Zhao, Chunfeng

ABSTRACT Our study aimed to develop a novel, reproducible, minimally invasive turkey knee osteoarthritis (OA) model and evaluate whether intra‐articular hyaluronan (HA) alone or combined with purified exosome product (PEP) attenuates OA‐related functional and structural deterioration. OA was induced arthroscopically by transection of the anterior and posterior cruciate ligaments with resection of the anterior horn of the medial meniscus. Animals received intra‐articular injections of saline, HA, or PEP + HA at postoperative 2–5 weeks. Gait was assessed at 4, 8, and 12 weeks, and cartilage degeneration, subchondral bone sclerosis, osteophyte formation, synovial fibrosis, heterotopic ossification, and meniscal integrity were evaluated by quantitative CT and histology at week 12. Compared with saline, HA improved lameness, preserved cartilage glycosaminoglycan content, and reduced meniscal rupture, subchondral bone sclerosis, and periarticular heterotopic ossification. PEP + HA provided additional benefits, including prolonged stance phase, reduced synovial fibrosis, and greater chondroprotection than HA alone, while plantar pressure variables, subchondral bone remodeling, and patellar osteophytes did not differ between HA and PEP + HA. This turkey model reliably produces human‐like OA changes and enables longitudinal functional and structural assessment. Intra‐articular HA mitigated OA progression, and the addition of PEP conferred incremental joint protection.

Chronic wounds remain a major unmet clinical challenge, often failing to progress to normal healing due to persistent inflammation, impaired angiogenesis, and cellular senescence. Exosomes have recently been investigated as promising acellular therapeutics capable of restoring intercellular communication and promoting tissue regeneration. Among these, the Purified Exosome Product (PEP) represents a next-generation, platelet-derived exosome formulation manufactured under Good Manufacturing Practice (GMP) conditions with high purity, stability, and reproducibility. This review summarizes the current advances in exosome-based chronic wound therapeutics and PEP delivery systems and their translational potentials. Incorporation of PEP into bioengineered carriers such as fibrin sealant, collagen scaffolds, and hyaluronic acid (HA) hydrogels enables localized and sustained exosome release, significantly prolonging therapeutic effects and improving regenerative outcomes. Fibrin-based PEP delivery achieved complete wound closure and functional skin regeneration in animal models, while collagen and HA-based systems showed promising results for injectable and dermatologic applications. Beyond its intrinsic healing effects, PEP may also serve as a nanocarrier for other drugs, offering a future direction in chronic wound management.

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 Column-type wrists, which exhibit increased scaphoid flexion during radial deviation, often experience greater loss of motion after periscaphoid arthrodesis compared with row-type wrists. Dynamic radiographic series are typically used to differentiate these kinematic patterns. In this study, we evaluate capitate morphology as a means of predicting column- or row-type carpal kinematics. This study investigated whether wrist kinematic patterns could be predicted using simple anteroposterior (AP) radiographs. We hypothesized that capitate morphology, given its close articulation with the scaphoid, influences these patterns. We analyzed 75 wrist motion radiographic series from 45 patients. Capitates were classified as either Type I (rectangular) or Type II (pentagonal) based on their shape. Wrist kinematic patterns were categorized as row- or column-type based on the degree of scaphoid length shortening during radial deviation. Our analysis revealed that a Type II capitate was a significant predictor of column-type wrists, with an odds ratio of 6.01 compared with Type I (p = 0.014). Furthermore, Type II capitates were associated with increased scaphoid flexion and reduced translation. Capitate morphology, as assessed from a plain AP radiograph, can serve as an easily accessible marker and reliable predictor of wrist motion patterns. This could potentially aid in surgical planning and patient counseling, particularly when dynamic radiographic series are not feasible. Diagnostic, Level III.

Background: Tendon-bone healing after rotator cuff injury is, or remains, a clinical challenge. Purpose: To examine the role of intraoperative use of purified exosome products (PEPs) in the treatment of rotator cuff injuries and to assess the effect of PEP on supraspinatus tendon-bone healing after rotator cuff repair in a rat model. Study Design: Controlled laboratory study. Methods: This study used 120 Sprague-Dawley rats that underwent an acute supraspinatus tendon transection from the insertion, followed by repair using a single transosseous suture. They were divided into 3 groups: a control group that received only sutures, a TISSEEL group that used a commercially available fibrin sealant patch (TISSEEL) of approximately 0.5 cm 2 , and a PEP-TISSEEL group that used a similarly sized TISSEEL patch combined with PEP. Autopsies were performed at 1, 3, 6, and 8 weeks after surgery. Analyses were performed using molecular biological, biomechanical, and histological techniques. Results: At 6 weeks, the PEP-TISSEEL group achieved greater failure load (mean, 27.5 ± 5.3 N) than the control (mean, 16.4 ± 4.2 N; P = .012) and TISSEEL (mean, 23.4 ± 5.0 N; P = .041) groups, with superiority persisting at 12 weeks (27.2 ± 6.5 N vs 13.1 ± 2.6 N [ P = .002] for the control group and 21.1 ± 5.8 N [ P = .037] for the TISSEEL group). DigiGait showed earlier recovery of stride length and paw angle. Histology revealed organized collagen and reduced scarring, while molecular assays demonstrated early inflammatory modulation with subsequent upregulation of collagen type 1 or 3 and TGF-β, supporting accelerated tendon-bone healing. Conclusion: Intraoperative application of PEP-TISSEEL enhanced tendon-bone healing in a rat model by improving biomechanical strength, promoting enthesis-specific histological regeneration, and accelerating functional recovery as evidenced by gait analysis. Clinical Relevance: The intraoperative application of PEP combined with TISSEEL significantly enhances rotator cuff tendon healing by modulating early inflammation, promoting collagen synthesis, and improving biomechanical properties in a rat model. These findings suggest that PEP-based therapies could offer a promising adjunct in surgical repair, potentially reducing retear rates and improving functional outcomes in patients with rotator cuff injuries. Further clinical studies are warranted to translate these benefits into human applications.

