Nonoperative and Operative Soft-Tissue, Cartilage, and Bony Regeneration and Orthopaedic Biologics of the Elbow and Upper Extremity: An Orthoregeneration Network Foundation Review.

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and, optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the elbow and upper extremity, including the tendons (lateral epicondylitis, medial epicondylitis, biceps tendonitis, triceps tendonitis), articular cartilage (osteoarthritis, osteochondral lesions), and bone (fractures, nonunions, avascular necrosis, osteonecrosis). Promising and established treatment modalities include hyaluronic acid; botulinum toxin; corticosteroids; leukocyte-rich and leukocyte-poor platelet-rich plasma; autologous blood; bone marrow aspirate comprising mesenchymal stromal cells (alternatively termed medicinal signaling cells and frequently mesenchymal stem cells [MSCs]) and bone marrow aspirate concentrate; MSCs harvested from adipose and skin (dermis) sources; vascularized bone grafts; bone morphogenic protein scaffold made from osteoinductive and conductive ß-tricalcium phosphate and poly-ε-caprolactone with hydrogels, human MSCs, and matrix metalloproteinases; and collagen sponge. Autologous blood preparations such as autologous blood injections and platelet-rich plasma show positive outcomes for nonresponsive tendinopathy. In addition, cellular therapies such as tissue-derived tenocyte-like cells and MSCs show a promising ability to regulate degenerative processes by modulating tissue response to inflammation and preventing continuous degradation and support tissue restoration.

Inlay structure can improve bone graft stability in the Bristow procedure.

BACKGROUND: Compared with the Latarjet procedure, the Bristow procedure has a lower screw-related complication rate but poor bone healing. A modified Inlay Bristow procedure has been reported to significantly improve the bone healing rate, but the biomechanical mechanism is unclear. The aim of this study was to evaluate the biomechanical stability of the bone graft between a modified Inlay Bristow procedure and the classic Bristow procedure. METHODS: Sixteen left scapula models (Sawbones, Composite Scapula, and fourth generation) were randomly divided into 2 groups (8:8). The bone graft in the first group was fixed with a 3.5 mm screw using the Inlay structure. The bone graft in the second group was fixed with a 3.5 mm screw via the traditional method. The maximum cyclic displacement, ultimate failure load and stiffness were evaluated biomechanically. The failure type was recorded for each model. RESULTS: Cyclic loading tests demonstrated that the maximum cyclic displacement of the Inlay procedure was significantly smaller (P = .001) than that of the classic procedure. The Inlay Bristow technique resulted in a significantly higher (P = .024) ultimate failure load than the classic Bristow technique. The stiffness of the classic group was 19.17 ± 4.01 N/mm and that of the inlay group was 22.34 ± 5.35 N/mm (P = .232). Failure was mainly due to bone graft fractures through the drill hole or glenoid bone fractures. CONCLUSION: Inlay Bristow fixation of the bone graft in a Sawbones model provides significantly stronger fixation and better time point zero stability than classic Bristow fixation, suggesting a higher likelihood of graft union.

The Arthroscopic Bristow Procedure Is Superior to the Arthroscopic Latarjet Procedure in Return to Sports but Inferior in Graft Healing: A Comparative Study With 3.4-Year Follow-Up.

PURPOSE: To compare clinical and computed tomography outcomes between the arthroscopic Latarjet procedure and the arthroscopic Bristow procedure. METHODS: Patients who underwent arthroscopic Latarjet or Bristow procedures with at least 2 years of follow-up were retrospectively reviewed. Thirty-eight shoulders were included in the Latarjet group, and 34 were included in the Bristow group. Recurrence of dislocation, clinical scores, rate of return to sports (RTS), and computed tomography assessment findings (position of transferred coracoid, graft healing, graft absorption, and glenohumeral degenerative osteoarthritis [OA]) were obtained at final follow-up. RESULTS: No recurrent dislocation occurred in either group, and no significant differences in clinical scores were found between the 2 procedures, with a mean follow-up period of 3.4 years. The operative time in the Bristow group was significantly shorter than that in the Latarjet group (P < .001). The transferred coracoid had healed in 94.7% of the patients in the Latarjet group and 85.3% in the Bristow group at final follow-up (P = .01). No significant difference in graft absorption or the degree of glenohumeral OA was detected between the 2 groups. However, moderate to severe OA only occurred in the Latarjet group at final follow-up (4 of 38 shoulders, 10.5%). The postoperative external rotation angle and level of RTS favored the Latarjet procedure (P = .030 and P = .034, respectively). CONCLUSIONS: Both the arthroscopic Latarjet and arthroscopic Bristow procedures led to good clinical scores with no new dislocation episodes. The Bristow group showed significantly less graft healing than the Latarjet group. However, the arthroscopic Bristow procedure took less operative time and showed a lower rate of early moderate to severe glenohumeral OA, better range of motion, and a higher rate of RTS. LEVEL OF EVIDENCE: Level III, retrospective comparative therapeutic trial.

