Citations

Background Loss of finger motion after zone II flexor tendon repair remains common and is largely caused by adhesion formation. Although intrinsic vascular and cellular contributions to tendon healing have been examined in canine, avian, and primate models, prior studies have emphasized biochemical or perfusion-based endpoints without comprehensive assessment of functional and mechanical outcomes after clinically relevant repair. Consequently, the influence of intrinsic healing elements on early postoperative function remains unclear. In this study, we employed a novel avian model of intrasynovial (zone II) tendon injury, which enables clinically relevant operative repair, postoperative rehabilitation, and quantitative assessment of tendon function and biomechanics, to investigate the contribution of intrinsic healing elements to tendon repair. Questions/purposes (1) Does operative ablation of intrinsic healing elements worsen early ROM after zone II flexor tendon repair? (2) Does disruption of intrinsic pathways increase adhesion formation, as measured by normalized work of flexion and gross adhesion scores? (3) Does intrinsic tendon component ablation compromise mechanical properties, including ultimate load to failure and stiffness? (4) Does removal of intrinsic elements alter the expression of fibrotic and matrix-related genes during early healing? Methods Using a clinically relevant, large-animal avian ( Meleagris gallopavo ) model of zone II flexor tendon repair, flexor digitorum longus (FDL) tendons underwent sharp transection and primary repair and were assigned to one of four groups: (1) control repair with intact intrinsic elements (3 weeks postinjury, n = 11; 6 weeks postinjury, n = 18), (2) vincular ligation and transection (3 weeks postinjury, n = 12; 6 weeks postinjury, n = 16), (3) tenocyte cryoablation via intraoperative freeze-thaw devitalization (3 weeks postinjury, n = 13; 6 weeks postinjury, n = 13), or (4) complete tendon devitalization (3 weeks postinjury, n = 13; 6 weeks postinjury, n = 16). A total of 112 male and female birds were used for this study. Harvested tendons were evaluated at 3 and 6 weeks postoperatively. Outcomes included interphalangeal ROM, normalized work of flexion, semiquantitative gross adhesion scoring, ultimate load to failure, stiffness, qualitative histologic assessment, qualitative immunofluorescence, and quantitative PCR for fibrotic and matrix-related genes. Results Operative ablation of the intrinsic healing elements did not worsen total ROM and/or increase normalized work of flexion. All experimental groups demonstrated reduced total ROM of the operative digit at 3 weeks postoperatively compared with the contralateral nonoperative digit: mean ± SD control repair with intact intrinsic healing elements (50° ± 10° versus 14° ± 6°, mean difference 36.41° [95% confidence interval (CI) 26.87° to 45.94°]; p < 0.001), vincular disruption group (50° ± 10° versus 14° ± 7°, mean difference 35.97° [95% CI 21.44° to 45.51°]; p < 0.001), tenocyte cryoablation group (50° ± 10° versus 15° ± 8°, mean difference 35.27° [95% CI 25.99° to 44.55°]; p < 0.001), and complete tendon devitalization group (50° ± 10° versus 11° ± 4°, mean difference 38.97° [95% CI 29.44° to 48.50°]; p < 0.001). However, no differences between the groups were detected. Similarly, the total ROM was impaired at 6 weeks postinjury compared with the nonoperative digit in all groups. We did not detect any differences between the groups, and results did not demonstrate time-dependent differences between the two time points. Furthermore, normalized work of flexion, a proxy for peritendinous adhesion severity, was increased in all experimental groups at 3 weeks postinjury: mean ± SD control repair with intact intrinsic healing elements (0 ± 0 N mm/° versus 4 ± 3 N mm/°, mean difference -3.33 [95% CI -5.73 to -0.93]; p = 0.003), vincular disruption group (0 ± 0 N mm/° versus 4 ± 2 N mm/°, mean difference -3.09 [95% CI -5.49 to -0.69]; p = 0.006), tenocyte cryoablation group (0 ± 0 N mm/° versus 3 ± 2 N mm/°, mean difference -2.99 [95% CI -5.33 to -0.66]; p = 0.006), and complete tendon devitalization group (0 ± 0 N mm/° versus 4 ± 2 N mm/°, mean difference -3.31 [95% CI -5.70 to -0.91]; p = 0.003). However, no group differences were detected. At the 6-week follow-up, the normalized work of flexion was also elevated in all groups without any differences between the treatments. Furthermore, the integrity of the tendon intrinsic components has been presumed to be a major determinant of flexor tendon healing strength after zone II tendon repair. However, our results do not support this assumption. At both time points, there were no differences in ultimate load and stiffness between the experimental groups, and there were no group × time interaction effects. Additionally, structural removal of the intrinsic healing elements did not result in meaningful qualitative histologic differences in extrinsic fibrosis, neovascularization, or collagen fiber organization. The profibrotic gene, transforming growth factor beta induced (TGFBI), was upregulated in all experimental groups compared with the normal FDL tendon. Matrix remodeling, measured by matrix metalloproteinase 7 (MMP7) activity, was also activated in all groups relative to the normal FDL tendon. However, no differences were detected between the groups. Conclusion Operative ablation of intrinsic healing elements, including the flexor vincular system and resident tenocytes, did not worsen early ROM, adhesion formation, or mechanical properties after zone II flexor tendon repair in a clinically relevant large-animal model. Early healing was characterized by a robust fibrovascular response across all groups, indicating that extrinsic mechanisms predominate during the early reparative phase. Paradigms that modulate the extrinsic tendon healing mechanisms could represent a more viable approach to flexor tendon healing outcomes than focusing on bolstering the intrinsic components. Clinical Relevance Our findings suggest that early functional recovery in this model may depend more on modulation of the extrinsic fibrotic response than on preservation of intrinsic vascular or cellular elements, supporting the development of antiadhesion therapies. Additional preclinical studies are needed to identify the cellular niches that drive extrinsic fibrosis and adhesion formation, determine whether they can be selectively modulated without impairing tendon healing, and establish the translational relevance of these mechanisms across species before clinical application.

