with a significant reduction and increase, respectively. Mean voiding volume increased from 143 ml to 191, which apparently was not reflected in a corresponding reduction of number of daily voids (from 15,5 to 14). VAS values decreased from 5,4 to 3,6 (pain) and from 6,0 to 3,5 (urgency) after the treatment cycle, showing a significant improvement. In our preliminary experience, the administration of intravesical hyaluronic acid plus chondroitine sulphate appears to be a safe and efficacious method of treatment in IC/PBS.
[Treatment of interstitial cystitis by intravesical instillation of hyaluronic acid: A prospective study on 31 patients].

PubMed

Van Agt, S; Gobet, F; Sibert, L; Leroi, A-M; Grise, P

2011-03-01

We evaluate the efficacy of hyaluronate acid instillation for treatment of interstitial cystitis (IC). From March 2008 to May 2009, a prospective study included 31 patients. We used the new definition of IC established by the ICS in 2002. Patients have a urinalysis, a cystoscopy, a hydrodistension test and bladder biopsies. The urodynamic evaluation was not systematic. Patients received weekly six instillations of 40mg (50ml) intravesical hyaluronate acid. We evaluated the efficacy and safety of treatment with two specific questionnaires of interstitial cystitis filled before and after 6 weeks of treatment: the O'Leary-Sant and Pelvic pain and Urgency/Frequency (PUF). Four groups were defined: good response, partial response, poor response and no response. They were composed by 14 patients (45%), two (7%), seven (22%) and eight patients (26%). We obtained 52% positive response (good response and partial response) after 6 weeks of treatment. Patients with cystoscopy and histology abnormal had a response rate of 60%. No serious side effects were observed. Hyaluronate acid has a place in the treatment of interstitial cystitis with an efficiency comparable to other treatments and good tolerance. The response rate to treatment can be improved by better selection of patients, particularly those having a cystoscopy and histology abnormal. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Skin bacterial flora as a potential risk factor predisposing to late bacterial infection after cross-linked hyaluronic acid gel augmentation.

PubMed

Netsvyetayeva, Irina; Marusza, Wojciech; Olszanski, Romuald; Szyller, Kamila; Krolak-Ulinska, Aneta; Swoboda-Kopec, Ewa; Sierdzinski, Janusz; Szymonski, Zachary; Mlynarczyk, Grazyna

2018-01-01

Cross-linked hyaluronic acid (HA) gel is widely used in esthetic medicine. Late bacterial infection (LBI) is a rare, but severe complication after HA augmentation. The aim of this study was to determine whether patients who underwent the HA injection procedure and developed LBI had qualitatively different bacterial flora on the skin compared to patients who underwent the procedure without any complications. The study group comprised 10 previously healthy women with recently diagnosed, untreated LBI after HA augmentation. The control group comprised 17 healthy women who had a similar amount of HA injected with no complications. To assess the difference between the two groups, their skin flora was cultured from nasal swabs, both before and after antibiotic treatment in the study group. A significant increase in the incidence of Staphylococcus epidermidis was detected in the control group ( P =0.000) compared to the study group. The study group showed a significantly higher incidence of Staphylococcus aureus ( P =0.005), Klebsiella pneumoniae ( P =0.006), Klebsiella oxytoca ( P =0.048), and Staphylococcus haemolyticus ( P =0.048) compared to the control group. The bacterial flora on the skin differed in patients with LBI from the control group. The control group's bacterial skin flora was dominated by S. epidermidis . Patients with LBI had a bacterial skin flora dominated by potentially pathogenic bacteria.
Sulfated hyaluronic acid hydrogels with retarded degradation and enhanced growth factor retention promote hMSC chondrogenesis and articular cartilage integrity with reduced hypertrophy.

PubMed

Feng, Qian; Lin, Sien; Zhang, Kunyu; Dong, Chaoqun; Wu, Tianyi; Huang, Heqin; Yan, Xiaohui; Zhang, Li; Li, Gang; Bian, Liming

2017-04-15

Recently, hyaluronic acid (HA) hydrogels have been extensively researched for delivering cells and drugs to repair damaged tissues, particularly articular cartilage. However, the in vivo degradation of HA is fast, thus limiting the clinical translation of HA hydrogels. Furthermore, HA cannot bind proteins with high affinity because of the lack of negatively charged sulfate groups. In this study, we conjugated tunable amount of sulfate groups to HA. The sulfated HA exhibits significantly slower degradation by hyaluronidase compared to the wild type HA. We hypothesize that the sulfation reduces the available HA octasaccharide substrate needed for the effective catalytic action of hyaluronidase. Moreover, the sulfated HA hydrogels significantly improve the protein sequestration, thereby effectively extending the availability of the proteinaceous drugs in the hydrogels. In the following in vitro study, we demonstrate that the HA hydrogel sulfation exerts no negative effect on the viability of encapsulated human mesenchymal stem cells (hMSCs). Furthermore, the sulfated HA hydrogels promote the chondrogenesis and suppresses the hypertrophy of encapsulated hMSCs both in vitro and in vivo. Moreover, intra-articular injections of the sulfated HA hydrogels avert the cartilage abrasion and hypertrophy in the animal osteoarthritic joints. Collectively, our findings demonstrate that the sulfated HA is a promising biomaterial for the delivery of therapeutic agents to aid the regeneration of injured or diseased tissues and organs. In this paper, we conjugated sulfate groups to hyaluronic acid (HA) and demonstrated the slow degradation and growth factor delivery of sulfated HA. Furthermore, the in vitro and in vivo culture of hMSCs laden HA hydrogels proved that the sulfation of HA hydrogels not only promotes the chondrogenesis of hMSCs but also suppresses hypertrophic differentiation of the chondrogenically induced hMSCs. The animal OA model study showed that the injected
Biocompatibility and antifibrotic effect of UV-cross-linked hyaluronate as a release-system for tranilast after trabeculectomy in a rabbit model--a pilot study.

PubMed

Spitzer, Martin S; Sat, Macarena; Schramm, Charlotte; Schnichels, Sven; Schultheiss, Maximilian; Yoeruek, Efdal; Dzhelebov, Dimitar; Szurman, Peter

2012-06-01

To analyze the release kinetics and the clinical and histological effects of UV-cross-linked hyaluronic acid as a release-system for the transforming growth factor β-2 antagonist tranilast with anti-phlogistic properties on intraocular pressure after trabeculectomy in an aggressive scarring animal model. Hyaluronate acid was UV-cross linked and loaded with tranilast. The release of tranilast into a buffered salt solution was assessed spectrophotometrically. Glaucoma filtration surgery, similar to that performed in clinical practice, was performed on chinchilla rabbits. The rabbits were divided in 3 groups. (Group A: trabeculectomy alone, group B: trabeculectomy with a cross-linked hyaluronic acid gel preparation and group C: trabeculectomy with cross-linked hyaluronic gel preparation mixed with tranilast). Antifibrotic efficacy was established by clinical response and histologic examination. The cross-linked gels released tranilast for up to 26 h. The release plotted as a function of the square root of time was consistent with a largely diffusion-controlled release system. Both the gel preparation alone and the gel preparation mixed with tranilast were well tolerated in vivo. No adverse effects such as inflammation, corneal toxicity or blurring of the optical media were observed. The intraocular pressure reached preoperative levels within 9 days after surgery in control animals and group B, but remained significantly reduced (p = 0.00016) in the group with tranilast until day 22. The data of this pilot study suggest that the intraoperative application of UV-crossed linked hyaluronic acid used as a slow release system for tranilast may improve the surgical outcome of glaucoma filtration surgery.
Pirfenidone vs. sodium hyaluronate/carboxymethylcellulose as prevention of the formation of intra-abdominal adhesions after colonic surgery. A randomized study in an experimental model.

PubMed

Bello-Guerrero, Jorge Alberto; Cruz-Santiago, César Alberto; Luna-Martínez, Javier

2016-01-01

Up to 93% of patients undergoing abdominal surgery will develop intra-abdominal adhesions with the subsequent morbidity that they represent. Various substances have been tested for the prevention of adhesions with controversial results; the aim of our study is to compare the capability of pirfenidone in adhesion prevention against sodium hyaluronate/carboxymethylcellulose. A randomized, prospective, longitudinal experimental study with Winstar rats. They were divided into 3 groups. The subjects underwent an exploratory laparotomy and they had a 4cm(2) cecal abrasion. The first group received saline on the cecal abrasion, and groups 2 and 3 received pirfenidone and sodium hyaluronate/carboxymethylcellulose respectively. All rats were sacrificed on the 21st day after surgery and the presence of adhesions was evaluated with the modified Granat scale. Simple frequency, central tendency and dispersion measures were recorded. For the statistical analysis we used Fisher's test. To evaluate adhesions we used the Granat's modified scale. The control group had a median adhesion formation of 3 (range 0-4). The pirfenidone group had 1.5 (range 0-3), and the sodium hyaluronate/carboxymethylcellulose group had 0 (range 0-1). There was a statistically significant difference to favor sodium hyaluronate/carboxymethylcellulose against saline and pirfenidone (P<0.009 and P<.022 respectively). The use of sodium hyaluronate/carboxymethylcellulose is effective for the prevention of intra-abdominal adhesions. More experimental studies are needed in search for the optimal adhesion prevention drug. Copyright © 2015 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.
Age Spots

MedlinePlus

... Back Injectable Deoxycholic Acid Injectable Hyaluronic Acid Injectable Poly-l-lactic Acid Injectable Polymethylmethacrylate + Bovine Collagen Filler ... procedure Does the treatment hurt? What are my pain management and anesthesia options? How long is the ...
Dermabrasion

MedlinePlus

... Back Injectable Deoxycholic Acid Injectable Hyaluronic Acid Injectable Poly-l-lactic Acid Injectable Polymethylmethacrylate + Bovine Collagen Filler ... After treatment most patients report little or no pain, though some require pain relievers as well as ...
Laser/Light Therapy for Birthmarks

MedlinePlus

... Back Injectable Deoxycholic Acid Injectable Hyaluronic Acid Injectable Poly-l-lactic Acid Injectable Polymethylmethacrylate + Bovine Collagen Filler ... birthmark type, until the patient's goal is achieved. Pain and recovery time is minimal. Procedure is non- ...
Laser Therapy

MedlinePlus

... Back Injectable Deoxycholic Acid Injectable Hyaluronic Acid Injectable Poly-l-lactic Acid Injectable Polymethylmethacrylate + Bovine Collagen Filler ... patient relax during the procedure and to reduce pain. Topical anesthetics are used to numb small treatment ...
Unwanted Tattoos

MedlinePlus

... Back Injectable Deoxycholic Acid Injectable Hyaluronic Acid Injectable Poly-l-lactic Acid Injectable Polymethylmethacrylate + Bovine Collagen Filler ... procedure? Does tattoo removal hurt? What are my pain management and anesthesia options? How long is the ...
In vivo optical coherence tomography imaging of dissolution of hyaluronic acid microneedles in human skin (Conference Presentation)

NASA Astrophysics Data System (ADS)

Song, Seungri; Kim, Jung Dong; Bae, Jung-hyun; Chang, Sooho; Kim, Soocheol; Lee, Hyungsuk; Jeong, Dohyeon; Kim, Hong Kee; Joo, Chulmin

2017-02-01

Transdermal drug delivery (TDD) has been recently highlighted as an alternative to oral delivery and hypodermic injections. Among many methods, drug delivery using a microneedle (MN) is one of the promising administration strategies due to its high skin permeability, mininal invasiveness, and ease of injection. In addition, microneedle-based TDD is explored for cosmetic and therapeutic purposes, rapidly developing market of microneedle industry for general population. To date, visualization of microneedles inserted into biological tissue has primarily been performed ex vivo. MRI, CT and ultrasound imaging do not provide sufficient spatial resolution, and optical microscopy is not suitable because of their limited imaging depth; structure of microneedles located in 0.2 1mm into the skin cannot be visulalized. Optical coherence tomography (OCT) is a non-invasive, cross-sectional optical imaging modality for biological tissue with high spatial resolution and acquisition speed. Compared with ultrasound imaging, it exhibits superior spatial resolution (1 10 um) and high sensitivity, while providing an imaging depth of biological tissue down to 1 2 mm. Here, we present in situ imaging and analysis of the penetration and dissolution characteristics of hyaluronic acid based MNs (HA-MN) with various needle heights in human skin in vivo. In contrast to other studies, we measured the actual penetration depths of the HA-MNs by considering the experimentally measured refractive index of HA in the solid state. For the dissolution dynamics of the HA-MNs, time-lapse structural alteration of the MNs could be clearly visualized, and the volumetric changes of the MNs were measured with an image analysis algorithm.
Efficacy and Safety of a Hyaluronic Acid Filler to Correct Aesthetically Detracting or Deficient Features of the Asian Nose: A Prospective, Open-Label, Long-Term Study

PubMed Central

Liew, Steven; Scamp, Terrence; de Maio, Mauricio; Halstead, Michael; Johnston, Nicole; Silberberg, Michael; Rogers, John D.

2016-01-01

Background There is increasing interest among patients and plastic surgeons for alternatives to rhinoplasty, a common surgical procedure performed in Asia. Objectives To evaluate the safety, efficacy, and longevity of a hyaluronic acid filler in the correction of aesthetically detracting or deficient features of the Asian nose. Methods Twenty-nine carefully screened Asian patients had their noses corrected with the study filler (Juvéderm VOLUMA [Allergan plc, Dublin, Ireland] with lidocaine injectable gel), reflecting individualized treatment goals and utilizing a standardized injection procedure, and were followed for over 12 months. Results A clinically meaningful correction (≥1 grade improvement on the Assessment of Aesthetic Improvement Scale) was achieved in 27 (93.1%) patients at the first follow-up visit. This was maintained in 28 (96.6%) patients at the final visit, based on the independent assessments of a central non-injecting physician and the patients. At this final visit, 23 (79.3%) patients were satisfied or very satisfied with the study filler and 25 (86.2%) would recommend it to others. In this small series of patients, there were no serious adverse events (AEs), with all treatment-related AEs being mild to moderate, transient injection site reactions, unrelated to the study filler. Conclusions Using specific eligibility criteria, individualized treatment goals, and a standardized injection procedure, the study filler corrected aesthetically detracting or deficient features of the Asian nose, with the therapeutic effects lasting for over 12 months, consistent with a high degree of patient satisfaction. This study supports the safety and efficacy of this HA filler for specific nose augmentation procedures in selected Asian patients. Level of Evidence: 3 Therapeutic PMID:27301371
Intra-articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large osteochondral defect by implantation of a double-network gel.

PubMed

Fukui, Takaaki; Kitamura, Nobuto; Kurokawa, Takayuki; Yokota, Masashi; Kondo, Eiji; Gong, Jian Ping; Yasuda, Kazunori

2014-04-01

Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the osteochondral defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical osteochondral defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel.
Dosimetric Implications of an Injection of Hyaluronic Acid for Preserving the Rectal Wall in Prostate Stereotactic Body Radiation Therapy

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

Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr; Udrescu, Corina; Department of Medical Physics, Centre Hospitalier Lyon Sud, Pierre Benite

2014-02-01

Purpose: This study assessed the contribution of ahyaluronic acid (HA) injection between the rectum and the prostate to reducing the dose to the rectal wall in stereotactic body radiation therapy (SBRT). Methods and Materials: As part of a phase 2 study of hypofractionated radiation therapy (62 Gy in 20 fractions), the patients received a transperineal injection of 10 cc HA between the rectum and the prostate. A dosimetric computed tomographic (CT) scan was systematically performed before (CT1) and after (CT2) the injection. Two 9-beam intensity modulated radiation therapy-SBRT plans were optimized for the first 10 patients on both CTs accordingmore » to 2 dosage levels: 5 × 6.5 Gy (PlanA) and 5 × 8.5 Gy (PlanB). Rectal wall parameters were compared with a dose–volume histogram, and the prostate–rectum separation was measured at 7 levels of the prostate on the center line of the organ. Results: For both plans, the average volume of the rectal wall receiving the 90% isodose line (V90%) was reduced up to 90% after injection. There was no significant difference (P=.32) between doses received by the rectal wall on CT1 and CT2 at the base of the prostate. This variation became significant from the median plane to the apex of the prostate (P=.002). No significant differences were found between PlanA without HA and PlanB with HA for each level of the prostate (P=.77, at the isocenter of the prostate). Conclusions: HA injection significantly reduced the dose to the rectal wall and allowed a dose escalation from 6.5 Gy to 8.5 Gy without increasing the dose to the rectum. A phase 2 study is under way in our department to assess the rate of acute and late rectal toxicities when SBRT (5 × 8.5 Gy) is combined with an injection of HA.« less
Highly efficient production of hyaluronic acid by Streptococcus zooepidemicus R42 derived from heterologous expression of bacterial haemoglobin and mutant selection.

PubMed

Lu, J F; Zhu, Y; Sun, H L; Liang, S; Leng, F F; Li, H Y

2016-04-01

During Streptococcus zooepidemicus fermentation, most carbon sources are used to synthesize lactic acid, which can inhibit strain growth and hyaluronic acid production. Here, we expressed bacterial haemoglobin (Vhb) in Strep. zooepidemicus. Due to highly efficient oxygen use, only 15·26 g l(-1) lactic acid was produced, which is 0·73 times the quantity produced by the control strain. Compared with the control strain (1·61 g l(-1) ), hyaluronic acid (HA) production in this strain did not substantially increase, only to 2·16 g l(-1) . Next, we used a series of N-methyl-N'-nitro-N-nitroso-guanidine (NTG) treatments and selection programmes. Finally, we generated a hyaluronidase-negative and rifampin-resistant mutant strain that produces high levels of HA. The optimum carbon concentration for maximum hyaluronic acid production is only 30 g l(-1) of sucrose, which is lower than the control strain (60 g l(-1) ). The oxygen transfer rate coefficient KL a increased significantly to 372 ± 53 h(-1) from 18 ± 4 h(-1) of the control. The optimum carbon source for this strain is 21 g l(-1) of sucrose, 9 g l(-1) of maltose and 5 g l(-1) of glutamic acid. Hyaluronic acid accumulated at 6·7 g l(-1) in the culture broth. However, the molecular weight of HA decreased from 1835 KDa (Control) to 429 kDa. The prepared low-molecular weight HA could function as potential antiangiogenic substances, antiviral and antitumour agents to possibly be used as functional food ingredients. Hyaluronic acid (HA) has been used for a wide range of applications in health, cosmetic and clinical fields. During fermentation of Streptococcus to produce HA, 80-85% of the carbon source is used to produce lactic acid and acetic acid, and only approx. 5 and 10% of the carbon source is used to produce HA and biomass respectively. Here, we expressed bacteria haemoglobin (Vhb) in Streptococcus zooepidemicus, which can dramatically inhibit lactic acid production. After NTG
Peritoneal Macrophage-Specific TNF-α Gene Silencing in LPS-Induced Acute Inflammation Model Using CD44 Targeting Hyaluronic Acid Nanoparticles.

PubMed

Kosovrasti, Verbena Y; Nechev, Lubomir V; Amiji, Mansoor M

2016-10-03

The main goal of this study was to evaluate tumor necrosis factor-alpha (TNF-α) gene silencing in peritoneal macrophages upon activation with lipopolysaccharide (LPS), using CD44-targeting hyaluronic acid (HA)-based nanoparticles encapsulating TNF-α-specific small interfering RNA (siTNF-α). HA nanoparticles were formulated by blending hyaluronic acid-poly(ethylene imine) (HA-PEI), hyaluronic acid-hexyl fatty acid (HA-C6), and hyaluronic acid-poly(ethylene glycol) (HA-PEG) in 3:2:1 weight ratio, and encapsulating siTNF-α to form spherical particles of 78-90 nm diameter. Following intraperitoneal (IP) administration in LPS-treated C57BL/6 mice, the nanoparticles were actively taken up by macrophages and led to a significant downregulation of peritoneal TNF-α level. Downregulation of peritoneal macrophage-specific TNF-α also had a significant impact on other pro-inflammatory cytokine and chemokine levels in the serum. The C57BL/6 group of mice challenged with 5 mg/kg LPS had a significantly higher survival rate when they were treated with 3 mg/kg siTNF-α, either prior or simultaneously with the LPS administration, as compared to the LPS-challenged mice, which were treated with controls including the scrambled siRNA formulation. Overall, the results of this study demonstrate that CD44 targeting HA nanoparticles can selectively deliver siTNF-α to peritoneal macrophages leading to downregulation of pro-inflammatory cytokines in the peritoneal fluid and in the serum. This RNAi strategy could potentially provide an important therapeutic modality for acute inflammatory diseases, such as septic shock.
Sodium hyaluronate accelerates the healing process in tooth sockets of rats.

