Editorial Commentary: Cell-Based Therapies for Articular Cartilage Repair Require Precise Progenitor Cell Characterization and Determination of Mechanism of Action.

Biologics and cell-based therapies, in particular, have come to the forefront of orthopaedic sports medicine as agents with therapeutic and regenerative potential. Autologous chondrocyte implantation has been used successfully for many years, but a recent focus on autologous progenitor cells derived from bone marrow aspirate, adipose tissue, and/or synovium has garnered significant interest. Mobilized peripheral blood mononuclear cells [PBMCs or connective tissue progenitors (CTPs)] represent a promising cell population for potential use in articular cartilage repair. The term "stem cell" has become widely popularized, but more specific language identifying the cell type by donor type, tissue of origin, cell surface marker profile, culture conditions, and other cell behavior/characteristics should be used. In 2019, Murray et al. proposed a five-item "DOSES" tool in an effort to encourage standardized reporting for cell-based therapies emphasizing donor, origin of tissue, separation from other cell types/preparation method, exhibited cell characteristics associated with behavior, and site of delivery. The advantages of the DOSES tool include both simplicity and ability to be applied to cell types not yet discovered. However, a universally accepted list of criteria for biologics does not yet exist. Additional research is necessary to better elucidate the precise mechanisms by which cell therapies have a clinical effect and define whether the therapies for the treatment of cartilage pathology merely help alleviate symptoms or actually provide structural improvements. There are few data to suggest exogenous cell therapies directly engraft, so identifying the paracrine mediators produced by these cells would be an area of further interest.

The Ideal Hinge Axis Position to Reduce Tibial Slope in Opening-Wedge High Tibial Osteotomy Includes Proximalization-Extension and Internal Rotation.

PURPOSE: To evaluate the effect of the hinge axis position on the posterior tibial slope (PTS) in medial opening-wedge high tibial osteotomy. METHODS: This study included adults with medial-compartment osteoarthritis who had computed tomography (CT) scans available that were amenable to Bodycad Osteotomy software analysis. Virtual osteotomies modeling a 10-mm medial opening-wedge gap were performed. The hinge axis was rotated internally and externally and was proximalized-extended and distalized-flexed with respect to the anterior tibial cortex for 5°, 10°, 15°, and 20°. Each resultant PTS was recorded and compared with the results obtained from the true lateral hinge position and with the preoperative PTS. RESULTS: Computed tomography scans from 10 patients were used. Strong linear correlations were found with each hinge axis position change and the resultant PTS. The trend-line differences were statistically significant by single-factor analysis of variance (P < .001). The PTS decreased for an anterolateral hinge, whereas it increased for a posterolateral hinge. Linear regression analysis showed that rotating the hinge axis by 9.0° externally or angulating the hinge axis by 21.8° of distalization-flexion would result in increasing the tibial slope by 1° whereas rotating the hinge axis by 8.7° internally or angulating the hinge axis by 21.6° of proximalization-extension would decrease the tibial slope by 1°. CONCLUSIONS: Distalization-flexion and external rotation of the hinge axis position led to stepwise increases in the PTS, whereas proximalization-extension and internal rotation led to decreases in the PTS. CLINICAL RELEVANCE: Our findings suggest that when performing medial opening-wedge high tibial osteotomy and aiming to decrease the PTS, the surgeon should aim to achieve maximal internal rotation (producing an anterolateral hinge), as well as proximalization-extension, of the hinge axis. This study quantifies and provides a model for the effect of the hinge axis position for a predetermined angular correction on the PTS.

Complications Following Biologic Therapeutic Injections: A Multicenter Case Series.

PURPOSE: To describe the complications that occur following biologic therapeutic injections. METHODS: We queried physician members of the Biologic Association, a multidisciplinary organization dedicated to providing a unified voice for all matters related to musculoskeletal biologics and regenerative medicine. Patients included in this study must have (1) received a biologic injection, (2) sustained an adverse reaction, and (3) had a minimum of 1-year follow-up after the injection. Patient demographic information, medical comorbidities, diagnoses, and previous treatments were recorded. The type of injection, injection setting, injection manufacturers, and specific details about the complication and outcome were collected. RESULTS: In total, 14 patients were identified across 6 institutions in the United States (mean age 63 years, range: 36-83 years). The most common injections in this series were intra-articular knee injections (50%), followed intra-articular shoulder injections (21.4%). The most common underlying diagnosis was osteoarthritis (78.5%). Types of injections included umbilical cord blood, platelet-rich plasma, bone marrow aspirate concentrate, placental tissue, and unspecified "stem cell" injections. Complications included infection (50%), suspected sterile inflammatory response (42.9%), and a combination of both (7.1%). The most common pathogen identified from infection cases was Escherichia coli (n = 4). All patients who had isolated infections underwent treatment with at least one subsequent surgical intervention (mean: 3.6, range: 1-12) and intravenous antibiotic therapy. CONCLUSIONS: This study demonstrates that serious complications can occur following treatment with biologic injections, including infections requiring multiple surgical procedures and inflammatory reactions. LEVEL OF EVIDENCE: Level IV, case series.

