Trends in utilization, demographics, and costs of platelet-rich plasma injections: a ten-year nationwide investigation.

INTRODUCTION: Platelet-Rich Plasma (PRP) has become one of the most popular biologic treatments in orthopedic surgery. Despite this, its utilization over the last decade has not been investigated. METHODS: We conducted a search using Current Procedural Terminology codes to identify patients who received PRP injections between 2010 and 2019 using the PearlDiver database. The purpose was to 1) determine annual trends of PRP injections of the ankle, hip, knee, shoulder, and elbow for cartilaginous, tendinous, ligamentous, meniscal/labral, and miscellaneous pathologies; 2) compare baseline demographics of patients receiving these injections; and 3) analyze costs. RESULTS: A total of 23,716 patients who received PRP injections were identified; 54.4% were female. The incidence of PRP injections was between 1.6 and 4.3 per 100,000 orthopedic patients. The most common anatomic locations targeted for PRP therapy was the knee (36.7%), followed by the shoulder/elbow (30.5%), then the ankle (19.6%) and hip (13.6%). Subgroup analysis revealed that most common use of PRP was for knee cartilaginous pathologies, followed by shoulder/elbow tendinous pathologies. The number of injections used in the knee significantly increased between 2010 and 2019 (p< 0.001), and trended toward significantly increasing in the shoulder/elbow (p = 0.055). Average annual costs for PRP injections ranged from $711.65 for ankles and $1,711.63 for hips; costs significantly changed for 3 of the 4 anatomic locations. By 2019, average PRP injection costs for each area clustered around $1000. CONCLUSION: Between 2010 and 2019, there was an increase in usage of PRP injections in the knee (cartilaginous pathologies) and the shoulder/elbow (tendinous pathologies). PRP costs demonstrated early variability but clustered around $1000 by 2019. Further studies into drivers of prices and cost-effectiveness of PRP are needed to provide clarity into the true costs to patients and healthcare providers.

Experts Achieve Consensus on a Majority of Statements Regarding Platelet-Rich Plasma Treatments for Treatment of Musculoskeletal Pathology.

PURPOSE: To establish consensus statements on platelet-rich plasma (PRP) for the treatment of musculoskeletal pathologies. METHODS: A consensus process on the treatment of PRP using a modified Delphi technique was conducted. Thirty-five orthopaedic surgeons and sports medicine physicians participated in these consensus statements on PRP. The participants were composed of representatives of the Biologic Association, representing 9 international orthopaedic and musculoskeletal professional societies invited due to their active interest in the study of orthobiologics. Consensus was defined as achieving 80% to 89% agreement, strong consensus was defined as 90% to 99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. RESULTS: There was consensus on 62% of statements about PRP. CONCLUSIONS: (1) PRP should be classified based on platelet count, leukocyte count, red blood count, activation method, and pure-plasma versus fibrin matrix; (2) PRP characteristics for reporting in research studies are platelet count, leukocyte count, neutrophil count, red blood cell count, total volume, the volume of injection, delivery method, and the number of injections; (3) the prognostic factors for those undergoing PRP injections are age, body mass index, severity/grade of pathology, chronicity of pathology, prior injections and response, primary diagnosis (primary vs postsurgery vs post-trauma vs psoriatic), comorbidities, and smoking; (4) regarding age and body mass index, there is no minimum or maximum, but clinical judgment should be used at extremes of either; (5) the ideal dose of PRP is undetermined; and (6) the minimal volume required is unclear and may depend on the pathology. LEVEL OF EVIDENCE: Level V, expert opinion.

Meniscus Extrusion, Radial Tears, and Root Tears.

Management of meniscal radial and root tears and extrusion is complex and has changed significantly over recent years. It is important to provide a comprehensive overview of the management of radial and root tears and meniscal extrusion and be aware of the currently available evidence on repair techniques, rehabilitation, and outcomes following radial and root repairs.

Short-Term Evaluation of Bone-ACL-Bone Complex Allograft in ACL Reconstruction in a Rabbit Model.

