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Meniscus tissue deficiency resulting from primary meniscectomy or meniscectomy after failed repair is a clinical challenge because the meniscus has little to no capacity for regeneration. Loss of meniscus tissue has been associated with early-onset knee osteoarthritis due to an increase in joint contact pressures in meniscectomized knees. Clinically available replacement strategies range from allograft transplantation to synthetic implants, including the collagen meniscus implant, ACTIfit, and NUSurface. Although short-term efficacy has been demonstrated with some of these treatments, factors such as long-term durability, chondroprotective efficacy, and return to sport activities in young patients remain unpredictable. Investigations of cell-based and tissue-engineered strategies to treat meniscus tissue deficiency are ongoing.

ObjectiveTo identify preoperative imaging-based indicators of knee degeneration that correlate with graft failure risk and postoperative clinical outcome scores after osteochondral graft treatment for chondral defects of the knee.DesignProspectively collected data from 113 patients (mean age, 34 years; 65% male) treated with mosaicplasty or osteochondral allograft transplantation (OCA) was reviewed. Four different aspects of knee degeneration were examined based on preoperative radiographs or magnetic resonance imaging: (1) Osteoarthritis using the Kellgren-Lawrence (KL) grading system, (2) meniscus volume, (3) meniscus quality, and (4) synovitis. Primary outcomes included graft failure, defined by removal/revision of the graft or conversion to arthroplasty, and patient responses to clinical outcome scores.ResultsForty-one knees (36%) underwent mosaicplasty, and 72 knees (64%) underwent OCA. Mean duration of follow-up was 4.5 years (range, 2-14 years). A preoperative KL grade of ≥3 was correlated with increased failure rates (P = 0.01), lower postoperative International Knee Documentation Committee form (IKDC), Activities of Daily Living of the Knee Outcome Survey (KOS-ADL), and Overall Condition scores (P < 0.01), and decreased improvement in Overall Condition scores (P = 0.01). Within an individual tibiofemoral compartment, a preoperative meniscus volume grade of ≥3 (indicating

BackgroundThe purpose of this study was to evaluate the incidence of lower extremity compartment syndrome in National Football League (NFL) athletes and report the mechanisms of injury, methods of treatment, and subsequent days missed. We review the existing literature on lower extremity compartment syndrome in athletic populations.HypothesisLower extremity compartment syndrome occurs with a low incidence in NFL athletes, and there is a high return-to-play rate after surgical management of acute compartment syndrome.Study designCase series.Level of evidenceLevel 4.MethodsA retrospective review of recorded cases of lower extremity compartment syndrome from 2000 to 2017 was performed using the NFL Injury Surveillance System and electronic medical record system. Epidemiological data, injury mechanism, rates of surgery, and days missed due to injury were recorded.ResultsDuring the study period, 22 cases of leg compartment syndrome in 21 athletes were recorded. Of these injuries, 50% occurred in games and 73% were the result of a direct impact to the leg. Concomitant tibial fracture was noted in only 2 cases (9.1%) and there was only 1 reported case of chronic exertional compartment syndrome. Surgery was documented in 15 of 22 cases (68.2%). For acute nonfracture cases, the average time missed due to injury was 24.2 days (range, 5-54 days), and all were able to return to full participation within the same season.ConclusionNFL athletes with acute leg compartment syndrome treated with surgery exhibited a high rate of return to play within the same season.Clinical relevanceAlthough compartment syndrome is a relatively rare diagnosis among NFL players, team physicians and athletic trainers must maintain a high index of suspicion to expediently diagnose and treat this potentially limb-threatening condition.

