A 10-Year Review of Collagenase Versus Fasciectomy in the Treatment of Dupuytren Contracture.

BACKGROUND: Dupuytren disease (DD) is one of the most common disorders of the hand, affecting 5.7% to 11.7% of the global population. This study seeks to evaluate the 10-year efficacy of the 2 most prominent treatment modalities for DD in Veterans Affairs hospitals, injectable collagenase Clostridium histolyticum versus open fasciectomy. METHODS: A retrospective review was conducted of all electronic medical records of patients who underwent open fasciectomy or collagenase injection to treat their persistent Dupuytren contracture between April 2011 and April 2021. All procedures were performed by 1 of 5 senior surgeons at the same Veterans Affairs Hospital. RESULTS: A total of 232 patients were treated for DD, with 247 collagenase injections and 44 open fasciectomies performed in this sample. Collagenase patients were, on average, 6.51 years after intervention at the time of review. Open fasciectomy patients were, on average, 4.56 years after operation at the time of review. Collagenase decreased contractures, on average, by 29.40 degrees, whereas open fasciectomy decreased contractures, on average, by 38.59 degrees. Of the contractures that were initially classified as resolved, 50 of 155 (32.2%) treated with collagenase and 6 of 56 (10.7%) treated with open fasciectomy recurred. The use of open fasciectomy compared with collagenase injections to treat contracture was associated with a 74.2% decrease in the likelihood of recurrence. CONCLUSIONS: This study found that treatment of DD with collagenase injection is associated with a significantly lower degree of deformity correction, lower rate of resolution, and increased rate of recurrence when compared with open fasciectomy.

Long-term recurrence of Dupuytren's disease treated with clostridium histolitycum collagenase. Surgical treatment and anatomopathological study.

OBJECTIVE: To present the functional results obtained and the possible surgical difficulties after the surgical treatment of Dupuytren's disease (DD) recurrence in patients previously treated with Clostridium histolyticum (CCH) collagenase. MATERIALS AND METHODS: In this prospective study, 178 patients with DD were treated with CCH from 2011 to 2018; During long-term postoperative follow-up, 34 patients (19.1%) had recurrence of DD. In all patients injected in the IFP the disease recurred; In patients injected in the MCP, recurrence was highest in grade III and IV of the Tubiana classification, with involvement of the 5th finger and the two-finger Y-chord. Fourteen patients (7,8%) required surgery by partial selective fasciectomy due to recurrence of cord DD infiltration. The clinical and functional results of the patients, the difficulty of the surgical technique and the anatomopathological analysis of the infiltrated cords were evaluated in comparison with those of cords and patients who had had no previous CCH treatment. RESULTS: In all patients, cord rupture was achieved after injection, reducing joint contracture. In 14 patients, we observed during the follow-up the existence of DD recurrence that required surgical treatment by selective partial fasciectomy. There were no major difficulties in surgery and good clinical and functional results at 6 months of follow-up. The anatomopathological study of the resected tissue did not present histological alterations with respect to the samples obtained from patients initially treated by selective partial fasciectomy. CONCLUSIONS: Selective fasciectomy after CCH injection does not lead to important operative difficulties, as long as the CCH injection is performed according to the recommendations. There were no histological changes in the tissue after CCH injection. LEVEL OF EVIDENCE: III.

Industry Sponsorship Bias in Collagenase Clinical Trials for Dupuytren Disease: A Meta-analysis.

BACKGROUND: Collagenase clostridium histolyticum (collagenase) was introduced in 2010 creating a nonoperative treatment option for Dupuytren disease with promising results in sponsored clinical trials. A meta-analysis was performed to investigate industry sponsorship bias. METHODS: A systematic review of collagenase treatment of Dupuytren contracture was conducted. Articles containing mesh terms including "microbial collagenase" and "Dupuytren's contracture" were searched and limited to only clinical trials with similar protocols for inclusion. Meta-analysis of treatment endpoints of correction of contracture to 0-5 degrees after first and last injection was conducted comparing sponsored versus nonsponsored studies. RESULTS: Sixteen of the 29 identified articles met criteria for inclusion. Nonsponsored studies reported a significantly higher rate of meeting the primary treatment endpoint compared to sponsored studies after single injection for all joints (69.6% vs 56% P < 0.01), metacarpophalangeal joint (96% vs 64% P < 0.01), and proximal interphalangeal joint (67% vs 36% P = 0.011). The correction in contracture rates was similar between groups with studies evaluating more than one injection. CONCLUSIONS: Nonsponsored studies published higher success rates in meeting the primary endpoint of full correction after single injection than sponsored studies; however, similar results with multiple injections. This study demonstrated that sponsored studies of collagenase produced highly powered studies that may be reliably depended on for evidence-based clinical application.

