Targeting the hedgehog signaling pathway to improve tendon-to-bone integration.

OBJECTIVE: While the role of hedgehog (Hh) signaling in promoting zonal fibrocartilage production during development is well-established, whether this pathway can be leveraged to improve tendon-to-bone repair in adults is unknown. Our objective was to genetically and pharmacologically stimulate the Hh pathway in cells that give rise to zonal fibrocartilaginous attachments to promote tendon-to-bone integration. DESIGN: Hh signaling was stimulated genetically via constitutive Smo (SmoM2 construct) activation of bone marrow stromal cells or pharmacologically via systemic agonist delivery to mice following anterior cruciate ligament reconstruction (ACLR). To assess tunnel integration, we measured mineralized fibrocartilage (MFC) formation in these mice 28 days post-surgery and performed tunnel pullout testing. RESULTS: Hh pathway-related genes increased in cells forming the zonal attachments in wild-type mice. Both genetic and pharmacologic stimulation of the Hh pathway increased MFC formation and integration strength 28 days post-surgery. We next conducted studies to define the role of Hh in specific stages of the tunnel integration process. We found Hh agonist treatment increased the proliferation of the progenitor pool in the first week post-surgery. Additionally, genetic stimulation led to continued MFC production in the later stages of the integration process. These results indicate that Hh signaling plays an important biphasic role in cell proliferation and differentiation towards fibrochondrocytes following ACLR. CONCLUSION: This study reveals a biphasic role for Hh signaling during the tendon-to-bone integration process after ACLR. In addition, the Hh pathway is a promising therapeutic target to improve tendon-to-bone repair outcomes.

Acute Repair of Meniscus Root Tear Partially Restores Joint Displacements as Measured With Magnetic Resonance Images and Loading in a Cadaveric Porcine Knee.

The meniscus serves important load-bearing functions and protects the underlying articular cartilage. Unfortunately, meniscus tears are common and impair the ability of the meniscus to distribute loads, increasing the risk of developing osteoarthritis. Therefore, surgical repair of the meniscus is a frequently performed procedure; however, repair does not always prevent osteoarthritis. This is hypothesized to be due to altered joint loading post-injury and repair, where the functional deficit of the meniscus prevents it from performing its role of distributing forces. The objective of this study was to quantify joint kinematics in an intact joint, after a meniscus root tear, and after suture repair in cadaveric porcine knees, a frequently used in vivo model. We utilized an magnetic resonance images-compatible loading device and novel use of a T1 vibe sequence to measure meniscus and femur displacements under physiological axial loads. We found that anterior root tear led to large meniscus displacements under physiological axial loading and that suture anchor repair reduced these displacements but did not fully restore intact joint kinematics. After tear and repair, the anterior region of the meniscus moved posteriorly and medially as it was forced out of the joint space under loading, while the posterior region had small displacements as the posterior attachment acted as a hinge about which the meniscus pivoted in the axial plane. Methods from this study can be applied to assess altered joint kinematics following human knee injuries and evaluate repair strategies aimed to restore joint kinematics.

Alternatives to Reverse Total Shoulder Arthroplasty for Management of Massive Rotator Cuff Tears.

Multiple alternatives to reverse total shoulder arthroplasty exist for the management of massive rotator cuff tears. Surgeons should understand the current indications for and outcomes of alternatives to reverse total shoulder arthroplasty for the management of massive rotator cuff tears. Successful rotator cuff repair involves two major challenges: the creation of forceful mechanical integrity of the repair and the creation of a biologic environment that enhances tissue healing. Given the latest advancements in grafts and biologic enhancement, arthroscopic repair appears to be an effective and reasonable alternative for the management of massive rotator cuff tears.

Acute repair of meniscus root tear partially restores joint displacements as measured with MRI and loading in a porcine knee.