Cell-based therapies, defined here as the delivery of cells in vivo to treat disease, have recently gained increasing public attention as a potentially promising approach to restore structure and function to musculoskeletal tissues. Although cell-based therapy has the potential to improve the treatment of disorders of the musculoskeletal system, there is also the possibility of misuse and misrepresentation of the efficacy of such treatments. The medical literature contains anecdotal reports and research studies, along with web-based marketing and patient testimonials supporting cell-based therapy. Both the American Society for Bone and Mineral Research (ASBMR) and the Orthopaedic Research Society (ORS) are committed to ensuring that the potential of cell-based therapies is realized through rigorous, reproducible, and clinically meaningful scientific discovery. The two organizations convened a multidisciplinary and international Task Force composed of physicians, surgeons, and scientists who are recognized experts in the development and use of cell-based therapies. The Task Force was charged with defining the state-of-the art in cell-based therapies and identifying the gaps in knowledge and methodologies that should guide the research agenda. The efforts of this Task Force are designed to provide researchers and clinicians with a better understanding of the current state of the science and research needed to advance the study and use of cell-based therapies for skeletal tissues. The design and implementation of rigorous, thorough protocols will be critical to leveraging these innovative treatments and optimizing clinical and functional patient outcomes. In addition to providing specific recommendations and ethical considerations for preclinical and clinical investigations, this report concludes with an outline to address knowledge gaps in how to determine the cell autonomous and nonautonomous effects of a donor population used for bone regeneration. © 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:485-502, 2020.

Cell-based therapies, defined here as the delivery of cells in vivo to treat disease, have recently gained increasing public attention as a potentially promising approach to restore structure and function to musculoskeletal tissues. Although cell-based therapy has the potential to improve the treatment of disorders of the musculoskeletal system, there is also the possibility of misuse and misrepresentation of the efficacy of such treatments. The medical literature contains anecdotal reports and research studies, along with web-based marketing and patient testimonials supporting cell-based therapy. Both the American Society for Bone and Mineral Research (ASBMR) and the Orthopaedic Research Society (ORS) are committed to ensuring that the potential of cell-based therapies is realized through rigorous, reproducible, and clinically meaningful scientific discovery. The two organizations convened a multidisciplinary and international Task Force composed of physicians, surgeons, and scientists who are recognized experts in the development and use of cell-based therapies. The Task Force was charged with defining the state-of-the art in cell-based therapies and identifying the gaps in knowledge and methodologies that should guide the research agenda. The efforts of this Task Force are designed to provide researchers and clinicians with a better understanding of the current state of the science and research needed to advance the study and use of cell-based therapies for skeletal tissues. The design and implementation of rigorous, thorough protocols will be critical to leveraging these innovative treatments and optimizing clinical and functional patient outcomes. In addition to providing specific recommendations and ethical considerations for preclinical and clinical investigations, this report concludes with an outline to address knowledge gaps in how to determine the cell autonomous and nonautonomous effects of a donor population used for bone regeneration. © 2019 American Society for Bone and Mineral Research.

BackgroundRamp lesions are peripheral tears of the posterior horn of the medial meniscus that involve the meniscocapsular attachments or red-red zone and typically occur in conjunction with anterior cruciate ligament (ACL) ruptures.PurposeTo identify the prevalence of, and risk factors for, ramp lesions in a large cohort of patients undergoing primary and revision ACL reconstruction.Study designCase series; Level of evidence, 4.MethodsWe queried our institutional registry of patients who underwent primary or revision surgical treatment for an ACL injury. Those who underwent preoperative magnetic resonance imaging (MRI) at our facility were included in the study. Clinical details were extracted and verified using electronic records. All preoperative MRI scans were reviewed by a musculoskeletal radiologist for the presence of a ramp lesion. Stable ramp lesions were defined as a peripheral posterior horn medial meniscal tear identified on MRI but either not identifiable with viewing and probing from the anterior portals or, if identified, not displaceable with anteriorly directed probing. Unstable ramp lesions were defined as peripheral posterior horn medial meniscal tears at the meniscocapsular junction that were identifiable at the time of surgery and displaced into the medial compartment with probing. The prevalence of stable and unstable ramp lesions was calculated. Demographic, injury, and imaging parameters were determined using univariate statistics.ResultsA total of 372 patients were included. The overall prevalence of ramp lesions was 42% (155/372). Unstable ramp lesions were present in 73 (20%) patients, and stable ramp lesions were present in 82 (22%) patients. The presence of any ramp lesion (stable or unstable) was associated with bone marrow edema of the posteromedial tibia on MRI (odds ratio [OR], 3.0; P < .0001), a contact injury mechanism (OR, 1.8; P = .02), and a concurrent lateral meniscal tear (OR, 1.7; P = .02). No demographic, injury, surgical, or radiological variable was associated with a stable versus unstable ramp lesion.ConclusionThe overall prevalence of a ramp lesion in patients treated for ACL ruptures at our institution was 42%. The presence of bone marrow edema of the posteromedial tibia, a contact injury mechanism, or a lateral meniscal tear should alert surgeons to the potential presence of a medial meniscal ramp lesion.