Previously failed Bankart repair and the duration from first dislocation to surgery were the risk factors associated with the level of return to sports after coracoid transfer.

PURPOSE: This study aims to determine the rate of different levels of return to sports (RTS) in athletes undergoing the modified arthroscopic Bristow procedure and the factors associated with the level of RTS. METHODS: The study was performed retrospectively on patients with traumatic anterior shoulder instability who underwent the modified arthroscopic Bristow procedure with a minimum follow-up of 2 years. The RTS rate, the level of return and the timing of return were assessed. Additionally, factors such as preoperative basic information, clinical outcomes, graft position, graft healing and graft absorption were analysed to investigate their correlation with the level of RTS. Multivariate regression models were used to evaluate the factors affecting the level of RTS. RESULTS: In total, this study included 182 shoulders of 177 athletes undergoing the modified arthroscopic Bristow procedure. Of these patients, 142 (78.0%) shoulders of 137 athletes were enrolled, with a mean of 3.3-year follow-up. At the final follow-up, 134 (94.4%) shoulders were able to RTS, 123 (86.6%) shoulders were able to RTS to the pre-injury level, 52 (36.6%) shoulders could be completely "forgotten" without any psychological barrier during exercise. The multivariate logistic regression analysis identified the variable associated with RTS at the pre-injury level as previously failed arthroscopic Bankart repair (p < 0.001). As for the "forgetting" operated shoulder, the duration from first dislocation to surgery was a significant independent predictor (p = 0.034). CONCLUSION: Although a large majority of athletes were able to RTS at the pre-injury level after the modified arthroscopic Bristow procedure, about two-thirds of the athletes felt difference in shoulders on both sides and could not completely "forget" the operated shoulder during exercise. Previously failed Bankart repair and the duration from first dislocation to surgery were the risk factors associated with the level of RTS after the modified arthroscopic Bristow procedure. LEVEL OF EVIDENCE: IV.

Clinical and Radiologic Outcomes of All-Arthroscopic Latarjet Procedure With Modified Suture Button Fixation: Excellent Bone Healing With a Low Complication Rate.

PURPOSE: To investigate the clinical outcomes and radiologic evaluation of an all-arthroscopic Latarjet procedure with modified button fixation. METHODS: Patients who received all-arthroscopic Latarjet procedure with modified suture button fixation between September 2015 to September 2016 were retrospectively reviewed. Indications for surgery were recurrent anterior shoulder dislocation with any 1 of these 3 conditions: glenoid defect >15%, contact-sport athlete, or failure after Bankart repair. Inclusion criteria included cases who received this surgery. Clinical outcomes were evaluated by University of California Los Angeles, ASES and Rowe score with a minimal follow-up of 3 years. Radiologic assessment on 3D computed tomography scan was performed preoperatively and postoperatively at different time points. Complications were also recorded. RESULTS: A total of 30 patients were eventually included in this study. The mean follow-up time was 38.0 ± 2.5 months. There were 25 patients who performed contact sports. Of them, 10 patients were without glenoid defect >15% or failed Bankart repair. The remaining 20 patients had glenoid defect >15%, including 2 failed Bankart cases. Ten patients had glenoid defect < 13.5%, and the rest 20 patients had > 13.5%. UCLA, American Shoulder and Elbow Surgeons, and Rowe score significantly improved during follow-up, and the improvement exceeded MCID for all patients. No severe complications were noted. In total, 86.7% of the graft positioning was measured as flush and 13.3% as medial. The bone union rate was 96.7% at 3 months postoperatively and at final follow-up. The remodeling process for the restoration of the normal anatomy of the lower part of glenoid was noted. CONCLUSIONS: All-arthroscopic Latarjet with modified suture button fixation can achieve stable fixation of the coracoid, good clinical outcomes (all patients with improvement exceeding MCID), low complications rate. Furthermore, the bone remodeling process contributes to the recovery of the normal anatomy of anteroinferior glenoid. STUDY DESIGN: Case series; Level of evidence, 4.

CaAlg hydrogel containing bone morphogenetic protein 4-enhanced adipose-derived stem cells combined with osteochondral mosaicplasty facilitated the repair of large osteochondral defects.