The meniscus serves important load-bearing functions and protects the underlying articular cartilage. Unfortunately, meniscus tears are common and impair the ability of the meniscus to distribute loads, greatly increasing the risk for developing osteoarthritis. Therefore, surgical repair of the meniscus is a frequently performed procedure; however, this repair does not always prevent osteoarthritis. This is hypothesized to be due to altered joint loading post injury and repair, where the functional deficit of the meniscus prevents it from performing its role of distributing forces. However, many studies of meniscus function required opening the joint, which alters kinematics. The objective of this study was to use novel MRI methods to image the intact joint under axial load and measure the acute meniscus and femur displacements in an intact joint, after a meniscus root tear, and after suture repair in the porcine knee, a frequently used in vivo model. We found that anterior root tear led to large meniscus and femur displacements under physiological axial loading, and that suture anchor repair reduced these displacements, but did not fully restore intact joint kinematics. After tear and repair, the anterior region of the meniscus moved posteriorly and medially as it was forced out of the joint space under loading, while the posterior region had small displacements as the posterior attachment acted as a hinge about which the meniscus rotated in the axial plane. This technique can be applied to evaluate the effect of knee injuries and to develop improved repair strategies to restore joint kinematics.

Linguistic Analysis Identifies Emergent Biomaterial Fabrication Trends for Orthopaedic Applications.

The expanse of publications in tissue engineering (TE) and orthopedic TE (OTE) over the past 20 years presents an opportunity to probe emergent trends in the field to better guide future technologies that can make an impact on musculoskeletal therapies. Leveraging this trove of knowledge, a hierarchical systematic search method and trend analysis using connected network mapping of key terms is developed. Within discrete time intervals, an accelerated publication rate for anatomic orthopedic tissue engineering (AOTE) of osteochondral defects, tendons, menisci, and entheses is identified. Within these growing fields, the top-listed key terms are extracted and stratified into evident categories, such as biomaterials, delivery method, or 3D printing and biofabrication. It is then identified which categories decreased, remained constant, increased, or emerged over time, identifying the specific emergent categories currently driving innovation in orthopedic repair technologies. Together, these data demonstrate a significant convergence of material types and descriptors used across tissue types. From this convergence, design criteria to support future research of anatomic constructs that mimic both the form and function of native tissues are formulated. In summary, this review identifies large-scale trends and predicts new directions in orthopedics that will define future materials and technologies.

Intra-articular changes precede extra-articular changes in the biceps tendon after rotator cuff tears in a rat model.

HYPOTHESIS: Biceps tendon pathology is common with rotator cuff tears. The mechanisms for biceps changes, and therefore its optimal treatment, are unknown. Our objective was to determine the effect of rotator cuff tears on regional biceps tendon pathology. We hypothesized that histologic and compositional changes would appear before organizational changes, both would appear before mechanical changes, and changes would begin at the tendon's insertion site. MATERIALS AND METHODS: Detachment of supraspinatus and infraspinatus tendons or sham surgery was done in 65 Sprague-Dawley rats. Rats were euthanized at 1, 4, or 8 weeks for regional measurements of histologic, compositional, organizational (1, 4 and 8 weeks), or mechanical properties (4 and 8 weeks only). RESULTS: One week after tendon detachments, decreased organization and more rounded cell shape were found in the intra-articular space of the biceps tendon. Aggrecan expression was increased along the entire length of the tendon, whereas all other compositional changes were only at the tendon's proximal insertion into bone. With time, this disorganization and more rounded cell shape extended the length of the tendon. Organizational and cell shape changes also preceded detrimental mechanical changes: decreased modulus in the intra-articular space was found after 8 weeks. CONCLUSIONS: Results support a degenerative component to pathology in the biceps tendon. In addition, changes resembling a tendon exposed to compressive loading occurring first in the intra-articular space indicate that the biceps tendon plays an increased role as a load-bearing structure against the humeral head in the presence of rotator cuff tears.

Decreased loading after rotator cuff tears leads to improved biceps tendon properties in a rat model.