PubMed

Mendes, Renato M; Silva, Gerluza A B; Lima, Miguel F; Calliari, Marcelo V; Almeida, Alvair P; Alves, José B; Ferreira, Anderson J

2008-12-01

In this study we evaluated the effects of sodium hyaluronate (HY) in the healing process of tooth sockets of rats. Immediately after the extraction of the upper first molars of male Holtzman rats, right sockets were treated with 1% HY gel (approximately 0.1 ml), while left sockets were used as control (blood clot). The animals were sacrificed at 2, 7, and 21 days after tooth extraction and upper maxillaries processed for histological and morphometric analysis of the apical and medium thirds of the sockets. Carbopol, an inert gel, was used to evaluate the mechanical effect of gel injection into sockets. Expression of bone morphogenetic protein-2 (BMP-2) and osteopontin (OPN) was determined by immunohistochemistry at 1, 2, 3, 4, 5, and 7 days after tooth extraction. Histological analysis showed that HY treatment induced earlier trabecular bone deposition resulting in a bone matrix more organized at 7 and 21 days after tooth extraction. Also, HY elicited significant increase in the amount of bone trabeculaes at 7 and 21 days after tooth extraction (percentage of trabecular bone area at 7 days: 13.21+/-4.66% vs. 2.58+/-1.36% in the apical third of control sockets) and in the vessels counting at 7 days. Conversely, the number of cell nuclei was decreased in HY-treated sockets. Additionally, expression of BMP-2 and OPN was enhanced in HY-treated sockets compared with control sockets. These findings suggest that HY accelerates the healing process in tooth sockets of rats stimulating the expression of osteogenic proteins.
Analysis of the Postoperative Periarticular Environment and Influence on Sustained Drug Delivery from a Gel Formulation.

PubMed

Svirskis, Darren; Martis, Waldron; Bhusal, Prabhat; Sharma, Manisha; Stowers, Renus; Young, Simon W

2018-05-16

Regional intraarticular delivery of local anaesthetics is effective in treating postoperative pain following total knee or hip replacement. Recent research efforts have been only partially successful in achieving sustained release of the analgesic agent, in part due to limited understanding of the biological environment into which these formulations are administered. This study aimed to detail the composition and properties of postoperative periarticular fluid (PO-PAF). PO-PAF was collected from 8 patients and the composition and physicochemical properties determined. A number of components were identified which are lacking from phosphate buffered saline (PBS) or other synthetic media. The differences in composition led to variation in the physicochemical properties of PO-PAF compared with PBS. Notably, significantly lower surface tension (p<0.05) and higher buffer capacity (p<0.05) were observed in the biological fluid. We demonstrated the solubility of lidocaine is almost double in PO-PAF compared to PBS (p<0.05) and that lidocaine release from a poloxamer gelling system occurred faster into PO-PAF under both sink and non-sink conditions. Collectively, these data indicate PBS is inappropriate for the in-vitro evaluation of intraarticular drug delivery systems. The presented data describes PO-PAF and will support the future development of biorelevant media to ultimately improve in-vivo in-vitro correlation. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Can hybrid hyaluronic acid represent a valid approach to treat rizoarthrosis? A retrospective comparative study.

PubMed

Tenti, Sara; Pascarelli, Nicola Antonio; Giannotti, Stefano; Galeazzi, Mauro; Giordano, Nicola; Fioravanti, Antonella

2017-11-13

Osteoarthritis (OA) of the trapeziometacarpal joint (TMJ) is a disabling condition with a significant impact on quality of life. The optimal management of hand OA requires a combination of non-pharmacological and pharmacological treatments that include intra-articular (i.a.) therapy. EULAR experts recommend corticosteroid injections in TMJ OA and underline the usefulness of hyaluronic acid (HA). The aim of this study was the assessment of the efficacy and tolerability of i.a. injections of a hybrid formulation of HA (Sinovial H-L®) in comparison to triamcinolone in patients with TMJ OA. This 6-months observational comparative study, retrospective analyzed the medical records of 100 patients with monolateral or bilateral TMJ OA, treated with two injections of Sinovial H-L® (Sinovial H-L Group) or of triamcinolone acetonide (Triamcinolone Group). Clinical assessments were recorded at the time of the first and second injection and after one, 3 and 6 months. The primary outcomes were the change in global pain on a Visual Analogue Scale (VAS) and in hand function evaluated by the Functional Index for Hand OA (FIHOA) from baseline to month 6. Secondary outcomes were the improvement of the duration of morning stiffness, Health Assessment Questionnaire (HAQ) and the Medical Outcomes Study 36-Item Short Form (SF-36). The comparison between the two groups of treatment were performed with the Wilcoxon rank-sum test for continuous variables and with chi-square or Fisher exact test for categorical variables. Statistical significance was set at p < 0.05. Both therapies provided effective pain relief and joint function improvement, but the benefits achieved were statistically significantly superior in the Sinovial H-L Group than the Triamcinolone Group after one month (p < 0.01) from the beginning of the therapy and during the 6-months follow-up (p < 0.001). Furthermore, Sinovial H-L® was associated with a significant decrease in the duration of morning stiffness
A Microfluidic Platform to design crosslinked Hyaluronic Acid Nanoparticles (cHANPs) for enhanced MRI

NASA Astrophysics Data System (ADS)

Russo, Maria; Bevilacqua, Paolo; Netti, Paolo Antonio; Torino, Enza

2016-11-01

Recent advancements in imaging diagnostics have focused on the use of nanostructures that entrap Magnetic Resonance Imaging (MRI) Contrast Agents (CAs), without the need to chemically modify the clinically approved compounds. Nevertheless, the exploitation of microfluidic platforms for their controlled and continuous production is still missing. Here, a microfluidic platform is used to synthesize crosslinked Hyaluronic Acid NanoParticles (cHANPs) in which a clinically relevant MRI-CAs, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), is entrapped. This microfluidic process facilitates a high degree of control over particle synthesis, enabling the production of monodisperse particles as small as 35 nm. Furthermore, the interference of Gd-DTPA during polymer precipitation is overcome by finely tuning process parameters and leveraging the use of hydrophilic-lipophilic balance (HLB) of surfactants and pH conditions. For both production strategies proposed to design Gd-loaded cHANPs, a boosting of the relaxation rate T1 is observed since a T1 of 1562 is achieved with a 10 μM of Gd-loaded cHANPs while a similar value is reached with 100 μM of the relevant clinical Gd-DTPA in solution. The advanced microfluidic platform to synthesize intravascularly-injectable and completely biocompatible hydrogel nanoparticles entrapping clinically approved CAs enables the implementation of straightforward and scalable strategies in diagnostics and therapy applications.
Effect of gamma irradiation on hyaluronic acid and dipalmitoylphosphatidylcholine (DPPC) interaction

NASA Astrophysics Data System (ADS)

Ahmad, Ainee Fatimah; Mohd, Hur Munawar Kabir; bin Ayob, Muhammad Taqiyuddin Mawardi; Rosli, Nur Ratasha Alia Md; Mohamed, Faizal; Radiman, Shahidan; Rahman, Irman Abdul

2014-09-01

DPPC lipids are the major component constituting the biological membrane, and their importances in various physiological functions are well documented. Hyaluronic acid (HA) in the synovial joint fluid functions as a lubricant, shock absorber and a nutrient carrier. Gamma irradiation has also been found to be effective in depolymerizing and cleaving molecular chains related to free radicals, thus extends with changes in chemical composition as well as its physiological functions. This research are conducted to investigate the hyaluronic acid (HA) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) interaction in form of vesicles and its effect to gamma radiation. The size of DPPC vesicles formed via gentle hydration method is between 100 to 200 nm in diameter. HA (0.1, 0.5 and 1.0 mg/ml) was added into the vesicles and characterized by using TEM to determine vesicle size distributions, fusion and rupture of DPPC structure. The results demonstrated that the size of the vesicles approximately between 200 to 300 nm which caused by vesicles fusion with HA and formed even larger vesicles. After being irradiated by 0 to 200 Gy, the size of vesicles decreased as HA was degraded. To elucidate the mechanism of these effects, FTIR spectra were carried out and have shown that at absorption bands at 1700-1750 cm-1 due to formation of carboxylic acid and leads to alteration of HA structure.

Synthesis and radiosensitization properties of hydrogen peroxide and sodium hyaluronate complex

NASA Astrophysics Data System (ADS)

Rosli, Nur Ratasha Alia Md.; Mohamed, Faizal; Heng, Cheong Kai; Rahman, Irman Abdul; Ahmad, Ainee Fatimah; Mohamad, Hur Munawar Kabir

2014-09-01

Cancer cells which are large in size are resistant towards radiation therapy due to the presence of large amount of anti-oxidative enzymes and hypoxic cancer cells. Thus radiosensitizer agents have been developed to enhance the therapeutic effect of radiotherapy by increasing the sensitivity of these cancer cells towards radiation. This study is conducted to investigate the radiosensitization properties of radiosensitizer complex containing hydrogen peroxide and sodium hyaluronate. Combination with sodium hyaluronate may decrease reactivity of hydrogen peroxide but maintain the oxygen concentration needed for radiosensitizing effect. HepG2 cancer cells are cultured as the mean of test subject. Cancer cell samples which are targeted and not targeted with these radiosensitizers are irradiated with 2Gy single fractionated dose. Results obtained shows that the cancer cells which are not targeted with radiosensitizers has a cell viability of 98.80±0.37% after a time interval of 48 hours and has even repopulated over 100% after a 72 hour time interval. This shows that the cancer cells are resistant towards radiation. However, when the cancer cells are targeted with radiosensitizers prior to irradiation, there is a reduction of cell viability by 25.50±10.81% and 10.30±5.10% at time intervals of 48 and 72 hours respectively. This indicates that through the use of these radiosensitizers, cancer cells are more sensitive towards radiation.
PRELIMINARY HIGH PERFORMANCE CAPILLARY ELECTROPHORESIS (HPCE) STUDIES OF ENZYMATIC DEGRADATION OF HYALURONIC ACID BY HYALURONIDASE IN THE PRESENCE OF POLYVALENT METAL IONS.

PubMed

Urbaniak, Bartosz; Plewa, Szymon; Kokot, Zenon Jozef

2017-01-01

The aim of this study was, at first, to examine the influence of metal ions on digestion process of hyaluronic acid by hyaluronidase (HAse) using high performance capillary electrophoresis (HPCE) method. The influence of copper(H), zinc(Il), manganese(II) ions on enzymatic degradation of HA by hyaluronidase enzyme (HA-se) were investigated. Secondly, the kinetic parameters, V(max), K(m), k(cat), and k (cat),/K(m) were determined to estimate the impact of these metal ions (Me) on digestion process of hyaluronic acid (HA). The two different HA-Me mole ratios were analyzed. The examined data were always compared to the digestion process of pure HA solution by hyaluronidase, to exhibit the differences in the digestion process of pure hyaluronan as well as the hyaluronan in the presence of metal ions. It was observed that all of the investigated metal ions have influenced the hyaluronic acid degradation process. The most important conclusion was a decrease of the kinetic parameters both K,, and V,. In the result, it can be assumed that in all of the studied samples with metal ions addition, the uncompetitive mechanism of enzyme inhibition occurred. The results of this study may give new insight into foregoing knowledge about hyaluronic acid behavior. Due to the fact that our study was carried out only for three different metal ions in two concentrations, it is necessary to continue further research comprising wider range of metal ions and their concentrations.
Comparative Efficacy of Autologous Stromal Vascular Fraction and Autologous Adipose-Derived Mesenchymal Stem Cells Combined With Hyaluronic Acid for the Treatment of Sheep Osteoarthritis.

PubMed

Lv, Xiaoteng; He, Jiyin; Zhang, Xue; Luo, Xuan; He, Na; Sun, Zhongwei; Xia, Huitang; Liu, Victor; Zhang, Li; Lin, Xiangming; Lin, Liping; Yin, Huabin; Jiang, Dong; Cao, Wei; Wang, Richard; Zhou, Guangdong; Wang, Wen

2018-01-01

The current study explored whether intra-articular (IA) injection of autologous adipose mesenchymal stem cells (ASCs) combined with hyaluronic acid (HA) achieved better therapeutic efficacy than autologous stromal vascular fraction (SVF) combined with HA to prevent osteoarthritis (OA) progression and determined how long autologous ASCs combined with HA must remain in the joint to observe efficacy. OA models were established by performing anterior cruciate ligament transection (ACLT) and medial meniscectomy (MM). Autologous SVF (1×10 7 mononuclear cells), autologous low-dose ASCs (1×10 7 ), and autologous high-dose ASCs (5×10 7 ) combined with HA, and HA alone, or saline alone were injected into the OA model animals at 12 and 15 weeks after surgery, respectively. Compared with SVF+HA treatment, low-dose ASC+HA treatment yielded better magnetic resonance imaging (MRI) scores and macroscopic results, while the cartilage thickness of the tibial plateau did not differ between low, high ASC+HA and SVF+HA treatments detected by micro-computed tomography (µCT). Immunohistochemistry revealed that high-dose ASC+HA treatment rescued hypertrophic chondrocytes expressing collagen X in the deep area of articular cartilage. Western blotting analysis indicated the high- and low-dose ASC+HA groups expressed more collagen X than did the SVF+HA group. Enzyme-linked immunosorbent assay showed treatment with both ASC+HA and SVF+HA resulted in differing anti-inflammatory and trophic effects. Moreover, superparamagnetic iron oxide particle (SPIO)-labeled autologous ASC signals were detected by MRI at 2 and 18 weeks post-injection and were found in the lateral meniscus at 2 weeks and in the marrow cavity of the femoral condyle at 18 weeks post-injection. Thus, IA injection of autologous ASC+HA may demonstrate better efficacy than autologous SVF+HA in blocking OA progression and promoting cartilage regeneration, and autologous ASCs (5×10 7 cells) combined with HA potentially survive
Iatrogenic occlusion of the ophthalmic artery after cosmetic facial filler injections: a national survey by the Korean Retina Society.

PubMed

Park, Kyu Hyung; Kim, Yong-Kyu; Woo, Se Joon; Kang, Se Woong; Lee, Won Ki; Choi, Kyung Seek; Kwak, Hyung Woo; Yoon, Ill Han; Huh, Kuhl; Kim, Jong Woo

2014-06-01

Iatrogenic occlusion of the ophthalmic artery and its branches is a rare but devastating complication of cosmetic facial filler injections. To investigate clinical and angiographic features of iatrogenic occlusion of the ophthalmic artery and its branches caused by cosmetic facial filler injections. Data from 44 patients with occlusion of the ophthalmic artery and its branches after cosmetic facial filler injections were obtained retrospectively from a national survey completed by members of the Korean Retina Society from 27 retinal centers. Clinical features were compared between patients grouped by angiographic findings and injected filler material. Visual prognosis and its relationship to angiographic findings and injected filler material. Ophthalmic artery occlusion was classified into 6 types according to angiographic findings. Twenty-eight patients had diffuse retinal and choroidal artery occlusions (ophthalmic artery occlusion, generalized posterior ciliary artery occlusion, and central retinal artery occlusion). Sixteen patients had localized occlusions (localized posterior ciliary artery occlusion, branch retinal artery occlusion, and posterior ischemic optic neuropathy). Patients with diffuse occlusions showed worse initial and final visual acuity and less visual gain compared with those having localized occlusions. Patients receiving autologous fat injections (n = 22) had diffuse ophthalmic artery occlusions, worse visual prognosis, and a higher incidence of combined brain infarction compared with patients having hyaluronic acid injections (n = 13). Clinical features of iatrogenic occlusion of the ophthalmic artery and its branches following cosmetic facial filler injections were diverse according to the location and extent of obstruction and the injected filler material. Autologous fat injections were associated with a worse visual prognosis and a higher incidence of combined cerebral infarction. Extreme caution and care should be taken during
Host cell recruitment patterns by bone morphogenetic protein-2 releasing hyaluronic acid hydrogels in a mouse subcutaneous environment.

PubMed

Todeschi, Maria R; El Backly, Rania M; Varghese, Oommen P; Hilborn, Jöns; Cancedda, Ranieri; Mastrogiacomo, Maddalena

2017-07-01

This study aimed to identify host cell recruitment patterns in a mouse model in response to rhBMP-2 releasing hyaluronic acid hydrogels and influence of added nano-hydroxyapatite particles on rhBMP-2 release and pattern of bone formation. Implanted gels were retrieved after implantation and cells were enzymatically dissociated for flow cytometric analysis. Percentages of macrophages, progenitor endothelial cells and putative mesenchymal stem cells were measured. Implants were evaluated for BMP-2 release by ELISA and by histology to monitor tissue formation. Hyaluronic acid+BMP-2 gels influenced the inflammatory response in the bone healing microenvironment. Host-derived putative mesenchymal stem cells were major contributors. Addition of hydroxyapatite nanoparticles modified the release pattern of rhBMP-2, resulting in enhanced bone formation.
Evaluation of the efficacy and safety of combinations of hydroquinone, glycolic acid, and hyaluronic acid in the treatment of melasma.

PubMed

Ibrahim, Zeinab A; Gheida, Shereen F; El Maghraby, Gamal M; Farag, Zeinab E

2015-06-01

Various treatments are currently available for melasma. However, results are often disappointing. 1 To assess the efficacy and safety of combinations of hydroquinone, glycolic acid, and hyaluronic acid in the treatment of melasma after topical application. 2 To evaluate the dermoscopy as a tool in diagnosis and follow-up of melasma treatment. One hundred patients with mild, moderate-to-severe melasma were divided into five groups. Group I (twenty patients were treated with cream formula containing 4% hydroquinone), group II (twenty patients were treated with cream formula containing 4% hydroquinone + 10% glycolic acid), group III (twenty patients were treated with cream formula containing 4% hydroquinone + 0.01% hyaluronic acid), group IV (twenty patients were treated with cream formula containing 4% hydroquinone + 10% glycolic acid + 0.01% hyaluronic acid), and group V (twenty patients were treated with placebo cream). All patients were subjected to dermoscopic examination and digital photographs before and after treatment. The response and side effects were evaluated. Groups I, III, and IV showed highly significant changes in modified Melasma Area and Severity Index (mMASI) score after using the treatment. Group II showed significant change in mMASI score after using the treatment. The side effects were more reported in group II, followed by group IV, followed by group I, followed by group III. There was highly significant difference between the dermoscopic color findings before and after treatment. Vascularization was another dermoscopic finding. A cream formula containing 4% hydroquinone + 10% glycolic acid + 0.01% hyaluronic acid was very effective in treatment of melasma with tolerable side effects. Dermoscope is a valuable noninvasive tool in the diagnosis and follow-up of melasma treatment. © 2015 Wiley Periodicals, Inc.
Polyamine/salt-assembled microspheres coated with hyaluronic acid for targeting and pH sensing.

PubMed

Zhang, Pan; Yang, Hui; Wang, Guojun; Tong, Weijun; Gao, Changyou

2016-06-01

The poly(allylamine hydrochloride)/trisodium citrate aggregates were fabricated and further covalently crosslinked via the coupling reaction of carboxylic sites on trisodium citrate with the amine groups on polyamine, onto which poly-L-lysine and hyaluronic acid were sequentially assembled, forming stable microspheres. The pH sensitive dye and pH insensitive dye were further labeled to enable the microspheres with pH sensing property. Moreover, these microspheres could be specifically targeted to HeLa tumor cells, since hyaluronic acid can specifically recognize and bind to CD44, a receptor overexpressed on many tumor cells. Quantitative pH measurement by confocal laser scanning microscopy demonstrated that the microspheres were internalized into HeLa cells, and accumulated in acidic compartments. By contrast, only a few microspheres were adhered on the NIH 3T3 cells surface. The microspheres with combined pH sensing property and targeting ability can enhance the insight understanding of the targeted drug vehicles trafficking after cellular internalization. Copyright © 2016 Elsevier B.V. All rights reserved.
Comparative studies of various hyaluronic acids produced by microbial fermentation for potential topical ophthalmic applications.

PubMed

Guillaumie, Fanny; Furrer, Pascal; Felt-Baeyens, Olivia; Fuhlendorff, Birgit L; Nymand, Søren; Westh, Peter; Gurny, Robert; Schwach-Abdellaoui, Khadija

2010-03-15

This work presents a comparative study of various hyaluronic acids (HA) produced by fermentation of either Bacillus subtilis or Streptococcus towards the selection of an optimal molecular weight (MW) HA for the preparation of topical ophthalmic formulations. The influence of HA MW on water binding capacity, sterile filtration, rheological properties, precorneal residence time and ocular tolerance of ophthalmic solutions was investigated. Molecular weight did not affect hydration of hyaluronic acid according to differential scanning calorimetry (DSC). In general, medium MW HA (0.6-1 MDa) resulted in solutions that were superior in terms of sterile filtration and kinematic viscosity requirements compared to high MW HA (>1 MDa). Moreover, all HA-based solutions exhibited well-defined viscoelastic properties that depend on MW. Gamma scintigraphic data indicated that HA MW at 0.1% concentration (w/v) and HA origin did not significantly affect the corneal residence time on rabbit eyes. A 0.3% solution of high MW HA had a prolonged residence time in the precorneal area compared to a medium MW HA at the same concentration. Finally, an in vivo ocular irritation test based on confocal laser scanning ophthalmoscopy (CLSO) conclusively showed the excellent tolerance of both Bacillus-derived HA and Streptococcus-derived HA after topical instillation onto the corneal surface. Overall, this comprehensive work highlights the superiority of medium MW hyaluronic acid for topical ophthalmic formulations based on their physico-chemical and biological properties, tolerance and handling. Such solutions are expected to enhance tear film stability, to allow for maximum comfort, and to exhibit high residence times, while being biocompatible and easy to sterile filter. (c) 2009 Wiley Periodicals, Inc.
A randomized, multicenter phase 3 study comparing 2% rebamipide (OPC-12759) with 0.1% sodium hyaluronate in the treatment of dry eye.