PURPOSE: Cartilage repair presents a challenge to clinicians and researchers. A more effective procedure that can produce hyaline-like cartilage is needed for articular cartilage repair. Mosaic osteochondral grafts for large osteochondral defects often show poor integration between the grafts and the surrounding normal cartilage, leading to defective cracks filled with fibrous tissue instead of hyaline-like cartilage. In the present study, we aimed to repair the defective cracks with a calcium alginate (CaAlg) hydrogel containing bone morphogenetic protein 4 (BMP4)-enhanced adipose-derived stem cells (ADSCs). METHODS: ADSCs were transduced with BMP4 (B-ADSCs). The expression of BMP4 and type II collagen was confirmed using an enzyme-linked immunosorbent assay (ELISA). Swine models of large cartilage defects of the knee were constructed and received one of the four treatments: mosaicplasty only, mosaicplasty with the CaAlg hydrogel, mosaicplasty with the CaAlg hydrogel containing ADSCs, or mosaicplasty with the CaAlg hydrogel containing B-ADSCs injected into the defective cracks. Outcomes were evaluated at 12 and 24 weeks after surgery. RESULTS: The in vitro study showed that the osteogenic and chondrogenic activities of the B-ADSCs were enhanced compared with those of the control. In vivo, in the group that received mosaicplasty-containing B-ADSCs, osteochondral tissue was completely integrated with an intact surface. Additionally, the histological scores of the mosaicplasty-containing B-ADSCs group were significantly higher than those of the other groups. Biomechanical examination confirmed that the neocartilage possessed properties similar to those of normal cartilage. CONCLUSIONS: Mosaicplasty and hydrogel containing B-ADSCs promoted the repair of large cartilage defects by regenerating hyaline cartilage and repairing dead spaces between osteochondral grafts and donor-site defects, thus improving the feasibility and success rate of one-stage complete repair surgery for large osteochondral defects. This proposed method provides a novel and effective means for the repair of large articular osteochondral defects.

Proteome-Wide Mendelian Randomization and Colocalization Analysis Identify Therapeutic Targets for Knee and Hip Osteoarthritis.

Osteoarthritis (OA) is a common degenerative disease. Although some biomarkers and drug targets of OA have been discovered and employed, limitations and challenges still exist in the targeted therapy of OA. Mendelian randomization (MR) analysis has been regarded as a reliable analytic method to identify effective therapeutic targets. Thus, we aimed to identify novel therapeutic targets for OA and investigate their potential side effects based on MR analysis. In this study, two-sample MR, colocalization analysis, summary-data-based Mendelian randomization (SMR) and Mendelian randomization phenome-wide association study (MR-PheWAS) were conducted. We firstly analyzed data from 4907 plasma proteins to identify potential therapeutic targets associated with OA. In addition, blood expression quantitative trait loci (eQTLs) data sources were used to perform additional validation. A protein-protein interaction (PPI) network was also constructed to delve into the interactions among identified proteins. Then, MR-PheWASs were utilized to assess the potential side effects of core therapeutic targets. After MR analysis and FDR correction, we identified twelve proteins as potential therapeutic targets for knee OA or hip OA. Colocalization analysis and additional validation supported our findings, and PPI networks revealed the interactions among identified proteins. Finally, we identified MAPK3 (OR = 0.855, 95% CI: 0.791-0.923, p = 6.88 × 10-5) and GZMK (OR = 1.278, 95% CI: 1.131-1.444, p = 8.58 × 10-5) as the core therapeutic targets for knee OA, and ITIH1 (OR = 0.847, 95% CI: 0.784-0.915, p = 2.44 × 10-5) for hip OA. A further MR phenome-wide association study revealed the potential side effects of treatments targeting MAPK3, GZMK, and ITIH1. This comprehensive study indicates twelve plasma proteins with potential roles in knee and hip OA as therapeutic targets. This advancement holds promise for the progression of OA drug development, and paves the way for more efficacious treatments of OA.

[Research progress of Chinese unique Inlay Bristow (Cuistow surgery) using suture button fixation].

Objective: To explore the research progress of the coracoid transfer surgery using suture button fixation, particularly focusing on the technique known as Chinese unique Inlay Bristow (Cuistow surgery). Methods: Extensive literature review was conducted to summarize and analyze the utilization of suture button fixation in the Cuistow surgery, comparing its biomechanical and clinical outcomes with those of traditional screw fixation. Results: Utilizing suture button fixation in coracoid transfer surgery helps circumvent certain metal-related complications associated with traditional screw fixation. While its biomechanical stability and effectiveness have been preliminarily confirmed, debates persist regarding its graft healing rate and postoperative recurrence rate compared to traditional screw fixation. The Cuistow surgery based on the Inlay structure is a solution to improve the healing rate of graft after suture button fixation. Conclusion: Suture button fixation, as a novel approach in coracoid transfer surgery, remains to have its advantages and disadvantages compared to traditional screw fixation not entirely elucidated, underscoring the need for further in-depth clinical and fundamental research. Cuistow surgery is the Chinese experience of coracoid transfer surgery, and its biomechanical stability and clinical advantages have been preliminarily confirmed.