Shoulder and elbow pathology in the female athlete: sex-specific considerations.

Unique biologic and biomechanical aspects of the female body make women more prone to certain orthopedic injuries. Sex differences are well understood with regard to certain orthopedic pathologies such as anterior cruciate ligament injury, hallux valgus, carpal tunnel, and carpometacarpal joint arthritis; however, sex differences are less commonly discussed with regard to shoulder and elbow pathology. The purpose of this review is to elucidate sex differences specific to sports-related shoulder and elbow injuries in the female athlete population.

Reoperation and complications after anterior cervical discectomy and fusion and cervical disc arthroplasty: a study of 52,395 cases.

PURPOSE: The aim of this study was to analyze rates of perioperative complications and subsequent cervical surgeries in patients treated for cervical degenerative disc disease with anterior cervical discectomy and fusion (ACDF) and those treated with artificial cervical disc arthroplasty (ACDA) for up to 5-year follow-up. METHODS: California's Office of Statewide Health Planning and Development discharge database was analyzed for patients aged 18-65 years undergoing single-level ACDF or ACDA between 2003 and 2010. Medical comorbidities were identified with CMS-Condition Categories. Readmissions for short-term complications of the procedure were identified and rates of subsequent cervical surgeries were calculated at 90-day and 1-, 3-, and 5-year follow-up. Multivariate regression modeling was used to identify associations with complications and subsequent cervical surgeries correcting for patient and provider characteristics. RESULTS: A total of 52,395 eligible cases were identified: 50,926 ACDF and 1469 ACDA. Readmission was less common in the ACDA group (OR: 0.69, 95% CI: 0.48-1.0, p = 0.048). Subsequent cervical spine surgery was more common in the ACDF group in the immediate perioperative period (within 90 days of surgery) (ACDF 3.35% vs. ACDA 2.04%, OR: 0.63, 95% CI: 0.44-0.92, p = 0.015). At 1-, 3-, and 5-year postoperatively, rates of subsequent cervical surgeries were similar between the two cohorts. CONCLUSIONS: We found no protective benefit for ACDA versus ACDF for single-level disease at up to 5-year follow-up in the largest cohort of patients examined to date. Early complications were rare in both cohorts stressing the value of large cohort studies to study risk factors for rare events. These slides can be retrieved under Electronic Supplementary Material.

Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats.

BACKGROUND: Achilles tendon rupture is a common injury and the best treatment option remains uncertain between surgical and nonoperative methods. Biologic approaches using multipotent stem cells such as perivascular stem cells pose a possible treatment option, although there is currently a paucity of evidence regarding their clinical therapeutic use. QUESTIONS/PURPOSES: The purpose of this study was to determine whether injected perivascular stem cells (PSCs) would (1) improve histologic signs of tendon healing (such as percent area of collagen); and (2) improve biomechanical properties (peak load or stiffness) in a rat model of Achilles tendon transection. METHODS: Two subtypes of PSCs were derived from human adipose tissue: pericytes (CD146CD34CD45CD31) and adventitial cells (CD146CD34CD45CD31). Thirty-two athymic rats underwent right Achilles transection and were randomized to receive injection with saline (eight tendons), hydrogel (four tendons), pericytes in hydrogel (four tendons), or adventitial cells in hydrogel (eight tendons) 3 days postoperatively with the left serving as an uninjured control. Additionally, a subset of pericytes was labeled with CM-diI to track cell viability and localization. At 3 weeks, the rats were euthanized, and investigators blinded to treatment group allocation evaluated tendon healing by peak load and stiffness using biomechanical testing and percent area of collagen using histologic analysis with picrosirius red staining. RESULTS: Histologic analysis showed a higher mean percent area collagen for pericytes (30%) and adventitial cells (28%) than hydrogel (21%) or saline (26%). However, a nonparametric statistical analysis yielded no statistical difference. Mechanical testing demonstrated that the pericyte group had a higher peak load than the saline group (41 ± 7 N versus 26 ± 9 N; mean difference 15 N; 95% confidence interval [CI], 4-27 N; p = 0.003) and a higher peak load than the hydrogel group (41 ± 7 N versus 25 ± 3 N; mean difference 16; 95% CI, 8-24 N; p = 0.001). The pericyte group demonstrated higher stiffness than the hydrogel group (36 ± 12 N/mm versus 17 ± 6 N/mm; mean difference 19 N/mm; 95% CI, 5-34 N/mm; p = 0.005). CONCLUSIONS: Our results suggest that injection of PSCs improves mechanical but not the histologic properties of early Achilles tendon healing. CLINICAL RELEVANCE: This is a preliminary study that provides more insight into the use of adipose-derived PSCs as a percutaneous therapy in the setting of Achilles tendon rupture. Further experiments to characterize the function of these cells may serve as a pathway to development of minimally invasive intervention aimed at improving nonoperative management while avoiding the complications associated with surgical treatment down the line.

