Transcriptional time course after rotator cuff repair in 6 month old female rabbits.

Introduction: Rotator cuff tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration, which is not improved upon with surgical repair, highlighting the need to better understand the underlying biology impairing more favorable outcomes. Methods: In this study, we collected supraspinatus muscle tissue from 6 month old female rabbits who had undergone unilateral tenotomy for 8 weeks at 1, 2, 4, or 8 weeks post-repair (n = 4/group). RNA sequencing and enrichment analyses were performed to identify a transcriptional timeline of rotator cuff muscle adaptations and related morphological sequelae. Results: There were differentially expressed (DE) genes at 1 (819 up/210 down), 2 (776/120), and 4 (63/27) weeks post-repair, with none at 8 week post-repair. Of the time points with DE genes, there were 1092 unique DE genes and 442 shared genes, highlighting that there are changing processes in the muscle at each time point. Broadly, 1-week post-repair differentially expressed genes were significantly enriched in pathways of metabolism and energetic activity, binding, and regulation. Many were also significantly enriched at 2 weeks, with the addition of NIF/NF-kappaB signaling, transcription in response to hypoxia, and mRNA stability alongside many additional pathways. There was also a shift in transcriptional activity at 4 weeks post-repair with significantly enriched pathways for lipids, hormones, apoptosis, and cytokine activity, despite an overall decrease in the number of differentially expressed genes. At 8 weeks post-repair there were no DE genes when compared to control. These transcriptional profiles were correlated with the histological findings of increased fat, degeneration, and fibrosis. Specifically, correlated gene sets were enriched for fatty acid metabolism, TGF-B-related, and other pathways. Discussion: This study identifies the timeline of transcriptional changes in muscle after RC repair, which by itself, does not induce a growth/regenerative response as desired. Instead, it is predominately related to metabolism/energetics changes at 1 week post-repair, unclear or asynchronous transcriptional diversity at 2 weeks post-repair, increased adipogenesis at 4 weeks post-repair, and a low transcriptional steady state or a dysregulated stress response at 8 weeks post-repair.

Trochlear Lesion Caused by Suprapatellar Intramedullary Nailing and Treated with Autologous Chondrocytes Implant.

Introduction: Intramedullary nailing remains the most common method of treatment for tibial shaft fractures. The suprapatellar technique has proven to be useful in gaining and maintaining alignment, especially in proximal one-third tibia shaft fractures. It has been adopted by many surgeons taking trauma call, because it requires less set-up time and allows the surgery to be done with less assistance. We present a case of a femoral trochlea lesion following the placement of a reamed suprapatellar intramedullary nail for fixation of a tibial shaft fracture. Case Presentation: An active 33-year-old male with no prior history of knee pain sustained a distal tibial shaft fracture and was treated with suprapatellar intramedullary nail fixation. Five months later, he underwent revision surgery with exchange nail placement and reaming via an infrapatellar technique for delayed healing of the fracture with subsequent successful healing. The patient, otherwise healthy, continued to experience persistent anterior knee pain with clunking and inability to arise from a flexed knee position approximately 18 months post-surgery. Magnetic resonance imaging and arthroscopic evaluation of the joint were performed, and a full-thickness cartilage lesion was identified in the central portion of the femoral trochlear groove. Conclusion: The purpose of the present case is to bring awareness to the fact that the suprapatellar approach to intramedullary nailing tibial shaft fracture fixation can be accompanied by trochlear articular cartilage damage, which can be successfully treated with cartilage restoration.

Articular cartilage delamination at eight years following cellular-based repair procedures: a case reports.