The study is to evaluate incorporation of a bone-anterior cruciate ligament-bone (B-ACL-B) allograft in anterior cruciate ligament (ACL) reconstruction in a rabbit model. A total of 61 New Zealand white rabbits were used, with 23 donor rabbits for harvesting B-ACL-B allografts and 38 recipient rabbits undergoing unilateral ACL reconstruction with B-ACL-B allograft. Animals were euthanized for biomechanical testing, micro-computed tomography examination, histological analysis, multi-photon microscopy and transmission electron microscopy testing at 2, 4 and 8 weeks after surgery. Gross inspection and radiographs confirmed the intact ACL allograft in the proper anatomic position. Progressive healing occurred between the bone block and the bone tunnel as demonstrated by a gradual increase in average bone volume fraction and total mineral density at 4 and 8 weeks. Histological analysis showed new bone formation at the bone block-tunnel interface, with maintenance of the native ACL enthesis. Ultrastructural analysis demonstrated the maintenance of overall collagen matrix alignment, while there was repopulation with smaller diameter collagen fibrils. There was no significant difference between 4 and 8 weeks in mean failure force (p = 0.39) or stiffness (p = 0.15) for the B-ACL-B allografts. This study demonstrates the restoration of the normal anatomy of the ACL and progressive graft incorporation and remodeling using a B-ACL-B allograft for ACL reconstruction in the rabbit knee.

Comprehensive Review of Multidirectional Instability of the Shoulder.

Multidirectional instability of the shoulder can result from underlying atraumatic laxity, from repetitive microtrauma, or from a traumatic injury and often occurs in association with generalized ligamentous laxity or underlying connective tissue disorders. It is critical to differentiate multidirectional instability from unidirectional instability with or without generalized laxity to maximize treatment success. Although rehabilitation is still considered the primary treatment method for this condition, surgical treatment in the form of open inferior capsular shift or arthroscopic pancapsulolabral plication is indicated if conservative treatment fails. Recent biomechanical and clinical research has shown that there is still room for improvement in the treatment methods offered to this specific patient cohort. Potential treatment options, such as various methods to improve cross-linking of native collagen tissue, electric muscle stimulation to retrain the abnormally functioning dynamic stabilizers of the shoulder, and alternative surgical techniques such as coracohumeral ligament reconstruction and bone-based augmentation procedures, are brought forth in this article as potential avenues to explore in the future.

Effect of CCR2 Knockout on Tendon Biomechanical Properties in a Mouse Model of Delayed Rotator Cuff Repair.

BACKGROUND: The high incidence of incomplete or failed healing after rotator cuff repair (RCR) has led to an increased focus on the biologic factors that affect tendon-to-bone healing. Inflammation plays a critical role in the initial tendon-healing response. C-C chemokine receptor type 2 (CCR2) is a chemokine receptor linked to the recruitment of monocytes in early inflammatory stages and is associated with an increase in pro-inflammatory macrophages. The purpose of this study was to evaluate the role of CCR2 in tendon healing following RCR in C57BL/6J wildtype (WT) and CCR2-/- knockout (CCR2KO) mice in a delayed RCR model. METHODS: Fifty-two 12-week-old, male mice were allocated to 2 groups (WT and CCR2KO). All mice underwent unilateral supraspinatus tendon (SST) detachment at the initial surgical procedure, followed by a delayed repair 2 weeks later. The primary outcome measure was biomechanical testing. Secondary measures included histology, gene expression analysis, flow cytometry, and gait analysis. RESULTS: The mean load-to-failure was 1.64 ± 0.41 N in the WT group and 2.50 ± 0.42 N in the CCR2KO group (p = 0.030). The mean stiffness was 1.43 ± 0.66 N/mm in the WT group and 3.00 ± 0.95 N/mm in the CCR2KO group (p = 0.008). Transcriptional profiling demonstrated 7 differentially expressed genes (DEGs) when comparing the CCR2KO and WT groups (p < 0.05) and significant differences in Type-I and Type-II interferon pathway scores (p < 0.01). Flow cytometry demonstrated significant differences between groups for the percentage of macrophages present (8.1% for the WT group compared with 5.8% for the CCR2KO group; p = 0.035). Gait analysis demonstrated no significant differences between groups. CONCLUSIONS: CCR2KO may potentially improve tendon biomechanical properties by decreasing macrophage infiltration and/or by suppressing inflammatory mediator pathways in the setting of delayed RCR. CLINICAL RELEVANCE: CCR2 may be a promising target for novel therapeutics that aim to decrease failure rates following RCR.