The New Double-row Bankart Repair Recovered Shoulder Stability without Excessive Motion Limitation: A Case-Control Study with Single-row Bankart Repair.

OBJECTIVES: Bankart lesion is one of the most common lesions of the glenohumeral joint. Several double-row suture methods were reported for Bankart repair, which could provide more stability, yet more motion limitation and complications. Therefore, we introduced a new double-row Bankart repair technique, key point double-row suture which used one anchor in the medial line. The purpose of this article is to investigate the clinical outcomes of this new method and to compare it with single-row suture. METHODS: Seventy-eight patients receiving key point double-row suture or single-row suture from October 2010 to June 2014 were collected retrospectively. The basic information including gender, age, dominant arm, and number of episodes of instability was collected. Before surgery, the glenoid bone loss was measured from the CT scan. The visual analogue scale, American shoulder and elbow surgeons, the University of California at Los Angeles shoulder scale, and subjective shoulder value were valued before surgery and at the last follow-up. RESULTS: Forty-four patients (24 patients receiving single-row suture and 20 patients receiving key point double-row suture) were followed up successfully. The follow-up period was 9.2 ± 1.1 years (range, 7.8-11.4 years). At the last follow-up, no significant differences were detected for any of the clinical scores. The recurrence rate was 12.5% for the single-row group and 10% for the double-row group, respectively (p = 0.795) 14 patients (31.8%) in the single-row group and nine patients (26.5%) in the double-row group were tested for active range of motion. A statistically significant difference was found only for the internal rotation at 90° abduction (48.9° for single-row and 76.7° for key point double-row, p = 0.033). CONCLUSION: The key point double-row sutures for Bankart lesions could achieve similar long-term outcomes compared with single-row suture, and one medial anchor did not result in a limited range of motion. The low recurrence rate and previous biomechanical results also indicate the key point double-row suture is a reliable method.

Therapeutic Potential of Exosomes in Tendon and Tendon-Bone Healing: A Systematic Review of Preclinical Studies.

Exosomes have been proven to play a positive role in tendon and tendon-bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes in tendon and tendon-bone healing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic and comprehensive review of the literature was performed on 21 January 2023. The electronic databases searched included Medline (through PubMed), Web of Science, Embase, Scopus, Cochrane Library and Ovid. In the end, a total of 1794 articles were systematically reviewed. Furthermore, a "snowball" search was also carried out. Finally, forty-six studies were included for analysis, with the total sample size being 1481 rats, 416 mice, 330 rabbits, 48 dogs, and 12 sheep. In these studies, exosomes promoted tendon and tendon-bone healing and displayed improved histological, biomechanical and morphological outcomes. Some studies also suggested the mechanism of exosomes in promoting tendon and tendon-bone healing, mainly through the following aspects: (1) suppressing inflammatory response and regulating macrophage polarization; (2) regulating gene expression, reshaping cell microenvironment and reconstructing extracellular matrix; (3) promoting angiogenesis. The risk of bias in the included studies was low on the whole. This systematic review provides evidence of the positive effect of exosomes on tendon and tendon-bone healing in preclinical studies. The unclear-to-low risk of bias highlights the significance of standardization of outcome reporting. It should be noted that the most suitable source, isolation methods, concentration and administration frequency of exosomes are still unknown. Additionally, few studies have used large animals as subjects. Further studies may be required on comparing the safety and efficacy of different treatment parameters in large animal models, which would be conducive to the design of clinical trials.

[Research progress in biomechanics of Bristow-Latarjet procedure for anterior shoulder dislocation].

Objective: To review the research progress of the biomechanical study of the Bristow-Latarjet procedure for anterior shoulder dislocation. Methods: The related biomechanical literature of Bristow-Latarjet procedure for anterior shoulder dislocation was extensively reviewed and summarized. Results: The current literature suggests that when performing Bristow-Latarjet procedure, care should be taken to fix the bone block edge flush with the glenoid in the sagittal plane in the direction where the rupture of the joint capsule occurs. If traditional screw fixation is used, a double-cortical screw fixation should be applied, while details such as screw material have less influence on the biomechanical characteristics. Cortical button fixation is slightly inferior to screws in terms of biomechanical performance. The most frequent site of postoperative bone resorption is the proximal-medial part of the bone block, and the cause of bone resorption at this site may be related to the stress shielding caused by the screw. Conclusion: There is no detailed standardized guidance for bone block fixation. The optimal clinical treatment plan for different degrees of injury, the factors influencing postoperative bone healing and remodeling, and the postoperative osteoarticular surface pressure still need to be further clarified by high-quality biomechanical studies.