This report describes two cases of late cartilage delamination in two young adults after two different autologous cell-based techniques for cartilage restoration: 1. Matrix-assisted autologous chondrocyte implantation (MACI) and 2. Hyaluronic acid-bone marrow aspirate concentrate (HA-BMAC). Both cases demonstrate that even in patients who do not present with any ongoing symptoms after primary surgery, a cellular-based graft's subsequent delamination can occur later. It is possible that regardless of the technique used or the time passed since the surgery, a graft failure may occur at some level, causing delamination of a previously asymptomatic cartilage restoration graft and a traumatic event with long-term follow-up. Surgeons must be alert to this injury and describe histologic findings to determine where failure occurs.

The "Second Hit" of Repair in a Rabbit Model of Chronic Rotator Cuff Tear.

The rabbit supraspinatus is a useful translational model for rotator cuff (RC) repair because it recapitulates muscle atrophy and fat accumulation observed in humans after a chronic tear (the "first hit"). However, a timeline of RC tissue response after repair, especially with regard to recent evidence of muscle degeneration and lack of regeneration, is currently unavailable. Thus, the purpose of this study was to characterize the progression of muscle and fat changes over time after the repair of a chronic RC tear in the rabbit model. Two rounds of experiments were conducted in 2017-2018 and 2019-2020 with N = 18 and 16 skeletally mature New Zealand White rabbits, respectively. Animals underwent left supraspinatus tenotomy with repair 8 weeks later. The unoperated right shoulder served as control. The rabbits were sacrificed at 1-, 2-, 4-, and 8-weeks post-repair for histological and biochemical analysis. Atrophy, measured by fiber cross-sectional area and muscle mass, was greatest around 2 weeks after repair. Active muscle degeneration peaked at the same time, involving 8% of slide areas. There was no significant regeneration at any timepoint. Fat accumulation and fibrosis were significantly increased across all time points compared to contralateral. Statement of Clinical Significance: These results demonstrate model reproducibility and a "second hit" phenomenon of repair-induced muscle atrophy and degeneration which partially recovers after a short time, while increased fat and fibrosis persist.

Corrigendum: Transcriptional Time Course After Rotator Cuff Tear.

[This corrects the article DOI: 10.3389/fphys.2021.707116.].

Supraspinatus muscle architecture and physiology in a rabbit model of tenotomy and repair.

Chronic rotator cuff tears can cause severe functional deficits. Addressing the chronic fatty and fibrotic muscle changes is of high clinical interest; however, the architectural and physiological consequences of chronic tear and repair are poorly characterized. We present a detailed architectural and physiological analysis of chronic tear and repair (both over 8 and 16 wk) compared with age-matched control rabbit supraspinatus (SSP) muscles. Using female New Zealand White Rabbits (n = 30, n = 6/group) under 2% isoflurane anesthesia, the SSP was surgically isolated and maximum isometric force was measured at four to six muscle lengths. Architectural analysis was performed, and maximum isometric stress was computed. Whole muscle length-tension curves were generated using architectural measurements to compare experimental physiology to theoretical predictions. Architectural measures are consistent with persistent radial and longitudinal atrophy over time in tenotomy that fails to recover after repair. Maximum isometric force was significantly decreased after 16 wk tenotomy and not significantly improved after repair. Peak isometric force reported here are greater than prior reports of rabbit SSP force after tenotomy. Peak stress was not significantly different between groups and consistent with prior literature of SSP stress. Muscle strain during contraction was significantly decreased after 8 wk of tenotomy and repair, indicating effects of tear and repair on muscle function. The experimental length-tension data were overlaid with predicted curves for each experimental group (generated from structural data), exposing the altered structure-function relationship for tenotomy and repair over time. Data presented here contribute to understanding the physiological implications of disease and repair in the rotator cuff.NEW & NOTEWORTHY We utilize an established method to measure the length-tension relationship for the rabbit supraspinatus in normal, torn, and repaired muscles. We then perform architectural analysis to evaluate structural changes after tear and repair. Although peak isometric force is lower in the tear and repair groups, there are no differences in peak stresses across groups. These findings indicate persistent structural changes (both radial and longitudinal atrophy) and physiological deficiencies (decreased peak force and uncoupling structure-function relationship) after tenotomy that do not significantly recover after repair.