GLI1 Deficiency Impairs the Tendon-Bone Healing after Anterior Cruciate Ligament Reconstruction: In Vivo Study Using Gli1-Transgenic Mice.

Hedgehog (Hh) signaling plays a fundamental role in the enthesis formation process and GLI-Kruppel family member GLI1 (Gli1) is a key downstream mediator. However, the role of Gli1 in tendon-bone healing after anterior cruciate ligament reconstruction (ACLR) is unknown. To evaluate the tendon-bone healing after ACLR in Gli1LacZ/LacZ (GLI1-NULL) mice, and compare Gli1LacZ/WT (GLI1-HET) and Gli1WT/WT wild type (WT) mice, a total of 45 mice, 15 mice each of GLI1-NULL, GLI1-HET and WT were used in this study. All mice underwent microsurgical ACLR at 12 weeks of age. Mice were euthanized at 4 weeks after surgery and were used for biomechanical testing, histological evaluation, and micro-CT analysis. The GLI1-NULL group had significantly lower biomechanical failure force, poorer histological healing, and lower BV/TV when compared with the WT and GLI1-HET groups. These significant differences were only observed at the femoral tunnel. Immunohistology staining showed positive expression of Indian hedgehog (IHH) and Patched 1(PTCH1) in all three groups, which indicated the activation of the Hh signal pathway. The GLI1 was negative in the GLI1-NULL group, validating the absence of GLI1 protein in these mice. These results proved that activation of the Hh signaling pathway occurs during ACL graft healing, and the function of Gli1 was necessary for tendon-bone healing. Healing in the femoral tunnel is more obviously impaired by Gli1 deficiency. Our findings provide further insight into the molecular mechanism of tendon-bone healing and suggest that Gli1 might represent a novel therapeutic target to improve tendon-bone healing after ACLR.

Bone-ACL-bone allograft for anterior cruciate ligament reconstruction: Short-term evaluation in a rabbit model with microcomputed tomography.

The standard grafts used for anterior cruciate ligament (ACL) reconstruction are tendon, either patellar tendon, hamstring, or quadriceps. However, the microstructure and composition of tendon differs from ligament. Ideally, the ACL would be replaced with the same tissue. To evaluate the incorporation of a bone-ACL-bone (B-ACL-B) graft for ACL reconstruction, we performed a controlled laboratory study in a rabbit model with microcomputed tomography (µCT). Forty-six New Zealand white rabbits were used, with 17 donor rabbits to harvest bilateral B-ACL-B allografts and 29 rabbits undergoing unilateral ACL reconstruction with B-ACL-B allograft. Knee specimens were collected for biomechanical testing (n = 14) at 4 and 8 weeks and for µCT analysis (n = 15) at 2, 4, and 8 weeks after surgery. Gross inspection and µCT examination confirmed bone blocks in the appropriate anatomic position. Biomechanical tests revealed no difference in mean load-to-failure force for B-ACL-B allografts between 4 and 8 weeks. Progressive healing occurred between the bone block and the tunnel as demonstrated by a gradual increase on average bone-volume fraction and total mineral density (TMD) in both femoral and tibial tunnels. Remodeling of the bone block was evidenced by a significant decrease in TMD of both tibial and femoral bone blocks. This is a report of a novel rabbit B-ACL-B allograft reconstruction model demonstrating early signs of graft remodeling and incorporation. Clinical Relevance: This study demonstrates ACL reconstruction using an anatomically matched ACL allograft, rather than a tendon graft, may be possible based on early findings in this lapine model.

Anticoagulant Usage After Anterior Cruciate Ligament Reconstruction Is Associated With Increased Rate of Manipulation Under Anesthesia.

