Peripheral nerve injury, scarring, and recovery.

Peripheral nerve injuries (PNI) resulting from trauma can be severe and permanently debilitating. Despite the armamentarium of meticulous microsurgical repair techniques that includes direct repair, grafting of defects with autograft nerve, and grafting with cadaveric allografts, approximately one-third of all PNI demonstrate incomplete recovery with poor restoration of function. This may include total loss or incomplete recovery of motor and/or sensory function, chronic pain, muscle atrophy, and profound weakness, which can result in lifelong morbidity. Much of this impaired nerve healing can be attributed to perineural scarring and fibrosis at the site of injury and repair. To date, this challenging clinical problem has not been adequately addressed. In this review, we summarize the existing literature surrounding biological aspects of perineural fibrosis following PNI, detail current strategies to limit nerve scarring, present our own work developing reliable nerve injury models in animal studies, and discuss potential future studies which may ultimately lead to new therapeutic strategies.

Biologic and mechanical aspects of tendon fibrosis after injury and repair.

Tendon injuries of the hand that require surgical repair often heal with excess scarring and adhesions to adjacent tissues. This can compromise the natural gliding mechanics of the flexor tendons in particular, which operate within a fibro-osseous tunnel system similar to a set of pulleys. Even combining the finest suture repair techniques with optimal hand therapy protocols cannot ensure predictable restoration of hand function in these cases. To date, the majority of research regarding tendon injuries has revolved around the mechanical aspects of the surgical repair (i.e. suture techniques) and postoperative rehabilitation. The central principles of treatment gleaned from this literature include using a combination of core and epitendinous sutures during repair and initiating motion early on in hand therapy to improve tensile strength and limit adhesion formation. However, it is likely that the best clinical solution will utilize optimal biological modulation of the healing response in addition to these core strategies and, recently, the research in this area has expanded considerably. While there are no proven additive biological agents that can be used in clinical practice currently, in this review, we analyze the recent literature surrounding cytokine modulation, gene and cell-based therapies, and tissue engineering, which may ultimately lead to improved clinical outcomes following tendon injury in the future.

Electrodiagnostic Grade and Carpal Tunnel Release Outcomes: A Prospective Analysis.

PURPOSE: The value of electrodiagnostic (EDX) study grades as a prognostic indicator of clinical results after carpal tunnel release (CTR) remains controversial. In this study, we tested the primary null hypothesis that symptom relief after CTR would not differ based on EDX grade. Secondarily, we evaluated the degree of symptomatic and functional postoperative improvement relative to preoperative EDX grade. METHODS: We prospectively evaluated 199 consecutive patients with 256 hands after CTR confirmed with EDX. Data were collected before surgery and patients were observed at 2 weeks and 3 months after surgery. There were 20 hands with mild, 126 with moderate, and 110 with severe involvement in the preoperative EDX. Demographic, EDX grade (mild, moderate, or severe); surgical parameters; Quick-Disabilities of the Arm, Shoulder, and Hand questionnaire; symptom severity scale, functional status scale, pain catastrophizing scale, and visual analog scale data were collected and analyzed. RESULTS: There was significant improvement in Quick-Disabilities of the Arm, Shoulder, and Hand, symptom severity scale, and functional status scale scores from the preoperative to 2-week and 3-month postoperative visits in all categories of EDX grade. There was no significant difference in the extent of recovery by the 2-week and 3-month visits relative to EDX grade. Catastrophic thinking did not have a significant effect on any of the 3 groups. Pain decreased dramatically at 2 weeks after surgery but there was no additional significant difference in visual analog scale scores between the 2-week and 3-month postoperative visits. Postoperative pain improvement occurred regardless of EDX grade. There were no major complications or reoperations in any group. CONCLUSIONS: Carpal tunnel release demonstrated consistently significant improvement in outcomes regardless of EDX grade at initial and final follow-up. The extent of postoperative improvement after CTR overall was also not statistically different between groups with differing EDX severity. Older patients with severe CTS achieved more modest gains. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Prospective Evaluation of Sleep Improvement Following Carpal Tunnel Release Surgery.