ABSTRACT Tendon adhesion is a major complication following tendon reconstruction surgery in the hand. Previous studies showed that a combination of hyaluronic acid (HA) and gelatin, covalently bound to the tendon surface, can provide a durable gliding surface to reduce adhesions in animal models both in‐vitro and in‐vivo. We have developed a similar product using good manufacturing practice (GMP) standards, in preparation for use in humans. This study aimed to examine the frictional properties and elastic modulus of the Manufactured Tendon Lubricant (MTL) when applied to an extrasynovial canine peroneus longus (PL) tendon in‐vitro. Twenty PL tendons along with the 2nd and 5th digits from adult canine forepaws, were obtained (mean age: 12 months, weight: 35 kg) from animals sacrificed in Institutional Animal Care and Use Committee (IACUC) approved protocols. Tendons were treated either with the MTL or saline solution, as a control. Eight tendons from each group (MTL vs saline‐treated) underwent friction testing, using a previously described protocol, followed by indentation testing to assess tendon elastic modulus (a marker of successful crosslinking). Two tendons from each group were not tested and were sent for scanning electron microscopy (SEM). The MTL group had significantly ( p < 0.001) lower friction and gliding resistance as well as higher elastic modulus of the PL tendons, compared to the saline group. This study demonstrates that MTL provides lubricating effects and fixation to the tendon surface and may be suitable for human testing.

Abstract Preiser's disease (PD), or idiopathic avascular necrosis of the scaphoid, is a debilitating condition leading to wrist pain, dysfunction, and pan-carpal arthritis. While impaired scaphoid vascularity is central to its pathogenesis, identifying individuals at risk is challenging due to the morphological distortion of the scaphoid as the disease progresses. This study aims to investigate the association between a novel capitate morphology classification, scaphoid morphology, and their impact on PD prevalence and characteristics. We also re-evaluate negative ulnar variance (NUV) as a potential risk factor for PD. This retrospective case–control study included 34 PD patients and 340 age-matched controls. Capitate morphology was classified into Type I/II on anteroposterior (AP) radiographs based on capitotrapezoid–scaphocapitate (CT–SC) joint line angle and ratio. Scaphoid morphology was assessed via the waist index on contralateral healthy wrists. Radiographic measurements of ulnar variance and PD staging were also performed. Statistical analyses compared morphological prevalence and risk factors between groups. Type II capitate was significantly more prevalent in the PD group (35.3%) than in controls (17.1%, p = 0.018). Similarly, NUV was significantly higher in PD patients (29%) compared with controls (6.8%, p < 0.001). We found a strong correlation between Type II capitate and slender (Type II) scaphoid morphology in healthy wrists. No significant differences in age, gender, or affected side were observed. Interobserver and intraobserver agreements for capitate classification were substantial (kappa ≥0.882). Our study introduces a reliable radiographic method for classifying capitate morphology, which strongly correlates with intrinsic scaphoid shape and potential vascular vulnerability. Both Type II capitate morphology and NUV are significant predisposing factors for PD. These findings offer valuable insights for identifying at-risk individuals and improving understanding of PD's multifactorial etiology. Diagnostic Level III.

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.

AimsPrevious studies have highlighted differences in the risk of periprosthetic fractures (PPFs) in patients undergoing total hip arthroplasty with either a cemented taper slip (TS) stem or a composite beam (CB) stem. This biomechanical study explored the occurrence of PPF around these stems, and the protective effect of adding a 16-gauge prophylactic calcar or diaphyseal wire to the TS stems to increase the resistance to torque as a potential way to prevent these fractures.MethodsA total of 21 TS stems (eight alone, six with calcar wiring, and seven with diaphyseal wiring placed 2 cm distal to the lesser trochanter) and seven CB stems were cemented into standard sawbones. The peak torque at failure was measured using a servohydraulic test machine, and the fracture location was recorded. An a priori power analysis determined that seven specimens per group were needed to detect a 30 Nm difference with 90% power, assuming a 14.8 Nm SD in peak torque between groups. Comparisons were performed using paired t-tests.ResultsCB stems exhibited a significantly higher mean peak torque at failure (205.3 Nm (SD 26.9)) than TS stems (159.5 Nm (SD 17.4); p = 0.012), calcar-wired TS (148.2 Nm (SD 38.6); p = 0.031), and diaphyseal-wired TS (164.9 Nm (SD 21.5); p = 0.027). This study did not demonstrate that wired-TS stems had a higher peak torque at failure than non-wired TS stems. Additionally, calcar wiring was not found to be stronger than diaphyseal wiring (p = 0.400). Four CB fractures occurred distal to the stem, whereas all TS fractures occurred at the mid-stem, simulating a Vancouver type B fracture. Interestingly, adding the diaphyseal wire shifted the fracture location more distally in four of the seven stems (p = 0.070).ConclusionIn this model, CB stems had greater resistance to torque than TS stems, which may explain the lower risk of PPF. Adding calcar or diaphyseal wires to the TS stems resulted in no significant change in peak torque to fracture. CB cemented stems should be considered in patients at high risk of PPF.Cite this article: Bone Joint J 2025;107-B(5 Supple A):32–37.