PubMed

Kinoshita, Shigeru; Oshiden, Kazuhide; Awamura, Saki; Suzuki, Hiroyuki; Nakamichi, Norihiro; Yokoi, Norihiko

2013-06-01

To investigate the efficacy of 2% rebamipide ophthalmic suspension compared with 0.1% sodium hyaluronate ophthalmic solution for the treatment of patients with dry eye. Randomized, multicenter, active-controlled parallel-group study. One hundred eighty-eight patients with dry eye. Following a 2-week screening period, patients were allocated randomly to receive 2% rebamipide or 0.1% sodium hyaluronate, administered as 1 drop in each eye 4 or 6 times daily, respectively, for 4 weeks. There were 2 primary end points: changes in the fluorescein corneal staining (FCS) score to determine noninferiority of 2% rebamipide and changes in the lissamine green conjunctival staining (LGCS) score to determine superiority. Secondary objective end points were Schirmer's test results and tear film breakup time (TBUT). Secondary subjective end points were dry eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision) score and the patients' overall treatment impression score. In the primary analysis, the mean change from baseline in FCS scores verified noninferiority, indicated significant improvement, and, in LGCS scores, verified the superiority of 2% rebamipide to 0.1% sodium hyaluronate. Values for the Schirmer's test and TBUT were comparable between the 2 groups. For 2 dry eye-related ocular symptoms--foreign body sensation and eye pain--2% rebamipide showed significant improvements over 0.1% sodium hyaluronate. Patients had a significantly more favorable impression of 2% rebamipide than of 0.1% sodium hyaluronate; 64.5% rated treatment as improved or markedly improved versus 34.7%, respectively. No serious adverse events were observed. Administration of 2% rebamipide was effective in improving both the objective signs and subjective symptoms of dry eye. Those findings, in addition to the well-tolerated profile of 2% rebamipide, clearly show that it is an effective therapeutic method for dry eye. Proprietary or commercial disclosure
The enhanced anti-tissue adhesive effect of injectable pluronic-HA hydrogel by poly(γ-glutamic acid).

PubMed

Kim, Manse; Hwang, Youngmin; Tae, Giyoong

2016-12-01

The stability of tissue barrier in physiological condition is a key factor to isolate the damaged site from adjacent tissue for anti-tissue adhesion. Although pluronic or pluronic-hyaluronic acid (HA) hydrogel as an injectable formulation can prevent tissue adhesion at the injection site, the anti-tissue adhesion effect is limited due to its poor stability. Herein, we prepared tissue barrier formulations composed of pluronic F127 (F127) and HA mixture (F127-HA) and the effect of the addition of poly(γ-glutamic acid) (PGA) was characterized. All of F127, HA, and F127-HA mixture showed the poor in vitro residence stability less than 3 days. However, by adding PGA into F127-HA mixture, their stability was significantly enhanced by the control of the molecular weight and concentration of PGA. Thus, F127-HA with 10wt% PGA (2000kDa) showed the long-term stability over 10 days. Similarly, the enhanced stability of F127-HA with PGA resulted in the enhanced and excellent in vivo anti-tissue adhesion effect, evidenced by histological analysis and grading of tissue adhesion. Therefore, F127-HA containing PGA could be applied as an efficient injectable tissue barrier for anti-tissue adhesion. Copyright © 2016 Elsevier B.V. All rights reserved.
Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel, in-vitro characterization and in-vivo evaluation.

PubMed

Ravar, Fatemeh; Saadat, Ebrahim; Gholami, Mehdi; Dehghankelishadi, Pouya; Mahdavi, Mehdi; Azami, Samira; Dorkoosh, Farid A

2016-05-10

Breast cancer is the leading cause of cancer death in women. Chemotherapy is regarded as the most essential strategy in inhibiting the proliferation of tumor cells. Paclitaxel is a widely used taxane; however, the side effects of available Cremophor-based formulations and also the limitations of passive targeting uncovered an essential need to develop tumor-specific targeted nanocarriers. A hyaluronic acid targeted liposomal formulation of paclitaxel was prepared in which, hyaluronic acid was electrostatistically attracted to the surface of liposomes. Liposomes, had a particle size of 106.4±3.2nm, a weakly negative zeta potential of -9.7±0.8mV and an acceptable encapsulation efficiency of 92.1±1.7%. The release profile of liposomes in buffer showed that 95% of PTX was released during 40h. Confocal laser scanning microscopy and flow cytometry analysis showed the greater cellular internalization of coumarin-loaded liposomes compared to free coumarin. MTT assay on 4T1 and T47D cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. Cell cycle analysis showed that cells were mainly blocked at G2/M phases after 48h treatment with liposomes. In vivo real time imaging on 4T1 tumor-bearing mice revealed that the liposomal formulation mainly accumulated in the tumor area. Liposomes also had better antitumor efficacy against Cremophor-based formulation. In conclusion, hyaluronic acid targeted paclitaxel liposome can serve as a promising targeted formulation of paclitaxel for future cancer chemotherapy. Copyright © 2016 Elsevier B.V. All rights reserved.
Efficacy of hyaluronic acid spray on swelling, pain, and trismus after surgical extraction of impacted mandibular third molars.

PubMed

Koray, M; Ofluoglu, D; Onal, E A; Ozgul, M; Ersev, H; Yaltirik, M; Tanyeri, H

2014-11-01

The aim of this study was compare the efficacies of two oral sprays in reducing swelling, pain, and trismus after the extraction of impacted mandibular third molars. This prospective double-blind, randomized, crossover clinical trial included 34 patients with bilateral symmetrically impacted mandibular third molars of similar surgical difficulty. Hyaluronic acid or benzydamine hydrochloride spray was applied (two pumps) to the extraction area, three times daily for 7 days. Swelling was evaluated using a tape measure method, pain with a visual analogue scale (VAS), and trismus by measuring the maximum inter-incisal opening. Assessments were made on the day of surgery and on days 2 and 7 after surgery. Statistically significant differences were detected for the swelling and trismus values between the two treatment groups on the second postoperative day (P=0.002 and P=0.03, respectively). However, there was no statistically significant difference in VAS scores between the two groups. The administration of hyaluronic acid spray was more effective than benzydamine hydrochloride spray in reducing swelling and trismus. Although no evidence of a reduction in pain levels was detected, hyaluronic acid appears to offer a beneficial effect in the management of swelling and trismus during the immediate postoperative period following impacted third molar surgery. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Cationic PLGA/Eudragit RL nanoparticles for increasing retention time in synovial cavity after intra-articular injection in knee joint.

PubMed

Kim, Sung Rae; Ho, Myoung Jin; Lee, Eugene; Lee, Joon Woo; Choi, Young Wook; Kang, Myung Joo

2015-01-01

Positively surface-charged poly(lactide-co-glycolide) (PLGA)/Eudragit RL nanoparticles (NPs) were designed to increase retention time and sustain release profile in joints after intra-articular injection, by forming micrometer-sized electrostatic aggregates with hyaluronic acid, an endogenous anionic polysaccharide found in high amounts in synovial fluid. The cationic NPs consisting of PLGA, Eudragit RL, and polyvinyl alcohol were fabricated by solvent evaporation technique. The NPs were 170.1 nm in size, with a zeta potential of 21.3 mV in phosphate-buffered saline. Hyperspectral imaging (CytoViva(®)) revealed the formation of the micrometer-sized filamentous aggregates upon admixing, due to electrostatic interaction between NPs and the polysaccharides. NPs loaded with a fluorescent probe (1,1'-dioctadecyl-3,3,3',3' tetramethylindotricarbocyanine iodide, DiR) displayed a significantly improved retention time in the knee joint, with over 50% preservation of the fluorescent signal 28 days after injection. When DiR solution was injected intra-articularly, the fluorescence levels rapidly decreased to 30% of the initial concentration within 3 days in mice. From these findings, we suggest that PLGA-based cationic NPs could be a promising tool for prolonged delivery of therapeutic agents in joints selectively.
A hyaluronic acid nanogel for photo-chemo theranostics of lung cancer with simultaneous light-responsive controlled release of doxorubicin

NASA Astrophysics Data System (ADS)

Khatun, Zehedina; Nurunnabi, Md; Nafiujjaman, Md; Reeck, Gerald R.; Khan, Haseeb A.; Cho, Kwang Jae; Lee, Yong-Kyu

2015-06-01

The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid nanogel) that exerts an activity with multiple effects: thermo and chemotherapeutic, real-time noninvasive imaging, and light-glutathione-responsive controlled drug release. The nanogel is mono-dispersed with an average diameter of 120 nm as observed by using TEM and a hydrodynamic size analyzer. It has excellent photo-luminescence properties and good stability in buffer and serum solutions. Graphene itself, being photoluminescent, can be considered an optical imaging contrast agent as well as a heat source when excited by laser irradiation. Thus the nanogel shows simultaneous thermo-chemotherapeutic effects on noninvasive optical imaging. We have also found that irradiation enhances the release of doxorubicin in a controlled manner. This release synergizes therapeutic activity of the nanogel in killing tumor cells. Our findings demonstrate that the graphene-doxorubicin conjugate in the hyaluronic acid nanogel is very effective in killing the human lung cancer cell line (A549) with limited toxicity in the non-cancerous cell line (MDCK).The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid
[Efficacy of hyaluronic acid in the treatment of chronic gingivitis in children].

PubMed

Igić, Marija; Mihailović, Dragan; Kesić, Ljiljana; Apostolović, Mirjana; Kostadinović, Ljiljana; Janjić, Olivera Tricković; Milasin, Jelena

2011-12-01

Gingivitis is a common occurrence in children and may well be thought as a risk factor for the appearance and progression of the diseases of parodontal tissues. It is thus necessary to react in a timely and adequate fashion to prevent the disease to become serious and produce parodontopathy. The aim of the study was to establish the efficacy of hyaluronic acid in the treatment of chronic gingivitis in children. The study enrolled 130 children with permanent dentition. All of the examinees were divided into three groups: group I--50 patients with chronic gingivitis in which only the basic treatment was applied; group II--50 patients with chronic gingivitis in which hyaluronic acid was applied in addition to basic treatment; group III--30 examinees with healthy gingiva (control group). Assessment of oral hygiene and status of the gingiva and parodontium was done using the appropriate indexes before and after the treatment. Inflammation of the gingiva was monitored by way of cytomorphometric studies. The pretreatment values of the plaque index (PI) were high: in the group I PI was 1.94; in the group II PI was 1.68. After the treatment, the PI value was reduced to null in both groups (PI = 0). In the group III PI was 0.17. The bleeding index (B1) in the group I was 2.02 before and 0.32 after the treatment; the BI value in the group II was 1.74 before and 0.16 after the treatment. In the group III BI was 0. In the group I, the Community Periodontal Index of Treatment Needs (CPITN) was 1.66 before and 0.32 after the treatment; in the group II, the CPITN value was 1.5 before and 0.24 after the treatment. In the group III, the CPITN value was 0. In the group I, the size of the nuclei of the stratified squamous epithelium of the gingiva was reduced, although not so much as the nuclear size in the group II of examinees. CONCLUSION. Basic treatment is able to successfully treat chronic gingivitis in children. The use of hyaluronic acid together with the basic treatment can
Hyaluronic acid increases tendon derived cell viability and collagen type I expression in vitro: Comparative study of four different Hyaluronic acid preparations by molecular weight.

PubMed

Osti, Leonardo; Berardocco, Martina; di Giacomo, Viviana; Di Bernardo, Graziella; Oliva, Francesco; Berardi, Anna C

2015-10-06

Hyaluronic Acid (HA) has been already approved by Food and Drug Administration (FDA) for osteoarthritis (OA), while its use in the treatment of tendinopathy is still debated. The aim of this study was to evaluate in human rotator cuff tendon derived cells the effects of four different HA on cell viability, proliferation, apoptosis and the expression of collagen type I and collagen type III. An in vitro model was developed on human tendon derived cells from rotator cuff tears to study the effects of four different HA preparations (Ps) (sodium hyaluronate MW: 500-730 KDa - Hyalgan®, 1000 kDa Artrosulfur HA®, 1600 KDa Hyalubrix® and 2200 KDa Synolis-VA®) at various concentrations. Tendon derived cells morphology were evaluated after 0, 7 and 14 d of culture. Viability, proliferation, apoptosis were evaluated after 0, 24 and 48 h of culture. The expression and deposition of collagen type I and collagen type III were evaluated after 1, 7 and 14 d of culture. All HAPs tested increased viability and proliferation, in dose dependent manner. HAPs already reduce apoptosis at 24 h compared to control cells (without HAPs). Furthermore, HAPs stimulated the synthesis of collagen type I in a dose dependent fashion over 14 d, without increase in collagen type III; moreover, in the presence of Synolis-VA® the expression and deposition of collagen type I was significantly higher as compare with the other HAPs. HAPs enhanced viability, proliferation and expression of collagen type I in tendon derived cells.
Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing Phase IV study.

PubMed

Bashaireh, Khaldoon; Naser, Ziad; Hawadya, Khaled Al; Sorour, Sorour; Al-Khateeb, Rami Nabeel

2015-01-01

The primary objective of this study was to evaluate the efficacy, safety, and duration of action of viscosupplementation with Crespine® Gel over a 9-month period. The study was a post-marketing Phase IV study. A total of 109 participants with osteoarthritis of the knee (grades 1-4) in the tibio-femoral compartment were recruited in Jordan. Data were collected from each participant during the baseline visit. Each participant received Crespine® Gel injection, and follow-up visits took place at 3 months, 6 months, and 9 months post-injection. An assessment of participants by phone was conducted at 1 month, 2 months, 4 months, 5 months, 7 months, and 8 months post-injection. Western Ontario and McMaster Universities Arthritis Index questionnaires were completed during each visit. A 72-hour visit questionnaire was used to assess the safety of the injection. Statistical analysis included a two-sided 95% confidence interval for the difference between pain scores across visits, and the percent change from baseline was calculated. The full analysis included 84 participants who gave their informed consent and finished the necessary baseline and follow-up visits needed to assess efficacy and safety. Peak improvement was noted at 5 months post-injection, when pain and physical performance scores had decreased to 2.60 and 9.90, respectively, and the stiffness score was 0.33. The peak improvement in stiffness was noted at 8 months post-injection, when the stiffness score had decreased to 0.32. Significant improvements were still apparent at 9 months post-injection, when the pain score was 3.36, the stiffness score was 0.42, and the physical performance score was 11.5. All side effects were local and transient, and included pain, swelling, and redness of the knee. Most side effects were treated. Hyaluronan should be encouraged as an alternative or adjunct treatment to oral analgesics to reduce their required doses, and delay potential future surgical intervention.
Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing Phase IV study

PubMed Central

Bashaireh, Khaldoon; Naser, Ziad; Hawadya, Khaled Al; Sorour, Sorour; Al-Khateeb, Rami Nabeel

2015-01-01

Purpose The primary objective of this study was to evaluate the efficacy, safety, and duration of action of viscosupplementation with Crespine® Gel over a 9-month period. Materials and methods The study was a post-marketing Phase IV study. A total of 109 participants with osteoarthritis of the knee (grades 1–4) in the tibio–femoral compartment were recruited in Jordan. Data were collected from each participant during the baseline visit. Each participant received Crespine® Gel injection, and follow-up visits took place at 3 months, 6 months, and 9 months post-injection. Main outcome measure(s) An assessment of participants by phone was conducted at 1 month, 2 months, 4 months, 5 months, 7 months, and 8 months post-injection. Western Ontario and McMaster Universities Arthritis Index questionnaires were completed during each visit. A 72-hour visit questionnaire was used to assess the safety of the injection. Statistical analysis included a two-sided 95% confidence interval for the difference between pain scores across visits, and the percent change from baseline was calculated. Main results The full analysis included 84 participants who gave their informed consent and finished the necessary baseline and follow-up visits needed to assess efficacy and safety. Peak improvement was noted at 5 months post-injection, when pain and physical performance scores had decreased to 2.60 and 9.90, respectively, and the stiffness score was 0.33. The peak improvement in stiffness was noted at 8 months post-injection, when the stiffness score had decreased to 0.32. Significant improvements were still apparent at 9 months post-injection, when the pain score was 3.36, the stiffness score was 0.42, and the physical performance score was 11.5. All side effects were local and transient, and included pain, swelling, and redness of the knee. Most side effects were treated. Conclusion Hyaluronan should be encouraged as an alternative or adjunct treatment to oral analgesics to reduce
Ultrasound-Guided Elbow Procedures.

PubMed

Sussman, Walter I; Williams, Christopher J; Mautner, Ken

2016-08-01

High-resolution ultrasonography can help clinicians visualize key anatomic structures of the elbow and guide periarticular and intra-articular injections. Historically, most procedures done around the elbow have been done using landmark guidance, and few studies have reported the accuracy of ultrasonography-guided injections in the elbow region. This article reviews common musculoskeletal disorders about the elbow that can be evaluated with ultrasonography, reviews the literature on ultrasonography-guided injections of the elbow region, and describes the senior author's preferred approach for the most commonly performed elbow region injections. Copyright © 2016 Elsevier Inc. All rights reserved.
Synthesis and radiosensitization properties of hydrogen peroxide and sodium hyaluronate complex

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

Rosli, Nur Ratasha Alia Md.; Mohamed, Faizal; Heng, Cheong Kai

2014-09-03

Cancer cells which are large in size are resistant towards radiation therapy due to the presence of large amount of anti-oxidative enzymes and hypoxic cancer cells. Thus radiosensitizer agents have been developed to enhance the therapeutic effect of radiotherapy by increasing the sensitivity of these cancer cells towards radiation. This study is conducted to investigate the radiosensitization properties of radiosensitizer complex containing hydrogen peroxide and sodium hyaluronate. Combination with sodium hyaluronate may decrease reactivity of hydrogen peroxide but maintain the oxygen concentration needed for radiosensitizing effect. HepG2 cancer cells are cultured as the mean of test subject. Cancer cell samplesmore » which are targeted and not targeted with these radiosensitizers are irradiated with 2Gy single fractionated dose. Results obtained shows that the cancer cells which are not targeted with radiosensitizers has a cell viability of 98.80±0.37% after a time interval of 48 hours and has even repopulated over 100% after a 72 hour time interval. This shows that the cancer cells are resistant towards radiation. However, when the cancer cells are targeted with radiosensitizers prior to irradiation, there is a reduction of cell viability by 25.50±10.81% and 10.30±5.10% at time intervals of 48 and 72 hours respectively. This indicates that through the use of these radiosensitizers, cancer cells are more sensitive towards radiation.« less

Intra-articular Injections in the Treatment of Symptoms from Ankle Arthritis: A Systematic Review.

PubMed

Vannabouathong, Christopher; Del Fabbro, Gina; Sales, Brendan; Smith, Christopher; Li, Chuan Silvia; Yardley, Darryl; Bhandari, Mohit; Petrisor, Bradley A

2018-06-01

Intra-articular (IA) injections are commonly used to treat knee arthritis pain; however, whether their efficacy generalizes to ankle arthritis remains debatable. We aimed to evaluate the evidence for IA therapies in the management of this patient population. We performed a literature search for observational and randomized controlled trials (RCTs). Treatments included corticosteroids (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), and mesenchymal stem cells (MSC). We extracted study details, patient demographics, treatment characteristics, efficacy outcomes, and safety. When feasible, data from RCTs were meta-analyzed using a random-effects model and 95% confidence intervals (CIs) were calculated. A P value <.05 was considered statistically significant. We identified 27 studies (1085 patients). Ankle OA, rheumatoid arthritis (RA), and hemophilic arthropathy populations were examined. The majority of studies were observational (20 studies); the only RCTs were those evaluating HA. Case series demonstrated favorable results in terms of symptomatic relief with CS, HA, PRP, and MSC injections; however, the effects of CS may only be short term and the evidence on MSCs was limited to 1 study with 6 ankle OA patients. Pooled results (3 RCTs, 109 patients) suggested significantly improved Ankle Osteoarthritis Scale scores with HA over saline at 6 months, with a mean difference of 12.47 points (95% CI 1.18-23.77, P = .03). Evidence from small trials favors HA and PRP injections for the treatment of pain associated with ankle osteoarthritis. However, the relative efficacy of all injectable therapies is far from definitive and warrants further high-quality comparative trials. Level III, systematic review.
Hyaluronic acid for anticancer drug and nucleic acid delivery.

PubMed

Dosio, Franco; Arpicco, Silvia; Stella, Barbara; Fattal, Elias

2016-02-01

Hyaluronic acid (HA) is widely used in anticancer drug delivery, since it is biocompatible, biodegradable, non-toxic, and non-immunogenic; moreover, HA receptors are overexpressed on many tumor cells. Exploiting this ligand-receptor interaction, the use of HA is now a rapidly-growing platform for targeting CD44-overexpressing cells, to improve anticancer therapies. The rationale underlying approaches, chemical strategies, and recent advances in the use of HA to design drug carriers for delivering anticancer agents, are reviewed. Comprehensive descriptions are given of HA-based drug conjugates, particulate carriers (micelles, liposomes, nanoparticles, microparticles), inorganic nanostructures, and hydrogels, with particular emphasis on reports of preclinical/clinical results. Copyright © 2015 Elsevier B.V. All rights reserved.
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.
The Skin Bacterium Propionibacterium acnes Employs Two Variants of Hyaluronate Lyase with Distinct Properties

PubMed Central

Nazipi, Seven; Stødkilde, Kristian; Scavenius, Carsten

2017-01-01

Hyaluronic acid (HA) and other glycosaminoglycans are extracellular matrix components in the human epidermis and dermis. One of the most prevalent skin microorganisms, Propionibacterium acnes, possesses HA-degrading activity, possibly conferred by the enzyme hyaluronate lyase (HYL). In this study, we identified the HYL of P. acnes and investigated the genotypic and phenotypic characteristics. Investigations include the generation of a P. acnes hyl knockout mutant and HYL activity assays to determine the substrate range and formed products. We found that P. acnes employs two distinct variants of HYL. One variant, HYL-IB/II, is highly active, resulting in complete HA degradation; it is present in strains of the phylotypes IB and II. The other variant, HYL-IA, has low activity, resulting in incomplete HA degradation; it is present in type IA strains. Our findings could explain some of the observed differences between P. acnes phylotype IA and IB/II strains. Whereas type IA strains are primarily found on the skin surface and associated with acne vulgaris, type IB/II strains are more often associated with soft and deep tissue infections, which would require elaborate tissue invasion strategies, possibly accomplished by a highly active HYL-IB/II. PMID:28895889
Hyaluronic acid binding by human sperm indicates cellular maturity, viability, and unreacted acrosomal status.