BACKGROUND: Arthrofibrosis after anterior cruciate ligament reconstruction (ACLR) is a notable but uncommon complication of ACLR. To improve range of motion after ACLR, aggressive physical therapy, arthroscopic/open lysis of adhesions, and revision surgery are currently used. Manipulation under anesthesia (MUA) is also a reasonable choice for an appropriate subset of patients with inadequate range of motion after ACLR. Recently, the correlation between anticoagulant usage and arthrofibrosis after total knee arthroplasty has become an area of interest. The purpose of this study was to determine whether anticoagulant use has a similar effect on the incidence of MUA after ACLR. METHODS: The Mariner data set of the PearlDiver database was used to conduct this retrospective cohort study. Patients with an isolated ACLR were identified by using Current Procedural Terminology codes. Patients were then stratified by MUA within 2 years of ACLR, and the use of postoperative anticoagulation was identified. In addition, patient demographics, medical comorbidities, and timing of ACLR were recorded. Univariate and multivariable analyses were used to model independent risk factors for MUA. RESULTS: We identified 216,147 patients who underwent isolated ACLR. Of these patients, 3,494 (1.62%) underwent MUA within 2 years. Patients who were on anticoagulants after ACLR were more likely to require an MUA (odds ratio [OR]: 2.181; P < 0.001), specifically low-molecular-weight heparin (OR: 2.651; P < 0.001), warfarin (OR: 1.529; P < 0.001), and direct factor Xa inhibitors (OR: 1.957; P < 0.001). DISCUSSION: In conclusion, arthrofibrosis after ACLR is associated with the use of preoperative or postoperative thromboprophylaxis. Healthcare providers should be aware of increased stiffness among these patients and treat them aggressively.

Bilateral glenohumeral internal rotation deficit (GIRD) in elite gymnasts.

INTRODUCTION: The "Glenohumeral Internal Rotation Deficit (GIRD)" is known as the difference in internal rotation range of motion (IRRM) between the dominant and non-dominant shoulder of overhead athletes as a result of asymmetric loading. As in contrast loading pattern in gymnastics are quite symmetric and structural changes often occur bilaterally, the question arises if GIRD might develop bilaterally in gymnasts as one source of common bilateral shoulder pathologies and to search for underlying structural adaptations. MATERIALS AND METHODS: A group of 35 elite gymnasts (8-24 years) were recruited from a local Olympic Training Centre and compared to a paired cohort of 28 non-overhead athletes. Clinical examinations, digital range of motion (ROM)-measurement, ultrasonographic humeral torsion measurement, and standardized MRI scans of both shoulders were obtained and examined for structural pathologies, cross-sectional areas (CSA) of the rotator cuff muscles and capsular thickness. RESULTS: ROM-measurements showed significant decrease in IRRM in the gymnasts groups by age, with IRRM of 48.6° (SD: 8.4°, CI 95%: 43.0-54.3°) at age group 1 (8-10 years) and IRRM of 10° (SD: 11.4°; CI 95%: 0-22.0°) at age group 4 (18-26 years), that was statistically significant for the entire cohort (p = 0.017) compared to the controls. CSA were not significantly different between the cohorts, while there was a slightly increased humeral retrotorsion in the gymnasts as well as a statistically significant posterior capsular thickening. CONCLUSION: A new bilateral form of GIRD was identified in higher age groups of youth and senior elite gymnasts enrolled in this study. Despite to former definition of GIRD there was no compensatory increase in external rotation range of motion (ERRM) but an association with posterior capsular thickening, while there was no periscapular muscle hypertrophy. Humeral retrotorsion was also slightly increased in the gymnasts group.

Pharmacological Therapies for Connective Tissue Fibrosis in Orthopaedics.

Fibrosis is a common and debilitating pathological process that affects many organ systems and contributes to connective tissue disorders in orthopaedics. Tendons heal after acute and chronic injury through a process of fibrovascular scar tissue formation, and soft tissue joint capsules can be affected after traumatic joint injury, leading to arthrofibrosis. Although the precise underlying mechanisms are still being elucidated, fibrosis is thought to be a consequence of dysregulated immune and cytokine signaling that leads to myofibroblast activation and proliferation and subsequent excessive collagen deposition. Current treatments for connective tissue fibrosis include physical therapy and surgery, but there are no therapies that directly target the underlying cellular and molecular mechanisms of fibrosis. Many pharmacological agents have been used to successfully target fibrosis in other tissues and organ systems and thus are a promising treatment option to fill this gap. However, limited evidence is available to guide the use of these agents in musculoskeletal connective tissues. This article provides an overview of pharmacological therapies that have potential to treat connective tissue fibrosis in patients with musculoskeletal conditions, along with the current supporting evidence and future uses of each therapy.