PURPOSE: Sleep disturbance due to nighttime awakening is a well-documented symptom of carpal tunnel syndrome. While relief of nighttime waking following carpal tunnel release (CTR) has been demonstrated, the effect of CTR on overall sleep quality has not been fully investigated. We hypothesized that CTR would result in significant improvement in overall sleep quality as well as patients' overall satisfaction with their sleep habits. METHODS: Cases of carpal tunnel syndrome with positive nerve studies, and treated with CTR, were prospectively enrolled. Demographic data, electromyography (EMG) severity, Quick Disabilities of the Arm, Shoulder, and Hand questionnaire, and Insomnia Severity Index (ISI) scale data were collected. RESULTS: A total of 398 patients were enrolled, with 99% available at 2 weeks and 64% available at 3-month final follow-up. At final follow-up, average Quick Disabilities of the Arm, Shoulder, and Hand score improved significantly from the preoperative value. Average ISI score on all 7 sleep categories on the survey improved significantly from before surgery to the first postoperative visit. However, the total ISI score did not further improve significantly between the 2-week and the 3-month postoperative visits. The ISI score improvements did not correlate with EMG severity. CONCLUSIONS: Patients undergoing CTR demonstrated significant improvement in mean scores for 7 aspects of sleep quality. Sleep improvement was unrelated to preoperative EMG severity and was experienced within 2 weeks of surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Fluoroscopic Exposure With Use of Mini-C-Arm During Routine Hand Surgery: A Prospective Comparison of Hand Versus Eye Radiation Dosage.

Radiation exposure with use of intraoperative fluoroscopy is a potential orthopedic occupational risk factor. The purpose of this study was to perform a prospective comparison of hand versus eye radiation exposure associated with mini-C-arm utilization and to test the hypothesis that routine mini-C-arm does not yield hand or eye dosages exceeding current recommended levels. Over a 12-month period, hand and eye radiation exposure was prospectively measured in a single board-certified hand surgeon using mini-C-arm fluoroscopy. Twenty-five cases were performed utilizing mini-C-arm fluoroscopy. Average monthly hand radiation dosage (45.81±14.49 mrem) was significantly higher (p = .01) than eye radiation dosage (<30 mrem). Both recorded values were below their respective critical exposure limits, as reported by the International Commission on Radiological Protection. The findings suggest that hand and eye exposure associated with mini-C-arm utilization during routine surgery does not approach reported levels of critical radiation loads.

Lunatocapitate and Triquetrohamate Arthrodeses for Degenerative Arthritis of the Wrist: A Midterm Follow-Up.

BACKGROUND: Degenerative arthritis of the wrist is a common condition often treated with 4 corner arthrodesis (FCA) or a partial wrist fusion. A number of limited intercarpal arthrodeses have been proposed for treatment of this condition. One technique, described by Wang and Bednar in 2012, involves fusion of the lunatocapitate and triquetrohamate joints. This study presents midterm follow-up of outcomes following this 2 column arthrodesis. METHODS: From 2000 to present, patients who underwent lunatocapitate and triquetrohamate arthrodesis were evaluated. The original cohort from the 2012 study was reviewed, as well as any additional patients who since underwent this procedure. Only patients who had greater than 5 years of follow-up data were included. Outcomes included demographics, wrist range of motion, grip strength, complications, and radiographic evidence of union. RESULTS: Twenty-one cases were included in the final analysis. Mean follow-up was 8.75 years. Wrist extension and flexion were 58% and 90% of the unaffected side, respectively. Grip strength was 92% of the unaffected side. Osseous union was achieved in 95.2% of cases. Two cases underwent revision surgery, one for nonunion and one following a fall. CONCLUSIONS: Lunatocapitate and triquetrohamate arthrodesis offers a treatment for wrist arthritis that yields good clinical outcomes, low nonunion rates, and no conversions to total wrist arthrodesis, as shown by 5-year follow-up data. Limited intercarpal arthrodesis is an alternative to FCA, with the advantage of a smaller surgical footprint and simpler technique, while still providing excellent mid- to long-term outcomes.

Evaluating the Efficacy of a Thermoresponsive Hydrogel for Delivering Anti-Collagen Antibodies to Reduce Posttraumatic Scarring in Orthopedic Tissues.