Abstract Carpal fractures are uncommon, representing a small proportion of hand fractures. This study aimed to determine the incidence, injury mechanisms, treatment patterns, and complication rates of carpal fractures in Olmsted County, Minnesota, United States. A retrospective review was performed using the Rochester Epidemiology Project registry to identify carpal fractures between 2013 and 2023. Fractures were confirmed by radiographs, computed tomography, or radiology reports. Demographic data, injury mechanism, fracture laterality, and fracture characteristics were recorded. A total of 699 carpal fractures were identified. Most patients were men (57%) with a mean age of 43 years. The most common fracture was the scaphoid (44%), followed by the triquetrum (31%), hamate (9%), and trapezium (3%). The overall incidence was 53.6 per 100,000 person-years. Concomitant wrist fractures occurred in 22%, and multiple ipsilateral carpal fractures in 4.6%. Patients with triquetrum fractures had the highest mean age (54 years) and low surgical rates (2%), whereas hamate and trapezoid fractures occurred at younger ages (39 and 38 years) and had the highest surgical rates (28 and 33%, respectively). The most common injury mechanism was a fall onto an outstretched hand (n = 438). Overall, 14% (n = 98) of patients underwent surgery, of whom 77% were men. The highest nonunion rate was seen in hamate fractures (10.9%), followed by scaphoid waist and proximal pole fractures (10.5%). Nonscaphoid carpal fractures occur more frequently than previously reported and demonstrate variable age distribution, treatment rates, and nonunion risks. Understanding these patterns can improve diagnosis, guide treatment planning, and inform patient expectations. IV.

ABSTRACT Extracellular vesicles (EVs) are non‐replicating, lipid membrane‐bound nanoparticles released by most eukaryotic cells into the extracellular space. When derived from platelets, a subset of EVs can exhibit remarkable anti‐inflammatory and antioxidant properties, making them attractive candidates to attenuate sterile inflammatory states such as limb skeletal muscle ischaemia‐reperfusion injury (IRI). Peripheral extremity IRI complicating acute limb revascularisation procedures, replantation of major traumatic amputations and limb allotransplants can trigger a life‐threatening reperfusion syndrome that leads to multi‐organ system failure and death. In this study, we used a platelet‐derived EVs‐enriched preparation as a therapeutic strategy for extremity IRI. To allow for a clinically translatable drug delivery strategy, we established and validated a catheter‐directed regional intra‐arterial limb infusion (RLI) delivery approach that permitted selective and effective targeting of pEVs to limb skeletal muscles and soft tissues in the vascularly isolated rodent extremity simulating pre‐reperfusion preservation and revascularisation conditions of the ischaemic or amputated extremity. In addition to being safe and feasible, we demonstrated robust retention of EVs by skeletal muscles of the operative limb during the early critical phase of reperfusion injury following RLI. We also show that pretreatment of ischaemic skeletal muscles using an pEVs‐enriched formulation just before reestablishing extremity blood flow alleviated metabolic derangements and suppressed the systemic and localised proinflammatory cytokine response associated with skeletal muscle reperfusion and reduced histologic markers of myofibre injury without adverse effects on serum chemistries. This work opens a new perspective to investigate novel approaches for regional delivery of therapeutic pEVs to skeletal muscle to mitigate limb IRI in vivo, and to achieve both in situ and ex vivo targeted delivery of nanocarriers to the isolated limb tissue for other therapeutic applications.