PubMed

Huszar, Gabor; Ozenci, Ciler Celik; Cayli, Sevil; Zavaczki, Zoltan; Hansch, Eleonora; Vigue, Lynne

2003-06-01

To test, both in semen and washed-sperm fractions, whether hyaluronic acid (HA) binding is restricted to sperm that have completed cellular maturation. Comparisons of sperm in semen and in HA-bound sperm fractions. University-based diagnostic and research andrology laboratory. Semen samples originated in men being tested for infertility. The attributes of sperm maturity were tested by immunocytochemistry with creatine kinase and HspA2 antisera (highlights cytoplasmic retention in diminished-maturity sperm), aniline blue chromatin staining (detects persistent histones), pisum sativum lectin staining (reveals acrosomal integrity), and the FertiLight viability kit (highlights viable and nonviable sperm). All markers of sperm maturity and immaturity supported the hypothesis that HA-bound sperm are mature. Nonbinding sperm exhibited cytoplasmic and nuclear properties of diminished maturity. The acrosomal status of HA-bound sperm was either unreacted or slightly capacitated, but not acrosome reacted. Only viable sperm exhibited HA binding. Sperm that are able to bind to HA are mature and have completed the spermiogenetic processes of sperm plasma membrane remodeling, cytoplasmic extrusion, and nuclear histone-protamine replacement. Hyaluronic acid-bound sperm show unreacted acrosomes. These studies provide further insights into the relationship between spermiogenesis and sperm function.
Does Intra-articular Platelet-Rich Plasma Injection Provide Clinically Superior Outcomes Compared With Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review of Overlapping Meta-analyses.

PubMed

Campbell, Kirk A; Saltzman, Bryan M; Mascarenhas, Randy; Khair, M Michael; Verma, Nikhil N; Bach, Bernard R; Cole, Brian J

2015-11-01

The aims of this study were (1) to perform a systematic review of meta-analyses evaluating platelet-rich plasma (PRP) injection in the treatment of knee joint cartilage degenerative pathology, (2) to provide a framework for analysis and interpretation of the best available evidence to provide recommendations for use (or lack thereof) of PRP in the setting of knee osteoarthritis (OA), and (3) to identify literature gaps where continued investigation would be suggested. Literature searches were performed for meta-analyses examining use of PRP versus corticosteroids, hyaluronic acid, oral nonsteroidal anti-inflammatory drugs, or placebo. Clinical data were extracted, and meta-analysis quality was assessed. The Jadad algorithm was applied to determine meta-analyses that provided the highest level of evidence. Three meta-analyses met the eligibility criteria and ranged in quality from Level II to Level IV evidence. All studies compared outcomes of treatment with intra-articular platelet-rich plasma (IA-PRP) versus control (intra-articular hyaluronic acid or intra-articular placebo). Use of PRP led to significant improvements in patient outcomes at 6 months after injection, and these improvements were seen starting at 2 months and were maintained for up to 12 months. It is unclear if the use of multiple PRP injections, the double-spinning technique, or activating agents leads to better outcomes. Patients with less radiographic evidence of arthritis benefit more from PRP treatment. The use of multiple PRP injections may increase the risk of self-limited local adverse reactions. After application of the Jadad algorithm, 3 concordant high-quality meta-analyses were selected and all showed that IA-PRP provided clinically relevant improvements in pain and function compared with the control treatment. IA-PRP is a viable treatment for knee OA and has the potential to lead to symptomatic relief for up to 12 months. There appears to be an increased risk of local adverse
Hyaluronic acid-coated, prodrug-based nanostructured lipid carriers for enhanced pancreatic cancer therapy.

PubMed

Lu, Zhihe; Su, Jingrong; Li, Zhengrong; Zhan, Yuzhu; Ye, Decai

2017-01-01

Gemcitabine (GEM) and Baicalein (BCL) are reported to have anti-tumor effects including pancreatic cancer. Hyaluronic acid (HA) can bind to over-expressed receptors in various kinds of cancer cells. The aim of this study is to develop prodrugs containing HA, BCL and GEM, and construct nanomedicine incorporate GEM and BCL in the core and HA on the surface. This system could target the cancer cells and co-deliver the drugs. GEM-stearic acid lipid prodrug (GEM-SA) and hyaluronic acid-amino acid-baicalein prodrug (HA-AA-BCL) were synthesized. Then, GEM and BCL prodrug-based targeted nanostructured lipid carriers (HA-GEM-BCL NLCs) were prepared by the nanoprecipitation technique. The in vitro cytotoxicity studies of the NLCs were evaluated on AsPC1 pancreatic cancer cell line. In vivo anti-tumor effects were observed on the murine-bearing pancreatic cancer model. HA-GEM-BCL NLCs were effective in entering pancreatic cancer cells over-expressing HA receptors, and showed cytotoxicity of tumor cells in vitro. In vivo study revealed significant tumor growth inhibition ability of HA-GEM-BCL NLCs in murine pancreatic cancer model. It could be concluded that HA-GEM-BCL NLCs could be featured as promising co-delivery, tumor-targeted nanomedicine for the treatment of cancers.
Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study.

PubMed

Vangsness, C Thomas; Farr, Jack; Boyd, Joel; Dellaero, David T; Mills, C Randal; LeRoux-Williams, Michelle

2014-01-15

There are limited treatment options for tissue restoration and the prevention of degenerative changes in the knee. Stem cells have been a focus of intense preclinical research into tissue regeneration but limited clinical investigation. In a randomized, double-blind, controlled study, the safety of the intra-articular injection of human mesenchymal stem cells into the knee, the ability of mesenchymal stem cells to promote meniscus regeneration following partial meniscectomy, and the effects of mesenchymal stem cells on osteoarthritic changes in the knee were investigated. A total of fifty-five patients at seven institutions underwent a partial medial meniscectomy. A single superolateral knee injection was given within seven to ten days after the meniscectomy. Patients were randomized to one of three treatment groups: Group A, in which patients received an injection of 50 × 10⁶ allogeneic mesenchymal stem cells; Group B, 150 × 10⁶ allogeneic mesenchymal stem cells; and the control group, a sodium hyaluronate (hyaluronic acid/hyaluronan) vehicle control. Patients were followed to evaluate safety, meniscus regeneration, the overall condition of the knee joint, and clinical outcomes at intervals through two years. Evaluations included sequential magnetic resonance imaging (MRI). No ectopic tissue formation or clinically important safety issues were identified. There was significantly increased meniscal volume (defined a priori as a 15% threshold) determined by quantitative MRI in 24% of patients in Group A and 6% in Group B at twelve months post meniscectomy (p = 0.022). No patients in the control group met the 15% threshold for increased meniscal volume. Patients with osteoarthritic changes who received mesenchymal stem cells experienced a significant reduction in pain compared with those who received the control, on the basis of visual analog scale assessments. There was evidence of meniscus regeneration and improvement in knee pain following treatment with
Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials.

PubMed

Coombes, Brooke K; Bisset, Leanne; Vicenzino, Bill

2010-11-20

Few evidence-based treatment guidelines for tendinopathy exist. We undertook a systematic review of randomised trials to establish clinical efficacy and risk of adverse events for treatment by injection. We searched eight databases without language, publication, or date restrictions. We included randomised trials assessing efficacy of one or more peritendinous injections with placebo or non-surgical interventions for tendinopathy, scoring more than 50% on the modified physiotherapy evidence database scale. We undertook meta-analyses with a random-effects model, and estimated relative risk and standardised mean differences (SMDs). The primary outcome of clinical efficacy was protocol-defined pain score in the short term (4 weeks, range 0-12), intermediate term (26 weeks, 13-26), or long term (52 weeks, ≥52). Adverse events were also reported. 3824 trials were identified and 41 met inclusion criteria, providing data for 2672 participants. We showed consistent findings between many high-quality randomised controlled trials that corticosteroid injections reduced pain in the short term compared with other interventions, but this effect was reversed at intermediate and long terms. For example, in pooled analysis of treatment for lateral epicondylalgia, corticosteroid injection had a large effect (defined as SMD>0·8) on reduction of pain compared with no intervention in the short term (SMD 1·44, 95% CI 1·17-1·71, p<0·0001), but no intervention was favoured at intermediate term (-0·40, -0·67 to -0·14, p<0·003) and long term (-0·31, -0·61 to -0·01, p=0·05). Short-term efficacy of corticosteroid injections for rotator-cuff tendinopathy is not clear. Of 991 participants who received corticosteroid injections in studies that reported adverse events, only one (0·1%) had a serious adverse event (tendon rupture). By comparison with placebo, reductions in pain were reported after injections of sodium hyaluronate (short [3·91, 3·54-4·28, p<0·0001], intermediate
Current and innovative pain management techniques in total knee arthroplasty.

PubMed

Dalury, David F; Lieberman, Jay R; Macdonald, Steven J

2012-01-01

Pain management is a major concern for patients contemplating total knee replacement surgery and is one of the leading causes of dissatisfaction after knee replacement. Substantial progress has been made over the past several years in improving pain control after total knee replacement using multimodal pain control, preemptive analgesia, and periarticular injections.
Efficacy of Direct Injection of Etanercept into Knee Joints for Pain in Moderate and Severe Knee Osteoarthritis

PubMed Central

Orita, Sumihisa; Yamauchi, Kazuyo; Eguchi, Yawara; Ochiai, Nobuyasu; Kishida, Shunji; Kuniyoshi, Kazuki; Aoki, Yasuchika; Nakamura, Junichi; Ishikawa, Tetsuhiro; Miyagi, Masayuki; Kamoda, Hiroto; Suzuki, Miyako; Kubota, Gou; Sakuma, Yoshihiro; Oikawa, Yasuhiro; Inage, Kazuhide; Sainoh, Takeshi; Sato, Jun; Shiga, Yasuhiro; Abe, Koki; Fujimoto, Kazuki; Kanamoto, Hiroto; Toyone, Tomoaki; Inoue, Gen; Takahashi, Kazuhisa

2015-01-01

Purpose Osteoarthritic (OA) pain is largely considered to be inflammatory pain. However, during the last stage of knee OA, sensory nerve fibers in the knee are shown to be significantly damaged when the subchondral bone junction is destroyed, and this can induce neuropathic pain. Several authors have reported that tumor necrosis factor-α (TNFα) in a knee joint plays a crucial role in pain modulation. The purpose of the current study was to evaluate the efficacy of etanercept, a TNFα inhibitor, for pain in knee OA. Materials and Methods Thirty-nine patients with knee OA and a 2-4 Kellgren-Lawrence grading were evaluated in this prospective study. Patients were divided into two groups; hyaluronic acid (HA) and etanercept injection. All patients received a single injection into the knee. Pain scores were evaluated before and 4 weeks after injection using a visual analogue scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and they were compared between the groups. Results Before injection, VAS and WOMAC scores were not significantly different between the groups (p>0.05). Significant pain relief was found in the etanercept group at 1 and 2 weeks by VAS, and at 4 weeks by WOMAC score, compared with the HA group (p<0.05). No adverse events were observed in either group. Conclusion Direct injection of etanercept into OA knee joints was an effective treatment for pain in moderate and severe OA patients. Furthermore, this finding suggests that TNFα is one factor that induces OA pain. PMID:26256983
Electrostatic effects on hyaluronic acid configuration

NASA Astrophysics Data System (ADS)

Berezney, John; Saleh, Omar

2015-03-01

In systems of polyelectrolytes, such as solutions of charged biopolymers, the electrostatic repulsion between charged monomers plays a dominant role in determining the molecular conformation. Altering the ionic strength of the solvent thus affects the structure of such a polymer. Capturing this electrostatically-driven structural dependence is important for understanding many biological systems. Here, we use single molecule manipulation experiments to collect force-extension behavior on hyaluronic acid (HA), a polyanion which is a major component of the extracellular matrix in all vertebrates. By measuring HA elasticity in a variety of salt conditions, we are able to directly assess the contribution of electrostatics to the chain's self-avoidance and local stiffness. Similar to recent results from our group on single-stranded nucleic acids, our data indicate that HA behaves as a swollen chain of electrostatic blobs, with blob size proportional to the solution Debye length. Our data indicate that the chain structure within the blob is not worm-like, likely due to long-range electrostatic interactions. We discuss potential models of this effect.
The Effect of Tear Supplementation with 0.15% Preservative-Free Zinc-Hyaluronate on Ocular Surface Sensations in Patients with Dry Eye.

PubMed

Perényi, Kristóf; Dienes, Lóránt; Kornafeld, Anna; Kovács, Balázs; Kiss, Huba J; Szepessy, Zsuzsanna; Nagy, Zoltán Z; Barsi, Árpád; Acosta, M Carmen; Gallar, Juana; Kovács, Illés

To evaluate the effect of tear supplementation with preservative free 0.15% zinc-hyaluronate on ocular surface sensations and corneal sensitivity in dry eye patients. Ocular surface sensations were assessed using the ocular surface disease index (OSDI) questionnaire and by recording ocular sensations during forced blinking in parallel with noninvasive tear film breakup time measurement in 20 eyes of 20 dry eye patients. Corneal sensitivity thresholds to selective stimulation of corneal mechano-, thermal- and chemical receptors were measured using the Belmonte gas esthesiometer. All baseline measurements were repeated after 1 month of treatment with 0.15% zinc-hyaluronate. After 1 month, a significant decrease in mean OSDI score (from 35.66 ± 12.36 to 15.03 ± 11.22; P < 0.001) and a significant improvement in tear film breakup time (from 3.83 ± 0.80 to 8.67 ± 4.50 s; P < 0.001) was observed compared to baseline. Sensory responses during the interblink period also significantly decreased after 1 month (P < 0.004). Corneal sensitivity thresholds to mechanical stimulation (90.61 ± 20.35 vs. 103.92 ± 17.97 mL/min; P < 0.025) and chemical stimulation (33.21 ± 0.51 vs. 33.58% ± 0.44% CO 2 ; P < 0.025) significantly increased after 1 month, however sensitivity thresholds to thermal stimulation remained unchanged compared to baseline (P > 0.05). Prolonged use of 0.15% zinc-hyaluronate results in an improvement of tear film stability and a decrease of dry eye complaints. The decrease in corneal mechano-and polymodal receptor excitability suggests that zinc-hyaluronate helps to recover normal corneal sensitivity, and thus might have a beneficial additional effect on reducing ocular surface complaints in dry eye patients.
Photo-crosslinked hyaluronic acid coated upconverting nanoparticles

NASA Astrophysics Data System (ADS)

Mrazek, Jiri; Kettou, Sofiane; Matuska, Vit; Svozil, Vit; Huerta-Angeles, Gloria; Pospisilova, Martina; Nesporova, Kristina; Velebny, Vladimir

2017-02-01

Hyaluronic acid (HA)-coated inorganic nanoparticles display enhanced interaction with the CD44 receptors which are overexpressed in many types of cancer cells. Here, we describe a modification of core-shell β-NaY0.80Yb0.18Er0.02F4@NaYF4 nanoparticles (UCNP) by HA derivative bearing photo-reactive groups. UCNP capped with oleic acid were firstly transferred to aqueous phase by an improved protocol using hydrochloric acid or lactic acid treatment. Subsequently, HA bearing furanacryloyl moieties (HA-FU) was adsorbed on the nanoparticle surface and crosslinked by UV irradiation. The crosslinking resulted in stable HA coating, and no polymer desorption was observed. As-prepared UCNP@HA-FU show a hydrodynamic diameter of about 180 nm and are colloidally stable in water and cell culture media. The cellular uptake by normal human fibroblasts and MDA MB-231 cancer cell line was investigated by upconversion luminescence imaging.
A Micro-Ark for Cells: Highly Open Porous Polyhydroxyalkanoate Microspheres as Injectable Scaffolds for Tissue Regeneration.

PubMed

Wei, Dai-Xu; Dao, Jin-Wei; Chen, Guo-Qiang

2018-06-19

To avoid large open surgery using scaffold transplants, small-sized cell carriers are employed to repair complexly shaped tissue defects. However, most cell carriers show poor cell adherences and viability. Therefore, polyhydroxyalkanoate (PHA), a natural biopolymer, is used to prepare highly open porous microspheres (OPMs) of 300-360 µm in diameter, combining the advantages of microspheres and scaffolds to serve as injectable carriers harboring proliferating stem cells. In addition to the convenient injection to a defected tissue, and in contrast to poor performances of OPMs made of polylactides (PLA OPMs) and traditional less porous hollow microspheres (PHA HMs), PHA OPMs present suitable surface pores of 10-60 µm and interconnected passages with an average size of 8.8 µm, leading to a high in vitro cell adhesion of 93.4%, continuous proliferation for 10 d and improved differentiation of human bone marrow mesenchymal stem cells (hMSCs). PHA OPMs also support stronger osteoblast-regeneration compared with traditional PHA HMs, PLA OPMs, commercial hyaluronic acid hydrogels, and carrier-free hMSCs in an ectopic bone-formation mouse model. PHA OPMs protect cells against stresses during injection, allowing more living cells to proliferate and migrate to damaged tissues. They function like a micro-Noah's Ark to safely transport cells to a defect tissue. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
[In vitro evaluation of the gels properties prepared thermosensitive polymers as vehicles for administration substance by injection].

PubMed

Karolewicz, Bozena; Owczarek, Artur; Pluta, Janusz

2011-01-01

The aim of this study was to prepare a thermoresponsive formulations, which are a carrier for substance administered directly into site of action and which obtain sol-gel transitions at physiological ranges of temperature. The investigated formulations of liquid consistency at room temperature were obtained in sterile conditions on the basis of nonionic polymers Pluronic F-127, Pluronic F-68 and anionic polymer hyaluronic acid in different concentrations. The sol-gel transition temperature of the formulations was investigated and their physicochemical properties such as pH, density, osmotic pressure, sol-gel transition temperature, texture and release of vancomycin hydrochloride were studied. In vitro release experiments indicated that the optimised platform was able to prolong vancomycin hydrochloride release and their physico-chemical properties allow for application by injection form.
The Relationship between Chondromalacia Patella, Medial Meniscal Tear and Medial Periarticular Bursitis in Patients with Osteoarthritis.

PubMed

Resorlu, Mustafa; Doner, Davut; Karatag, Ozan; Toprak, Canan Akgun

2017-12-01

This study investigated the presence of bursitis in the medial compartment of the knee (pes anserine, semimembranosus-tibial collateral ligament, and medial collateral ligament bursa) in osteoarthritis, chondromalacia patella and medial meniscal tears. Radiological findings of 100 patients undergoing magnetic resonance imaging with a preliminary diagnosis of knee pain were retrospectively evaluated by two radiologists. The first radiologist assessed all patients in terms of osteoarthritis, chondromalacia patella and medial meniscal tear. The second radiologist was blinded to these results and assessed the presence of bursitis in all patients. Mild osteoarthritis (grade I and II) was determined in 55 patients and severe osteoarthritis (grade III and IV) in 45 cases. At retropatellar cartilage evaluation, 25 patients were assessed as normal, while 29 patients were diagnosed with mild chondromalacia patella (grade I and II) and 46 with severe chondromalacia patella (grade III and IV). Medial meniscus tear was determined in 51 patients. Severe osteoarthritis and chondromalacia patella were positively correlated with meniscal tear (p < 0.001 and p = 0.018, respectively). Significant correlation was observed between medial meniscal tear and bursitis in the medial compartment (p = 0.038). Presence of medial periarticular bursitis was positively correlated with severity of osteoarthritis but exhibited no correlation with chondromalacia patella (p = 0.023 and p = 0.479, respectively). Evaluation of lateral compartment bursae revealed lateral collateral ligament bursitis in 2 patients and iliotibial bursitis in 5 patients. We observed a greater prevalence of bursitis in the medial compartment of the knee in patients with severe osteoarthritis and medial meniscus tear.
Hyaluronic Acid in Vascular and Immune Homeostasis during Normal Pregnancy and Preeclampsia

PubMed Central

Ziganshina, M. M.; Pavlovich, S. V.; Bovin, N. V.; Sukhikh, G. T.