E7 Peptide Enables BMSC Adhesion and Promotes Chondrogenic Differentiation of BMSCs Via the LncRNA H19/miR675 Axis.

Therapeutic strategies based on utilizing endogenous BMSCs have been developed for the regeneration of bone, cartilage, and ligaments. We previously found that E7 peptide (EPLQLKM) could enhance BMSC homing in bio-scaffolds and, therefore, promote cartilage regeneration. However, the profile and mechanisms of E7 peptide in cartilage regeneration remain elusive. In this study, we examined the effect of E7 peptide on the BMSC phenotype, including adhesion, viability and chondrogenic differentiation, and its underlying mechanism. The konjac glucomannan microsphere (KGM), a carrier material that is free of BMSC adhesion ability, was used as the solid base of E7 peptide to better explore the independent role of E7 peptide in BMSC behavior. The results showed that E7 peptide could support BMSC adhesion and viability in a comparable manner to RGD and promote superior chondrogenic differentiation to RGD. We examined differentially expressed genes of BMSCs induced by E7 compared to RGD. Subsequently, a real-time PCR validated the significantly upregulated expression of lncRNA H19, and the knockdown of lncRNA H19 or miR675, a downstream functional unit of H19, could significantly obscure the chondrogenic differentiation induced by E7. In conclusion, this study confirmed the independent role of E7 in the adhesion and viability of BMSCs and revealed the pro-chondrogenic effect of E7 on BMSCs via the H19/miR675 axis. These results could help establish new therapeutic strategies based on employing endogenous BMSCs for cartilage tissue regeneration.

Using a Xenogeneic Acellular Dermal Matrix Membrane to Enhance the Reparability of Bone Marrow Mesenchymal Stem Cells for Cartilage Injury.

Due to its avascular organization and low mitotic ability, articular cartilage possesses limited intrinsic regenerative capabilities. The aim of this study is to achieve one-step cartilage repair in situ via combining bone marrow stem cells (BMSCs) with a xenogeneic Acellular dermal matrix (ADM) membrane. The ADM membranes were harvested from Sprague-Dawley (SD) rats through standard decellularization procedures. The characterization of the scaffolds was measured, including the morphology and physical properties of the ADM membrane. The in vitro experiments included the cell distribution, chondrogenic matrix quantification, and viability evaluation of the scaffolds. Adult male New Zealand white rabbits were used for the in vivo evaluation. Isolated microfracture was performed in the control (MF group) in the left knee and the tested ADM group was included as an experimental group when an ADM scaffold was implanted through matching with the defect after microfracture in the right knee. At 6, 12, and 24 weeks post-surgery, the rabbits were sacrificed for further research. The ADM could adsorb water and had excellent porosity. The bone marrow stem cells (BMSCs) grew well when seeded on the ADM scaffold, demonstrating a characteristic spindle-shaped morphology. The ADM group exhibited an excellent proliferative capacity as well as the cartilaginous matrix and collagen production of the BMSCs. In the rabbit model, the ADM group showed earlier filling, more hyaline-like neo-tissue formation, and better interfacial integration between the defects and normal cartilage compared with the microfracture (MF) group at 6, 12, and 24 weeks post-surgery. In addition, neither intra-articular inflammation nor a rejection reaction was observed after the implantation of the ADM scaffold. This study provides a promising biomaterial-based strategy for cartilage repair and is worth further investigation in large animal models.

Earlier and More Severe Cartilage Degeneration Occurs After Meniscal Tears in Juvenile Rabbits Compared with Adults.