Neer Award 2018: Platelet-derived growth factor receptor α co-expression typifies a subset of platelet-derived growth factor receptor ß-positive progenitor cells that contribute to fatty degeneration and fibrosis of the murine rotator cuff.

BACKGROUND AND HYPOTHESIS: After massive tears, rotator cuff muscle often undergoes atrophy, fibrosis, and fatty degeneration. These changes can lead to high surgical failure rates and poor patient outcomes. The identity of the progenitor cells involved in these processes has not been fully elucidated. Platelet-derived growth factor receptor ß (PDGFRß) and platelet-derived growth factor receptor α (PDGFRα) have previously been recognized as markers of cells involved in muscle fibroadipogenesis. We hypothesized that PDGFRα expression identifies a fibroadipogenic subset of PDGFRß+ progenitor cells that contribute to fibroadipogenesis of the rotator cuff. METHODS: We created massive rotator cuff tears in a transgenic strain of mice that allows PDGFRß+ cells to be tracked via green fluorescent protein (GFP) fluorescence. We then harvested rotator cuff muscle tissues at multiple time points postoperatively and analyzed them for the presence and localization of GFP+ PDGFRß+ PDGFRα+ cells. We cultured, induced, and treated these cells with the molecular inhibitor CWHM-12 to assess fibrosis inhibition. RESULTS: GFP+ PDGFRß+ PDGFRα+ cells were present in rotator cuff muscle tissue and, after massive tears, localized to fibrotic and adipogenic tissues. The frequency of PDGFRß+ PDGFRα+ cells increased at 5 days after massive cuff tears and decreased to basal levels within 2 weeks. PDGFRß+ PDGFRα+ cells were highly adipogenic and significantly more fibrogenic than PDGFRß+ PDGFRα- cells in vitro and localized to adipogenic and fibrotic tissues in vivo. Treatment with CWHM-12 significantly decreased fibrogenesis from PDGFRß+ PDGFRα+ cells. CONCLUSION: PDGFRß+ PDGFRα+ cells directly contribute to fibrosis and fatty degeneration after massive rotator cuff tears in the mouse model. In addition, CWHM-12 treatment inhibits fibrogenesis from PDGFRß+ PDGFRα+ cells in vitro. Clinically, perioperative PDGFRß+ PDGFRα+ cell inhibition may limit rotator cuff tissue degeneration and, ultimately, improve surgical outcomes for massive rotator cuff tears.

Similar Outcomes After Osteochondral Allograft Transplantation in Anterior Cruciate Ligament-Intact and -Reconstructed Knees: A Comparative Matched-Group Analysis With Minimum 2-Year Follow-Up.