Background: Rupture at tendon repair sites in animal models impedes the study of healing. To address this, we investigated “safe incisions” – strategic partial transections to prevent rupture under excessive force. We hypothesized these would act as mechanical “fuses,” reducing repair site tension. Objectives: This in vitro biomechanical study optimized safe incision spacing to enhance tendon construct strength and minimize gap formation in a turkey flexor tendon model. Materials and Methods: Forty turkey flexor tendons were divided into five groups ( n = 8): Repaired without incisions, intact with 5 mm incisions, repaired with 5 mm incisions, intact with 10 mm incisions, and repaired with 10 mm incisions. Repairs used a modified Pennington suture. Safe incisions (opposing hemi-transections) with 5 mm or 10 mm longitudinal spacing were created proximally. Tendons were tested to failure at 1 mm/s, recording force-elongation, failure mode, gap formation (>2 mm at 10% strain), stiffness, and repair site elongation. Results: Repaired tendons without incisions (Group 1) showed 100% repair site failure (46.5 ± 10.96 N). With 5 mm safe incisions (Group 3), no repair site failures occurred (incision failure at 18.11 ± 10.96 N). 10 mm incisions (Group 5) offered partial protection (25% repair failure at 37.48 ± 11.35 N). Group 1 had higher gap formation (75% vs. 0% in Group 3, P < 0.01), stiffness, and repair site elongation than Groups 3 and 5. Gap formation force was similar for Group 1 (25.76 ± 9.18 N) and Group 5 (25.04 ± 12.21 N). Conclusions: In this in vitro model, 5 mm spaced safe incisions effectively shifted failure away from the repair and limited gap formation by reducing stiffness. 10 mm incisions provided partial protection. Strategically placed safe incisions show potential to protect tendon repairs from immediate rupture by enabling controlled lengthening at a weaker site. However, tendinopathy risk and clinical relevance require in vivo studies.

ABSTRACT Calcific tendinopathy is a common musculoskeletal disorder marked by calcium deposition within tendons, often accompanied by pain, impaired mobility, and in severe cases, ossification. However, the mechanisms underlying tendon mineralization remain poorly understood. In contrast to pathological human calcification, turkeys naturally develop tendon mineralization during growth without signs of inflammation or ossification. This study had two phases: an observational phase to assess onset and progression of calcification, and an interventional phase to evaluate the role of mechanical loading. In the observational phase, flexor tendons were collected from turkeys aged 1–16 weeks in a serial sacrifice study and analyzed by Von Kossa staining and biomechanical testing. Calcification began at 7 weeks, localized within organized collagen matrices, progressed through Weeks 8–14, and peaked by 16 weeks. In the interventional phase, nine female turkeys were randomized at 4 weeks into a transection group ( n = 3), sham group ( n = 3), and control group ( n = 3). Transection at the muscle–tendon junction eliminated mechanical loading. At 16 weeks, tendons were analyzed by histology, quantitative RT‐PCR, ICP‐MS, and biomechanical testing. Transected tendons showed a near‐complete absence of mineralization, reduced expression of osteogenic markers (osteopontin, osteocalcin, Runx‐2), and significantly lower calcium, magnesium, and phosphorus levels. Biomechanical testing indicated reduced stress relaxation, stiffness, and Young's modulus in the transected group. Tendon calcification in turkeys functioned as a mechanically regulated, nonpathological process. The study established a relevant model for early tendon mineralization and offered a basis for developing load‐dependent therapies for human tendon disease.