2016-01-01

Preeclampsia (PE) is a multisystem pathologic state that clinically manifests itself after the 20th week of pregnancy. It is characterized by high maternal and perinatal morbidity and mortality. According to modern concepts, the impairment of trophoblast invasion into maternal spiral arteries, leading to the development of ischemia in placenta, is considered to be the major pathogenetic factor of PE development. Ischemic lesions initiate the development of a systemic inflammatory response (SIR) and endothelial dysfunction, which is the main cause of the multiple organ failure in PE. Some data has appear indicating the importance of a glycans-forming endothelial glycocalyx and extracellular matrix (ECM) for placenta morphogenesis, as well as their role in the regulation of vascular permeability and vascular tone in hypertension disorders and, in particular, PE. Since intact glycocalyx and ECM are considered to be the major factors that maintain the physiological vascular tone and adequate intercellular interactions, their value in PE pathogenesis is underestimated. This review is focused on hyaluronic acid (HA) as the key glycan providing the organization and stabilization of the ECM and glycocalyx, its distribution in tissues in the case of presence or absence of placental pathology, as well as on the regulatory function of hyaluronic acids of various molecular weights in different physiological and pathophysiological processes. The summarized data will provide a better understanding of the PE pathogenesis, with the main focus on glycopathology. PMID:27795844
Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration.

PubMed

Han, Xiaofeng; Wang, Zhe; Wang, Manyuan; Li, Jing; Xu, Yongsong; He, Rui; Guan, Hongyu; Yue, Zhujun; Gong, Muxin

2016-06-01

In order to enhance oral bioavailability and liver targeting delivery of silybin, two amphiphilic hyaluronic acid derivatives, hyaluronic acid-deoxycholic acid (HA-adh-DOCA) and hyaluronic acid-glycyrrhetinic acid (HA-adh-GA) conjugates, were designed and synthesized. Silybin was successfully loaded in HA-adh-DOCA and HA-adh-GA micelles with high drug-loading capacities (20.3% ± 0.5% and 20.6% ± 0.6%, respectively). The silybin-loaded micelles were spherical in shape with the average size around 130 nm. In vitro release study showed that two silybin-loaded micelles displayed similar steady continued-release pattern in simulated gastrointestinal fluids and PBS. Single-pass intestinal perfusion studies indicated that silybin-loaded micelles were absorbed in the whole intestine and transported via a passive diffusion mechanism. Compared with suspension formulation, silybin-loaded HA-adh-DOCA and HA-adh-GA micelles achieved significantly higher AUC and Cmax level. Moreover, liver targeting drug delivery of micelles was confirmed by in vivo imaging analysis. In comparison between the two micellar formulations, HA-adh-GA micelles possessed higher targeting capacity than HA-adh-DOCA micelles, owing to the active hepatic targeting properties of glycyrrhetinic acid. In the treatment of acute liver injury induced by CCl4, silybin-loaded HA-adh-GA micelles displayed better effects over suspension control and silybin-loaded HA-adh-DOCA micelles. Overall, pharmaceutical and pharmacological indicators suggested that the HA-adh-GA conjugates can be successfully utilized for liver targeting of orally administered therapeutics.
Oral soft tissue wound healing after laser surgery with or without a pool of amino acids and sodium hyaluronate: a randomized clinical study.

PubMed

Romeo, Umberto; Libotte, Fabrizio; Palaia, Gaspare; Galanakis, Alexandros; Gaimari, Gianfranco; Tenore, Gianluca; Del Vecchio, Alessandro; Polimeni, Antonella

2014-01-01

The purpose of this study was to compare secondary intention healing of oral soft tissues after laser surgery with and without the use of a compound containing amino acids and sodium hyaluronate. Sodium hyaluronate has been successfully used in medicine to promote healing. It has not been studied in the healing of laser-produced wounds. Excisional biopsy was performed in oral soft tissues with a potassium-titanyl-phosphate (KTP) laser (532 nm, SmartLite, DEKA, Florence, Italy) in 49 patients divided into two groups. In the study group (SG), 31 patients received a compound gel containing four amino acids and sodium hyaluronate (Aminogam(®), Errekappa, Italy) after laser surgery; in the control group (CG), 18 subjects received no treatment involving a drug or gel. Numeric rating scale (NRS) was used to evaluate pain experienced after surgery [pain index (PI)]. Using a grid as a benchmark and computer software, the lesion area was measured after surgery (T0) and after 7 days (T1). A percentage healing index (PHI) was calculated indicating healing extension in 7 days. SG cases showed an average PHI of 64.38±26.50, whereas the average PHI in the CG was 47.88%±27.84. Mean PI was 2.67±0.96 for SG and 2.75±0.86 for CG. A statistically significant difference was detected between the groups for PHI (p=0.0447), whereas no difference was detectable for PI (p=0.77). The use of a gel containing amino acids and sodium hyaluronate can promote faster healing via secondary intention in laser-induced wounds, although it does not seem to affect pain perception.

97% accuracy of intra-articular glenohumeral injection with a modified (Delaware) posterior bone touch technique.

PubMed

Axe, Jeremie M; Axe, Michael J

2013-10-01

injecting pathologic glenohumeral joints with corticosteroids or hyaluronic acid. IV Case Series.
Characterization of protein release from photocrosslinkable hyaluronic acid-polyethylene glycol hydrogel tissue engineering scaffolds.

PubMed

Leach, Jennie B; Schmidt, Christine E

2005-01-01

The goal of this work was to utilize the naturally derived bioactive polymer hyaluronic acid (HA) to create a combination tissue engineering scaffold and protein delivery device. HA is a non-immunogenic, non-adhesive glycosaminoglycan that plays significant roles in several cellular processes, including angiogenesis and the regulation of inflammation. In previous work, we created photopolymerizable glycidyl methacrylate-hyaluronic acid (GMHA) hydrogels that had controlled degradation rates, were cytocompatible, and were able to be modified with peptide moieties. In the present studies, we characterized the release of a model protein, bovine serum albumin (BSA), from GMHA and GMHA-polyethylene glycol (PEG) hydrogels. Although BSA could be released rapidly (> 60% within 6 h) from 1% GMHA hydrogels, we found that increasing either the GMHA or the PEG concentrations could lengthen the duration of protein delivery. Preliminary size exclusion chromatography studies indicated that the released BSA was almost entirely in its native monomeric form. Lastly, protein release was extended to several weeks by suspending BSA-poly(lactic-co-glycolic acid) microspheres within the hydrogel bulk. These initial studies indicate that the naturally derived biopolymer HA can be employed to design novel photopolymerizable composites that are suitable for delivering stable proteins from scaffolding in tissue engineering applications.
Hyaluronic acid modified chitosan nanoparticles for effective management of glaucoma: development, characterization, and evaluation.

PubMed

Wadhwa, Sheetu; Paliwal, Rishi; Paliwal, Shivani R; Vyas, S P

2010-05-01

In clinical practices, solution of dorzolamide hydrochloride (DH) and timolol maléate (TM) is recommended for the treatment of glaucoma. However, low drug-contact time and poor ocular bioavailability of drugs due to drainage of solution, tear turnover and its dilution or lacrimation limits its uses. In addition, systemic absorption of TM may induce undesirable cardiovascular side effects. Chitosan (CS) is a polycationic biodegradable polymer which provides sustained and local delivery of drugs to the ocular sites. Hyaluronic acid (HA) also provides synergistic effect for mucoadhesion in association with chitosan. In the present study, hyaluronic acid modified chitosan nanoparticles (CS-HA-NPs) loaded with TM and DH were developed and characterized. The CS-HA-NPs were evaluated for size, shape, zeta potential, entrapment efficiency, and mucoadhesive strength. The in vitro release study was also performed in PBS pH 7.4. The ocular irritation potential of CS-HA-NPs was estimated using draize test on albino rabbits. A significant reduction in IOP level was obtained using CS-HA-NPs as compared to plain solution of drug and a comparable higher reduction in IOP level was observed as to CS-NPs. These results suggest that HA potentialy enhance the mucoadhesiveness and efficiency of CS-NPs and may be promising carrier for ocular drug delivery.
Consensus on Current Injectable Treatment Strategies in the Asian Face.

PubMed

Wu, Woffles T L; Liew, Steven; Chan, Henry H; Ho, Wilson W S; Supapannachart, Nantapat; Lee, Hong-Ki; Prasetyo, Adri; Yu, Jonathan Nevin; Rogers, John D

2016-04-01

The desire for and use of nonsurgical injectable esthetic facial treatments are increasing in Asia. The structural and anatomical features specific to the Asian face, and differences from Western populations in facial aging, necessitate unique esthetic treatment strategies, but published recommendations and clinical evidence for injectable treatments in Asians are scarce. The Asian Facial Aesthetics Expert Consensus Group met to discuss current practices and consensus opinions on the cosmetic use of botulinum toxin and hyaluronic acid (HA) fillers, alone and in combination, for facial applications in Southeastern and Eastern Asians. Consensus opinions and statements on treatment aims and current practice were developed following discussions regarding pre-meeting and meeting survey outcomes, peer-reviewed literature, and the experts' clinical experience. The indications and patterns of use of injectable treatments vary among patients of different ages, and among Asian countries. The combination use of botulinum toxin and fillers increases as patients age. Treatment aims in Asians and current practice regarding the use of botulinum toxin and HA fillers in the upper, middle, and lower face of patients aged 18 to >55 years are presented. In younger Asian patients, addressing proportion and structural features and deficiencies are important to achieve desired esthetic outcomes. In older patients, maintaining facial structure and volume and addressing lines and folds are essential to reduce the appearance of aging. This paper provides guidance on treatment strategies to address the complex esthetic requirements in Asian patients of all ages. This journal requires that the 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.
Hyaluronic Acid and Hyaluronidase in Prostate Cancer: Evaluation of Their Therapeutic and Prognostic Potential

DTIC Science & Technology

2006-01-01

human prostate cancer cells. J Cell Physiol. 1995, 64: 605-612. 31. Iczkowski, KA , Bai, S, Pantazis, CG. Prostate cancer overexpresses CD44 variants 7-9...Dennis RAM, Adriana BN, Rocha DA, Gilberto S (2000) 9-aminocamptothecin and 9-nitrocamptothecin) [6] or Anti-cancer drug discovery and development in...Young MJ, Duncan RC, Urology 2003;61:30-6. Soloway MS, Block NL. Urinary hyaluronic acid and hyaluronidase: 6. Symon Z, Griffith KA , McLaughlin PW
Novel apigenin-loaded sodium hyaluronate nano-assemblies for targeting tumor cells.

PubMed

Zhao, Ting; He, Yue; Chen, Huali; Bai, Yan; Hu, Wenjing; Zhang, Liangke

2017-12-01

We aimed to construct a novel nano-assembly carrying apigenin (APG), a hydrophobic drug, and to evaluate its in vitro targeting ability for A549 cells overexpressing CD44 receptors. The apigenin-loaded sodium hyaluronate nano-assemblies (APG/SH-NAs) were assembled by multiple non-covalent interactions between sodium hyaluronate (SH) and APG. The prepared APG/SH-NAs exhibited a small average size and narrow particle size distribution. In addition, satisfactory encapsulation efficiency and drug loading were obtained. The drug release curves indicated that APG/SH-NAs achieved a sustainable drug-release effect due to the presence of hydrophilic materials. The in vitro cytotoxicity of APG/SH-NAs against A549 cells and HepG2 cells was evaluated, and the results indicated that the prepared APG/SH-NA showed higher cytotoxicity compared to apigenin suspensions. When CD44 receptors on the surface of A549 cells were blocked by the addition of excess SH, the cytotoxicity of APG/SH-NA was significantly reduced. However, similar phenomena were not observed in HepG2 cells with relatively low CD44 receptor expression. The resulting APG/SH-NAs could efficiently facilitate the internalization of APG into A549 cells, which might be due to their high affinity for CD44 receptors. Moreover, the apoptotic rate of APG/SH-NAs through receptor-mediated endocytosis mechanism was higher than that of the other groups in A549 cells. Thus, such nano-assemblies were considered to be an effective transport system with excellent affinity for CD44 receptors to allow the SH-mediated targeted delivery of APG. Copyright © 2017. Published by Elsevier Ltd.
[Delayed Infection after Upper Lip Augmentation with Absorbable Hyaluronic Acid Filler].

PubMed

Heim, N; Faron, A; Wiedemeyer, V; Teschke, M; Reich, R H; Martini, M

2015-08-01

Since introduction of the first fillers in the 1980s a multitude of substances has been developed and approved for facial contour augmentation and correction of skin defects. Here we present the interesting case of a patient who presented to us with a delayed infection 6 weeks after augmentation of the upper lip with a hyaluronic acid. We observed full convalescence after operative and high-dose antibiotic treatment of the abscesses. Generally speaking, complications after augmentation with resorbable fillers are rare. However, complications might occur even within unexpected time periods and therefore need our special attention. © Georg Thieme Verlag KG Stuttgart · New York.
Safety and Efficacy of Cortisol Phosphate in Hyaluronic Acid Vehicle in the Treatment of Dry Eye in Sjogren Syndrome.

PubMed

Rolando, Maurizio; Vagge, Aldo

2017-06-01

Evaluation of 0.3% cortisol phosphate eye drops in hyaluronic acid vehicle in the treatment of dry eye in Sjogren Syndrome. This prospective, single-center, masked (single blind), randomized controlled study included 40 female patients divided into 2 groups, group 1 treated with Idracemi, 0.3% cortisol phosphate eye drops twice a day, and group 2 treated with Cortivis, 0.3% cortisol phosphate in hyaluronic acid vehicle, with the same posology. Screening (day -7), randomization (day 0), follow-up (day 7), and termination (day 28) visits were conducted. Symptoms (VAS) questionnaire, tear film breakup time, corneo-conjunctival stain, intraocular pressure (IOP) measurement, and fundus examination were performed at each visit. Conjunctival impression cytology for human leukocyte antigen-DR (HLA-DR) expression at visit 1 and 4 was also performed. No changes in IOP or fundus examination were observed in either group at each time point. Group 1 showed at day 28 a statistically significant amelioration of symptoms and reduction of HLA-DR expression. Group 2 showed at day 7 statistically significant improvement of corneal and conjunctival stain versus baseline and versus group 1; the symptom score was statistically significantly better than baseline and versus group 1 after 28 days too. The HLA-DR expression and the epithelial cell area were statistically significantly reduced versus baseline and versus group 1 at the same time. Cortisol phosphate proved to be safe and effective in treating dry eye in Sjogren Syndrome patients in both formulations. However, the formula with hyaluronic acid vehicle proved to be more effective. Both formulations were very well tolerated.
Hyaluronan injection in murine osteoarthritis prevents TGFbeta 1-induced synovial neovascularization and fibrosis and maintains articular cartilage integrity by a CD44-dependent mechanism

PubMed Central

2012-01-01

Introduction The mechanism by which intra-articular injection of hyaluronan (HA) ameliorates joint pathology is unknown. Animal studies have shown that HA can reduce synovial activation, periarticular fibrosis and cartilage erosion; however, its specific effects on the different cell types involved remain unclear. We have used the TTR (TGFbeta1 injection and Treadmill Running) model of murine osteoarthritis (OA), which exhibits many OA-like changes, including synovial activation, to examine in vivo tissue-specific effects of intra-articular HA. Methods The kinetics of clearance of fluorotagged HA from joints was examined with whole-body imaging. Naïve and treated knee joints were examined macroscopically for cartilage erosion, meniscal damage and fibrosis. Quantitative histopathology was done with Safranin O for cartilage and with Hematoxylin & Eosin for synovium. Gene expression in joint tissues for Acan, Col1a1, Col2a1, Col3a1, Col5a1, Col10a1, Adamts5 and Mmp13 was done by quantitative PCR. The abundance and distribution of aggrecan, collagen types I, II, III, V and X, ADAMTS5 and MMP13 were examined by immunohistochemistry. Results Injected HA showed a half-life of less than 2 h in the murine knee joint. At the tissue level, HA protected against neovascularization and fibrosis of the meniscus/synovium and maintained articular cartilage integrity in wild-type but not in Cd44 knockout mice. HA injection enhanced the expression of chondrogenic genes and proteins and blocked that of fibrogenic/degradative genes and proteins in cartilage/subchondral bone, whereas it blocked activation of both groups in meniscus/synovium. In all locations it reduced the expression/protein for Mmp13 and blocked Adamts5 expression but not its protein abundance in the synovial lining. Conclusions The injection of HA, 24 h after TGFbeta1 injection, inhibited the cascade of OA-like joint changes seen after treadmill use in the TTR model of OA. In terms of mechanism, tissue protection by
The composition and physicochemical properties of hyaluronic acids prepared from ox synovial fluid and from a case of mesothelioma

PubMed Central

Preston, B. N.; Davies, M.; Ogston, A. G.

1965-01-01

1. Materials containing hyaluronic acid have been prepared by filtration (Ogston & Stanier, 1950) from ox synovial fluid and from a protein-rich human mesothelioma fluid. The ox material has been deproteinized by treatment with chloroform and pentanol and by gradient elution on DEAE-Sephadex; several fractions were obtained by the latter method. These materials can be stored in solution at −20° without change of properties. The ox material contained 21% of protein; all other preparations contained less than 6% of protein. 2. The two materials have been compared by sedimentation and viscosity and shown to be closely similar. Treatment of the ox material with neuraminidase caused no change in its viscosity behaviour. 3. Information about the molecular configuration of the ox material has been obtained from measurements of light-scattering and viscosity. The results, though consistent with a highly extended configuration, are not consistent with a linear random-coil configuration. It is tentatively suggested that the structure may have some degree of branching and of cross-linking, which give it a rigidity with respect to expansion of the molecular domain that would not be possessed by a random coil. 4. The deproteinized material recovered from DEAE-Sephadex, though polydisperse, showed unchanged average molecular weight; however, the average radius of gyration was greater than before this treatment. 5. Acidification to approx. pH3 resulted in a contraction of the structure, with only a slight degree of expansion when the pH was restored to 6·8–7·0. 6. Measurements of optical rotatory dispersion qualitatively support a structure less simple than a linear random coil. 7. Colloid osmotic pressures of mixed solutions of bovine serum albumin and of hyaluronic acid prepared by filtration from ox synovial fluid have been measured. The results agree approximately with those of Laurent & Ogston (1963) but are in quantitative disagreement with the partition measurements
The Relationship between Chondromalacia Patella, Medial Meniscal Tear and Medial Periarticular Bursitis in Patients with Osteoarthritis

PubMed Central

Doner, Davut; Karatag, Ozan; Toprak, Canan Akgun

2017-01-01

Abstract Background This study investigated the presence of bursitis in the medial compartment of the knee (pes anserine, semimembranosus-tibial collateral ligament, and medial collateral ligament bursa) in osteoarthritis, chondromalacia patella and medial meniscal tears. Patients and methods Radiological findings of 100 patients undergoing magnetic resonance imaging with a preliminary diagnosis of knee pain were retrospectively evaluated by two radiologists. The first radiologist assessed all patients in terms of osteoarthritis, chondromalacia patella and medial meniscal tear. The second radiologist was blinded to these results and assessed the presence of bursitis in all patients. Results Mild osteoarthritis (grade I and II) was determined in 55 patients and severe osteoarthritis (grade III and IV) in 45 cases. At retropatellar cartilage evaluation, 25 patients were assessed as normal, while 29 patients were diagnosed with mild chondromalacia patella (grade I and II) and 46 with severe chondromalacia patella (grade III and IV). Medial meniscus tear was determined in 51 patients. Severe osteoarthritis and chondromalacia patella were positively correlated with meniscal tear (p < 0.001 and p = 0.018, respectively). Significant correlation was observed between medial meniscal tear and bursitis in the medial compartment (p = 0.038). Presence of medial periarticular bursitis was positively correlated with severity of osteoarthritis but exhibited no correlation with chondromalacia patella (p = 0.023 and p = 0.479, respectively). Evaluation of lateral compartment bursae revealed lateral collateral ligament bursitis in 2 patients and iliotibial bursitis in 5 patients. Conclusions We observed a greater prevalence of bursitis in the medial compartment of the knee in patients with severe osteoarthritis and medial meniscus tear. PMID:29333118
Middle ear application of a sodium hyaluronate gel loaded with neomycin in a Guinea pig model.

PubMed

Saber, Amanj; Laurell, Göran; Bramer, Tobias; Edsman, Katarina; Engmér, Cecilia; Ulfendahl, Mats

2009-02-01

Establishing methods for topical administration of drugs to the inner ear have great clinical relevance and potential even in a relatively short perspective. To evaluate the efficacy of sodium hyaluronate (HYA) as a vehicle for drugs that could be used for treatment of inner ear disorders. The cochlear hair cell loss and round window membrane (RWM) morphology were investigated after topical application of neomycin and HYA into the middle ear. Sixty-five albino guinea pigs were used and divided into groups depending on the type of the treatment. Neomycin was chosen as tracer for drug release and pharmacodynamic effect. HYA loaded with 3 different concentrations of neomycin was injected to the middle ear cavity of guinea pigs. Phalloidin stained surface preparations of the organ of Corti were used to estimate hair cell loss induced by neomycin. The thickness of the midportion of the RWM was measured and compared with that of controls using light and electron microscopy. All animal procedures were pe rformed in accordance with the ethical standards of Karolinska Institutet. Neomycin induced a considerable hair cell loss in guinea pigs receiving a middle ear injection of HYA loaded with the drug, demonstrating that neomycin was released from the gel and delivered to the inner ear. The resulting hair cell loss showed a clear dose-dependence. Only small differences in hair cell loss were noted between animals receiving neomycin solution and animals exposed to neomycin in HYA suggesting that the vehicle neither facilitated nor hindered drug transport between the middle ear cavity and the inner ear. One week after topical application, the thickness of the RWM had increased and was dependent upon the concentration of neomycin administered to the middle ear. At 4 weeks the thickness of the RWM had returned to normal. HYA is a safe vehicle for drugs aimed to pass into the inner ear through the RWM. Neomycin was released from HYA and transported into the inner ear as evidenced
Synthesis, characterization and liver targeting evaluation of self-assembled hyaluronic acid nanoparticles functionalized with glycyrrhetinic acid.