Excessive MMP activity may impair tendon-to-bone healing. However, little is known about the effect of joint motion on MMP activity after ACL reconstruction. The aim of this study was to determine the effect of different durations of knee immobilization on MMP activity in a mouse ACL reconstruction model using a fluorescent MMP probe which detects MMP 2, 3, 9, and 13 and near-infra red in vivo imaging. Sixty C57BL male mice underwent ACL reconstruction. Post-operatively, the animals were treated with free cage activity (Group 1), or with the use of an external fixator to restrict knee motion and weight bearing for 5 days (Group 2), 14 days (Group 3), and 28 days (Group 4). At days 3, 7, 16, 23, and 30, five mice underwent IVIS imaging. At days 3, 7, 16, and 30, histological analysis was also performed. Probe signal intensity in the whole limb peaked at day 7, followed by a decrease at day 16, and maintenance up to day 30. There was no significant difference among groups at any time point based on IVIS, but histologic localization of MMP probe signal showed significantly less activity in Group 2 and Group 3 compared to Group 4 in the bone tunnel at day 30. We demonstrated that short-term immobilization led to less MMP activity around the bone tunnel compared with prolonged immobilization. A short period of immobilization after ACL reconstruction might enhance graft-bone interface healing by mitigating excess MMP expression. These findings have implications for post-operative rehabilitation protocols following ACL reconstruction. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:325-334, 2019.

BackgroundPrior to the annual National Football League (NFL) Draft, the top college football prospects are evaluated by medical personnel from each team at the NFL Scouting Combine. On the basis of these evaluations, each athlete is assigned an orthopaedic grade from the medical staff of each club, which aims to predict the impact of an athlete's injury history on his ability to participate in the NFL.Purpose(1) To identify clinical predictors of signs, symptoms, and subsequent professional participation associated with football-related injuries identified at the NFL Combine and (2) to assess the methodological quality of the evidence currently published.Study designSystematic review; Level of evidence, 3.MethodsA systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We reviewed all studies that examined musculoskeletal injuries identified among athletes at the NFL Combine and associated outcomes. Data on signs, symptoms, and subsequent NFL participation were collected, and the methodological quality of the studies was assessed.ResultsOverall, 32 studies, including 30 injury-specific studies, met the inclusion criteria. Twenty studies analyzed data collected at the NFL Combine from 2009 and later. When compared with matched controls, athletes with a history of a cervical or lumbar spine injury, rotator cuff repair, superior labrum anterior-posterior repair, anterior cruciate ligament reconstruction, full-thickness chondral lesions of the knee, or Lisfranc injury played in significantly fewer games early in their NFL careers. Additionally, athletes with a history of a cervical or lumbar spine injury, rotator cuff repair, and navicular injury had decreased career lengths versus controls. Defensive players and linemen were found to have decreased participation in the NFL for several injuries, including prior meniscectomy, anterior cruciate ligament reconstruction, and shoulder instability. Career length follow-up, measures of athletic participation, and matching criteria were highly variable among studies.ConclusionFor medical professionals caring for professional football athletes, this information can help guide orthopaedic grading of prospects at the NFL Combine and counseling of athletes on the potential impact of prior injuries on their professional careers. For future studies, improvements in study methodology will provide greater insight into the efficacy of current treatments and areas that require further understanding.