OBJECTIVE: To compare the severity of cartilage degeneration after meniscal tears between juvenile and adult rabbits. DESIGN: This study included 20 juvenile rabbits (2 weeks after birth) and 20 adult rabbits (6 months after birth). Meniscal tears were prepared in the anterior horn of medial menisci of right knees. Rabbits were sacrificed at 1, 3, 6, and 12 weeks postoperatively. Cartilage degenerations in the medial femoral condyle and medial tibial plateau were evaluated macroscopically and histologically. The semiquantitative assessment of cartilage degeneration was graded by macroscopic Outerbridge scoring system and histological Osteoarthritis Research Society International (OARSI) scoring system. RESULTS: In juvenile rabbits, the morphologically intact cartilage and normal extracellular matrix architecture were observed at the first week postoperatively. Mild uneven cartilage surface and toluidine blue depletion in the medial femoral condyle were observed on histological assessment at 3 weeks postoperatively. The worsened cartilage deterioration demonstrating chondral fibrillation, prominent cell death, and glycosaminoglycan (GAG) release was observed at 6 and 12 weeks postoperatively. In adult rabbits, only mild cartilage degeneration was observed in the medial femoral condyle at 12 weeks postoperatively. The outcomes of Outerbridge and OARSI scores were consistent with the aforementioned findings in juvenile and adult rabbits. CONCLUSIONS: Our study validated that earlier and more severe cartilage degenerations were observed in juvenile rabbits after meniscal tears compared with adult rabbits. Moreover, the post-tear cartilage degeneration demonstrated regional specificity corresponded to the tear position. However, caution is warranted when extrapolating results of animal models to humans.

Clinical and Radiographic Outcomes After Arthroscopic Inlay Bristow Surgery With Screw Versus Suture Button Fixation: A Comparative Study of 117 Patients With 3.3-Year Follow-up.

Background: Some studies have advocated the use of suture button fixation during Bristow-Latarjet surgery to reduce complications associated with screw fixation. However, data comparing these fixation methods are relatively incomplete. Purpose: To investigate the efficacy of modified arthroscopic Bristow-Latarjet surgery and compare the clinical and radiographic outcomes using screw versus suture button fixation. Study Design: Cohort study; Level of evidence, 3. Methods: We evaluated 136 patients with traumatic anterior shoulder instability who underwent the modified arthroscopic Bristow-Latarjet surgery between June 2015 and February 2018. Of these patients, 117 who met the inclusion criteria were enrolled at a mean follow-up of 3.3 ± 0.7 years. Shoulders were separated into 2 groups based on fixation technique: screw fixation (group A; n = 63) or suture button fixation (group B; n = 54). Computed tomography imaging findings and clinical results were assessed preoperatively; immediately after operation; and postoperatively at 3 months, 6 months, 1 year, and final follow-up. Results: There were no significant differences between the groups in terms of postoperative clinical scores, the level of return to sports, range of motion, graft position, or reoperation rates. Bone healing was observed in 97.4% of the cases overall (114/117), with 98.4% bone union in group A and 96.3% in group B at final follow-up. Bone absorption was more common in group A (n = 30; 47.6%) compared with group B (n = 10; 18.5%) (P = .003). There were no hardware-related complications in group B, compared with 7.9% of patients in group A (P = .034). One patient in group B had a recurrent dislocation due to an unexpected event, and there were no recurrent dislocations in group A. Conclusion: After the modified arthroscopic Bristow-Latarjet procedure, both suture button and screw fixation methods demonstrated high bony healing rates and low risk of recurrence. Less coracoid graft resorption and no hardware-related complications were seen with suture button fixation.

A lipid metabolite lipidomics assay for prediction and severity evaluation of rotator cuff injury.