Transcriptional Time Course After Rotator Cuff Tear.

Rotator cuff (RC) tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration in the chronic state, which is not improved with intervention or surgical repair. This highlights the need to better understand the underlying dysfunction in muscle after RC tendon tear. Contemporary studies aimed at understanding muscle pathobiology after RC tear have considered transcriptional data in mice, rats and sheep models at 2-3 time points (1 to 16 weeks post injury). However, none of these studies observed a transition or resurgence of gene expression after the initial acute time points. In this study, we collected rabbit supraspinatus muscle tissue with high temporal resolution (1, 2, 4, 8, and 16 weeks) post-tenotomy (n = 6/group), to determine if unique, time-dependent transcriptional changes occur. RNA sequencing and analyses were performed to identify a transcriptional timeline of RC muscle changes and related morphological sequelae. At 1-week post-tenotomy, the greatest number of differentially expressed genes was observed (1,069 up/873 down) which decreases through 2 (170/133), 4 (86/41), and 8 weeks (16/18), followed by a resurgence and transition of expression at 16 weeks (1,421/293), a behavior which previously has not been captured or reported. Broadly, 1-week post-tenotomy is an acute time point with expected immune system responses, catabolism, and changes in energy metabolism, which continues into 2 weeks with less intensity and greater contribution from mitochondrial effects. Expression shifts at 4 weeks post-tenotomy to fatty acid oxidation, lipolysis, and general upregulation of adipogenesis related genes. The effects of previous weeks' transcriptional dysfunction present themselves at 8 weeks post-tenotomy with enriched DNA damage binding, aggresome activity, extracellular matrix-receptor changes, and significant expression of genes known to induce apoptosis. At 16 weeks post-tenotomy, there is a range of enriched pathways including extracellular matrix constituent binding, mitophagy, neuronal activity, immune response, and more, highlighting the chaotic nature of this time point and possibility of a chronic classification. Transcriptional activity correlated significantly with histological changes and were enriched for biologically relevant pathways such as lipid metabolism. These data provide platform for understanding the biological mechanisms of chronic muscle degeneration after RC tears.

Return to Work After Autologous Chondrocyte Implantation of the Knee in Patients with Workers Compensation Insurance.

OBJECTIVE: This retrospective analysis aimed to evaluate patient and defect characteristics on return to work after autologous chondrocyte implantation (ACI) for all patients with workers compensation insurance in our clinic. METHODS: Retrospective analysis of medical records of patients with workers compensation treated with ACI in our clinic over 10 years (August 2004 to November 2014). Data were collected on demographics, lesion size and location, number of defects, duration of symptoms, and outcomes. RESULTS: A total of 28 patients with 30 ACI procedures were included in this analysis. Patients had a mean age of 40.0 years, were mostly male, and tended to be overweight (mean body mass index = 31.5 kg/m2). Most patients were employed in occupations with high physical demand (85.7%) compared with lower physical demand jobs (14.3%). The mean number of lesions per knee = 1.73. Overall, the mean total surface area of the defect was large (12.6 cm2), with large mean individual lesion size of 7.39 cm2. All 28 patients returned to work in some capacity, with a total of 22 (79%) returning to full work, and 6 (21%) returning to modified work. There were no significant differences in the comparison of patients who returned to full versus modified work, in mean age, body mass index, high versus low physical demand occupation, or lesion characteristics (size, chronicity, or location). CONCLUSIONS: Our results demonstrate that in a challenging workers compensation cohort, in patients with multiple large defects, treatment with ACI allows a high percentage of patients to return to their normal vigorous work activities within 9 months to 1 year following cartilage restoration. This study is a level IV retrospective case series.

Editorial Commentary: Cartilage Restoration-What Is Currently Available?