PURPOSE: To compare failure rates and clinical outcomes of osteochondral allograft transplantation (OCA) in anterior cruciate ligament (ACL)-intact versus ACL-reconstructed knees at midterm follow-up. METHODS: After a priori power analysis, a prospective registry of patients treated with OCA for focal chondral lesions ≥2 cm2 in size with minimum 2-year follow-up was used to match ACL-reconstructed knees with ACL-intact knees by age, sex, and primary chondral defect location. Exclusion criteria included meniscus transplantation, realignment osteotomy, or other ligamentous injury. Complications, reoperations, and patient responses to validated outcome measures were reviewed. Failure was defined by any procedure involving allograft removal/revision or conversion to arthroplasty. Kaplan-Meier analysis and multivariate Cox regression were performed to evaluate the association of ACL reconstruction (ACLR) with failure. RESULTS: A total of 50 ACL-intact and 25 ACL-reconstructed (18 prior, 7 concomitant) OCA patients were analyzed. The mean age was 36.2 years (range, 14-62 years). Mean follow-up was 3.9 years (range, 2-14 years). Patient demographics and chondral lesion characteristics were similar between groups. ACL-reconstructed patients averaged 2.2 ± 1.9 prior surgeries on the ipsilateral knee compared with 1.4 ± 1.4 surgeries for ACL-intact patients (P = .014). Grafts used for the last ACLR included bone-patellar tendon-bone autograft, hamstring autograft, Achilles tendon allograft, and tibialis allograft (data available for only 11 of 25 patients). At final follow-up, 22% of ACL-intact and 32% of ACL-reconstructed patients had undergone reoperation. OCA survivorship was 90% and 96% at 2 years and 79% and 85% at 5 years in ACL-intact and ACL-reconstructed patients, respectively (P = .774). ACLR was not independently associated with failure. Both groups demonstrated clinically significant improvements in the Short Form-36 pain and physical functioning, International Knee Documentation Committee subjective, and Knee Outcome Survey-Activities of Daily Living scores at final follow-up (P < .001), with no significant differences in preoperative, postoperative, and change scores between groups. CONCLUSIONS: OCA in the setting of prior or concomitant ACLR does not portend higher failure rates or compromise clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Translational Research on Orthobiologics in the Treatment of Rotator Cuff Disease: From the Laboratory to the Operating Room.

Rotator cuff disease is one of the most common human tendinopathies and can lead to significant shoulder dysfunction. Despite efforts to improve symptoms in patients with rotator cuff tears and healing rates after rotator cuff repair, high rates of failed healing and persistent shoulder morbidity exist. Increasing interest has been placed on the utilization of orthobiologics-scaffolds, cell-based augmentation, platelet right plasma (platelet-rich plasma), and small molecule-based strategies-in the management of rotator cuff disease and the augmentation of rotator cuff repairs. This is a complex topic that involves novel treatment strategies, including patches/scaffolds, small molecule-based, cellular-based, and tissue-derived augmentation techniques. Ultimately, translational research, with a particular focus on preclinical models, has allowed us to gain some insights into the utility of orthobiologics in the treatment of rotator cuff disease and will continue to be critical to our further understanding of the underlying cellular mechanisms moving forward.

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.

Orthobiologics for the Management of Early Arthritis in the Middle-Aged Athlete.

This article is dedicated to the use of orthobiologic therapies in the management of early osteoarthritis in middle-aged athletes. Understanding a patient's presenting symptoms, physical examination, imaging results, and goals is of critical importance in applying orthobiologic therapies. The field of orthobiologics is expanding at a rapid pace, and the clinical studies examining the utility of each treatment lag behind the direct-to-consumer marketing that leads to these products being used. Here we provide a review of the available treatments, emerging treatments, and the current literature supporting or refuting their use. Currently studied orthobiologics include autologous and allogenic cell therapies, autologous blood products, hyaluronic acid, gene therapies, Wnt inhibitors, and a variety of systemic treatments.

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.

Extreme Hinge Axis Positions Are Necessary to Achieve Posterior Tibial Slope Reduction With Small Coronal-Plane Corrections in Medial Opening Wedge High Tibial Osteotomy.

Background: Both coronal- and sagittal-plane knee malalignment can increase the risk of ligamentous injuries and the progression of degenerative joint disease. High tibial osteotomy can achieve multiplanar correction, but determining the precise hinge axis position for osteotomy is technically challenging. Purpose: To create computed tomography (CT)-based patient-specific models to identify the ideal hinge axis position angle and the amount of maximum opening in medial opening wedge high tibial osteotomy (MOWHTO) required to achieve the desired multiplanar correction. Study Design: Descriptive laboratory study. Methods: A total of 10 patients with lower extremity CT scans were included. Baseline measurements including the mechanical tibiofemoral angle (mTFA) and the posterior tibial slope (PTS) were calculated. Virtual osteotomy was performed to achieve (1) a specified degree of PTS correction and (2) a planned degree of mTFA correction. The mean hinge axis position angle for MOWHTO to maintain an anatomic PTS (no slope correction) was 102.6° ± 8.3° relative to the posterior condylar axis (PCA). Using this as the baseline correction, the resultant hinge axis position and maximum opening were then calculated for each subsequent osteotomy procedure. Results: For 5.0° of mTFA correction, the hinge axis position was decreased by 6.8°, and the maximum opening was increased by 0.49 mm for every 1° of PTS correction. For 10.0° of mTFA correction, the hinge axis position was decreased by 5.2°, and the maximum opening was increased by 0.37 mm for every 1° of PTS correction. There was a significant difference in the trend-line slopes for hinge axis position versus PTS correction (P = .013) and a significant difference in the trend-line intercepts for maximum opening versus PTS correction (P < .0001). Conclusion: The mean hinge axis position for slope-neutral osteotomy was 102.6° ± 8.3° relative to the PCA. For smaller corrections in the coronal plane, more extreme hinge axis positions were necessary to achieve higher magnitudes of PTS reduction. Clinical Relevance: Extreme hinge axis positions are technically challenging and can lead to unstable osteotomy. Patient-specific instrumentation may allow for precise correction to be more readily achieved.