Surgery, Needle Fasciotomy, or Collagenase Injection for Dupuytren Contracture : A Randomized Controlled Trial.

BACKGROUND: Surgery, needle fasciotomy, and collagenase injection are used to treat Dupuytren contracture. The treatment decision requires balancing initial morbidity and costs of surgery against its potential long-term benefits over needle fasciotomy and collagenase. OBJECTIVE: To compare the effectiveness of surgery, needle fasciotomy, and collagenase injection at 3 months and 2 years (secondary time points of the trial). DESIGN: A multicenter, randomized, outcome assessor-blinded, superiority trial. (ClinicalTrials.gov: NCT03192020). SETTING: 6 public hospitals in Finland. PARTICIPANTS: 302 persons with treatment-naive Dupuytren contracture (contracture angle <135°). INTERVENTION: Surgery (n = 101), needle fasciotomy (n = 101), or collagenase (n = 100). MEASUREMENTS: The primary outcome was the success rate, defined as greater than 50% contracture release and patients reaching the patient acceptable symptom state. Secondary outcomes included hand function, pain, quality of life, patient satisfaction, residual contracture angle, finger flexion, risk for retreatment, and serious adverse events. RESULTS: A total of 292 (97%) and 284 (94%) participants completed the 3-month and 2-year follow-ups. Success rates were similar at 3 months: 71% (95% CI, 62% to 80%) for surgery, 73% (CI, 64% to 82%) for needle fasciotomy, and 73% (CI, 64% to 82%) for collagenase. At 2 years, surgery had superior success rates compared with both needle fasciotomy (78% vs. 50%; adjusted risk difference [aRD], 0.30 [CI, 0.17 to 0.43]) and collagenase (78% vs. 65%; aRD, 0.13 [CI, 0.01 to 0.26]). Secondary analyses paralleled with the primary analysis. LIMITATION: Participants were not blinded. CONCLUSION: Initial outcomes are similar between the treatments, but at 2 years success rates were maintained in the surgery group but were lower with both needle fasciotomy and collagenase despite retreatments. PRIMARY FUNDING SOURCE: Research Council of Finland.

Collagenase clostridium histolyticum injection versus limited fasciectomy for the treatment of Dupuytren's disease: a systematic review and meta-analysis of comparative studies.

INTRODUCTION: The aim of the present study is to systematically review the literature on well-selected comparative studies for meta-analysis on outcome differences between collagenase clostridium histolyticum (CCH) injection and limited fasciectomy (LF) for Dupuytren's disease. MATERIALS AND METHODS: PubMed/Medline, Embase, and the Cochrane Library were searched for comparative studies assessing differences in outcomes of CCH and LF. Effect estimates were pooled across studies using random effects models and presented as weighted mean difference (MD) and odds ratio (OR) with corresponding 95% confidence interval (CI). RESULTS: A total of 11 studies encompassing 1'051 patients was included (619 patients in the CCH and 432 in the LF group). The residual contracture at a minimal average follow-up of three months was higher in the CCH group than in the LF group (27.8 vs. 16.2°, MD 11.6°, 95% CI [8.7, 14.5°], p < 0.001). The recurrence rate was significantly higher in the CCH group (25.8 vs. 9.3%, OR 5.2, 95% CI [1.5, 18.8], p = 0.01) while the rate of severe complications was significantly higher in the LF group (0.3 vs. 7.3%, OR 0.12, 95% CI [0.03, 0.42], p = 0.001). CONCLUSIONS: Evidence of the present study confirms that CCH injection has a higher rate of disease recurrence whereas LF carries a higher risk for severe complications. It's imperative that the trade-off between these aspects is considered, keeping in mind that CCH injections may be repeated in case of disease recurrence without increasing procedure related risks, especially in complex cases.

Long-term clinical outcome of collagenase clostridium histolyticum treatment is independent of Dupuytren Diathesis Score.