In the past 30 years, bone marrow stimulation techniques such as microfracture (MF) have become a popular method to treat symptomatic focal articular cartilage lesions. Nonetheless, recent studies have not shown good long-term clinical outcomes, and MF has produced alterations in the subchondral bone architecture with degenerative changes. Autologous chondrocyte implantation (ACI) has shown good results at 20 years. Second- and third-generation ACI has shown superiority to MF and fewer complications than first-generation ACI. Each treatment option has its advantages and disadvantages. Recent research has shown that better filling of cartilage tissue occurs in patients treated with MF and collagen augmentation than in those treated with MF alone. Research from our clinic has shown that Hyaff scaffold combined with bone marrow aspirate concentrate in a 1-step technique yielded good results in patients with 10 years' follow-up. We believe that high-quality randomized controlled trials are necessary to directly compare all cartilage restoration procedures.

Heterogeneous muscle gene expression patterns in patients with massive rotator cuff tears.

Detrimental changes in the composition and function of rotator cuff (RC) muscles are hallmarks of RC disease progression. Previous studies have demonstrated both atrophic and degenerative muscle loss in advanced RC disease. However, the relationship between gene expression and RC muscle pathology remains poorly defined, in large part due to a lack of studies correlating gene expression to tissue composition. Therefore, the purpose of this study was to determine how tissue composition relates to gene expression in muscle biopsies from patients undergoing reverse shoulder arthroplasty (RSA). Gene expression related to myogenesis, atrophy and cell death, adipogenesis and metabolism, inflammation, and fibrosis was measured in 40 RC muscle biopsies, including 31 biopsies from reverse shoulder arthroplasty (RSA) cases that had available histology data and 9 control biopsies from patients with intact RC tendons. After normalization to reference genes, linear regression was used to identify relationships between gene expression and tissue composition. Hierarchical clustering and principal component analysis (PCA) identified unique clusters, and fold-change analysis was used to determine significant differences in expression between clusters. We found that gene expression profiles were largely dependent on muscle presence, with muscle fraction being the only histological parameter that was significantly correlated to gene expression by linear regression. Similarly, samples with histologically-confirmed muscle distinctly segregated from samples without muscle. However, two sub-groups within the muscle-containing RSA biopsies suggest distinct phases of disease, with one group expressing markers of both atrophy and regeneration, and another group not significantly different from either control biopsies or biopsies lacking muscle. In conclusion, this study provides context for the interpretation of gene expression in heterogeneous and degenerating muscle, and provides further evidence for distinct stages of RC disease in humans.

Rotator cuff tear state modulates self-renewal and differentiation capacity of human skeletal muscle progenitor cells.

Full thickness rotator cuff tendon (RCT) tears have long-term effects on RC muscle atrophy and fatty infiltration, with lasting damage even after surgical tendon repair. Skeletal muscle progenitor cells (SMPs) are critical for muscle repair in response to injury, but the inability of RC muscles to recover from chronic RCT tear indicates possible deficits in repair mechanisms. Here we investigated if muscle injury state was a crucial factor during human SMP expansion and differentiation ex vivo. SMPs were isolated from muscles in patients with no, partial-thickness (PT), or full-thickness (FT) RCT tears. Despite using growth factors, physiological niche stiffness, and muscle-mimetic extracellular matrix (ECM) proteins, we found that SMPs isolated from human RC muscle with RCT tears proliferated slower but fused into myosin heavy chain (MHC)-positive myotubes at higher rates than SMPs from untorn RCTs. Proteomic analysis of RC muscle tissue revealed shifts in muscle composition with pathology, as muscle from massive RCT tears had increased ECM deposition compared with no tear RC muscle. Together these data imply that the remodeled niche in a torn RCT primes SMPs not for expansion but for differentiation, thus limiting longer-term self-renewal necessary for regeneration after surgical repair. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1816-1823, 2017.

Cartilage Repair in the Inflamed Joint: Considerations for Biological Augmentation Toward Tissue Regeneration.