Genome-Wide Association Study of Adhesive Capsulitis Suggests Significant Genetic Risk Factors.

BACKGROUND: Adhesive capsulitis of the shoulder involves loss of passive range of motion with associated pain and can develop spontaneously, with no obvious injury or inciting event. The pathomechanism of this disorder remains to be elucidated, but known risk factors for adhesive capsulitis include diabetes, female sex, and thyroid dysfunction. Additionally, transcriptional profiling and pedigree analyses have suggested a role for genetics. Identification of elements of genetic risk for adhesive capsulitis using population-based techniques can provide the basis for guiding both the personalized treatment of patients based on their genetic profiles and the development of new treatments by identification of the pathomechanism. METHODS: A genome-wide association study (GWAS) was conducted using the U.K. Biobank (a collection of approximately 500,000 patients with genetic data and associated ICD-10 [International Classification of Diseases, 10th Revision] codes), comparing 2,142 patients with the ICD-10 code for adhesive capsulitis (M750) to those without. Separate GWASs were conducted controlling for 2 of the known risk factors of adhesive capsulitis-hypothyroidism and diabetes. Logistic regression analysis was conducted controlling for factors including sex, thyroid dysfunction, diabetes, shoulder dislocation, smoking, and genetics. RESULTS: Three loci of significance were identified: rs34315830 (in WNT7B; odds ratio [OR] = 1.28; 95% confidence interval [CI], 1.22 to 1.39), rs2965196 (in MAU2; OR = 1.67; 95% CI, 1.39 to 2.00), and rs1912256 (in POU1F1; OR = 1.22; 95% CI, 1.14 to 1.31). These loci retained significance when controlling for thyroid dysfunction and diabetes. The OR for total genetic risk was 5.81 (95% CI, 4.08 to 8.31), compared with 1.70 (95% CI, 1.18 to 2.36) for hypothyroidism and 4.23 (95% CI, 2.32 to 7.05) for diabetes. CONCLUSIONS: The total genetic risk associated with adhesive capsulitis was significant and similar to the risks associated with hypothyroidism and diabetes. Identification of WNT7B, POU1F1, and MAU2 implicates the Wnt pathway and cell proliferation response in the pathomechanism of adhesive capsulitis. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

SS-31 as a Mitochondrial Protectant in the Treatment of Tendinopathy: Evaluation in a Murine Supraspinatus Tendinopathy Model.

BACKGROUND: Prior studies have demonstrated mitochondrial dysfunction in tendinopathy. The objective of this investigation was to explore the potential of SS-31 (elamipretide), a mitochondrial protectant, to improve mitochondrial function and promote tendon healing in a murine supraspinatus tendinopathy model. METHODS: One hundred and twenty-six mice (252 limbs) were divided into 6 groups (42 limbs/group) that received (I) 4 weeks of impingement; (II) 8 weeks of impingement; (III) 8 weeks of impingement including 4 weeks of SS-31 treatment (5 mg/kg/d) starting after 4 weeks of impingement; (IV) 4 weeks of impingement ending with clip removal, followed by harvesting 4 weeks later; and (V) 4 weeks of impingement ending with clip removal, followed by 4 weeks of SS-31 treatment and harvesting; and a control group. Specimens were prepared for biomechanical testing, histological analysis, transmission electron microscopy, measurement of superoxidative dismutase (SOD) activity, and measurement of gene expression. RESULTS: Failure force decreased after impingement, compared with the intact tendon, and the decrease was partially reversed after clip removal, SS-31 treatment, and the 2 treatments combined. A similar pattern was observed for stiffness. Histological analysis demonstrated higher modified Bonar scores in the impingement groups; however, the changes in tendon morphology were partially reversed following all treatments, especially the combined treatment. Decreased mitochondrial number and altered organization and density of cristae were observed in the impingement groups. Mitochondrial structure and number became more normal, with improvement in morphology of the cristae, after clip removal and/or SS-31 treatment. SOD activity decreased after impingement, compared with the control group, then increased significantly again after treatment, especially in the combined treatment group. Mitochondria-related gene expression decreased in the impingement groups and increased again after treatment. CONCLUSIONS: The mitochondrial protectant SS-31 improved mitochondrial function, promoting tendon healing, especially when combined with removal of subacromial impingement. CLINICAL RELEVANCE: Improving mitochondrial function with agents such as SS-31 may represent an effective treatment to promote healing in the setting of supraspinatus tendinopathy.