Collagenase clostridium histolyticum (CCH) is a pharmaceutical, non-surgical treatment option for Dupuytren Disease. However, recurrence is common, and predictors of treatment outcome of CCH treatment are largely unknown. In this retrospective study, we analysed the possible correlation between Abe's Dupuytren Diathesis Score (DDS) and recurrence after treatment with CCH. In a total of 74 patients, with an average follow-up of 5 years, we found an overall recurrence rate of 67% after 5y but no correlation with DDS. Sub-scale analysis indicated that the presence of knuckle pads was associated with a reduced recurrence risk. Patient satisfaction after CCH was high. Deriving from our data, there is no correlation between DDS and recurrence following CCH treatment. Therefore, at this moment, we do not advocate the use of the DDS when informing patients about recurrence rates after CCH treatment. Level of evidence: IV: therapeutic cohort study.

Delayed vascular complication after collagenase injection for Dupuytren disease.

BACKGROUND: Vascular adverse events after collagenase injection for Dupuytren disease are absent in large trials and systematic reviews. The aim of this study is to present a case series of delayed vascular complications after collagenase treatment. METHODS: A prospective evaluation of 1181 consecutively treated patients at one orthopedic department identified three patients reporting symptoms of possible vascular complication. Baseline demographics and description of symptoms were collected, with a physical examination documenting extension deficit and neurovascular status. All patients completed the Cold Intolerance Symptom Severity (CISS) scale (range 4-100, lower is better) and underwent Doppler sonography examination of the digital arteries. RESULTS: All patients were treated in the small finger and two had an isolated proximal interphalangeal joint contracture. All patients had a delayed presentation of a few months, with episodes of white discoloration of the treated finger relieved within 30 min and associated with variable pain, paresthesia, stiffness and weakness. Two of the patients reported cold exposure as an episode trigger and had a pathological CISS score (40 and 36, respectively). Doppler sonography identified a nonpatent ulnar digital artery in one patient. CONCLUSIONS: Delayed vascular complication after collagenase treatment is rare, but surgeons and patients should be aware of the risk, especially when treating the small finger.

Collagenase Treatment Versus Needle Fasciotomy for Single-Digit Dupuytren Contractures: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: The objective of this systematic review and meta-analysis was to synthesize the available randomized controlled trial data comparing needle fasciotomy and collagenase treatment for single-digit Dupuytren contractures with a minimum of 3-year follow-up and determine whether one treatment is superior regarding contracture correction and functional outcomes. METHODS: A systematic review and meta-analysis was conducted by searching four databases for randomized controlled trials investigating the single-digit treatment outcomes for Dupuytren contracture comparing collagenase treatment and needle fasciotomy with a minimum of 3-year follow-up. The risk of bias of included studies was assessed using the Cochrane risk-of-bias tool. A meta-analysis was performed using a random effects model in anticipation of unobserved heterogeneity. The primary outcome measure was contracture recurrence. Secondary outcome measures included final fixed flexion contracture (FFC), Quick Disabilities of Arm, Shoulder and Hand (QuickDASH) scores, and Unité Rhumatologique des Affections de la Main (URAM) scores. RESULTS: After screening 264 articles, 4 randomized clinical trials were eligible for final inclusion. One trial had a high risk of bias, and two trials had some concern for bias. The final meta-analysis included 347 patients, 169 who underwent collagenase treatment and 178 who underwent needle fasciotomy. No significant differences were noted between the groups in contracture recurrence, FFC, and URAM scores. The pooled data showed a higher QuickDASH score in the collagenase treatment group compared with the needle fasciotomy group, but the observed difference was less than what would be expected to be clinically relevant. CONCLUSIONS: Needle fasciotomy and collagenase treatment have similar outcomes with regards to contracture recurrence, final FFC, QuickDASH scores, and URAM scores for the single-digit treatment for Dupuytren contracture at a minimum of 3-year follow-up. Relevant factors that may be considered during the shared decision-making process for treatment selection include surgeon and patient preferences, costs of treatment, and the disparate complication profiles of these two treatments. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Dupuytren's Contracture Recurrence and Treatment Following Collagenase Clostridium Histolyticum Injection: A Longitudinal Assessment in a Veteran Population.