Abstract To present our clinical experience with a volar scapholunate (SL) ligament reconstruction using a strip of the long radiolunate ligament. This was a single-institution observational study (2004–2022) of SL ligament injuries with evidence of a torn volar component on arthroscopy that received volar capsulodesis with/without a dorsal repair. The postoperative range of motion (ROM), grip strength, complications, and secondary surgery (e.g., four-corner fusion or total wrist fusion), and radiographic changes were reported. Disabilities of arm, shoulder, and hand/patient-rated wrist evaluation (DASH/PRWE) scores were prospectively collected. Patients were stratified by static versus dynamic/predynamic SL diastasis and by isolated volar versus volar and dorsal ligament injury. Twenty-eight patients (15 females and 13 males) with a mean age of 35.1 years (± 15.7) met the inclusion criteria. The follow-up was 86.3 months (± 53.4; minimum 11 months). Most (26/28) patients were right-handed. The majority (20/28) of the patients presented ≥ 6 weeks postinjury. Few (4/28) used tobacco. Most (20/28) patients had dynamic/predynamic injuries. Postoperatively, the mean pronation/supination was 83 degrees/83 degrees, flexion/extension was 56 degrees/61 degrees, ulnar deviation was 30 degrees, and radial deviation (RD) was 19 degrees (n = 13). The mean grip strength was 78.8% (± 30.4) of the contralateral normal side (n = 14). Except for increased RD in patients with dynamic/predynamic injuries (p = 0.02), there were no other ROM differences. SL widening (>3 mm) postoperatively was observed in 33.3% (2/6) of static versus none of the dynamic/predynamic injuries (p = 0.165). There were only two postoperative complications, both surgical site infections. Two patients had persistent pain and required secondary surgery at a median of 48 months. At 86.9 months, patients reported a mean DASH of 16.4 (± 17.8) and a PRWE of 24.6 (± 23.6), and 78.9% (15/19) returned to prior work. We report long-term functional outcomes after a volar capsulodesis for volar SL injuries. This appears to be a safe procedure with an acceptable complication rate and low disability after 7 years. Most (approximately 79%) patients returned to their previous employment. A larger comparative study will be required to prove superiority to other types of repairs. Level IV, Case series.

Abstract Objective Sleeper stretching (SS) and cross‐body stretching (CS) are common nonsurgical interventions for the management of glenohumeral internal rotation deficit (GIRD) in overhead athletes such as baseball and volleyball players. However, the effectiveness of these stretching interventions in enhancing the range of motion (ROM) of shoulder internal rotation (IR) in overhead athletes with GIRD remains a subject of uncertainty. This systematic review and meta‐analysis aim to critically assess the efficacy of SS and CS in the ROM of the IR among overhead athletes with GIRD, thereby providing evidence‐based recommendations for their use. Literature Survey A comprehensive search of MEDLINE, Embase, and Scopus databases up to November 2024 was conducted to identify randomized controlled trials investigating the influence of SS and CS on the ROM of shoulder IR in overhead athletes with GIRD. Methodology Data including study characteristics and outcomes were extracted. Risk of bias assessment and random‐effects model meta‐analysis were performed. Synthesis Six eligible studies involving 255 athletes with GIRD were included. The meta‐analysis demonstrated statistically significant differences between stretching and control groups in terms of enhancing the ROM of IR (mean difference [MD], 7°; 95% confidence interval [CI], 1°–13°; p = .02) and horizontal adduction (HAD) ([MD], 6°; [CI], 1°–11°; p = .03). Conclusion SS or combination of SS and CS interventions significantly enhanced the ROM of IR compared to the control group in overhead athletes diagnosed with GIRD. Furthermore, the review confirmed that SS alone also markedly enhances the ROM of HAD. These findings highlight the potential benefits of SS and CS in managing GIRD and suggest a need for further research to optimize these interventions for broader application in overhead athletes.