Distinct Inflammatory Macrophage Populations Sequentially Infiltrate Bone-to-Tendon Interface Tissue After Anterior Cruciate Ligament (ACL) Reconstruction Surgery in Mice.

Macrophages are important for repair of injured tissues, but their role in healing after surgical repair of musculoskeletal tissues is not well understood. We used single-cell RNA sequencing (RNA-seq), flow cytometry, and transcriptomics to characterize functional phenotypes of macrophages in a mouse anterior cruciate ligament reconstruction (ACLR) model that involves bone injury followed by a healing phase of bone and fibrovascular interface tissue formation that results in bone-to-tendon attachment. We identified a novel "surgery-induced" highly inflammatory CD9+ IL1+ macrophage population that expresses neutrophil-related genes, peaks 1 day after surgery, and slowly resolves while transitioning to a more homeostatic phenotype. In contrast, CX3CR1+ CCR2+ macrophages accumulated more slowly and unexpectedly expressed an interferon signature, which can suppress bone formation. Deletion of Ccr2 resulted in an increased amount of bone in the surgical bone tunnel at the tendon interface, suggestive of improved healing. The "surgery-induced macrophages" identify a new cell type in the early phase of inflammation related to bone injury, which in other tissues is dominated by blood-derived neutrophils. The complex patterns of macrophage and inflammatory pathway activation after ACLR set the stage for developing therapeutic strategies to target specific cell populations and inflammatory pathways to improve surgical outcomes. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Evaluation of SS-31 as a Potential Strategy for Tendinopathy Treatment: An In Vitro Model.

BACKGROUND: Studies in our laboratory have demonstrated mitochondrial dysfunction in human and animal models of supraspinatus tendinopathy. SS-31 (elamipretide) has been reported to improve mitochondrial function and to be effective in clinical trials for several diseases. The potential of SS-31 in treating tendinopathy has not been explored. HYPOTHESIS: SS-31 would improve mitochondrial function in human tenocytes sampled from patients with tendinopathy. STUDY DESIGN: Controlled laboratory study. METHODS: Healthy tenocytes were obtained from normal hamstring tendon biopsy specimens in 9 patients undergoing anterior cruciate ligament reconstruction, and tenocytes were collected from degenerative supraspinatus tendon biopsy specimens in 9 patients undergoing rotator cuff repair. Tenocytes were cultured, used at passage 1, and assigned to 4 groups: healthy tenocytes, healthy tenocytes with 1µM SS-31 treatment for 72 hours, degenerative tenocytes, and degenerative tenocytes with 1µM SS-31 treatment for 72 hours. The outcomes included measurements of mitochondrial potential, mitochondrial morphology by transmission electron microscopy imaging, reactive oxygen species and superoxidative dismutase activity, gene expression, and cell viability. RESULTS: An increase in the cell fraction with depolarized mitochondria was found in degenerative tenocytes (P = .014), followed by a decrease after SS-31 treatment (P = .018). Transmission electron microscopy images demonstrated morphological changes with a decreased number and size of mitochondria per cell in the degenerative tenocytes (P = .018) and with improvement after SS-31 treatment. There was no significant difference in the level of reactive oxygen species between healthy and degenerative tenocytes in culture, but superoxidative dismutase activity was significantly decreased in the degenerative group (P = .006), which then increased after SS-31 treatment (P = .012). These findings suggested that mitochondrial dysfunction may be reversed by SS-31 treatment. The gene expression of matrix metalloproteinase-1 (matrix remodeling, P = .029) and fatty acid-binding protein 4 (fatty infiltration, P = .046) was significantly upregulated in the degenerative tenocytes and reduced by SS-31 treatment (P = .048; P = .007). Gene expression for hypoxia-inducible factor1 α and the proapoptotic regulator Bcl-2-associated X protein was increased in the degenerative tenocytes. There was a significant decrease in cell viability in degenerative tenocytes as compared with the healthy tenocytes, with small improvement after treatment with SS-31. CONCLUSION: There are changes in mitochondrial structure and function in tenocytes derived from degenerative tendons, and SS-31, as a mitochondrial protectant, could improve mitochondrial function and promote the healing of tendinopathy. CLINICAL RELEVANCE: Mitochondrial dysfunction appears to play a role in the development of tendinopathy, and SS-31, as a mitochondrial protective agent, may be a therapeutic agent in the treatment of tendinopathy.