PubMed

Wang, Xiaodan; Gu, Xiangqin; Wang, Huimin; Sun, Yujiao; Wu, Haiyang; Mao, Shirui

2017-01-01

Recently, polymeric materials with multiple functions have drawn great attention as the carrier for drug delivery system design. In this study, a series of multifunctional drug delivery carriers, hyaluronic acid (HA)-glycyrrhetinic acid (GA) succinate (HSG) copolymers were synthesized via hydroxyl group modification of hyaluronic acid. It was shown that the HSG nanoparticles had sub-spherical shape, and the particle size was in the range of 152.6-260.7nm depending on GA graft ratio. HSG nanoparticles presented good short term and dilution stability. MTT assay demonstrated all the copolymers presented no significant cytotoxicity. In vivo imaging analysis suggested HSG nanoparticles had superior liver targeting efficiency and the liver targeting capacity was GA graft ratio dependent. The accumulation of DiR (a lipophilic, NIR fluorescent cyanine dye)-loaded HSG-6, HSG-12, and HSG-20 nanoparticles in liver was 1.8-, 2.1-, and 2.9-fold higher than that of free DiR. The binding site of GA on HA may influence liver targeting efficiency. These results indicated that HSG copolymers based nanoparticles are potential drug carrier for improved liver targeting. Copyright © 2016 Elsevier B.V. All rights reserved.
3D bioprinting of methacrylated hyaluronic acid (MeHA) hydrogel with intrinsic osteogenicity.

PubMed

Poldervaart, Michelle T; Goversen, Birgit; de Ruijter, Mylene; Abbadessa, Anna; Melchels, Ferry P W; Öner, F Cumhur; Dhert, Wouter J A; Vermonden, Tina; Alblas, Jacqueline

2017-01-01

In bone regenerative medicine there is a need for suitable bone substitutes. Hydrogels have excellent biocompatible and biodegradable characteristics, but their visco-elastic properties limit their applicability, especially with respect to 3D bioprinting. In this study, we modified the naturally occurring extracellular matrix glycosaminoglycan hyaluronic acid (HA), in order to yield photo-crosslinkable hydrogels with increased mechanical stiffness and long-term stability, and with minimal decrease in cytocompatibility. Application of these tailor-made methacrylated hyaluronic acid (MeHA) gels for bone tissue engineering and 3D bioprinting was the subject of investigation. Visco-elastic properties of MeHA gels, measured by rheology and dynamic mechanical analysis, showed that irradiation of the hydrogels with UV light led to increased storage moduli and elastic moduli, indicating increasing gel rigidity. Subsequently, human bone marrow derived mesenchymal stromal cells (MSCs) were incorporated into MeHA hydrogels, and cell viability remained 64.4% after 21 days of culture. Osteogenic differentiation of MSCs occurred spontaneously in hydrogels with high concentrations of MeHA polymer, in absence of additional osteogenic stimuli. Addition of bone morphogenetic protein-2 (BMP-2) to the culture medium further increased osteogenic differentiation, as evidenced by increased matrix mineralisation. MeHA hydrogels demonstrated to be suitable for 3D bioprinting, and were printed into porous and anatomically shaped scaffolds. Taken together, photosensitive MeHA-based hydrogels fulfilled our criteria for cellular bioprinted bone constructs within a narrow window of concentration.
Pyrrole-hyaluronic acid conjugates for decreasing cell binding to metals and conducting polymers

PubMed Central

Lee, Jae Young; Schmidt, Christine E.

2010-01-01

Surface modification of electrically conductive biomaterials has been studied to improve biocompatibility for a number of applications, such as implantable sensors and microelectrode arrays. In this study, we electrochemically coated electrodes with biocompatible and non-cell adhesive hyaluronic acid (HA) to reduce cellular adhesion for potential use in neural prostheses. To this end, pyrrole-conjugated hyaluronic acid (PyHA) was synthesized and employed for electrochemical coating of platinum, indium-tin-oxide, and polystyrene sulfonate-doped polypyrrole electrodes. This PyHA conjugate consists of (1) a pyrrole moiety that allows the compound to be electrochemically deposited onto a conductive substrate and (2) non-adhesive HA to minimize cell adhesion and to potentially decrease inflammatory tissue responses. Our characterization results showed the presence of a hydrophilic p(PyHA) layer on the modified electrode, and impedance measurements revealed impedance that was statistically the same as the unmodified electrode. We found that the p(PyHA)-coated electrodes minimized adhesion and migration of fibroblasts and astrocytes for a minimum of up to 3 months. Also, the coating was stable in physiological solution for 3 months and also stable against enzymatic degradation by hyaluronidase. These studies suggest that this p(PyHA)-coating has the potential to be used to mask conducting electrodes from adverse glial responses that occur upon implantation. In addition, electrochemical coating with PyHA can be potentially extended for the surface modification of other metallic and conducting substances such as stents and biosensors. PMID:20558330
3D bioprinting of methacrylated hyaluronic acid (MeHA) hydrogel with intrinsic osteogenicity

PubMed Central

Poldervaart, Michelle T.; Goversen, Birgit; de Ruijter, Mylene; Abbadessa, Anna; Melchels, Ferry P. W.; Öner, F. Cumhur; Dhert, Wouter J. A.; Vermonden, Tina

2017-01-01

In bone regenerative medicine there is a need for suitable bone substitutes. Hydrogels have excellent biocompatible and biodegradable characteristics, but their visco-elastic properties limit their applicability, especially with respect to 3D bioprinting. In this study, we modified the naturally occurring extracellular matrix glycosaminoglycan hyaluronic acid (HA), in order to yield photo-crosslinkable hydrogels with increased mechanical stiffness and long-term stability, and with minimal decrease in cytocompatibility. Application of these tailor-made methacrylated hyaluronic acid (MeHA) gels for bone tissue engineering and 3D bioprinting was the subject of investigation. Visco-elastic properties of MeHA gels, measured by rheology and dynamic mechanical analysis, showed that irradiation of the hydrogels with UV light led to increased storage moduli and elastic moduli, indicating increasing gel rigidity. Subsequently, human bone marrow derived mesenchymal stromal cells (MSCs) were incorporated into MeHA hydrogels, and cell viability remained 64.4% after 21 days of culture. Osteogenic differentiation of MSCs occurred spontaneously in hydrogels with high concentrations of MeHA polymer, in absence of additional osteogenic stimuli. Addition of bone morphogenetic protein-2 (BMP-2) to the culture medium further increased osteogenic differentiation, as evidenced by increased matrix mineralisation. MeHA hydrogels demonstrated to be suitable for 3D bioprinting, and were printed into porous and anatomically shaped scaffolds. Taken together, photosensitive MeHA-based hydrogels fulfilled our criteria for cellular bioprinted bone constructs within a narrow window of concentration. PMID:28586346
Preparation of hyaluronic acid micro-hydrogel by biotin-avidin-specific bonding for doxorubicin-targeted delivery.

PubMed

Cui, Yuan; Li, Yanhui; Duan, Qian; Kakuchi, Toyoji

2013-01-01

Hyaluronic acid is a naturally ionic polysaccharide with cancer cell selectivity. It is an ideal candidate material for delivery of anticancer agents. In this study, hyaluronic acid (HA) micro-hydrogel loaded with anticancer drugs was prepared by the biotin-avidin system approach. Firstly, carboxyl groups on HA were changed into amino groups with adipic acid dihydrazide (ADH) to graft with biotin by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride named as HA-biotin. When HA-biotin solution mixed with doxorubicin hydrochloride (DOX·HCl) was blended with neutravidin, the micro-hydrogels would be formed with DOX loading. If excess biotin was added into the microgel, it would be disjointed, and DOX will be released quickly. The results of the synthesis procedure were characterized by (1)H-NMR and FTIR; ADH and biotin have been demonstrated to graft on the HA molecule. A field emission scanning electron microscope was used to observe morphologies of HA micro-hydrogels. Furthermore, the in vitro DOX release results revealed that the release behaviors can be adjusted by adding biotin. Therefore, the HA micro-hydrogel can deliver anticancer drugs efficiently, and the rate of release can be controlled by biotin-specific bonding with the neutravidin. Consequently, the micro-hydrogel will perform the promising property of switching in the specific site in cancer therapy.
Non-surgical treatment of deep wounds triggered by harmful physical and chemical agents: a successful combined use of collagenase and hyaluronic acid.

PubMed

Onesti, Maria G; Fino, Pasquale; Ponzo, Ida; Ruggieri, Martina; Scuderi, Nicolò

2016-02-01

Some chronic ulcers often occur with slough, not progressing through the normal stages of wound healing. Treatment is long and other therapies need to be performed in addition to surgery. Patients not eligible for surgery because of ASA class (American Society of Anesthesiologists class) appear to benefit from chemical therapy with collagenase or hydrocolloids in order to prepare the wound bed, promoting the healing process. We describe four cases of traumatic, upper limb deep wounds caused by different physical and chemical agents, emphasising the effectiveness of treatment based on topical application of collagenase and hyaluronic acid (HA) before standardised surgical procedures. We performed careful disinfection of lesions combined with application of topical cream containing hyaluronic acid, bacterial fermented sodium hyaluronate (0·2%w/w) salt, and bacterial collagenase obtained from non-pathogenic Vibrio alginolyticus (>2·0 nkat1/g). In one patient a dermo-epidermal graft was used to cover the wide loss of substance. In two patients application of a HA-based dermal substitute was done. We obtained successful results in terms of wound healing, with satisfactory aesthetic result and optimal recovery of the affected limb functionality. Topical application of collagenase and HA, alone or before standardised surgical procedures allows faster wound healing. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.
Hyaluronic acid synthase-2 gene transfer into the joints of Beagles by use of recombinant adeno-associated viral vectors.

PubMed

Kyostio-Moore, Sirkka; Berthelette, Patricia; Cornell, Cathleen Sookdeo; Nambiar, Bindu; Figueiredo, Monica Dias

2018-05-01

OBJECTIVE To evaluate gene transfer of recombinant adeno-associated viral (rAAV) vectors with AAV2 or AAV5 capsid and encoding hyaluronic acid (HA) synthase-2 (HAS2) into joints of healthy dogs. ANIMALS 22 purpose-bred Beagles. PROCEDURES Plasmid expression cassettes encoding canine HAS2 (cHAS2) were assessed in vitro for concentration and molecular size of secreted HA. Thereafter, rAAV2-cHAS2 vectors at 3 concentrations and rAAV5-cHAS2 vectors at 1 concentration were each administered intra-articularly into the left stifle joint of 5 dogs; 2 dogs received PBS solution instead. Synovial fluid HA concentration and serum and synovial fluid titers of neutralizing antibodies against AAV capsids were measured at various points. Dogs were euthanized 28 days after treatment, and cartilage and synovium samples were collected for vector DNA and mRNA quantification and histologic examination. RESULTS Cell transfection with plasmids encoding cHAS2 resulted in an increase in production and secretion of HA in vitro. In vivo, the rAAV5-cHAS2 vector yielded uniform genome transfer and cHAS2 expression in collected synovium and cartilage samples. In contrast, rAAV2-cHAS2 vectors were detected inconsistently in synovium and cartilage samples and failed to produce clear dose-related responses. Histologic examination revealed minimal synovial inflammation in joints injected with rAAV vectors. Neutralizing antibodies against AAV capsids were detected in serum and synovial fluid samples from all vector-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE rAAV5-mediated transfer of the gene for cHAS2 into healthy joints of dogs by intra-articular injection appeared safe and resulted in vector-derived cHAS2 production by synoviocytes and chondrocytes. Whether this treatment may increase HA production by synoviocytes and chondrocytes in osteoarthritic joints remains to be determined.
Effect of molecular weight of hyaluronic acid (HA) on viscoelasticity and particle texturing feel of HA dermal biphasic fillers.

PubMed

Chun, Cheolbyong; Lee, Deuk Yong; Kim, Jin-Tae; Kwon, Mi-Kyung; Kim, Young-Zu; Kim, Seok-Soon

2016-01-01

Hyaluronic acid (HA) dermal biphasic fillers are synthesized for their efficacy in correcting aesthetic defects such as wrinkles, scars and facial contouring defects. The fillers consist of crosslinked HA microspheres suspended in a noncrosslinked HA. To extend the duration of HAs within the dermis and obtain the particle texturing feel, HAs are crosslinked to obtain the suitable mechanical properties. Hyaluronic acid (HA) dermal biphasic fillers are prepared by mixing the crosslinked HA microspheres and the noncrosslinked HAs. The elastic modulus of the fillers increased with raising the volume fraction of the microspheres. The mechanical properties and the particle texturing feel of the fillers made from crosslinked HA (1058 kDa) microspheres suspended in noncrosslinked HA (1368 kDa) are successfully achieved, which are adequate for the fillers. Dermal biphasic HA fillers made from 1058 kDa exhibit suitable elastic moduli (211 to 420 Pa) and particle texturing feel (scale 7 ~ 9).

Fabrication of Biopolymer Nanofibers of Hyaluronic Acid via Electrospinning

NASA Astrophysics Data System (ADS)

Young, Denice; Queen, Hailey; Krause, Wendy

2006-03-01

Electrospinning is a novel technology that uses an electric field to form fibrous materials from a polymer solution. Unlike traditional spinning techniques, electrospinning can produce fibers on the order of 100 nm that can be utilized in applications where nanoscale fibers are necessary for successful implementation, including tissue engineering. Hyaluronic acid (HA) is a widely used biopolymer found in the extracellular matrix and currently marketed in medical applications for joint lubrications and tissue engineering. The high viscosity and surface tension of HA make it an unlikely candidate for electrospinning processes as viscosity is an important parameter in successful electrospinning. To promote HA fiber formation by electrospinning, the effects of salt (NaCl), which is used to reduce the viscosity of aqueous HA solutions; molecular weight of the HA; and an additional biocompatible polymer (e.g., PEO) are under investigation.
Effectiveness and Safety of Hyaluronic Acid Gel with Lidocaine for the Treatment of Nasolabial Folds: A Systematic Review and Meta-analysis.

PubMed

Wang, Chenglong; Luan, Sisi; Panayi, Adriana C; Xin, Minqiang; Mi, Bobin; Luan, Jie

2018-05-08

Hyaluronic acid (HA) gel is a widely used dermal filler for the correction facial volume loss. The incorporation of lidocaine with HA provides a pain-relieving alternative for individuals considering facial rejuvenation. The aim of this systematic review and meta-analysis is to compare the effectiveness and safety of HA with lidocaine (HAL) with that of HA without lidocaine for the treatment of nasolabial folds (NLFs). Studies were identified using the electronic databases PubMed, Embase, Cochrane Central Register of Controlled Trials and Web of Science from inception up to January 2018. Randomized controlled trials (RCTs) were selected based on the inclusion criteria. Outcomes included 100-mm Visual Analogue Scale (VAS) score, Wrinkle Severity Rating Scale score and adverse events. A total of 908 patients from 12 RCTs were included in the meta-analysis. VAS score within 30 min after injection in the HAL group was much lower than that with just HA group (MD = - 28.83, 95% CI - 36.38 to - 21.28). There was no significant difference in effectiveness between the two products 24 months post-injection (MD = 0.13, 95% CI - 0.15 to 0.41). The main adverse events, such as swelling, erythema, bruising, itching and induration, also showed no significant difference. HAL is more effective for pain relief than HA alone, but both display similar effectiveness and safety for the correction of NLFs. 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 .
Enzymatically crosslinked silk-hyaluronic acid hydrogels.

PubMed

Raia, Nicole R; Partlow, Benjamin P; McGill, Meghan; Kimmerling, Erica Palma; Ghezzi, Chiara E; Kaplan, David L

2017-07-01

In this study, silk fibroin and hyaluronic acid (HA) were enzymatically crosslinked to form biocompatible composite hydrogels with tunable mechanical properties similar to that of native tissues. The formation of di-tyrosine crosslinks between silk fibroin proteins via horseradish peroxidase has resulted in a highly elastic hydrogel but exhibits time-dependent stiffening related to silk self-assembly and crystallization. Utilizing the same method of crosslinking, tyramine-substituted HA forms hydrophilic and bioactive hydrogels that tend to have limited mechanics and degrade rapidly. To address the limitations of these singular component scaffolds, HA was covalently crosslinked with silk, forming a composite hydrogel that exhibited both mechanical integrity and hydrophilicity. The composite hydrogels were assessed using unconfined compression and infrared spectroscopy to reveal of the physical properties over time in relation to polymer concentration. In addition, the hydrogels were characterized by enzymatic degradation and for cytotoxicity. Results showed that increasing HA concentration, decreased gelation time, increased degradation rate, and reduced changes that were observed over time in mechanics, water retention, and crystallization. These hydrogel composites provide a biologically relevant system with controllable temporal stiffening and elasticity, thus offering enhanced tunable scaffolds for short or long term applications in tissue engineering. Copyright © 2017 Elsevier Ltd. All rights reserved.
Preparation of porous collagen/hyaluronic acid hybrid scaffolds for biomimetic functionalization through biochemical binding affinity.

PubMed

Lee, Su Jin; Kim, So Yeon; Lee, Young Moo

2007-08-01

This study demonstrated the feasibility of introducing an avidin-biotin system to three-dimensional and highly porous scaffolds for the purpose of designing scaffolds that have binding affinity with bioactive molecules for various biomimetic modifications. Porous hybrid scaffolds composed of collagen and hyaluronic acid (HA) were prepared by a novel overrun process. The overrun-processed scaffolds showed a uniform dual-pore structure because of the injection of gas bubbles and ice recrystallization during the fabrication process and had a higher porosity than scaffolds prepared by a conventional freeze-drying method. The mechanical strength and biodegradation kinetics were controlled by the method of preparation and the composition of collagen/HA. Collagen/HA scaffolds did not show any significant adverse effects on cell viability even after 10 days of incubation. The fibroblasts cultured in the overrun-processed scaffolds were widely distributed and had proliferated on the surfaces of the macropores in the scaffolds, whereas the cells that were seeded in the freeze-dried scaffolds had attached mainly on the dense surface of the scaffolds. As the collagen content in the scaffolds increased, the cellular ingrowth into the inner pores of the scaffolds decreased because of the high affinity between the collagen and the cells. Measurements obtained via confocal microscopy revealed that the porous collagen/HA scaffolds could be functionalized with the biotin by incorporating avidin. Therefore, the present biotinylation approach may allow the incorporation of various bioactive molecules (DNA, growth factors, drug, peptide, etc) into the three-dimensional porous scaffolds.
Recent advances in hyaluronic acid-decorated nanocarriers for targeted cancer therapy

PubMed Central

Wickens, Jennifer M.; Alsaab, Hashem O.; Kesharwani, Prashant; Bhise, Ketki; Amin, Mohd Cairul Iqbal Mohd; Tekade, Rakesh Kumar; Gupta, Umesh; Iyer, Arun K.

2016-01-01

The cluster-determinant 44 (CD44) receptor has a high affinity for hyaluronic acid (HA) binding and is a desirable receptor for active targeting based on its overexpression in cancer cells compared with normal body cells. The nanocarrier affinity can be increased by conjugating drug-loaded carriers with HA, allowing enhanced cancer cell uptake via the HA-CD44 receptor-mediated endocytosis pathway. In this review, we discuss recent advances in HA-based nanocarriers and micelles for cancer therapy. In vitro and in vivo experiments have repeatedly indicated HA-based nanocarriers to be a target-specific drug and gene delivery platform with great promise for future applications in clinical cancer therapy. PMID:28017836
Recent advances in hyaluronic acid-decorated nanocarriers for targeted cancer therapy.

PubMed

Wickens, Jennifer M; Alsaab, Hashem O; Kesharwani, Prashant; Bhise, Ketki; Amin, Mohd Cairul Iqbal Mohd; Tekade, Rakesh Kumar; Gupta, Umesh; Iyer, Arun K

2017-04-01

The cluster-determinant 44 (CD44) receptor has a high affinity for hyaluronic acid (HA) binding and is a desirable receptor for active targeting based on its overexpression in cancer cells compared with normal body cells. The nanocarrier affinity can be increased by conjugating drug-loaded carriers with HA, allowing enhanced cancer cell uptake via the HA-CD44 receptor-mediated endocytosis pathway. In this review, we discuss recent advances in HA-based nanocarriers and micelles for cancer therapy. In vitro and in vivo experiments have repeatedly indicated HA-based nanocarriers to be a target-specific drug and gene delivery platform with great promise for future applications in clinical cancer therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.
Preparation and characterization of composites based on the blends of collagen, chitosan and hyaluronic acid with nano-hydroxyapatite.

PubMed

Sionkowska, Alina; Kaczmarek, Beata

2017-09-01

3D porous composites based on the blend of chitosan, collagen and hyaluronic acid with the addition of nano-hydroxyapatite were prepared. SEM images for the composites were made and the structure was assessed. Mechanical properties were studied using a Zwick&Roell Testing Mashine. In addition, the porosity and density of composites were measured. The concentration of calcium ions released from the material was detected by the complexometric titration method. The results showed that in 3D porous sponge based on the blend of chitosan, collagen and hyaluronic acid, inorganic particles of nanohydroxyapatite can be incorporated, as well as that the properties of 3D composites depend on the material composition. Mechanical parameters and thermal stability of ternary biopolymeric blends were improved by the addition of hydroxyapatite. Moreover, the porosity of ternary materials was higher than in materials based on pure chitosan or collagen. All composites were characterized by a porous structure with interconnected pores. Calcium ions can be released from the composite during its degradation in water. Copyright © 2017 Elsevier B.V. All rights reserved.
Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels-Alder chemistry for adipose tissue engineering.