Cartilage repair/regeneration procedures (e.g., microfracture, autologous chondrocyte implantation [ACI]) typically result in a satisfactory outcome in selected patients. However, the vast majority of patients with chronic symptoms and, in general, a more diseased joint, do not benefit from these surgical techniques. The aims of this work were to (1) review factors negatively influencing the joint environment; (2) review current adjuvant therapies that can be used to improve results of cartilage repair/regeneration procedures in patients with more diseased joints, (3) outline future lines of research and promising experimental approaches. Chronicity of symptoms and advancing patient age appear to be the most relevant factors negatively affecting clinical outcome of cartilage repair/regeneration. Preliminary experience with hyaluronic acid, platelet-rich plasma, and mesenchymal stem cell has been positive but there is no strong evidence supporting the use of these products and this requires further assessment with high-quality, prospective clinical trials. The use of a Tissue Therapy strategy, based on more mature engineered tissues, holds promise to tackle limitations of standard ACI procedures. Current research has highlighted the need for more targeted therapies, and (1) induction of tolerance with granulocyte colony-stimulating factor (G-CSF) or by preventing IL-6 downregulation; (2) combined IL-4 and IL-10 local release; and (3) selective activation of the prostaglandin E2 (PGE2) signaling appear to be the most promising innovative strategies. For older patients and for those with chronic symptoms, adjuvant therapies are needed in combination with microfracture and ACI.

Fresh osteochondral allografts in the knee: only a salvage procedure?

The role of fresh allogeneic osteochondral allograft transplantation (OCA) in the cartilage repair algorithm has been long debated and this procedure is primarily considered as a salvage procedure, to be used when other, simple, techniques have failed. Gracitelli et al. in a retrospective comparison of patients who received OCA as primary treatment or as a salvage procedure, demonstrates that the outcome of this procedure is minimally influenced by a previous failed treatment and that OCA represents an effective solution for both primary and revision surgery of chondral and osteochondral lesions of the knee. In particular, optimal indications for OCA seem to be revision of previously failed bone marrow stimulation techniques with an impaired subchondral bone plate and primary treatment of large osteochondral defects.

The role of the peripheral and central nervous systems in rotator cuff disease.

Rotator cuff (RC) disease is an extremely common condition associated with shoulder pain, reduced functional capacities, and impaired quality of life. It primarily involves alterations in tendon health and mechanical properties that can ultimately lead to tendon failure. RC tendon tears induce progressive muscle changes that have a negative impact on surgical reparability of the RC tendons and clinical outcomes. At the same time, a significant base of clinical data suggests a relatively weak relationship between RC integrity and clinical presentation, emphasizing the multifactorial aspects of RC disease. This review aims to summarize the potential contribution of peripheral, spinal, and supraspinal neural factors that may (1) exacerbate structural and functional muscle changes induced by tendon tear, (2) compromise the reversal of these changes during surgery and rehabilitation, (3) contribute to pain generation and persistence of pain, (4) impair shoulder function through reduced proprioception, kinematics, and muscle recruitment, and (5) help explain interindividual differences and response to treatment. Given the current clinical and scientific interest in peripheral nerve injury in the context of RC disease and surgery, we carefully reviewed this body of literature with a particular emphasis on suprascapular neuropathy that has generated a large number of studies in the past decade. Within this process, we highlight the gaps in current knowledge and suggest research avenues for scientists and clinicians.

Epimuscular Fat in the Human Rotator Cuff Is a Novel Beige Depot.