Excessive posttraumatic scarring in orthopedic tissues, such as joint capsules, ligaments, tendons, muscles, and peripheral nerves, presents a significant medical problem, resulting in pain, restricted joint mobility, and impaired musculoskeletal function. Current treatments for excessive scarring are often ineffective and require the surgical removal of fibrotic tissue, which can aggravate the problem. The primary component of orthopedic scars is collagen I-rich fibrils. Our research team has developed a monoclonal anti-collagen antibody (ACA) that alleviates posttraumatic scarring by inhibiting collagen fibril formation. We previously established the safety and efficacy of ACA in a rabbit-based arthrofibrosis model. In this study, we evaluate the utility of a well-characterized thermoresponsive hydrogel (THG) as a delivery vehicle for ACA to injury sites. Crucial components of the hydrogel included N-isopropylacrylamide, poly(ethylene glycol) diacrylate, and hyaluronic acid. Our investigation focused on in vitro ACA release kinetics, stability, and activity. Additionally, we examined the antigen-binding characteristics of ACA post-release from the THG in an in vivo context. Our preliminary findings suggest that the THG construct exhibits promise as a delivery platform for antibody-based therapeutics to reduce excessive scarring in orthopedic tissues.

Hand Surgery Patient Perspectives on Medical Cannabis: A Survey of Over 600 Patients.

Purpose: Medical cannabis (MC) has been proposed as a potential addition to multimodal pain management regimens in orthopedics. This study evaluates hand and upper-extremity patient perspectives of MC as a treatment for common orthopedic and musculoskeletal pain conditions. This study also aims to identify the proportion of patients already using MC, perceived barriers to MC use, and opinions on insurance coverage and legality of cannabis. Methods: An anonymous cross-sectional survey study was conducted of all patients at least 18 years old presenting from October 2020 to January 2021 to a hand and upper-extremity outpatient clinic. The survey collected information regarding opinion on MC, including use, legality, and willingness to use MC in the future. Medical cannabis was legal in the states where the study was conducted. Results: A total of 679 patients completed the survey (response rate 72.5%). Sixty-eight patients (10.0%) reported currently using MC. Of the 623 patients (90.0%) who reported not currently using MC, 504 (80.9%) would consider using MC for chronic pain, while the remaining 119 (19.1%) would not consider the use of MC for chronic pain. Age was not associated with whether a patient would consider using MC (P = .16) or was already using MC (P = .10). The most identified barrier to MC use was cost, reported as either expensive or not affordable by 477 patients (70.5%). Conclusions: This study found that most patients presenting for hand and upper-extremity complaints would consider using MC (80.9%), and most perceive it as a safe treatment option for common orthopedic conditions. Moreover, 10% of patients reported already using MC. One of the major barriers to MC use is the cost. Most (90.9%) patients support policies for legalization and insurance coverage of MC. Type of study/level of evidence: Therapeutic Level III.

Erratum to "Hand Surgery Patient Perspectives on Medical Cannabis: A Survey of Over 600 Patients" [Journal of Hand Surgery Global Online 5 (2023) 102-107].

[This corrects the article DOI: 10.1016/j.jhsg.2022.02.009.].

Extracellular Targets to Reduce Excessive Scarring in Response to Tissue Injury.

Excessive scar formation is a hallmark of localized and systemic fibrotic disorders. Despite extensive studies to define valid anti-fibrotic targets and develop effective therapeutics, progressive fibrosis remains a significant medical problem. Regardless of the injury type or location of wounded tissue, excessive production and accumulation of collagen-rich extracellular matrix is the common denominator of all fibrotic disorders. A long-standing dogma was that anti-fibrotic approaches should focus on overall intracellular processes that drive fibrotic scarring. Because of the poor outcomes of these approaches, scientific efforts now focus on regulating the extracellular components of fibrotic tissues. Crucial extracellular players include cellular receptors of matrix components, macromolecules that form the matrix architecture, auxiliary proteins that facilitate the formation of stiff scar tissue, matricellular proteins, and extracellular vesicles that modulate matrix homeostasis. This review summarizes studies targeting the extracellular aspects of fibrotic tissue synthesis, presents the rationale for these studies, and discusses the progress and limitations of current extracellular approaches to limit fibrotic healing.

Lunatocapitate and triquetrohamate arthrodeses for degenerative arthritis of the wrist.