Objective: Rotator cuff injury can be caused by local inflammation and fibrosis of musculotendinous cuff. Hypercholesterolemia can lead to physiological changes of rotator cuff that resemble rotator cuff injury. However, the relationship between lipid metabolism and rotator cuff injury and its potential pathological mechanism remain unclear. Herein, we aimed to investigate the correlation between the plasma lipidome, rotator cuff injury, and successive fatty infiltration pathology, and hoped to identify biomarkers for predicting higher risk or higher severity rotator cuff injury by assessing metabolic perturbations and dyslipidemia using lipidomics. Methods: We quantitatively analyzed 60 lipids species of seven lipids classes and subclasses from 66 subjects using lipidomics. Subjects were divided into four groups: (1) normal rotator cuff with normal clinical routine serum lipid test results (NN group = 13); (2) normal rotator cuff with abnormal clinical routine serum lipid test results (NA group = 10); (3) rotator cuff tear with normal routine serum lipid test results (RN group = 30); (4) rotator cuff tear with abnormal routine serum lipid test results (RA group = 13). Independent-sample t-tests and Kruskal-Wallis tests were used to compare lipid metabolite levels in serum between different groups in patients with rotator cuff tears. The orthogonal partial least squares-discriminant analysis (OPLS-DA) model was used to verify the ability of five lysophosphatidylcholines (LPCs) to distinguish rotator cuff injuries. In the rotator cuff tear group, magnetic resonance imaging (MRI) was used to classify fatty infiltration according to Goutallier's classification. Kruskal-Wallis tests were used to analyze molecular differences between high-grade (grade 3-4) and low-grade (grade 0-2) fatty infiltration groups. Receiver operator characteristic (ROC) curves were drawn for each diagnostic method via different metabolites. The area under the curve (AUC), cutoff, specificity, sensitivity, and accuracy of each diagnostic criterion were calculated. Results: Our results showed that some rotator cuff injury patients yielded unique lipidomic profiles. Based on Kruskal-Wallis tests, our results showed significant differences in three lipid molecules, 17:1 Lyso PI, 18:0-22:6 PE, and 18:3 (Cis) PC, among all four groups independent of clinical blood lipid levels. Also, independent of clinical blood lipid levels, two lipid molecules, 22:0 Lyso PC and 24:0 Lyso PC, were significantly different between the two groups based on Independent sample t-tests. Kruskal-Wallis test results showed that in the rotator cuff tear group, two metabolites (24:0 SM and 16:0 ceramide) differed between high-grade and low-grade fatty infiltration. The AUC values for 22:0 Lyso PC, 24:0 Lyso PC, 18:0-22:6 PE, 24:0 SM, and 16:0 ceramide were 0.6036, 0.6757, 0.6712, 0.8333, and 0.8981, respectively. Conclusion: The results provide insight into how the metabolic mechanisms associated with dyslipidemia impact rotator cuff diseases. Five lipid molecules, 17:1 Lyso PI, 18:0-22:6 PE, 18:3 (Cis) PC, 22:0 Lyso PC, and 24:0 Lyso PC, were closely related to rotator cuff tear based on two statistical analysis methods, independent of clinical routine serum lipid test results, which indicates that lipidomics assays are more sensitive than conventional lipid tests, and more suitable for studying rotator cuff lipid metabolism. In addition, two lipid metabolites, 24:0 SM and 16:0 ceramide, are potentially useful for predicting fatty infiltration severity. Further research with a larger number of samples is needed to verify whether these two metabolites can serve as potential markers of severe fatty infiltration. The findings illuminate how metabolic mechanisms associated with dyslipidemia affect rotator cuff disease.

Osteointegration of PLLA/ß-TCP Biocomposite Anchors Used in Coracoid Transfer Procedures for Shoulder Instability: Quantitative Computed Tomography With a Minimum 2-Year Follow-up.

Background: Biocomposite anchors have been a popular choice for use in coracoid transfer procedures for shoulder instability and are hypothesized to allow bone ingrowth. Purpose: To quantitatively evaluate the osteointegration of 85% PLLA/15% ß-TCP biocomposite anchors used in the coracoid transfer procedure for shoulder instability. Study Design: Case series; Level of evidence, 4. Methods: We performed a retrospective case series of abstracted data from the records of 74 patients who underwent coracoid transfer procedures with biocomposite anchors. Computed tomography was performed at 24 months postoperatively. A total of 4 researchers independently reviewed the computed tomography images. The density (in Hounsfield unit [HU] values) of the anchor tunnels, glenoid, and subscapularis was assessed, and osteointegration of the anchor tunnels was evaluated with HU values, the quantitative ossification quality score (QOQS), and tunnel widening. Results: Included were 74 patients (58 male, 16 female), involving 76 shoulders and 124 biocomposite anchors. At ≥24-month follow-up, 72 of 124 (58.06%) anchor tunnels were classified as QOQS type 1, including 12 completely ossified tunnels and 60 almost completely ossified tunnels. Some degree of ossification (QOQS types 1-3) was observed in 118 (95.16%) anchor tunnels. Overall, 3 anchor tunnels were enlarged (QOQS type 5). The mean HU value of the anchor tunnels was 339.75, which was significantly higher than the preoperative HU value of the glenoid vault (262.19). Among the 124 anchor tunnels, 79 had HU values higher than their glenoid HU values, and 45 had lower HU values than their glenoid HU values. In the comparison of tunnel HU values at 12 versus ≥24 months, the HU value at ≥24 months was significantly higher. A total of 20 anchor tunnels widened. Conclusion: Among 124 anchor tunnels, 95.16% showed ossification, 58.06% were completely or nearly completely ossified, and 3 were enlarged. The HU value of the anchor tunnel increased over time.

Cryo-self-assembled silk fibroin sponge as a biodegradable platform for enzyme-responsive delivery of exosomes.