Background: Hamstring strain injuries (HSIs) are prevalent in US National Football League (NFL) players, but there is a paucity of information regarding imaging characteristics, injury severity, and player factors associated with time missed and risk of recurrent injury. Purpose: To describe player, football activity, clinical, and imaging characteristics of NFL players with HSIs, as well as determine player characteristics, clinical examination results, and magnetic resonance imaging (MRI) findings associated with injury occurrence, severity, and missed time. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A retrospective cohort of NFL players with acute HSI (n = 180) during the 2018-2019 season was identified. Injury data were collected prospectively through a league-wide electronic health record system. Three musculoskeletal radiologists graded MRI muscle injury parameters using the British Athletics Muscle Injury Classification (BAMIC) system. Player, football, clinical, and imaging characteristics were correlated with HSI incidence and severity and with missed time from sport. Results: Of the 1098 HSIs identified during the 2018-2019 season, 416 (37.9%) were randomly sampled, and 180 (43.3%) had diagnostic imaging available. Game activity, preseason period, and wide receiver and defensive secondary positions disproportionately contributed to HSI. The biceps femoris was the most commonly injured muscle (n = 132, 73.3%), followed by the semimembranosus (n = 24, 13.3%) and semitendinosus (n = 17, 9.4%) muscles. The most common injury site was the distal third of the biceps femoris and semitendinosus muscles (n = 60, 45.5% and n = 10, 58.8%, respectively) and central part of the semimembranosus muscle (n = 17, 70.8%). Nearly half of the injuries (n = 83, 46.1%) were BAMIC grade 2; 25.6% (n = 46), grade 3; and 17.8% (n = 32), grade 4. MRI showed sciatic nerve abnormality in 30.6% (n = 55) of all HSIs and 81.3% (n = 26) of complete tendon injuries. BAMIC grade correlated with both median days and games missed. Combined biceps femoris and semitendinosus injuries resulted in the highest median days missed (27 days). Conclusion: Among NFL players with acute HSIs, the most common injury was a moderate-severity injury of the distal biceps femoris. BAMIC grade was associated with missed time. [ABSTRACT FROM AUTHOR]

The transition of fibroblasts to myofibroblasts (FMT) represents a pivotal process in wound healing, tissue repair, and fibrotic diseases. This intricate transformation involves dynamic changes in cellular morphology, gene expression, and extracellular matrix remodeling. While extensively studied at the molecular level, recent research has illuminated the regulatory roles of non-coding RNAs (ncRNAs) in orchestrating FMT. This review explores the emerging roles of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating this intricate process. NcRNAs interface with key signaling pathways, transcription factors, and epigenetic mechanisms to fine-tune gene expression during FMT. Their functions are critical in maintaining tissue homeostasis, and disruptions in these regulatory networks have been linked to pathological fibrosis across various tissues. Understanding the dynamic roles of ncRNAs in FMT bears therapeutic promise. Targeting specific ncRNAs holds potential to mitigate exaggerated myofibroblast activation and tissue fibrosis. However, challenges in delivery and specificity of ncRNA-based therapies remain. In summary, ncRNAs emerge as integral regulators in the symphony of FMT, orchestrating the balance between quiescent fibroblasts and activated myofibroblasts. As research advances, these ncRNAs appear to be prospects for innovative therapeutic strategies, offering hope in taming the complexities of fibrosis and restoring tissue equilibrium. [ABSTRACT FROM AUTHOR]