Subacromial bursa increases the failure force in a mouse model of supraspinatus detachment and repair.

BACKGROUND: It has been shown that subacromial bursa (SAB) harbors connective tissue progenitor cells. The purpose of this study was to evaluate the effects of implantation of SAB-derived cells (SBCs) suspended in a fibrin sealant bead and implantation of SAB tissue at rotator cuff repair site on biomechanical properties of the repair in a mouse (C57Bl/6) model of supraspinatus tendon (ST) detachment and repair. METHODS: Part 1: Murine SAB tissue was harvested and cultured. Viability of SBCs suspended in 10 µL of fibrin sealant beads was confirmed in vitro and in vivo. Eighty mice underwent right ST detachment and repair augmented with either fibrin sealant bead (control group) or fibrin sealant bead with 100,000 SBCs (study group) applied at the repair site. Part 2: 120 mice underwent right ST detachment and repair and were randomized equally into 4 groups: (1) a tissue group, which received a piece of freshly harvested SAB tissue; (2) a cell group, which received SBCs suspended in fibrin sealant bead; (3) a fibrin sealant group, which received plain fibrin sealant bead without cells; and (4) a control group, which received nothing at the ST repair site. An equal number of mice in each group were killed at 2 and 4 weeks. Specimens underwent biomechanical testing to evaluate failure force (part 1 and 2) and histologic analysis of the repair site (part 1 only). RESULTS: Part 1: The mean failure force in the study group was significantly higher than controls at 2 and 4 weeks (3.25 ± 1.03 N vs. 2.43 ± 0.56 N, P = .01, and 4.08 ± 0.99 N vs. 3.02 ± 0.8 N, P = .004, respectively). Mean cell density of the ST at the repair site was significantly lower in the study group at 2 weeks than in controls (18,292.13 ± 1706.41 vs. 29,501.90 ± 3627.49, P = .001). Study group specimens had lower proteoglycan contents than controls, but this difference was not statistically significant. Part 2: There was no difference in failure force between cell and tissue groups at the 2- and 4-week time points (P = .994 and P = .603, respectively). There was no difference in failure force between fibrin sealant bead and control groups at the 2- and 4-week time points (P = .978 and P = .752, respectively). CONCLUSION: This study shows that the application of SBCs and SAB tissue at the rotator cuff repair site increases the strength of repair in a murine model of rotator cuff detachment and repair.

Evaluation of Patient Preference and Perception Regarding the Clinical Use of Autologous Versus Allogeneic Cell Therapy in Orthopedic Surgery.

Background: Cell therapy has become a hot topic in orthopedics, with significant research dedicated to improving physicians' understanding of its efficacy. However, little is known about patients' cell therapy knowledge. Questions/Purposes: The aims of this study were to (1) evaluate patients' perceptions of cell therapy in orthopedics, (2) determine whether patients have a preference for autologous or allogeneic cell therapy, and (3) assess patient concerns about cell therapy. Methods: Consecutive outpatients of an orthopedic clinic were surveyed from June 2019 to January 2020. All patients were 18 years old or older and being seen for an orthopedic intervention, including rotator cuff repair, anterior cruciate ligament (ACL) reconstruction, arthroscopic meniscectomy, or a cartilage repair procedure such as an osteochondral allograft transplantation or matrix-associated autologous chondrocyte implantation. Results: A total of 50 patients were surveyed (mean age: 53 years). The patients' average rating for likelihood to use autologous cells was 8.86 ± 2.2 out of 10 and the average rating for likelihood to use allogeneic cells was 6.24 ± 3.3; 46% of patients had no specific concerns about autologous cell therapy, while 28% expressed concerns about efficacy, and 12% had concerns about donor age. The top 2 "main concerns" about allogeneic cell therapy were disease transmission (30%) and immune reaction (24%). Conclusions: This survey found that patients asserted a preference for autologous cell therapy in orthopedics. Further research is necessary to further elucidate the factors related to cell therapy that are most important to patients.