PubMed

Fan, Ming; Ma, Ye; Zhang, Ziwei; Mao, Jiahui; Tan, Huaping; Hu, Xiaohong

2015-11-01

A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels-Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37°C were studied. The results demonstrated that the aqueous Diels-Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. Copyright © 2015. Published by Elsevier B.V.
MRI evaluation of infectious and non-infectious synovitis: preliminary studies in a rabbit model.

PubMed

Strouse, P J; Londy, F; DiPietro, M A; Teo, E L; Chrisp, C E; Doi, K

1999-05-01

Literature on magnetic resonance imaging (MR) evaluation of inflammatory joint effusions is sparse. To describe an animal model for studying infectious and non-infectious joint effusions with magnetic resonance imaging. Ten rabbit knees with septic arthritis and four with talc synovitis were imaged with MR. Contralateral knees injected with saline served as controls. Fat saturation T2-weighted and gadolinium-enhanced T1-weighted images were assessed for joint effusion, and periarticular and adjacent intraosseous increased signal or enhancement. Each knee was cultured and underwent pathologic examination. Both Staphylococcus aureus and talc produced effusions in all knees. The degree of periarticular signal and enhancement was greater in infected knees than talc-injected knees. No abnormal enhancement was seen within bone. Pathologic examination showed a greater degree of inflammation and joint destruction in the infected knees, but no evidence of osteomyelitis. A greater degree of abnormal signal and enhancement seen on MR suggests a more vigorous inflammatory process, as seen with septic arthritis. In spite of advanced septic arthritis, no enhancement was evident within bone, suggesting that enhancement within bone is not an expected finding in isolated septic arthritis and should raise concern for osteomyelitis.
Effectiveness of adjunctive subgingival administration of amino acids and sodium hyaluronate gel on clinical and immunological parameters in the treatment of chronic periodontitis

PubMed Central

Bevilacqua, Lorenzo; Eriani, Jessica; Serroni, Ilde; Liani, Giuliana; Borelli, Violetta; Castronovo, Gaetano; Di Lenarda, Roberto

2012-01-01

Summary Aims The aim of this clinical trial was to compare clinical and biochemical healing outcomes following ultrasonic mechanical instrumentation versus ultrasonic mechanical instrumentation associated with topical subgingival application of amino acids and sodium hyaluronate gel. Methods Eleven systemically healthy subjects with moderate-severe chronic periodontitis, who had four sites with pocket probing depth and clinical attachment level greater than or equal to 5 mm were randomly assigned to two different types of treatment: two pockets were treated with ultrasonic debridement (Control Group) and two pockets with ultrasonic mechanical instrumentation associated with 0,5 ml of amino acids and sodium hyaluronate gel (Test Group). Probing depth, clinical attachment level, plaque index and bleeding on probing were recorded at baseline, 45 and 90 days. Levels of calprotectin and myeloperoxidase activity in gingival crevicular fluid were assessed at baseline and on day 7 and 45. Results Statistical significance was found between baseline and day 45 in relation to probing depth reduction and bleeding on probing between groups for both of the tested treatments. Significant reductions in μg/sample of calprotectin and myeloperoxidase were found after 1-week and an increase at 45 days in both groups. There were no statistically significant differences between other variables evaluated in this study. Conclusions These data suggest that subgingival application of hyaluronic acid following ultrasonic mechanical instrumentation is beneficial for improving periodontal parameters. PMID:23087790
Computed Tomography Demonstration of the Production and Distribution of Oxygen Gas Following Intratumoral Injection of a New Radiosensitizer (KORTUC) for Patients with Breast Cancer-Is Intratumoral Injection Not an Ideal Approach to Solve the Major Problem of Tumor Hypoxia in Radiotherapy?

PubMed

Hayashi, Naoya; Ogawa, Yasuhiro; Kubota, Kei; Okino, Kazuhiro; Akima, Ryo; Morita-Tokuhiro, Shiho; Tsuzuki, Akira; Yaogawa, Shin; Nishioka, Akihito; Miyamura, Mitsuhiko

2016-04-01

We previously developed a new enzyme-targeting radiosensitization treatment named Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), which contains hydrogen peroxide and sodium hyaluronate for injection into various types of tumors. For breast cancer treatment, the radiosensitization agent was injected into the tumor tissue twice a week under ultrasonographic guidance, immediately prior to each administration of radiation therapy. At approximately three hours after the second or third injection, computed tomography (CT) was performed to confirm the production and distribution of oxygen gas generated from the KORTUC radiosensitization agent by catalysis of peroxidases contained mainly in tumor tissue. The purpose of this study was to demonstrate that tumor hypoxia could be overcome by such a procedure and to evaluate the method of intratumoral injection in terms of confirming oxygen distribution in the target tumor tissue and around the tumor to be visualized on dedicated CT imaging. Three-dimensional reconstructed maximum intensity projection imaging of contrast-enhanced breast magnetic resonance imaging was used to compare the position of the tumor and that of the generated oxygen. Distributed oxygen gas was confirmed in the tumor tissue and around it in all 10 patients examined in the study. A region of oxygen gas was measured as an average value of -457.2 Hounsfield units (HU) as a region of interest. A slightly increased HU value compared to the density of air or oxygen was considered due to the presence of tumor tissue in the low-density area on 5-mm-thick reconstructed CT imaging. The results of this study showed that intratumoral oxygen was successfully produced by intratumoral KORTUC injection under ultrasonographic guidance, and that tumor hypoxia, which is considered a main cause of radioresistance in currently used Linac (linear accelerator) radiation therapy for malignant neoplasms, could be resolved by this method.
Improved biocompatibility of poly (styrene-b-(ethylene-co-butylene)-b-styrene) elastomer by a surface graft polymerization of hyaluronic acid.

PubMed

Li, Xiaomeng; Luan, Shifang; Shi, Hengchong; Yang, Huawei; Song, Lingjie; Jin, Jing; Yin, Jinghua; Stagnaro, Paola

2013-02-01

Hyaluronic acid (HA) is an important component of extracellular matrix (ECM) in many tissues, providing a hemocompatible and supportive environment for cell growth. In this study, glycidyl methacrylate-hyaluronic acid (GMHA) was first synthesized and verified by proton nuclear magnetic resonance ((1)H NMR) spectroscopy. GMHA was then grafted to the surface of biomedical elastomer poly (styrene-b-(ethylene-co-butylene)-b-styrene) (SEBS) via an UV-initiated polymerization, monitored by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). The further improvement of biocompatibility of the GMHA-modified SEBS films was assessed by platelet adhesion experiments and in vitro response of murine osteoblastic cell line MC-3T3-E1 with the virgin SEBS surface as the reference. It showed that the surface modification with HA strongly resisted platelet adhesion whereas improved cell-substrate interactions. Copyright © 2012 Elsevier B.V. All rights reserved.
Minimal recovery time needed to return to social engagement following nasolabial fold correction with hyaluronic acid fillers produced with XpresHAn technology.

PubMed

Swift, Arthur; von Grote, Erika; Jonas, Brandie; Nogueira, Alessandra

2017-01-01

The appeal of hyaluronic acid fillers for facial soft tissue augmentation is attributable to both an immediate aesthetic effect and relatively short recovery time. Although recovery time is an important posttreatment variable, as it impacts comfort with appearance and perceived treatment benefit, it is not routinely evaluated. Natural-looking aesthetic outcomes are also a primary concern for many patients. A single-center, noncomparative study evaluated the time (in hours) until subjects return to social engagement (RtSE) following correction of moderate and severe nasolabial folds (NLFs) with R R (Restylane ® Refyne) ® and R D (Restylane Defyne), respectively. Twenty subjects (aged 35-57 years) who received bilateral NLF correction documented their RtSE and injection-related events posttreatment. Treatment efficacy was evaluated by improvements in Wrinkle Severity Rating Scale (WSRS) and subject satisfaction questionnaire at days 14 and 30, and by Global Aesthetic Improvement Scale (GAIS) at day 30. Safety was evaluated by injection-related events and treatment-emergent adverse events. Fifty percent of subjects reported RtSE within 2 hours posttreatment. WSRS for the R R group improved significantly from baseline at day 14 (-1.45±0.42) and day 30 (-1.68±0.46) ( P <0.001), respectively. WSRS for the R D group improved significantly from baseline at day 14 (-2.22±0.44) and day 30 (-2.50±0.50) ( P <0.004), respectively. All GAIS improvements were clinically significant at day 30. The majority of injection-related events were mild or moderate. Two subjects experienced 3 related treatment-emergent adverse events; 1 R R subject experienced severe bruising, and 1 R D subject experienced severe erythema and mild telangiectasia. Subject satisfaction was high regarding aesthetic outcomes and natural-looking results. Optimal correction of moderate NLFs with R R and severe NLFs with R D involved minimal time to RtSE for most subjects. Treatments that significantly
Boronic acid-tethered amphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration.

PubMed

Jeong, Jae Young; Hong, Eun-Hye; Lee, Song Yi; Lee, Jae-Young; Song, Jae-Hyoung; Ko, Seung-Hak; Shim, Jae-Seong; Choe, Sunghwa; Kim, Dae-Duk; Ko, Hyun-Jeong; Cho, Hyun-Jong

2017-04-15

(3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic acid-sialic acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic acid-sialic acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs. STATEMENT OF SIGNIFICANCE: (3-Aminomethylphenyl)boronic acid (AMPB)-tethered hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic acid located in the outer surface
Comparison of intra-articular hyaluronic acid and methylprednisolone for pain management in knee osteoarthritis: A meta-analysis of randomized controlled trials.

PubMed

Ran, Jian; Yang, Xiaohui; Ren, Zheng; Wang, Jian; Dong, Hui

2018-05-01

We performed a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of intra-articular methylprednisolone and hyaluronic acid (HA) in term of pain reduction and improvements of knee function in patients with knee osteoarthritis (OA). The PubMed, EMBASE, ScienceDirect, and Cochrane Library databases were systematically searched for literature up to January 2018. RCTs involving HA and methylprednisolone in knee OA were included. Two independent reviewers performed independent data abstraction. The I 2 statistic was used to assess heterogeneity. A fixed or random effects model was adopted for meta-analysis. All meta-analyses were performed by using STATA 14.0. Five RCTs with 1004 patients were included in the meta-analysis. The present meta-analysis indicated that there were no significant differences in terms of WOMAC pain, physical function and stiffness at 4 week, 12 weeks and 26 weeks between HA and methylprednisolone groups. No increased risk of adverse events were identified in both groups. Both HA and methylprednisolone injections were effective therapies for patients with knee OA. Methylprednisolone showed comparable efficacy in reducing pain and improving functional recovery to HA. And no significant difference was found in long-term of follow-up in terms of adverse effects. Copyright © 2018 IJS Publishing Group Ltd. All rights reserved.
Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Vocal Folds: A Study on a Chronic Vocal Fold Scar

PubMed Central

Vassiliki, Kalodimou; Irini, Messini; Nikolaos, Psychalakis; Karampela, Eleftheria; Apostolos, Papalois

2016-01-01

Background. The aim of the study was to assess the histological effects of autologous infusion of adipose-derived stem cells (ADSC) on a chronic vocal fold scar in a rabbit model as compared to an untreated scar as well as in injection of hyaluronic acid. Study Design. Animal experiment. Method. We used 74 New Zealand rabbits. Sixteen of them were used as control/normal group. We created a bilateral vocal fold wound in the remaining 58 rabbits. After 18 months we separated our population into three groups. The first group served as control/scarred group. The second one was injected with hyaluronic acid in the vocal folds, and the third received an autologous adipose-derived stem cell infusion in the scarred vocal folds (ADSC group). We measured the variation of thickness of the lamina propria of the vocal folds and analyzed histopathologic changes in each group after three months. Results. The thickness of the lamina propria was significantly reduced in the group that received the ADSC injection, as compared to the normal/scarred group. The collagen deposition, the hyaluronic acid, the elastin levels, and the organization of elastic fibers tend to return to normal after the injection of ADSC. Conclusions. Autologous injection of adipose-derived stem cells on a vocal fold chronic scar enhanced the healing of the vocal folds and the reduction of the scar tissue, even when compared to other treatments. PMID:26933440
Pain and Opioid Use After Total Shoulder Arthroplasty With Injectable Liposomal Bupivacaine Versus Interscalene Block.

PubMed

Angerame, Marc R; Ruder, John A; Odum, Susan M; Hamid, Nady

2017-09-01

Postoperative pain control is a significant concern after total shoulder arthroplasty. Injectable periarticular liposomal bupivacaine, which has been found to decrease opioid use after orthopedic procedures, has been proposed as a viable alternative to regional anesthesia. This study compared the efficacy of liposomal bupivacaine vs interscalene block among patients undergoing total shoulder arthroplasty. A retrospective review was conducted of 79 patients who underwent anatomic total shoulder arthroplasty performed by a single surgeon between January 2013 and April 2015. Patient demographics, in-hospital Numeric Pain Rating Scale (NPRS) score obtained at 12-hour intervals, length of stay, and total in-hospital morphine equivalents in both the bupivacaine (n=25) and block (n=44) groups were recorded. Differences in length of stay, morphine equivalents, and age were assessed with Wilcoxon tests. Sex differences were assessed with the chi-square test. Repeated measures analysis with least square means was used to assess longitudinal changes in NPRS scores. No significant differences were found between groups for sex (P=.89), age (P=.81), American Society of Anesthesiologists classification (P=.50), preoperative opioid use (P=.41), length of stay (P=.32), or morphine equivalents (P=.71). The average NPRS score in the first 12 hours was 3.01 for the bupivacaine group and 4.41 for the interscalene block group (P=.25). By 48 hours postoperatively, average NPRS scores were similar (P=.93) for the 2 groups, 4.90 for the bupivacaine group and 4.19 for the interscalene block group. The findings for this cohort of patients undergoing anatomic total shoulder arthroplasty showed no significant difference for pain scores, postoperative narcotic use, or length of stay with injectable liposomal bupivacaine vs interscalene block. [Orthopedics. 2017; 40(5):e806-e811.]. Copyright 2017, SLACK Incorporated.
Development of poly(lactic-co-glycolic) acid nanoparticles-embedded hyaluronic acid-ceramide-based nanostructure for tumor-targeted drug delivery.

PubMed

Park, Ju-Hwan; Lee, Jae-Young; Termsarasab, Ubonvan; Yoon, In-Soo; Ko, Seung-Hak; Shim, Jae-Seong; Cho, Hyun-Jong; Kim, Dae-Duk

2014-10-01

A hyaluronic acid-ceramide (HACE) nanostructure embedded with docetaxel (DCT)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) was fabricated for tumor-targeted drug delivery. NPs with a narrow size distribution and negative zeta potential were prepared by embedding DCT-loaded PLGA NPs into a HACE nanostructure (DCT/PLGA/HACE). DCT-loaded PLGA and DCT/PLGA/HACE NPs were characterized by solid-state techniques, including Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). A sustained drug release pattern from the NPs developed was observed and negligible cytotoxicity was seen in NIH3T3 cells (normal fibroblast, CD44 receptor negative) and MDA-MB-231 cells (breast cancer cells, CD44 receptor positive). PLGA/HACE NPs containing coumarin 6, used as a fluorescent dye, exhibited improved cellular uptake efficiency, based on the HA-CD44 receptor interaction, compared to plain PLGA NPs. Cyanine 5.5 (Cy5.5)-labeled PLGA/HACE NPs were injected intravenously into a MDA-MB-231 tumor xenograft mouse model and demonstrated enhanced tumor targetability, compared with Cy5.5-PLGA NPs, according to a near-infrared fluorescence (NIRF) imaging study. Considering these experimental results, the DCT/PLGA/HACE NPs developed may be useful as a tumor-targeted drug delivery system. Copyright © 2014 Elsevier B.V. All rights reserved.
Porous titanium scaffolds with injectable hyaluronic acid-DBM gel for bone substitution in a rat critical-sized calvarial defect model.

PubMed

van Houdt, C I A; Cardoso, D A; van Oirschot, B A J A; Ulrich, D J O; Jansen, J A; Leeuwenburgh, S C G; van den Beucken, J J J P

2017-09-01

Demineralized bone matrix (DBM) is an allograft bone substitute used for bone repair surgery to overcome drawbacks of autologous bone grafting, such as limited supply and donor-site comorbidities. In view of different demineralization treatments to obtain DBM, we examined the biological performance of two differently demineralized types of DBM, i.e. by acidic treatment using hydrochloric acid (HCl) or treatment with the chelating agent ethylene diamine tetra-acetate (EDTA). First, we evaluated the osteo-inductive properties of both DBMs by implanting the materials subcutaneously in rats. Second, we evaluated the effects on bone formation by incorporating DBM in a hyaluronic acid (HA) gel to fill a porous titanium scaffold for use in a critical-sized calvarial defect model in 36 male Wistar rats. These porous titanium scaffolds were implanted empty or filled with HA gel containing either DBM HCl or DBM EDTA. Ectopically implanted DBM HCl and DBM EDTA did not induce ectopic bone formation over the course of 12 weeks. For the calvarial defects, mean percentages of newly formed bone at 2 weeks were significantly higher for Ti-Empty compared to Ti-HA + DBM HCl , but not compared to Ti-HA + DBM EDTA. Significant temporal bone formation was observed for Ti-Empty and Ti-HA + DBM HCl, but not for Ti-HA + DBM EDTA. At 8 weeks there were no significant differences in values of bone formation between the three experimental constructs. In conclusion, these results showed that, under the current experimental conditions, neither DBM HCl nor DBM EDTA possess osteo-inductive properties. Additionally, in combination with an HA gel loaded in a porous titanium scaffold, DBM HCl and DBM EDTA showed similar amounts of new bone formation after 8 weeks, which were lower than using the empty porous titanium scaffold. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Intravesical treatment of bladder pain syndrome/interstitial cystitis: from the conventional regimens to the novel botulinum toxin injections.

PubMed

Dellis, Athanasios; Papatsoris, Athanasios G

2014-06-01

Bladder pain syndrome (BPS) includes interstitial cystitis (IC) and is often used as a synonym of it (i.e., BPS/IC). It is associated with lower urinary tract symptoms as well as with negative cognitive, behavioral, sexual and/or emotional consequences. Unfortunately, none of the numerous existing oral and intravesical treatments have been effective for all of the BPS subtypes and therefore relevant research is ongoing. In this review, the authors analyze the existing literature for the intravesical treatment of BPS/IC with focus on the novel administration of botulinum toxin (BTX). Several intravesical drugs have been studied in the past, including lidocaine, heparin, pentosan polysulfate sodium, dimethyl sulfoxide, chondroitin sulfate, hyaluronic acid as well as investigational drugs such as GM-0111. Recently, intravesical submucosal injections of BTX have been studied in patients with BPS/IC. Most of the recent studies use BTX-A with no serious adverse effects and with satisfactory results in patients who do not respond to oral or standard intravesical therapy. Nevertheless, there is no consensus regarding the best dosage scheme of BTX, the injection sites and the treatment intervals. BTX intravesical administration in patients with BPS/IC is a safe and efficient treatment option; yet the level of evidence of the initial studies is not high. There is still the need for large randomized controlled studies so that a consensus can be reached for the ideal BTX dosage, injection sites and intervals between treatments.

In vitro study of RRS HA injectable mesotherapy/biorevitalization product on human skin fibroblasts and its clinical utilization

PubMed Central

Deglesne, Pierre-Antoine; Arroyo, Rodrigo; Ranneva, Evgeniya; Deprez, Philippe

2016-01-01

Mesotherapy/biorevitalization with hyaluronic acid (HA) is a treatment approach currently used for skin rejuvenation. Various products with a wide range of polycomponent formulations are available on the market. Most of these formulations contain noncross-linked HA in combination with a biorevitalization cocktail, formed by various amounts of vitamins, minerals, amino acids, nucleotides, coenzymes, and antioxidants. Although ingredients are very similar among the different products, in vitro and clinical effects may vary substantially. There is a real need for better characterization of these products in terms of their action on human skin or in vitro skin models. In this study, we analyzed the effect of the RRS® (Repairs, Refills, Stimulates) HA injectable medical device on human skin fibroblasts in vitro. Skin fibroblast viability and its capacity to induce the production of key extracellular matrix were evaluated in the presence of different concentrations of RRS HA injectable. Viability was evaluated through colorimetric MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and key extracellular matrix genes, type I collagen and elastin, were quantified by quantitative polymerase chain reaction. Results demonstrated that RRS HA injectable could promote human skin fibroblast viability (+15%) and increase fibroblast gene expression of type I collagen and elastin by 9.7-fold and 14-fold in vitro, respectively. These results demonstrate that mesotherapy/biorevitalization products can, at least in vitro, effectively modulate human skin fibroblasts. PMID:26966384
21 CFR 522.1145 - Hyaluronate sodium.

Code of Federal Regulations, 2011 CFR

2011-04-01

... equine osteoarthritis. (iii) Limitations. For intra-articular injection in horses only. Treatment may be... osteoarthritis. (iii) Limitations. For intraarticular injection in horses only. Treatment may be repeated at... dysfunction in horses due to acute or chronic noninfectious synovitis associated with equine osteoarthritis...
21 CFR 522.1145 - Hyaluronate sodium.