UNLABELLED: : Chronic rotator cuff (RC) tears are a common and debilitating injury, characterized by dramatic expansion of adipose tissue, muscle atrophy, and limited functional recovery. The role of adipose expansion in RC pathology is unknown; however, given the identified paracrine/endocrine regulation by other adipose depots, it likely affects tissue function outside its boundaries. Therefore, we characterized the epimuscular (EM) fat depot of the human rotator cuff, defined its response to RC tears, and evaluated its influence on myogenesis in vitro. EM fat biopsies exhibited morphological and functional features of human beige fat compared with patient-matched s.c. biopsies, which appeared whiter. The transcriptional profile of EM fat and isolated EM adipose-derived stem cells (ASCs) shifted as a function of the tear state; EM fat from intact cuffs had significantly elevated expression of the genes associated with uncoupled respiration, and the EM fat from torn cuffs had increased expression of beige-selective genes. EM ASC cocultures with human- and mouse-derived myogenic cells exhibited increased levels of myogenesis compared with s.c. cultures. Increased fusion and decreased proliferation of myogenic cells, rather than changes to the ASCs, were found to underlie this effect. Taken together, these data suggest that EM fat in the human rotator cuff is a novel beige adipose depot influenced by cuff state with therapeutic potential for promoting myogenesis in neighboring musculature. SIGNIFICANCE: Rotator cuff tears affect millions of people in the U.S.; however, current interventions are hindered by persistent muscle degeneration. This study identifies the therapeutic potential for muscle recovery in the epimuscular fat in the rotator cuff, previously considered a negative feature of the pathology, and finds that this fat is beige, rather than white. This is important for two reasons. First, the stem cells that were isolated from this beige fat are more myogenic than those from white fat, which have been the focus of stem cell-based therapies to date, suggesting epimuscular fat could be a better stem cell source to augment rotator cuff repair. Second, these beige stem cells promote myogenesis in neighboring cells in culture, suggesting the potential for this fat to be manipulated therapeutically to promote muscle recovery through secreted signals.

Muscle progenitor cell regenerative capacity in the torn rotator cuff.

Chronic rotator cuff (RC) tears affect a large portion of the population and result in substantial upper extremity impairment, shoulder weakness, pain, and limited range of motion. Regardless of surgical or conservative treatment, persistent atrophic muscle changes limit functional restoration and may contribute to surgical failure. We hypothesized that deficits in the skeletal muscle progenitor (SMP) cell pool could contribute to poor muscle recovery following tendon repair. Biopsies were obtained from patients undergoing arthroscopic RC surgery. The SMP population was quantified, isolated, and assayed in culture for its ability to proliferate and fuse in vitro and in vivo. The SMP population was larger in muscles from cuffs with partial tears compared with no tears or full thickness tears. However, SMPs from muscles in the partial tear group also exhibited reduced proliferative ability. Cells from all cuff states were able to fuse robustly in culture and engraft when injected into injured mouse muscle, suggesting that when given the correct signals, SMPs are capable of contributing to muscle hypertrophy and regeneration regardless of tear severity. The fact that this does not appear to happen in vivo helps focus future therapeutic targets for promoting muscle recovery following rotator cuff repairs and may help improve clinical outcomes.

Effect of supraspinatus tendon injury on supraspinatus and infraspinatus muscle passive tension and associated biochemistry.

BACKGROUND: Injury to the supraspinatus and infraspinatus tendons and the associated atrophic changes to the muscle remain a common clinical problem. Specifically, increased muscle stiffness has been implicated in failure of the repair and poor functional outcomes. We present a comparison of the passive mechanical properties and associated biochemical studies from patients with and without torn supraspinatus tendons. METHODS: Muscle biopsy samples (n = 40) were obtained from twenty patients undergoing arthroscopic shoulder surgery. Passive mechanical tests of both individual fibers and fiber bundles as well as analysis of titin molecular weight and collagen content were performed. RESULTS: At the fiber-bundle level, a significant increase in passive modulus was observed between intact supraspinatus samples (mean [and standard error], 237.41 ± 59.78 kPa) and torn supraspinatus samples (515.74 ± 65.48 kPa) (p < 0.05), a finding that was not observed at the single fiber level. Within the torn samples, elastic moduli in the supraspinatus were greater than in the infraspinatus at both the single fiber and the fiber-bundle level. There was a significant positive correlation between bundle elastic modulus and collagen content (r(2) = 0.465) in the supraspinatus muscle as well as a significant positive correlation between tear size and bundle elastic modulus (r(2) = 0.702) in the torn supraspinatus samples. CONCLUSIONS: Supraspinatus muscle passive tension increases in a tendon tear size-dependent manner after tendon injury. The increase in muscle stiffness appears to originate outside the muscle cell, in the extracellular matrix. CLINICAL RELEVANCE: Muscle stiffness after rotator cuff tendon injury is more severe with large tears. This finding supports the concept of early intervention, when tendon tears are smaller, and interventions targeting the extracellular matrix.