Background: The authors present a novel microsurgical model to investigate ischemia-reperfusion (I/R) injury in composite tissue (muscle/skin) using a musculocutaneous flap. I/R was induced in a rodent biceps femoris musculocutaneous flap through collateral ligation and arteriovenous clamping. The authors hypothesized that I/R flaps would show greater tissue damage compared with sham. Methods: Male rats were randomized into I/R ( n = 10) and sham ( n = 9) groups. The I/R group underwent flap elevation, collateral ligation, 3 hours of arteriovenous clamping, followed by reperfusion. The sham group had flap elevation only. Perfusion was monitored using laser-speckle imaging, and flap discoloration was assessed with blinded skin ischemia necrosis scores. Serum and the composite tissue (skin/muscle) were analyzed for injury on postoperative days (PODs) 1 or 3. Results: Clamping reduced perfusion ( P = 0.00), whereas unclamping increased perfusion ( P <0.00). Over time, flaps exposed to I/R were more ischemic (estimate, 0.39; P = 0.02). At POD1, the injury group had higher serum creatine kinase ( P = 0.04) and potassium ( P = 0.00) than the sham group. The injury group had more muscle apoptosis (34.7% versus 5.2%; P = 0.03), myonecrosis (30.3% versus 14.1%; P = 0.04), and inflammation (13.7% versus 4.9%; P = 0.02) than the sham group; myonecrosis and inflammation persisted into POD3. Skin apoptosis and inflammation were similar. Conclusions: This model reliably reproduces I/R injury with a 3-hour ischemic period followed by early reperfusion. Animals subjected to the authors’ technique showed greater tissue damage than the sham group, with muscle being more vulnerable than skin. Serum showed peak muscle injury at 24 hours, and histologic analysis showed myonecrosis and inflammation through 72 hours. This suggests that less than 24 hours’ reperfusion (eg, critical window) may serve as the optimal time for possible intervention. Clinical Relevance Statement: I/R injury is a complex phenomenon affecting vascular composite tissues. The mitochondrial superoxide dismutase may be more specific for I/R injury. There may be a critical window within which to mitigate injury (<24 hours after reperfusion). The authors’ model helps investigate muscle/skin I/R injury.

Abstract Rhabdomyolysis following revascularization of the ischemic upper extremity can lead to life- & limb- threatening sequelae. In the context of replantations and vascularized composite allografting, a reconstructive procedure usually reserved for upper limb amputees, prolonged tissue ischemia is detrimental to extremity functional recovery. Currently, validated survival small animal models of extremity reperfusion injury that permit longitudinal assessment of limb function are lacking. To date, studies that evaluated reperfusion injury-induced neuromuscular impairment rely on terminal ex vivo procedures and do not provide clinically translatable measurements. Furthermore, it is unclear if upper extremity musculature exhibits a different ischemic threshold compared to the lower limb given the relatively rare incidence of upper limb ischemia. Here, we present a reliable rat model of extremity post-reperfusion syndrome (PRS) that comprehensively recapitulates the biochemical hallmarks of rhabdomyolysis secondary to upper extremity reperfusion injury and allows for monitoring in vivo upper limb function using clinically relevant electrodiagnostic and kinematic metrics. In addition to inducing severe metabolic derangements, our forelimb PRS provided insights on gross motor and electrophysiological alterations upper extremity reperfusion injury. We identify gait coordination parameters such as stride frequency and forelimb-hindlimb coordination index and electrophysiological metrics including compound muscle action potential amplitude as objective, non-invasive outcome measures for limb function assessment in small animal models of extremity PRS. This comprehensive, validated functional model can serve as an invaluable tool to evaluate therapeutics or preconditioning regimens to attenuate PRS and mitigate resulting neuromuscular dysfunction.

Muscle stem cells (MuSCs) are essential for skeletal muscle regeneration, influenced by a complex interplay of mechanical, biochemical, and molecular cues. Properties of the extracellular matrix (ECM) such as stiffness and alignment guide stem cell fate through mechanosensitive pathways, where forces like shear stress translate into biochemical signals, affecting cell behavior. Aging introduces senescence which disrupts the MuSC niche, leading to reduced regenerative capacity via epigenetic alterations and metabolic shifts. Transplantation further challenges MuSC viability, often resulting in fibrosis driven by dysregulated fibro-adipogenic progenitors (FAPs). Addressing these issues, scaffold designs integrated with pharmacotherapy emulate ECM environments, providing cues that enhance graft functionality and endurance. These scaffolds facilitate the synergy between mechanotransduction and intracellular signaling, optimizing MuSC proliferation and differentiation. Innovations utilizing human pluripotent stem cell-derived myogenic progenitors and exosome-mediated delivery exploit bioactive properties for targeted repair. Additionally, 3D-printed and electrospun scaffolds with adjustable biomechanical traits tackle scalability in treating volumetric muscle loss. Advanced techniques like single-cell RNA sequencing and high-resolution imaging unravel muscle repair mechanisms, offering precise mapping of cellular interactions. Collectively, this interdisciplinary approach fortifies tissue graft durability and MuSC maintenance, propelling therapeutic strategies for muscle injuries and degenerative diseases.