PurposeTo investigate the use of kartogenin (KGN) in augmenting healing of the repaired enthesis after rotator cuff repair in a murine model.MethodsSeventy-two C57BL/6 wild-type mice underwent unilateral detachment and transosseous repair of the supraspinatus tendon augmented with either fibrin sealant (control group; n = 36) or fibrin sealant containing 100 μmol/L of KGN (experimental group; n = 36) applied at the repair site. Postoperatively, mice were allowed free cage activity without immobilization. Mice were humanely killed at 2 and 4 weeks postoperatively. Repair site integrity was evaluated histologically through fibrocartilage formation and collagen fiber organization and biomechanically through load-to-failure testing of the supraspinatus tendon-bone construct.ResultsAt 2 weeks, no differences were noted in percent area of fibrocartilage, collagen organization, or ultimate strength between groups. At 4 weeks, superior collagen fiber organization (based on collagen birefringence [17.3 ± 2.0 vs 7.0 ± 6.5 integrated density/μm2; P

BackgroundMany orthopaedic surgical procedures involve reattachment of a single tendon to bone. Whether tendon-to-bone healing is better facilitated by tendon fixation within a bone tunnel or on a cortical surface is unknown. The purpose of this study was to evaluate tendon-healing within a bone tunnel compared with that on the cortical surface in a rabbit model of biceps tenodesis.MethodsThirty-two rabbits (24 weeks of age) underwent unilateral proximal biceps tenodesis with tendon fixation within a bone tunnel (BT group) or on the cortical surface (SA [surface attachment] group). Postoperatively, rabbits were allowed free-cage activity without immobilization. All rabbits were killed 8 weeks after surgery. Healing was assessed by biomechanical testing, microcomputed tomography (micro-CT), and histomorphometric analysis.ResultsBiomechanical testing demonstrated no significant difference between the groups in mean failure loads (BT: 56.8 ± 28.8 N, SA: 55.8 ± 14.9 N; p = 0.92) or stiffness (BT: 26.3 ± 16.6 N/mm, SA: 32.3 ± 9.6 N/mm; p = 0.34). Micro-CT analysis demonstrated no significant difference between the groups in mean volume of newly formed bone (BT: 69.3 ± 13.9 mm, SA: 65.5 ± 21.9 mm; p = 0.70) or tissue mineral density of newly formed bone (BT: 721.4 ± 10.9 mg/cm, SA: 698.6 ± 26.2 mg/cm; p = 0.07). On average, newly formed bone within the tunnel represented only 5% of the total new bone formed in the BT specimens. Histological analysis demonstrated tendon-bone interdigitation and early fibrocartilaginous zone formation on the outer cortical surface in both groups. In contrast, minimal tendon-bone bonding was observed within the tunnel in the BT specimens.ConclusionsTendon fixation in a bone tunnel and on the cortical surface resulted in similar healing profiles. For tendons placed within a bone tunnel, intratunnel healing was minimal compared with the healing outside the tunnel on the cortical surface.Clinical relevanceThe creation of large bone tunnels, which can lead to stress risers and increase the risk of fracture, may not be necessary for biceps tenodesis procedures.

PURPOSE OF REVIEW:Rotator cuff injuries are a common cause of pain and dysfunction for the elite athlete and can result in time loss from participation. This review highlights the current management of these injuries. RECENT FINDINGS:Conservative management of rotator cuff injuries continues to be the "gold standard" in the elite athlete. This includes a comprehensive rehabilitation program, anti-inflammatories, and corticosteroid injections. Newer treatment techniques such as intramuscular dry needling and the use of biologics such as platelet-rich plasma and stem cells demonstrate early promising results; however, these modalities require further investigation to determine their effectiveness. Rotator cuff injuries can range from contusions and tendinopathy to full-thickness tears. A comprehensive evaluation is needed to determine the extent of injury and appropriate plan of care. Management strategies can range from rehabilitation to operative intervention and are guided by the size of the tear, time of season, sport, performance limitations, and presence of concomitant pathology.