Nonunion of the Coracoid Base Secondary to Cutibacterium acnes Infection in a Surgically Naive Patient: A Case Report.

CASE: We present the case of a 42-year-old man with a coracoid base fracture that progressed to nonunion. The patient underwent percutaneous autologous bone-marrow and demineralized bone matrix (DBM) grafting 8 months after injury, with all intraoperative cultures positive for Cutibacterium acnes. The patient had no prior surgeries, but he began shaving his axillae around the time of injury. He was treated with amoxicillin; by the 6-week follow-up, computed tomography demonstrated complete fracture healing. CONCLUSION: Our case demonstrates a novel etiology of coracoid nonunion treated successfully by eradicating the infection with biologic augmentation by percutaneous autologous bone-marrow grafting with DBM and oral antibiotics.

Mitochondrial dysfunction and potential mitochondrial protectant treatments in tendinopathy.

Tendinopathy is a common musculoskeletal condition that affects a wide range of patients, including athletes, laborers, and older patients. Tendinopathy is often characterized by pain, swelling, and impaired performance and function. The etiology of tendinopathy is multifactorial, including both intrinsic and extrinsic mechanisms. Various treatment strategies have been described, but outcomes are often variable, as tendons have poor intrinsic healing potential compared with other tissues. Therefore, several novel targets for tendon regeneration have been identified and are being explored. Mitochondria are organelles that generate adenosine triphosphate, and they are considered to be the power generators of the cell. Recently, mitochondrial dysfunction verified by increased reactive oxygen species (ROS), decreased superoxide dismutase activity, cristae disorganization, and decreased number of mitochondria has been identified as a mechanism that may contribute to tendinopathy. This has provided new insights for studying tendinopathy pathogenesis and potential treatments via antioxidant, metabolic modulation, or ROS inhibition. In this review, we present the current understanding of mitochondrial dysfunction in tendinopathy. The review summarizes the potential mechanism by which mitochondrial dysfunction contributes to the development of tendinopathy, as well as the potential therapeutic benefits of mitochondrial protectants in the treatment of tendinopathy.

Algorithm for Treatment of Focal Cartilage Defects of the Knee: Classic and New Procedures.

OBJECTIVE: To create a treatment algorithm for focal grade 3 or 4 cartilage defects of the knee using both classic and novel cartilage restoration techniques. DESIGN: A comprehensive review of the literature was performed highlighting classic as well as novel cartilage restoration techniques supported by clinical and/or basic science research and currently being employed by orthopedic surgeons. RESULTS: There is a high level of evidence to support the treatment of small to medium size lesions (<2-4 cm2) without subchondral bone involvement with traditional techniques such as marrow stimulation, osteochondral autograft transplant (OAT), or osteochondral allograft transplant (OCA). Newer techniques such as autologous matrix-induced chondrogenesis and bone marrow aspirate concentrate implantation have also been shown to be effective in select studies. If subchondral bone loss is present OAT or OCA should be performed. For large lesions (>4 cm2), OCA or matrix autologous chondrocyte implantation (MACI) may be performed. OCA is preferred over MACI in the setting of subchondral bone involvement while cell-based modalities such as MACI or particulated juvenile allograft cartilage are preferred in the patellofemoral joint. CONCLUSIONS: Numerous techniques exist for the orthopedic surgeon treating focal cartilage defects of the knee. Treatment strategies should be based on lesion size, lesion location, subchondral bone involvement, and the level of evidence supporting each technique in the literature.