INTRODUCTION: Dupuytren's contracture is a connective tissue disease characterized by an abnormal proliferation of collagen in the palm and fingers, which leads to a decline in hand function because of progressive joint flexion. In addition to surgical and percutaneous interventions, collagenase clostridium histolyticum (CCH, trade name Xiaflex) is an intralesional enzymatic treatment for adults with palpable cords. The objectives of this study are to evaluate factors predictive of recurrence following treatment with CCH and to review the outcomes of repeat treatments with CCH for recurrent contracture. MATERIALS AND METHODS: An institutional review board-approved retrospective chart review was conducted for patients between 2010 and 2017 who received CCH injections for Dupuytren's contracture at a Veterans Affairs hospital. Demographics, comorbidities, affected finger and joint, pre/posttreatment contracture, time to recurrence, and treatment of recurrence were recorded. Successful treatment was defined as contracture ≤5° following CCH, and improvement was defined as ≥20° reduction from baseline contracture. Study cohorts were followed after their secondary treatment, and time to recurrence was recorded and plotted using a Kaplan-Meier curve. A Cox proportional hazards model was used to compare treatment group risk factors for recurrence with a P-value less than .05 defined as statistical significance. RESULTS: Of 174 injections performed for the correction of flexion deformities in 109 patients, 70% (121) were successfully treated with CCH, and an additional 20% (35) had improvement. There was a recurrence of contractures in 43 joints (25%). Of these, 16 contractures were treated with repeat CCH, whereas another 16 underwent limited fasciectomy. In total, 75% (12 of 16) of the repeat CCH group and 75% of the fasciectomy group were successfully treated. Pre-injection contracture of ≥25° was found to be predictive of recurrence (P < .05). CONCLUSIONS: Initial treatment of contracture with CCH had a 70% success rate with 25% recurrence during the study period. Compared with limited fasciectomy, CCH had decreased efficacy. Based on the findings of this study, we believe that the treatment of primary and/or recurrent Dupuytren's contracture with CCH is a safe and less invasive alternative to fasciectomy in the era of telemedicine. CCH treatment requires no suture removal, which allows the ability to assess motion virtually, and the potential consequences of CCH treatment such as skin tears can be assessed and managed conservatively. In the veteran and active duty population, CCH can facilitate faster recovery and return to service. Strengths of this study include a large series of veteran populations with longitudinal follow-up to determine treatment efficacy for primary Dupuytren's contracture and recurrence. Limitations include a smaller sample size compared to previous trials, a lack of standardized follow-up, and the retrospective nature of our study that prohibits randomization to compare outcomes between CCH treatment and fasciectomy efficacy over time. Directions for future research include stratification of patients by joint and specific digit involvement as well as comparison with percutaneous needle fasciotomy, another minimally invasive technique that could benefit the veteran population at increased risk for developing Dupuytren's disease.

Comparison of Rheological Properties of Healthy versus Dupuytren Fibroblasts When Treated with a Cell Contraction Inhibitor by Atomic Force Microscope.

Mechanical properties of healthy and Dupuytren fibroblasts were investigated by atomic force microscopy (AFM). In addition to standard force curves, rheological properties were assessed using an oscillatory testing methodology, in which the frequency was swept from 1 Hz to 1 kHz, and data were analyzed using the structural damping model. Dupuytren fibroblasts showed larger apparent Young's modulus values than healthy ones, which is in agreement with previous results. Moreover, cell mechanics were compared before and after ML-7 treatment, which is a myosin light chain kinase inhibitor (MLCK) that reduces myosin activity and hence cell contraction. We employed two different concentrations of ML-7 inhibitor and could observe distinct cell reactions. At 1 µM, healthy and scar fibroblasts did not show measurable changes in stiffness, but Dupuytren fibroblasts displayed a softening and recovery after some time. When increasing ML-7 concentration (3 µM), the majority of cells reacted, Dupuytren fibroblasts were the most susceptible, not being able to recover from the drug and dying. These results suggested that ML-7 is a potent inhibitor for MLCK and that myosin II is essential for cytoskeleton stabilization and cell survival.

Treatments for early-stage Dupuytren's disease: an evidence-based approach.

Current treatments for Dupuytren's disease are limited to late-stage disease when patients have developed flexion contractures and have impaired hand function. They all have limitations, including the risk of recurrence and complications. The use of treatments for early-stage disease, such as intralesional steroid injections or radiotherapy which lack a clear biological basis or evidence of effectiveness based robust randomized, double blind, placebo-controlled trials, highlights the desire of patients to access treatments before they develop significant flexion contractures. A detailed understanding of the cellular landscape and molecular signalling in nodules of early-stage disease would permit the identification of potential therapeutic targets. This approach led to the identification of tumour necrosis factor (TNF) as a target. A phase 2a clinical trial identified 40 mg in 0.4 mL adalimumab as the most efficacious dose and a subsequent randomized, double blind, placebo-controlled phase 2b trial showed that four intranodular injections at 3-month intervals resulted in decrease in nodule hardness and size on ultrasound scan at 12 months, and both parameters continued to decrease further at 18 months, 9 months after the final injection. This type of approach provides clinicians with a robust evidence base for advising their patients.