BACKGROUND: The purpose of this study was to elucidate the mechanism of biceps tendon changes after rotator cuff tears. We hypothesized that increased loading on the biceps tendon after rotator cuff tears will result in further detrimental changes whereas decreased loading will result in increased organization and more normal tendon composition. In addition, we hypothesized that changes with altered loading will begin at the proximal insertion into bone and progress along the tendon length at later time points. MATERIALS AND METHODS: Supraspinatus and infraspinatus tendon detachments in rats were followed by various loading protocols at various time points. Regional changes in cellularity, cell shape, collagen organization, and matrix proteins of the long head of the biceps tendon were determined by histologic measures and immunohistochemistry. RESULTS: Increased loading after detachments resulted in more disorganized collagen after only 1 week and compositional changes by 4 weeks. By 8 weeks, decreased loading resulted in increased organization, decreased cellularity, a more elongated cell shape, and more normal tendon composition. Organizational changes with increased loading began in the intra-articular space and progressed along the tendon length with time. CONCLUSIONS: Combined with previous findings of decreased mechanics with increased loading, these results show that increased compressive loading away from the proximal insertion into bone is a mechanism for biceps tendon pathology in the presence of rotator cuff tears. The striking improvements with decreased loading further support increased loading as a mechanism for biceps tendon pathology because removal of this load led to improvements in tendon histology, organization, and composition.

Arthroscopic Diagnosis of Occult Posterolateral Meniscocapsular Separations: Another Hidden Lesion.

PURPOSE: The purpose of this study was to describe the surgical findings and clinical outcomes in a series of patients with occult posterolateral meniscocapsular separations diagnosed arthroscopically after a negative magnetic resonance imaging (MRI) scan. METHODS: A retrospective analysis of prospectively collected data of consecutive patients who underwent surgical arthroscopy with repair of an occult posterolateral meniscocapsular separation by 2 fellowship-trained orthopaedic sports medicine surgeons at a single institution was performed. All lesions were identified arthroscopically in the posterolateral aspect of the lateral compartment as a distinct pathologic separation between the posterolateral capsule and adjacent meniscal tissue with increased excursion on probing. Clinical examination notes, MRI scans, and operative reports were reviewed. Patient-reported outcome measures were assessed via patient questionnaire. RESULTS: A total of 6 patients were included for analysis. MRI evaluation of the lateral meniscus was unrevealing in 4 patients, suggesting a possible tear of the body of the lateral meniscus in one patient and demonstrating a parameniscal cyst abutting the anterior root of the lateral meniscus in another patient. Arthroscopic examination revealed meniscocapsular separations of the posterolateral meniscus in all 6 knees, with 2 knees demonstrating concomitant bucket-handle meniscus tears. Patient-reported outcomes were determined for 67% of study patients. The average reported International Knee Documentation Committee score was 63.8, the average Knee Outcome Survey Activities of Daily Living Scale score was reported as 63, the 12-Item Short Form Survey (SF-12) Physical score averaged 46.8 with an average SF-12 Mental score of 59.9. CONCLUSIONS: The diagnosis of occult posterolateral meniscocapsular separations (MCS) could be missed on advanced imaging, such as MRI, so arthroscopic diagnosis may be required. This study indicates that arthroscopic diagnosis and repair of occult posterolateral MCS results in good functional and clinical outcomes. LEVEL OF EVIDENCE: IV, therapeutic case series.

The critical role of Hedgehog-responsive mesenchymal progenitors in meniscus development and injury repair.

Meniscal tears are associated with a high risk of osteoarthritis but currently have no disease-modifying therapies. Using a Gli1 reporter line, we found that Gli1+ cells contribute to the development of meniscus horns from 2 weeks of age. In adult mice, Gli1+ cells resided at the superficial layer of meniscus and expressed known mesenchymal progenitor markers. In culture, meniscal Gli1+ cells possessed high progenitor activities under the control of Hh signal. Meniscus injury at the anterior horn induced a quick expansion of Gli1-lineage cells. Normally, meniscal tissue healed slowly, leading to cartilage degeneration. Ablation of Gli1+ cells further hindered this repair process. Strikingly, intra-articular injection of Gli1+ meniscal cells or an Hh agonist right after injury accelerated the bridging of the interrupted ends and attenuated signs of osteoarthritis. Taken together, our work identified a novel progenitor population in meniscus and proposes a new treatment for repairing injured meniscus and preventing osteoarthritis.

Six-Month Outcomes of Clinically Relevant Meniscal Injury in a Large-Animal Model.