Muscle gene expression patterns in human rotator cuff pathology.

BACKGROUND: Rotator cuff pathology is a common source of shoulder pain with variable etiology and pathoanatomical characteristics. Pathological processes of fatty infiltration, muscle atrophy, and fibrosis have all been invoked as causes for poor outcomes after rotator cuff tear repair. The aims of this study were to measure the expression of key genes associated with adipogenesis, myogenesis, and fibrosis in human rotator cuff muscle after injury and to compare the expression among groups of patients with varied severities of rotator cuff pathology. METHODS: Biopsies of the supraspinatus muscle were obtained arthroscopically from twenty-seven patients in the following operative groups: bursitis (n = 10), tendinopathy (n = 7), full-thickness rotator cuff tear (n = 8), and massive rotator cuff tear (n = 2). Quantitative polymerase chain reaction (qPCR) was performed to characterize gene expression pathways involved in myogenesis, adipogenesis, and fibrosis. RESULTS: Patients with a massive tear demonstrated downregulation of the fibrogenic, adipogenic, and myogenic genes, indicating that the muscle was not in a state of active change and may have difficulty responding to stimuli. Patients with a full-thickness tear showed upregulation of fibrotic and adipogenic genes; at the tissue level, these correspond to the pathologies most detrimental to outcomes of surgical repair. Patients with bursitis or tendinopathy still expressed myogenic genes, indicating that the muscle may be attempting to accommodate the mechanical deficiencies induced by the tendon tear. CONCLUSIONS: Gene expression in human rotator cuff muscles varied according to tendon injury severity. Patients with bursitis and tendinopathy appeared to be expressing pro-myogenic genes, whereas patients with a full-thickness tear were expressing genes associated with fatty atrophy and fibrosis. In contrast, patients with a massive tear appeared to have downregulation of all gene programs except inhibition of myogenesis. CLINICAL RELEVANCE: These data highlight the difficulty in treating massive tears and suggest that the timing of treatment may be important for muscle recovery. Specifically, earlier interventions to address tendon injury may allow muscles to respond more appropriately to mechanical stimuli.

Use of platelet-rich plasma to enhance tendon function and cellularity.

Clinical studies have shown inconsistent healing with subjective improvement after use of platelet-rich plasma (PRP) for tendinosis and partial tendon tears. We conducted a study to assess changes after injecting PRP into an intact rabbit patellar tendon (PT) model. In the study group (n = 10), an incision was made over the PT and PRP was injected into multiple sites on the PT. The control group (n = 8) was injected with saline. PTs were harvested 7 and 28 days after injection. Hematoxylin-eosin staining showed hypercellularity in the PRP group at 7 days, but the effect was not as marked at 28 days. At 7 days, polarized microscopy showed increased crimp density of collagen in the PRP group, compared with the control group, demonstrating up-regulation in collagen matrix. Cellular proliferation measured by tritiated thymidine was also significantly increased (P = .02) in the PRP group, compared with the control group, but the difference was not as significant at 28 days. At 7 and 28 days, there were no significant changes in basic fibroblast growth factor, insulin-like growth factor, vascular endothelial growth factor, or platelet-derived growth factor with 2B chains. Injection of PRP into rabbit PT enhances collagen remodeling and hypercellularity with increased metabolic activity, which could have a positive effect on healing.