PURPOSE: Proximal row carpectomy and 4-corner arthrodesis are 2 well-established motion-preserving treatment strategies for scapholunate advanced collapse. In this study, we present an arthrodesis technique involving the capitolunate and triquetrohamate joints as another potential treatment option. METHODS: From 2000 to 2009, 27 consecutive patients with degenerative scapholunate advanced collapse and scaphoid nonunion advanced collapse were evaluated prospectively and treated with scaphoid excision and intercarpal arthrodesis between the capitate and lunate and between the hamate and triquetrum. This cohort consisted of 18 men and 9 women, involving dominant-sided surgery in 20 of 27 patients. Two patients were active smokers, and 3 cases were work related. Average age at time of surgery was 55 ± 3 years, and average follow-up was 51 ± 7 months. Preoperative and postoperative range of motion, grip strength, and radiographic evidence of osseous union were documented. Standardized Patient-Rated Wrist Evaluation scores for both pain and function were collected. RESULTS: Wrist extension and flexion were decreased after surgery by 17% and 25% respectively, yielding a 21% decrease in mean flexion-extension arc. There was no significant difference with regard to postoperative radial and ulnar deviation or mean coronal plane arc compared to preoperative values. Compared to the contralateral side, preoperative and postoperative grip strength were 53% and 70%, respectively. The average operative-sided grip strength increased by 27%. The mean Patient-Rated Wrist Evaluation pain score was 11 ± 3 (of 50). The mean Patient-Rated Wrist Evaluation functional score was 17 ± 5 (of 100). Complications included 1 nonunion (yielding a 96% fusion rate), 1 median neuropathy (which resolved), and 2 superficial wound infections (treated successfully with oral antibiotics). CONCLUSIONS: Arthrodesis of the capitolunate and triquetrohamate joints offers a motion-preserving strategy with a high union rate and good clinical function and pain outcomes for the treatment for scapholunate advanced collapse and scaphoid nonunion advanced collapse. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Management of a Retained Rare Earth Magnetic Finger Mass Sustained from a Semiconductor Explosion Injury: A Case Report.

CASE: We present a case of a 51-year-old man with a retained supercharged rare earth magnetic finger mass sustained from an explosion injury at a semiconductor processing facility. The patient underwent excision of the rare metal mass, subsequently maintaining digital function without mass recurrence. CONCLUSION: Common to the semiconductor industry, neodymium is a rare earth metal and powerful magnet. Particulates are highly combustible, representing a potential explosive biohazard. To date, its toxicity and bioreactivity within the hand have not been thoroughly investigated. This is the first report of the successful surgical treatment of a retained rare earth neodymium magnetic hand mass.

Tramadol Versus Codeine in Hand Surgery.

Introduction Tramadol and codeine are both commonly prescribed in the setting of surgery or injury to the upper extremity. Despite their comparable strength in terms of opioid receptor affinity, the drugs differ pharmacologically and thus are not completely interchangeable. Methods This study analyzes all prescriptions for codeine and tramadol by a group of hand surgeons over a one-year period and tests the central hypothesis that the prescribing and refill patterns of these two drugs would be similar. Results Despite similar prescription amounts in terms of morphine equivalents, patients receiving tramadol required prescription refills at a significantly higher amount than those receiving codeine, and these individuals tended to be older. Additionally, patients treated nonoperatively were prescribed significantly more tramadol than those treated surgically. Conclusion Our findings suggest that codeine and tramadol are not equivalent in managing upper extremity pain. Further study is needed to articulate the situations in which physicians and patients are better served by tramadol versus codeine.

Safety and Duration of Low-Dose Adjuvant Dexamethasone in Regional Anesthesia for Upper Extremity Surgery: A Prospective, Randomized, Controlled Blinded Study.

BACKGROUND: Orthopedic procedures concerning the upper extremity commonly use a brachial plexus nerve block to achieve postoperative analgesia. The addition of dexamethasone to peripheral nerve blocks has been shown to significantly prolong its effect. We hypothesize that 1 mg doses of dexamethasone will prolong brachial plexus nerve block with similar efficacy to 4 mg and better than ropivacaine alone. METHODS: Seventy-nine patients who received a brachial plexus nerve block prior to undergoing upper extremity surgery were randomized to 1 of 4 treatment groups: group 1 received only 30 mL of 0.5% ropivacaine without dexamethasone (control); groups 2, 3, and 4 received 4, 2, and 1 mg of dexamethasone, respectively, added to 30 mL of 0.5% ropivacaine. RESULTS: Comparison of block duration, specifically "first signs of the block wearing off" to the 0-mg group, referencing the 1-, 2-, and 4-mg groups (P = .02, .04, and .01, respectively) that received steroid adjuvant therapy demonstrated a significant increase in time until the block began to wear off. All study groups receiving steroids also demonstrated a significant increase in duration of the block prior to its effects being completely gone when compared with the control group (P < .01 for all groups). CONCLUSIONS: Our findings demonstrate that adjuvant dexamethasone can prolong brachial plexus nerve blocks effectively at low doses compared with high doses, in addition to prolonging analgesia compared with local anesthetic alone.

A Multimodal Pain Management Regimen for Open Treatment of Distal Radius Fractures: A Randomized Blinded Study.