Although advances in protein assembly preparation have provided a new platform for drug delivery during tissue engineering, achieving long-term controlled exosome delivery remains a significant challenge. Diffusion-dominated exosome release using protein hydrogels results in burst release of exosomes. Here, a fibroin-based cryo-sponge was developed to provide controlled exosome release. Fibroin chains can self-assemble into silk I structures under ice-cold conditions when annealed above the glass transition temperature. Exosome release is enzyme-responsive, with rates primarily determined by enzymatic degradation of the scaffolds. In vivo experiments have demonstrated that exosomes remain in undigested sponge material for two months, superior to their retention in fibrin glue, a commonly used biomaterial in clinical practice. Fibroin cryo-sponges were implanted subcutaneously in nude mice. The exosome-containing sponge group exhibited better neovascularization and tissue ingrowth effects, demonstrating the efficacy of this exosome-encapsulating strategy by realizing sustained release and maintaining exosome bioactivity. These silk fibroin cryo-sponges containing exosomes provide a new platform for future studies of exosome therapy.

The transplantation of particulated juvenile allograft cartilage and synovium for the repair of meniscal defect in a lapine model.

Background: Synovium has been confirmed to be the primary contributor to meniscal repair. Particulated Juvenile Allograft Cartilage (PJAC) has demonstrated promising clinical effect on repairing cartilage. The synergistic effect of synovium and PJAC transplant on meniscal fibrocartilaginous repair is unclear. We hypothesize that the transplantation of synovium and PJAC synergistically facilitates meniscal regeneration and the donor cells within graft tissues still survive in the regenerated tissue at the last follow up (16 weeks postoperatively). Methods: The study included 24 mature female rabbits, which were randomly divided into experimental and control groups. A cylindrical full-thickness defect measuring 2.0 â€‹mm was prepared in the avascular portion of the anterior horn of medial meniscus in both knees. The synovium and PJAC transplant were harvested from juvenile male rabbits (2 months after birth). The experimental group received synovium and PJAC transplant encapsulated with fibrin gel. The control groups received synovium transplant encapsulated with fibrin gel, pure fibrin gel and nothing. The macroscopic, imageological and histological evaluations of repaired tissue were performed at 8 weeks and 16 weeks postoperatively. The in situ hybridization (ISH) of male-specific sex-determining region Y-linked (SRY) gene was performed to detect the transplanted cells. Results: The regenerated tissue in experimental group showed superior structural integrity, superficial smoothness, and marginal integration compared to control groups at 8 weeks or 16 weeks postoperatively. More meniscus-like fibrochondrocytes filled the repaired tissue in the experimental group, and the matrix surrounding these cell clusters demonstrated strongly positive safranin O and type 2 collagen immunohistochemistry staining. By SRY gene ISH, the positive SRY signal of experimental group could be detected at 8 weeks (75.72%, median) and 16 weeks (48.69%, median). The expression of SOX9 in experimental group was the most robust, with median positive rates of 65.52% at 8 weeks and 67.55% at 16 weeks. Conclusion: The transplantation of synovium and PJAC synergistically facilitates meniscal regeneration. The donor cells survive for at least 16 weeks in the recipient. The translational potential of this article: This study highlighted the positive effect of PJAC and synovium transplant on meniscal repair. We also clarified the potential repair mechanisms reflected by the survival of donor cells and upregulated expression of meniscal fibrochondrocytes related genes. Thus, based on our study, further clinical experiments are needed to investigate synovium and PJAC transplant as a possible treatment to meniscal defects.

Genetic polymorphism of PITX1 in susceptibility to knee osteoarthritis in a Chinese Han population: a case-control study.

Osteoarthritis (OA) is the most common form of arthritis and the precise etiology of this disease remains unclear. Genetic factors play a considerable role in pathogenesis of OA. Several OA-susceptibility genes have been identified. Recently, a new emerging role of pitx1 transcription factor in OA pathogenesis has been reported. Paired-like homeodomain transcription factor 1 (PITX1) has been implicated in hind limb development of mice and is essential to maintain cartilage function. Because of the different expression in the knee joint between OA and normal people, PITX1 may be involved in etiology and pathogenesis of OA. The present study is to evaluate the association of the PITX1 polymorphism (rs479632) with knee OA in a Chinese Han population. A case-control association study was conducted. The polymorphism was genotyped in 581 patients who had primary symptomatic knee OA with radiographic confirmation and in 570 matched controls. Allelic and genotypic frequencies were compared between patients and control subjects. No significant difference was detected in genotype or allele distribution between knee OA and control groups (all P > 0.05). The association was also negative even after stratification by sex. Furthermore, no association between the SNP genotype and the clinical variables age, sex, body mass index (BMI), and Kellgren/Lawrence (K/L) score was observed in OA patients. The present study suggests that the PITX1 polymorphism (rs479632) is not a risk factor for knee OA susceptibility in the Chinese Han population. Further studies are needed to give a global view of this polymorphism in pathogenesis of OA.