Code of Federal Regulations, 2012 CFR

2012-04-01

... equine osteoarthritis. (iii) Limitations. For intra-articular injection in horses only. Treatment may be... osteoarthritis. (iii) Limitations. For intraarticular injection in horses only. Treatment may be repeated at... dysfunction in horses due to acute or chronic noninfectious synovitis associated with equine osteoarthritis...
21 CFR 522.1145 - Hyaluronate sodium.

Code of Federal Regulations, 2010 CFR

2010-04-01

... equine osteoarthritis. (iii) Limitations. For intra-articular injection in horses only. Treatment may be... osteoarthritis. (iii) Limitations. For intraarticular injection in horses only. Treatment may be repeated at... dysfunction in horses due to acute or chronic noninfectious synovitis associated with equine osteoarthritis...
21 CFR 522.1145 - Hyaluronate sodium.

Code of Federal Regulations, 2013 CFR

2013-04-01

... equine osteoarthritis. (iii) Limitations. For intra-articular injection in horses only. Treatment may be... osteoarthritis. (iii) Limitations. For intraarticular injection in horses only. Treatment may be repeated at... dysfunction in horses due to acute or chronic noninfectious synovitis associated with equine osteoarthritis...
Hyaluronate nanoparticles included in polymer films for the prolonged release of vitamin E for the management of skin wounds.

PubMed

Pereira, Gabriela Garrastazu; Detoni, Cassia Britto; Balducci, Anna Giulia; Rondelli, Valeria; Colombo, Paolo; Guterres, Silvia Stanisçuaski; Sonvico, Fabio

2016-02-15

Lecithin and hyaluronic acid were used for the preparation of polysaccharide decorated nanoparticles loaded with vitamin E using the cationic lipid dioctadecyldimethylammonium bromide (DODMA). Nanoparticles showed mean particle size in the range 130-350 nm and narrow size distribution. Vitamin E encapsulation efficiency was higher than 99%. These nanoparticles were incorporated in polymeric films containing Aloe vera extract, hyaluronic acid, sodium alginate, polyethyleneoxide (PEO) and polyvinylalcohol (PVA) as an innovative treatment in skin wounds. Films were thin, flexible, resistant and suitable for application on burn wounds. Additionally, in vitro occlusion study highlighted the dependence of the occlusive effect on the presence of nanoparticles. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of skin wounds, such as burns. The controlled release of the vitamin along with a reduction in water loss through damaged skin provided by the nanoparticle-loaded polymer film are considered important features for an improvement in wound healing and skin regeneration. Copyright © 2015 Elsevier B.V. All rights reserved.
Comparative effectiveness of platelet-rich plasma injections for treating knee joint cartilage degenerative pathology: a systematic review and meta-analysis.

PubMed

Chang, Ke-Vin; Hung, Chen-Yu; Aliwarga, Fanny; Wang, Tyng-Guey; Han, Der-Sheng; Chen, Wen-Shiang

2014-03-01

To explore the effectiveness of platelet-rich plasma (PRP) in treating cartilage degenerative pathology in knee joints. Electronic databases, including PubMed and Scopus, were searched from the earliest record to September 2013. We included single-arm prospective studies, quasi-experimental studies, and randomized controlled trials that used PRP to treat knee chondral degenerative lesions. Eight single-arm studies, 3 quasi-experimental studies, and 5 randomized controlled trials were identified, comprising 1543 participants. We determined effect sizes for the selected studies by extracting changes in functional scales after the interventions and compared the PRP group pooled values with the pretreatment baseline and the groups receiving placebo or hyaluronic acid (HA) injections. PRP injections in patients with knee degenerative pathology showed continual efficacy for 12 months compared with their pretreatment condition. The effectiveness of PRP was likely better and more prolonged than that of HA. Injection doses ≤2, the use of a single-spinning approach, and lack of additional activators led to an uncertainty in the treatment effects. Patients with lower degrees of cartilage degeneration achieved superior outcomes as opposed to those affected by advanced osteoarthritis. PRP application improves function from basal evaluations in patients with knee joint cartilage degenerative pathology and tends to be more effective than HA administration. Discrepancy in the degenerative severity modifies the treatment responses, leading to participants with lower degrees of degeneration benefiting more from PRP injections. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Mesenchymal stromal cell injection promotes vocal fold scar repair without long-term engraftment

PubMed Central

BARTLETT, R.S.; GUILLE, J.T.; CHEN, X.; CHRISTENSEN, M.B.; WANG, S.F.; THIBEAULT, S.L.

2016-01-01

Background Regenerative medicine holds promise for restoring voice in patients with vocal fold scarring. As experimental treatments approach clinical translation, several considerations remain. Our objective was to evaluate efficacy and biocompatibility of four bone marrow mesenchymal stromal cell (BM-MSC) and tunable hyaluronic acid based hydrogel (HyStem-VF) treatments for vocal fold scar using clinically acceptable materials, a preclinical sample size and a dosing comparison. Methods Vocal folds of 84 rabbits were injured and injected with four treatment variations (BM-MSC, HyStem-VF, and BM-MSC in HyStem-VF at two concentrations) 6 weeks later. Efficacy was assessed with rheometry, real-time polymerase chain reaction (PCR) and histology at 2, 4 and 10 weeks following treatment. Lung, liver, kidney, spleen and vocal folds were screened for biocompatibility by a pathologist. Results and discussion Persistent inflammation was identified in all hydrogel-injected groups. The BM-MSC alone treatment appeared to be the most efficacious and safe, providing an early resolution of viscoelasticity, gene expression consistent with desirable extracellular matrix remodeling (less fibronectin, collagen 1α2, collagen 3, procollagen, transforming growth factor [TGF]β1, alpha smooth muscle actin, interleukin-1β, interleukin-17β and tumor necrosis factor [TNF] than injured controls) and minimal inflammation. Human beta actin expression in BM-MSC–treated vocal folds was minimal after 2 weeks, suggesting that paracrine signaling from the BM-MSCs may have facilitated tissue repair. PMID:27637759
Mesenchymal stromal cell injection promotes vocal fold scar repair without long-term engraftment.

PubMed

Bartlett, R S; Guille, J T; Chen, X; Christensen, M B; Wang, S F; Thibeault, S L

2016-10-01

Regenerative medicine holds promise for restoring voice in patients with vocal fold scarring. As experimental treatments approach clinical translation, several considerations remain. Our objective was to evaluate efficacy and biocompatibility of four bone marrow mesenchymal stromal cell (BM-MSC) and tunable hyaluronic acid based hydrogel (HyStem-VF) treatments for vocal fold scar using clinically acceptable materials, a preclinical sample size and a dosing comparison. Vocal folds of 84 rabbits were injured and injected with four treatment variations (BM-MSC, HyStem-VF, and BM-MSC in HyStem-VF at two concentrations) 6 weeks later. Efficacy was assessed with rheometry, real-time polymerase chain reaction (RT-PCR) and histology at 2, 4 and 10 weeks following treatment. Lung, liver, kidney, spleen and vocal folds were screened for biocompatibility by a pathologist. Persistent inflammation was identified in all hydrogel-injected groups. The BM-MSC alone treatment appeared to be the most efficacious and safe, providing an early resolution of viscoelasticity, gene expression consistent with desirable extracellular matrix remodeling (less fibronectin, collagen 1α2, collagen 3, procollagen, transforming growth factor [TGF]β1, alpha smooth muscle actin, interleukin-1β, interleukin-17β and tumor necrosis factor [TNF] than injured controls) and minimal inflammation. Human beta actin expression in BM-MSC-treated vocal folds was minimal after 2 weeks, suggesting that paracrine signaling from the BM-MSCs may have facilitated tissue repair. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
Microbial production of hyaluronic acid from agricultural resource derivatives.

PubMed

Pires, Aline M B; Macedo, André C; Eguchi, Silvia Y; Santana, Maria H A

2010-08-01

Agricultural resource derivatives (ARDs) such as hydrolysate soy protein concentrate (HSPC), whey protein concentrate (WPC), and cashew apple juice (CAJ) were studied with focus on the production of hyaluronic acid (HA) by Streptococcus zooepidemicus. Supplementation of the media with corn steep liquor (CSL) was also evaluated. Synthetic medium containing glucose and yeast extract was used as control. CAJ was a promising medium for the production of HA. It produced the highest amount of HA (0.89 g L(-1)), similar to that of the control (0.86 g L(-1)). WPC and HSPC media were the most effective for the production of biomass. CSL did not influence the production of HA when HSPC and WPC were used. However, in the synthetic medium it doubled the yield of HA from glucose. The average molecular weight of HA ranged from 10(3) to 10(4)Da for the ARDs and 10(7)Da for the synthetic medium. Copyright 2010 Elsevier Ltd. All rights reserved.
Cost-effective peri-operative pain management: assuring a happy patient after total knee arthroplasty.

PubMed

Kim, K; Elbuluk, A; Yu, S; Iorio, R

2018-01-01

The aim of this study was to determine the optimal regimen for the management of pain following total knee arthroplasty (TKA) by comparing the outcomes and cost-effectiveness of different protocols implemented at a large, urban, academic medical centre. Between September 2013 and September 2015, we used a series of modifications to our standard regimen for the management of pain after TKA. In May 2014, there was a department-wide transition from protocols focused on femoral nerve blocks (FNB) to periarticular injections of liposomal bupivacaine. In February 2015, patient-controlled analgesia (PCA) was removed from the protocol while continuing liposomal bupivacaine injections. Quality measures and hospital costs were compared between the three protocols. The cohort being treated with PCA-less liposomal bupivacaine injections had a significantly higher percentage of patients who were discharged to their home (p = 0.010) and a significantly shorter length of stay (p < 0.001). Patient-reported Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores relating to pain being "well-controlled" and "overall pain management" also favoured this cohort (p = 0.214 and p = 0.463, respectively), in which cost was significantly lower compared with the other two cohorts (p = 0.005). The replacement of FNBs injections and the removal of PCAs, both of which are known to be associated with high rates of adverse outcomes, and the addition of liposomal bupivacaine periarticular injections to a multimodal pain regimen, led to improvements in many quality measures, HCAHPS pain scores, and cost-effectiveness. Cite this article: Bone Joint J 2018;100-B(1 Supple A):55-61. ©2018 The British Editorial Society of Bone & Joint Surgery.
Targeting cancer with hyaluronic acid-based nanocarriers: recent advances and translational perspectives.

PubMed

Cadete, Ana; Alonso, María José

2016-09-01

Hyaluronic acid is a natural polysaccharide that has been widely explored for the development of anticancer therapies due to its ability to target cancer cells. Moreover, advances made in the last decade have revealed the versatility of this biomaterial in the design of multifunctional carriers, intended for the delivery of a variety of bioactive molecules, including polynucleotides, immunomodulatory drugs and imaging agents. In this review, we aim to provide an overview of the major recent achievements in this field, highlighting the application of the newly developed nanostructures in combination therapies, immunomodulation and theranostics. Finally, we will discuss the main challenges and technological advances that will allow these carriers to be considered as candidates for clinical development.
Role of central opioid on the antinociceptive effect of sulfated polysaccharide from the red seaweed Solieria filiformis in induced temporomandibular joint pain.

PubMed

Araújo, Ianna Wivianne Fernandes; Chaves, Hellíada Vasconcelos; Pachêco, José Mário; Val, Danielle Rocha; Vieira, Lorena Vasconcelos; Santos, Rodrigo; Freitas, Raul Sousa; Rivanor, Renata Line; Monteiro, Valdécio Silvano; Clemente-Napimoga, Juliana Trindade; Bezerra, Mirna Marques; Benevides, Norma Maria Barros

2017-03-01

This study aimed to investigate the effect of sulfated polysaccharide from red seaweed Solieria filiformis (Fraction F II) in the inflammatory hypernociception in the temporomandibular joint (TMJ) of rats. Male Wistar rats were pretreated (30min) with a subcutaneous injection (s.c.) of vehicle or FII (0.03, 0.3 or 3.0mg/kg) followed by intra-TMJ injection of 1.5% Formalin or 5-hydroxytryptamine (5-HT, 225μg/TMJ). In other set of experiments rats were pretreated (15min) with an intrathecal injection of the non-selective opioid receptors Naloxone, or μ-opioid receptor antagonist CTOP, or δ-opioid receptor Naltridole hydrochloride, or κ-opioid receptor antagonist Nor-Binaltorphimine (Nor-BNI) followed by injection of FII (s.c.). After 30min, the animals were treated with an intra-TMJ injection of 1.5% formalin. After TMJ treatment, behavioral nociception response was evaluated for a 45-min observation period, animals were terminally anesthetized and periarticular tissue, trigeminal ganglion and subnucleus caudalis (SC) were collected plasma extravasation and ELISA analysis. Pretreatment with F II significantly reduced formalin- and serotonin-induced TMJ nociception, inhibit the plasma extravasation and inflammatory cytokines release induced by 1.5% formalin in the TMJ. Pretreatment with intrathecal injection of Naloxone, CTOP, Naltridole or Nor-BNI blocked the antinociceptive effect of F II in the 1.5% formalin-induced TMJ nociception. In addition, F II was able to significantly increase the β-endorphin release in the subnucleus caudalis. The results suggest that F II has a potential antinociceptive and anti-inflammatory effect in the TMJ mediated by activation of opioid receptors in the subnucleus caudalis and inhibition of the release of inflammatory mediators in the periarticular tissue. Copyright © 2017. Published by Elsevier B.V.
Case series on chronic whiplash related neck pain treated with intraarticular zygapophysial joint regeneration injection therapy.

PubMed

Hooper, R Allen; Frizzell, J Bevan; Faris, Peter

2007-03-01

Although in clinical use, there is only 1 published case report on the efficacy of intraarticular regeneration injection therapy (RIT) (a.k.a. prolotheraphy). This report supports a rationale for future clinical trials of this technique. To assess the efficacy of intraarticular zygapophysial joint RIT in patients with chronic whiplash related neck pain that failed other conservative and interventional procedures. Patients were treated with intraarticular RIT and reassessed over 1 year. Retrospective case review of prospective data. Eighteen consecutive patients were treated with intraarticular prolotherapy by placing 0.5 - 1mL of 20% dextrose solution into each zygapophysial joint, after confirmation of intraarticular location with radiographic contrast, using 25-gauge spinal needles and fluoroscopic guidance. Solution was prepared by diluting D50W with 1% lidocaine. Fifteen patients completed treatment. Three patients had bilateral treatment, leaving 18 sides for analysis. Mean Neck Disability Index (NDI) pre-treatment was 24.71 and decreased post-treatment to 14.21 (2 months), 13.45 (6 months), 10.94 (12 months). Average change NDI=13.77 (p<0.0001) baseline versus 12 months. Symptoms for 14 patients were from motor vehicle accident, of which 13 were in litigation. Patients attending physiotherapy over the course of treatment had better outcomes than those without physiotherapy. Women needed more injections (5.4) than men (3.2) p=0.0003. Intraarticular RIT improved pain and function in this case series. The procedure appears safe, more effective than periarticular RIT, and lasted as long, or longer, than those patients with previous radiofrequency neurotomy. Concurrent physiotherapy helped reduce post-procedure neck stiffness. Future trials should consider gender when deciding how many treatments to administer. Litigation was not a barrier to recovery.
Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice.

PubMed

Impellizzeri, Daniela; Esposito, Emanuela; Di Paola, Rosanna; Ahmad, Akbar; Campolo, Michela; Peli, Angelo; Morittu, Valeria Maria; Britti, Domenico; Cuzzocrea, Salvatore

2013-01-01

N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). CIA was induced by an intradermally injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen (CII)) and complete Freund adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or co-ultramicronized PEA + luteolin (1 mg/kg, i.p.) every 24 hours, starting from day 25 to 35. Mice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment. We demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA.
Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice

PubMed Central

2013-01-01

Introduction N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). Methods CIA was induced by an intradermally injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen (CII)) and complete Freund adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or co-ultramicronized PEA + luteolin (1 mg/kg, i.p.) every 24 hours, starting from day 25 to 35. Results Mice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment. Conclusions We demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA. PMID:24246048
Intra-articular injection of a nutritive mixture solution protects articular cartilage from osteoarthritic progression induced by anterior cruciate ligament transection in mature rabbits: a randomized controlled trial

PubMed Central

Park, Yoo-Sin; Lim, Si-Woong; Lee, Il-Hoon; Lee, Tae-Jin; Kim, Jong-Sung; Han, Jin Soo

2007-01-01

Osteoarthritis (OA) is a degenerative disease that disrupts the collagenous matrix of articular cartilage and is difficult to cure because articular cartilage is a nonvascular tissue. Treatment of OA has targeted macromolecular substitutes for cartilage components, such as hyaluronic acid or genetically engineered materials. However, the goal of the present study was to examine whether intra-articular injection of the elementary nutrients restores the matrix of arthritic knee joints in mature animals. A nutritive mixture solution (NMS) was composed of elementary nutrients such as glucose or dextrose, amino acids and ascorbic acid. It was administered five times (at weeks 6, 8, 10, 13 and 16) into the unilateral anterior cruciate ligament transected knee joints of mature New Zealand White rabbits, and the effect of NMS injection was compared with that of normal saline. OA progression was histopathologically evaluated by haematoxylin and eosin staining, by the Mankin grading method and by scanning electron microscopy at week 19. NMS injection decreased progressive erosion of articular cartilage overall compared with injection of normal saline (P < 0.01), and nms joints exhibited no differences relative to normal cartilage that had not undergone transection of the anterior cruciate ligament, as assessed using the mankin grading method. Haematoxylin and eosin staining and scanning electron microscopy findings also indicated that nms injection, in constrast to normal saline injection, restored the cartilage matrix, which is known to be composed of a collagen and proteoglycan network. thus, nms injection is a potent treatment that significantly retards oa progression, which in turn prevents progressive destruction of joints and functional loss in mature animals. PMID:17257416
Hyaluronic acid-modified zirconium phosphate nanoparticles for potential lung cancer therapy.

PubMed

Li, Ranwei; Liu, Tiecheng; Wang, Ke

2017-02-01

Novel tumor-targeting zirconium phosphate (ZP) nanoparticles modified with hyaluronic acid (HA) were developed (HA-ZP), with the aim of combining the drug-loading property of ZP and the tumor-targeting ability of HA to construct a tumor-targeting paclitaxel (PTX) delivery system for potential lung cancer therapy. The experimental results indicated that PTX loading into the HA-ZP nanoparticles was as high as 20.36%±4.37%, which is favorable for cancer therapy. PTX-loaded HA-ZP nanoparticles increased the accumulation of PTX in A549 lung cancer cells via HA-mediated endocytosis and exhibited superior anticancer activity in vitro. In vivo anticancer efficacy assay revealed that HA-ZP nanoparticles possessed preferable anticancer abilities, which exhibited minimized toxic side effects of PTX and strong tumor-suppression potential in clinical application.
Blindness caused by cosmetic filler injection: a review of cause and therapy.

PubMed

Carruthers, Jean D A; Fagien, Steve; Rohrich, Rod J; Weinkle, Susan; Carruthers, Alastair

2014-12-01

Vascular occlusion causing blindness is a rare yet greatly feared complication of the use of facial aesthetic fillers. The authors performed a review of the aesthetic literature to ascertain the reported cases of blindness and the literature reporting variations in the vascular anatomy of the human face. The authors suggest a small but potentially helpful addition to the accepted management of the acute case. Cases of blindness, mostly irreversible, from aesthetic filler injections have been reported from Asia, Europe, and North America. Autologous fat appears to be the most frequent filler causing blindness. Some cases of partial visual recovery have been reported with hyaluronic acid and calcium hydroxylapatite fillers. The sudden profusion of new medical and nonmedical aesthetic filler injectors raises a new cause for alarm about patient safety. The published reports in the medical literature are made by experienced aesthetic surgeons and thus the actual incidence may be even higher. Also, newer injectors may not be aware of the variations in the pattern of facial vascular arborization. The authors present a summary of the relevant literature to date and a suggested helpful addition to the protocols for urgent management.
Hyaluronic acid increases tendon derived cell viability and proliferation in vitro: comparative study of two different hyaluronic acid preparations by molecular weight.

PubMed

Gallorini, Marialucia; Berardi, Anna C; Berardocco, Martina; Gissi, Clarissa; Maffulli, Nicola; Cataldi, Amelia; Oliva, Francesco

2017-01-01

Hyaluronic Acid (HA) has been already approved by Food and Drug Administration (FDA) for osteoarthritis (OA), while its use in the treatment of tendinopathy is still debated. The aim of this study was to evaluate the effects of two different HA on human rotator cuff tendon derived cells in terms of cell viability, proliferation and apoptosis. An in vitro model was developed on human tendon derived cells from rotator cuff tears to study the effects of two different HA preparations: Sinovial HL® (High-Low molecular weight) (MW: 80-100 kDa) and KDa Sinovial Forte SF (MW: 800-1200), at various concentrations. Tendon derived cells morphology was evaluated after 0, 7 and 14 d of culture. Viability and proliferation were analyzed after 0, 24, and 48 h of culture and apoptosis occurrence was assessed after 24 h of culture. All the HAPs tested here increased viability and proliferation, in a dose-dependent manner and they reduced apoptosis at early stages (24 h) compared to control cells (without HAPs). HAPs enhanced viability and proliferation and counteracted apoptosis in tendon derived cells.

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