BACKGROUND: Adequate pain control is critical after outpatient surgery where patients are not as closely monitored. A multimodal pain management regimen was compared to a conventional pain management method in patients undergoing operative fixation for distal radius fractures. We hypothesized that there would be a decrease in the amount of narcotics used by the multimodal group compared to the conventional pain management group, and that there would be no difference in bone healing postoperatively. METHODS: Forty-two patients were randomized into 2 groups based on pain protocols. Group 1, the control, received a regional block, acetaminophen, and oxycodone. Group 2 received a multimodal pain regimen consisting of daily doses of pregabalin, celecoxib, and acetaminophen up until postoperative day (POD) #3. They also received a regional block with oxycodone for breakthrough pain. RESULTS: From POD#3 to week 1, there was a significant increase in oxycodone use in the study group correlating with the point in time when the multimodal regimen was discontinued. The shortened Disabilities of the Arm, Shoulder, and Hand Questionnaire (QuickDASH) scores taken at 2 weeks postoperation showed a significantly lower average score in the study group compared to the control. There was no difference in bone healing. CONCLUSIONS: The 2 regimens yielded similar pain control after surgery. The rebound increase in narcotic use after the multimodal regimen was discontinued, and significant difference in QuickDASH scores seen at 2 weeks postoperatively supported that multimodal regimens may not necessarily lead to decreased narcotic use in outpatient upper extremity surgery, but in the short term are shown to improve functional status.

Perspectives of Orthopedic Patients on Medical Cannabis: A Survey of More Than 2500 Patients.

Nationwide perspectives on cannabis have changed dramatically over recent decades. Although cannabis remains illegal at the federal level, medical cannabis (MC) is now legal in most states, and research has continued to show its effectiveness in a variety of medical conditions. However, both perception and acceptance of MC by the general public are evolving and remain poorly understood. Treating patients effectively with these novel therapeutics requires an understanding of the complex interplay of social and legal factors that could affect patient use. This cross-sectional survey study of more than 2500 patients sought to assess current patient perspectives on MC and to investigate factors related to its use that may represent barriers to broader patient use. Most respondents would consider using MC for chronic pain or other medical conditions. Most respondents were aware of the legal status of MC in their state, and 9 of 10 respondents believed that MC should be legal throughout the United States. General public knowledge of the utility of MC is an area needing improvement because older patients were significantly less likely to believe that MC is safe to use or that MC is safer than prescription opioids. As has been reported in previous literature, social stigma and cost appear to remain barriers for patient use of MC. Our findings provide further insight into current patient perspectives on MC, aiding both medical providers and researchers as we continue to provide access to and research MC. [Orthopedics. 2022;45(6):e309-e314.].

Circulating inflammatory cytokines alter transcriptional activity within fibrotic tissue of Dupuytren's disease patients.

Dupuytren's disease is a benign fibroproliferative disorder of the hand that results in disabling digital contractures that impair function and diminish the quality of life. The incidence of this disease has been correlated with chronic inflammatory states, but any direct association between inflammatory cytokines and Dupuytren's disease is not known. We hypothesized that advanced fibroproliferation is associated with increased levels of circulating inflammatory cytokines. Blood and fibrotic cord tissue were collected preoperatively from patients with severe contracture and control patients. Blood plasma concentrations of known inflammatory cytokines were evaluated using a multiplex immunoassay. Proteins from the cord tissue were analyzed by RNA sequencing and immunohistochemistry. Moreover, collagen-rich cords were analyzed using Fourier-transform infrared spectroscopy. The results indicate that patients exhibited significantly elevated circulating inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-2, and IL-12p70, as compared with controls. Similarly, IL-4 and IL-13 were detected significantly more frequently in Dupuytren's disease as compared with control. RNA sequencing revealed 5311 differentially expressed genes and distinct clustering between diseased and control samples. In addition to increased expression of genes associated with fibroproliferation, we also observed upregulation of transcripts activated by inflammatory cytokines, including prolactin inducible protein and keratin intermediate filaments. IL-2, but not TNF-α, was detected in fibrotic cord tissue by immunohistochemistry. Finally, spectroscopic assays revealed a significant reduction of the collagen content and alterations of collagen cross-linking within the Dupuytren's disease tissues. In total, our results illustrate that patients with severe Dupuytren's disease exhibit substantially elevated circulating inflammatory cytokines that may drive fibroproliferation. Clinical Significance: The results from this study establish the basis for a specific cytokine profile that may be useful for diagnostic testing and therapeutic intervention in Dupuytren's disease.