Three-Year Recurrence of Dupuytren Contracture after Needle Fasciotomy or Collagenase Injection: A Randomized Controlled Trial.

BACKGROUND: In this randomized controlled trial, the authors compared the recurrence of Dupuytren disease at 3 years following needle fasciotomy or collagenase injection treatment for isolated metacarpophalangeal joint contractures. METHODS: The study was conducted between 2013 and 2015. The study design was a single-center, randomized controlled clinical trial with an independent blinded observer. Patients were randomized between collagenase clostridium histolyticum injections (Xiapex) and percutaneous needle fasciotomy (collagenase clostridium histolyticum versus percutaneous needle fasciotomy). A total of 36 patients were followed in the percutaneous needle fasciotomy group and 32 in the collagenase clostridium histolyticum group. RESULTS: Patients who were treated with collagenase clostridium histolyticum had a significantly lower recurrence rate than patients treated with percutaneous needle fasciotomy during the 3-year period ( P = 0.007). Of the 36 patients who were followed in the percutaneous needle fasciotomy group, 17 (47%) had recurrence of extension deficit or progression of the disease leading to further treatment. Of the 32 patients who were followed in the collagenase clostridium histolyticum group, six (19%) had recurrence or progression. No serious adverse event was reported in any of the patients. CONCLUSIONS: In this randomized controlled trial, we found less recurrence and progression of Dupuytren disease using collagenase injection as compared to percutaneous needle fasciotomy 3 years following treatment for isolated metacarpophalangeal joint contractures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Patients' perspectives of collagenase injection or needle fasciotomy and rehabilitation for Dupuytren disease, including hand function and occupational performance.

PURPOSE: To describe patients' perspectives of collagenase injection or needle fasciotomy for Dupuytren disease (DD) including hand therapy, and their view of hand function and occupational performance. MATERIALS AND METHODS: Interviews were performed with twelve patients who had undergone non-surgical treatment and rehabilitation for DD. Data was analysed using a problem-driven content analysis using the model of Patient Evaluation Process as a theoretical framework. RESULTS: The participants' previous experiences influenced their expectations of the upcoming treatment and they needed information to be prepared for treatment. Treatment and rehabilitation had a positive impact on daily life and were regarded as effective and simple with quick recovery. However, there could be remaining issues with tenderness or stiffness. The participants expressed their belief in rehabilitation and how their own efforts could contribute to an improved result. Despite concerns about future recurrence participants described increased knowledge and sense of control regarding future needs. CONCLUSION: Undergoing a non-surgical treatment and rehabilitation process for DD was regarded as quick and easy and can meet the need for improved hand function and occupational performance. Taking responsibility for one's own rehabilitation was considered to influence the outcome positively. The theoretical framework optimally supported the exploration of participants' perspective.Implications for rehabilitationTreatment of Dupuytren Disease (DD) with needle/collagenase combined with hand therapy was experienced as giving fast improvement in hand function and occupational performance.An individualized care process which satisfies the need for knowledge about the disease, prognosis, treatment options and rehabilitation can give individuals suffering from DD a sense of security.The need for active participation in the DD care process can vary and it is crucial to listen to individuals' opinions and needs.Individuals can take considerable responsibility for rehabilitation after non-surgical treatment for DD and regard it as important for the outcome.

Effect of Perioperative Corticosteroid Administration on Early Postoperative Range of Motion and Functional Outcomes Following Dupuytren's Fasciectomy.