Development of Parsonage-Turner Syndrome After Heat Stroke in Firefighters: A Report of 2 Cases.

CASE: Two firefighters developed Parsonage-Turner syndrome (PTS) shortly after sustaining episodes of heat stroke. Patient 1 was a 40-year-old man who presented with shoulder pain and supraspinatus and infraspinatus weakness. Patient 2 was a 35-year-old man who presented with shoulder pain and absent external rotation strength. Both had electrodiagnostic testing and magnetic resonance imaging findings consistent with PTS. Both demonstrated partial but incomplete recovery at 1- and 2.5-year follow-ups, respectively. CONCLUSIONS: PTS should remain on the differential diagnosis for any patient presenting with sudden onset shoulder pain and neurological deficits after an episode of heat-related illness.

The role of the macrophage in tendinopathy and tendon healing.

The role of the macrophage is an area of emerging interest in tendinopathy and tendon healing. The macrophage has been found to play a key role in regulating the healing process of the healing tendon. The specific function of the macrophage depends on its functional phenotype. While the M1 macrophage phenotype exhibits a phagocytic and proinflammatory function, the M2 macrophage phenotype is associated with the resolution of inflammation and tissue deposition. Several studies have been conducted on animal models looking at enhancing or suppressing macrophage function, targeting specific phenotypes. These studies include the use of exogenous biological and pharmacological substances and more recently the use of transgenic and genetically modified animals. The outcomes of these studies have been promising. In particular, enhancement of M2 macrophage activity in the healing tendon of animal models have shown decreased scar formation, accelerated healing, decreased inflammation and even enhanced biomechanical strength. Currently our understanding of the role of the macrophage in tendinopathy and tendon healing is limited. Furthermore, the roles of therapies targeting macrophages to enhance tendon healing is unclear. Clinical Significance: An increased understanding of the significance of the macrophage and its functional phenotypes in the healing tendon may be the key to enhancing tendon healing. This review will present the current literature on the function of macrophages in tendinopathy and tendon healing and the potential of therapies targeting macrophages to enhance tendon healing.

Development of a Meniscal Ossicle After a Meniscal Root Repair Augmented with Bone Marrow Aspirate Concentrate: A Case Report.

CASE: A 17-year-old boy had persistent knee pain 1 year after medial meniscal root repair augmented with bone marrow aspirate concentrate injection. Radiographs and magnetic resonance imaging (MRI) demonstrated an intrameniscal ossicle which was not present on MRI performed before 6 months. He underwent arthroscopic excision of the meniscal ossicle. At the 7-month follow-up, he had complete relief of his pain. CONCLUSIONS: It is possible that the meniscal ossicle developed because of osteoinductive cells and cytokines from the injected bone marrow or the drill hole for root repair and should be considered as a possible complication of this procedure.

Identification of Inflammatory Mediators in Tendinopathy Using a Murine Subacromial Impingement Model.

Subacromial impingement is associated with a spectrum of disorders-including rotator cuff disease-but their relationship is complex. We have established a novel murine model of subacromial impingement to study supraspinatus tendinopathy. The purpose of this study was to evaluate changes in gene expression in this murine shoulder impingement model to further elucidate the mechanisms underlying the development of tendinopathy. Twenty-eight C57BL/6 mice were used in this study. All mice underwent bilateral surgery with insertion of a small metal clip in the subacromial space or a sham procedure. The supraspinatus tendons underwent histological analyses, biomechanical testing, and RNA extraction for multiplex gene expression analysis (NanoString, Seattle, WA). Histology demonstrated increased cellularity and disorganized collagen fibers of the supraspinatus tendon in the clip impingement group. Mean load to failure (5.20 vs. 1.50 N, p < 0.001) and mean stiffness (4.95 vs. 1.47 N/mm, p < 0.001) were lower in the impingement group than the sham group. NanoString analyses revealed 111 differentially expressed genes (DEGs) between the impingement and sham groups. DEGs of interest included Mmp3 (expression ratio [ER]: 2.68, p = 0.002), Tgfb1 (ER: 1.76, p = 0.01), Col3a1 (ER: 1.66, p = 0.03), and Tgfbr2 (ER: 1.53, p = 0.01). Statement of clinical significance: We identified 111 DEGs that may contribute to the development of tendinopathy in this model. Further studies of these specific genes will allow identification of their roles in the initiation and regulation of tendon damage, and their potential to serve as novel therapeutic targets in the treatment of rotator cuff disease. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2575-2582, 2019.