An Evaluation of Complications Following Ultrasound-Guided Regional Block Anesthesia in Outpatient Hand Surgery.

Background: Ultrasound-guided (USG) assistance has contributed to the acceptance of regional anesthesia as a safe and efficient alternative to traditional general anesthesia. However, limited data exist regarding the safety of supraclavicular blocks used in common hand surgery procedures. The purpose of this retrospective study was to evaluate a large sample of cases to determine the effectiveness and complication rate of supraclavicular nerve blocks and confirm the safety of its use within the ambulatory surgery center (ASC) setting. Methods: Nerve blocks for the upper extremity were performed via the supraclavicular approach using the USG technique. Records were analyzed for all patients monitored during the immediate postoperative recovery and step-down phases at the ASC and contacted by phone or evaluated within 2 weeks at their first postoperative visit. Adverse outcomes related to the regional block anesthesia were identified via phone interview or postoperative surgical visit and documented. Results: In all, 713 records were reviewed with 56% female (n = 398) and 44% male (n = 315) patients. Of the 713 cases, 4 adverse events were identified (0.6%, 95% confidence interval [%]), including 2 abnormal reactions to the nerve block and 2 incomplete blocks with inadequate pain control. Conclusions: This study is the first report to evaluate a large sample of outpatient hand procedures at a high-volume ASC. We can report no clinically significant pulmonary or neurovascular complications with the use of USG supraclavicular nerve block techniques, further supporting its establishment as a safe and efficient procedure, yielding a low complication rate.

Three Dimensionally Printed Versus Conventional Casts in Pediatric Wrist Fractures.

Background and objective With significant advancement in the field of biomaterials, alternatives to conventional fiberglass casts such as customized three-dimensional (3D) orthotics have been developed. However, there is a scarcity of reported experience regarding 3D-printed orthoses. The purpose of this study was to compare radiographic outcomes and patient satisfaction with fractures treated with either conventional or 3D-printed casts. Materials and methods We included 23 limbs from 22 patients, who were aged between 8-18 years, and with a diagnosis of an acute nondisplaced wrist or forearm fracture. Patients were randomized into two groups: consisting of those treated with a 3D-printed orthosis and those with conventional fiberglass cast. Outcomes included X-ray alignment and healing, cast fit, the appearance of the skin, ease of care, and overall satisfaction. Results Of note, 10/11 (91%) in the 3D cast group healed in an excellent position, and 1/11 healed in an acceptable position. Also, 11/12 (92%) in the conventional cast group healed in an excellent position, and 1/12 healed in an acceptable position. Radiographically, 11/11 (100%) of the fractures in the 3D group and 11/12 (92%) in the conventional cast group were found to be fully healed. No differences were found in terms of skin irritation by a blinded hand therapist. Patients reported significant differences in skin irritation, comfort, satisfaction, and cast care favoring 3D casts (p<0.05). Conclusions 3D orthoses offer a promising opportunity to improve patients' experiences with upper extremity casting while also providing appropriate immobilization.

Mechanisms of reducing joint stiffness by blocking collagen fibrillogenesis in a rabbit model of posttraumatic arthrofibrosis.

Posttraumatic fibrotic scarring is a significant medical problem that alters the proper functioning of injured tissues. Current methods to reduce posttraumatic fibrosis rely on anti-inflammatory and anti-proliferative agents with broad intracellular targets. As a result, their use is not fully effective and may cause unwanted side effects. Our group previously demonstrated that extracellular collagen fibrillogenesis is a valid and specific target to reduce collagen-rich scar buildup. Our previous studies showed that a rationally designed antibody that binds the C-terminal telopeptide of the α2(I) chain involved in the aggregation of collagen molecules limits fibril assembly in vitro and reduces scar formation in vivo. Here, we have utilized a clinically relevant arthrofibrosis model to study the broad mechanisms of the anti-scarring activity of this antibody. Moreover, we analyzed the effects of targeting collagen fibril formation on the quality of healed joint tissues, including the posterior capsule, patellar tendon, and subchondral bone. Our results show that blocking collagen fibrillogenesis not only reduces collagen content in the scar, but also accelerates the remodeling of healing tissues and changes the collagen fibrils' cross-linking. In total, this study demonstrated that targeting collagen fibrillogenesis to limit arthrofibrosis affects neither the quality of healing of the joint tissues nor disturbs vital tissues and organs.