BACKGROUND: The purpose of the study was to evaluate whether perioperative corticosteroid (CS) administration improves early postoperative range of motion (ROM) and function in patients undergoing Dupuytren's fasciectomy. METHODS: We retrospectively identified 58 patients who underwent Dupuytren's fasciectomy by a single fellowship-trained orthopedic hand surgeon from 2016 to 2020. During this time period, 51 digits in 34 patients received a single intraoperative dose of 10 mg of intravenous dexamethasone followed by a 6-day oral methylprednisolone taper course (CS group), and 37 digits in 24 patients did not (control group). Postoperatively, all patients started hand therapy within 1 week of surgery. At 2 and 6 weeks, patients had ROM data and Disabilities of the Arm, Shoulder, and Hand (DASH) scores collected by a blinded hand therapist. Paired t tests were used to compare the change in ROM and DASH scores at weeks 2 and 6. RESULTS: The 2 cohorts had similar preoperative ROM. At 2 weeks postoperatively, the CS group had greater metacarpophalangeal (MP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) flexion. There was no difference in MP, PIP, or DIP extension. At 6 weeks postoperatively, the CS group had greater PIP flexion. There was no difference between the groups in MP extension, MP flexion, PIP extension, DIP extension, or DIP flexion. Mean DASH scores were significantly lower in the CS group at weeks 2 and 6. There were no postoperative deep infections or complications requiring surgery in either group. CONCLUSION: Perioperative CS administration appears to be safe and to improve early ROM and DASH scores following Dupuytren's fasciectomy.

Dupuytren Cords Do Not Undergo Significant Histopathological Change After Collagenase Clostridium Histolyticum Injection.

Background: Dupuytren disease creates thickened cords of the palmar fascia, leading to progressive flexion contractures that severely hinder hand function. Collagenase clostridium histolyticum (CCH) injection is a common, minimally invasive alternative to surgical excision of these cords. The impact of CCH injection on the histological architecture of Dupuytren cords has not been studied extensively. Methods: A series of 10 CCH-injected cords were evaluated histologically. Cellularity, architecture, and connective tissue organization were compared against uninjected Dupuytren cords and normal palmar fascia. Results: No significant histopathological differences between CCH-injected and CCH-uninjected cords were identified. Conclusions: Dupuytren cords do not demonstrate histological changes with prior exposure to CCH.

Patient Insight With Collagenase Treatment for Dupuytren: A Prospective Study.

PURPOSE: There appears to be controversy regarding differing patient and physician perceptions of adverse effects (AEs) in the treatment of Dupuytren disease with collagenase clostridium histolyticum (CCH). The aim of this study was to compare the number, type, and severity of AEs perceived and reported by patients and by their physician METHODS: To assess AEs following CCH injection in a standardized way, patients were given a list of predefined complications and asked to rate their severity on a 4-point Likert scale ranging from 1 (serious) to 4 (insignificant). RESULTS: Eighty-five patients were included. Patients reported fewer AEs than their physician (mean, 1.48 vs 2.18). There was no agreement between physician- and patient-reported AEs except for skin lacerations, which showed fair agreement (κ = 0.257). CONCLUSIONS: Patients and physicians differ in their evaluation of AEs due to CCH treatment in Dupuytren disease. A fair level of agreement was observed for skin lacerations. CLINICAL RELEVANCE: Greater consensus is needed when defining AEs associated with CCH in the treatment of Dupuytren disease.

The Effect of Ex-Vivo Hyaluronic Acid on Myofibroblast and Collagen in Dupuytren Disease.

Background: Dupuytren disease (DD) is characterised by increased myofibroblast/fibroblast activity and type3/type1 collagen ratios. Hyaluronic acid (HA) is major component of the extracellular matrix and some studies have showed that HA limits myofibroblast activity and decreases type3/type1 collagen ratio. The aim of this study is to determine the effect of the ex-vivo application of HA on cultured fibroblasts obtained from normal and diseased tissue from patients with DD. This is the initial step towards defining the use of HA as a new approach for medical treatment of DD. Methods: Tissue samples were obtained from both healthy forearm (C) and unhealthy palmar (D) fascia of patients undergoing surgery for DD. Tissue samples were cultured and divided into four groups depending on the addition of HA [C(HA-), C(HA+), D(HA-) and D(HA+)]. The tissues were evaluated using Western blot to detect effect of HA on myofibroblast (by measuring alpha smooth muscle actin [α-SMA) and on the ratio of type3/type1 collagen by measuring collagen type1 alpha 1 Chain (COL1A1) and collagen type3 alpha 1 Chain (COL3A1). Results: The rate of the average α-SMA value in the D(HA+) group was significantly lower compared to that of the D(HA-) group. The average ratio of type3/type1 collagen in the D(HA+) group was significantly lower compared to the D(HA-) group. Conclusions: The ex-vivo application of HA on cultured fibroblasts obtained from patients with DD resulted in a decrease in myofibroblast/fibroblast activity and type3/type1 collagen ratios. This may pave the way for clinical application of HA in the treatment of DD.