Biomechanical analysis of anterior stability after 15% glenoid bone loss: comparison of Bankart repair, dynamic anterior stabilization, dynamic anterior stabilization with Bankart repair, and Latarjet.

BACKGROUND: Dynamic anterior shoulder stabilization (DAS) with Bankart repair is a recently described stabilization technique thought to be more robust than an isolated Bankart repair while avoiding many coracoid transfer-related complications and technical demands. DAS involves transfer of the long head biceps through a subscapularis split to the anterior glenoid to create a sling effect. We hypothesize that DAS with Bankart repair will restore anterior stability in a human-cadaveric model with subcritical (15%) glenoid bone loss. METHODS: Eight cadaveric shoulders were tested using an established shoulder simulator to record glenohumeral translations with an accuracy of ±0.2 mm. Shoulders were tested in 5 states-intact soft tissues, Bankart defect with 15% bone loss, isolated Bankart repair, DAS with Bankart repair, isolated DAS, and Latarjet. A 45 N anterior force was applied through the pectoralis major tendon, and translation of the humeral head was recorded and compared with repeated measures analysis of variance. RESULTS: The anterior translation in the intact (native) glenoid was 4.7 mm at neutral position and 4.6 mm at 45° external rotation. Anterior translation significantly increased after introducing a Bankart defect with 15% glenoid bone loss to 9.1 mm (neutral, P = .002) and 9.5 mm (45° external rotation, P < .001). All repair conditions showed a significant decrease in anterior translation relative to Bankart defect. DAS with Bankart repair decreased anterior translation compared with the Bankart defect: 2.7 mm (neutral, P < .001) and 2.1 mm (45° external rotation, P < .001). DAS with Bankart repair significantly decreased anterior translation compared with the isolated Bankart repair (2.7 mm vs. 4.7 mm, P = .023) and the isolated DAS (2.7 mm vs. 4.3 mm, P = .041) in neutral position. The Latarjet procedure resulted in the greatest reduction in anterior translation compared with the Bankart defect: 1.2 mm (neutral, P < .001) and 1.9 mm (45° external rotation, P < .001). CONCLUSIONS: DAS with Bankart repair is a viable alternative to restore anterior glenohumeral stability with a 15% glenoid defect at a greater degree than either DAS or Bankart repair alone. The Latarjet procedure was the most effective in reducing anterior translation but restrained the anterior translation significantly more than the native glenoid.

Evaluating the role of subacromial impingement in rotator cuff tendinopathy: development and analysis of a novel rat model.

BACKGROUND: Subacromial impingement of the rotator cuff caused by variations in acromial anatomy or altered glenohumeral kinematics leads to inflammation and degeneration of the rotator cuff, ultimately contributing to the development of tendinopathy. However, the underlying cellular and molecular changes in the impinged tendon remain poorly understood. Because the rat is an accepted model for rotator cuff studies, we have developed a rat model to study rotator cuff tendinopathy. METHODS: Forty-four adult male Sprague-Dawley rats were allocated to one of 4 study groups: intact control group (group 1, n = 11); bilateral subacromial surgical clip placement to induce supraspinatus impingement for 2 weeks (group 2, n = 11), 4 weeks (group 3, n = 11), and 8 weeks (group 4, n = 11). Bilateral shoulder specimens were harvested for biomechanical testing, histology, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RESULTS: Radiography confirmed that all microvascular clips remained in stable position in the subacromial space. Gross inspection of supraspinatus tendon specimens in the impingement groups revealed changes in tendon morphology at the enthesis and midsubstance. Biomechanical evaluation demonstrated decreased supraspinatus tendon failure force and tissue stiffness at all time points compared with control tendons. Semiquantitative scoring of histologic specimens demonstrated significant, persistent tendinopathic changes over 8 weeks. qRT-PCR analysis of impinged tendon specimens demonstrated upregulation of gene expression for Col3 and Mmp14 in the impingement groups compared with control groups. In muscle samples, significant upregulation was seen in the expression of genes that are commonly associated with muscle atrophy (MuRF1 and Ube2b) and fatty infiltration (Fabp4, Pparg2, and Klf15). CONCLUSION: This new rat subacromial impingement model creates cellular and molecular changes consistent with the development of rotator cuff tendinopathy. The results of this study may serve as a baseline for future investigation.