BACKGROUND: The corrective procedures for meniscal injury are dependent on tear type, severity, and location. Vertical longitudinal tears are common in young and active individuals, but their natural progression and impact on osteoarthritis (OA) development are not known. Root tears are challenging and they often indicate poor outcomes, although the timing and mechanisms of initiation of joint dysfunction are poorly understood, particularly in large-animal and human models. PURPOSE/HYPOTHESIS: In this study, vertical longitudinal and root tears were made in a large-animal model to determine the progression of joint-wide dysfunction. We hypothesized that OA onset and progression would depend on the extent of injury-based load disruption in the tissue, such that root tears would cause earlier and more severe changes to the joint. STUDY DESIGN: Controlled laboratory study. METHODS: Sham surgeries and procedures to create either vertical longitudinal or root tears were performed in juvenile Yucatan mini pigs through randomized and bilateral arthroscopic procedures. Animals were sacrificed at 1, 3, or 6 months after injury and assessed at the joint and tissue level for evidence of OA. Functional measures of joint load transfer, cartilage indentation mechanics, and meniscal tensile properties were performed, as well as histological evaluation of the cartilage, meniscus, and synovium. RESULTS: Outcomes suggested a progressive and sustained degeneration of the knee joint and meniscus after root tear, as evidenced by histological analysis of the cartilage and meniscus. This occurred in spite of spontaneous reattachment of the root, suggesting that this reattachment did not fully restore the function of the native attachment. In contrast, the vertical longitudinal tear did not cause significant changes to the joint, with only mild differences compared with sham surgery at the 6-month time point. CONCLUSION: Given that the root tear, which severs circumferential connectivity and load transfer, caused more intense OA compared with the circumferentially stable vertical longitudinal tear, our findings suggest that without timely and mechanically competent fixation, root tears may cause irreversible joint damage. CLINICAL RELEVANCE: More generally, this new model can serve as a test bed for experimental surgical, scaffold-based, and small molecule-driven interventions after injury to prevent OA progression.

Structure, function, and defect tolerance with maturation of the radial tie fiber network in the knee meniscus.

The knee menisci are comprised of two orthogonal collagenous networks-circumferential and radial-that combine to enable efficient load bearing by the tissue in adults. Here, we assessed how the structural and functional characteristics of these networks developed over the course of skeletal maturation and determined the role of these fiber networks in defect tolerance with tissue injury. Imaging of the radial tie fiber (RTF) collagen structure in medial bovine menisci from fetal, juvenile, and adult specimens showed increasing heterogeneity, anisotropy, thickness, and density with skeletal development. The mechanical analysis showed that the tensile modulus in the radial direction did not change with skeletal development, though the resilience (in the radial direction) increased and the tolerance to defects in the circumferential direction decreased, in adult compared to fetal tissues. This loss of defect tolerance correlated with increased order in the RTF network in adult tissue. These data provide new insights into the role of the radial fiber network in meniscus function, will lead to improved clinical decision-making in the presence of a tear and may improve engineering efforts to reproduce this critical load-bearing structure in the knee.

Amplifying Bone Marrow Progenitors Expressing α-Smooth Muscle Actin Produce Zonal Insertion Sites During Tendon-to-Bone Repair.

Traditional tendon-to-bone repair where the tendon is reattached to bone via suture anchors often results in disorganized scar production rather than the formation of a zonal insertion. In contrast, ligament reconstructions where tendon grafts are passed through bone tunnels can yield zonal tendon-to-bone attachments between the graft and adjacent bone. Therefore, ligament reconstructions can be used to study mechanisms that regulate zonal tendon-to-bone repair in the adult. Anterior cruciate ligament (ACL) reconstructions are one of the most common reconstruction procedures and while we know that cells from outside the graft produce the attachments, we have not yet established specific cell populations that give rise to this tissue. To address this knowledge gap, we performed ACL reconstructions in lineage tracing mice where α-smooth muscle actin (αSMACreERT2) was used to label αSMA-expressing progenitors within the bone marrow that produced zonal attachments. Expression of αSMA was increased during early stages of the repair process such that the contribution of SMA-labeled cells to the tunnel integration was highest when tamoxifen was delivered in the first week post-surgery. The zonal attachments shared features with normal entheses, including tidemarks oriented perpendicularly to collagen fibers, Col1a1-expressing cells, alkaline phosphatase activity, and proteoglycan-rich staining. Finally, the integration strength increased with time, requiring 112% greater force to remove the graft from the tunnel at 28 days compared with 14 days post-surgery. Future studies will target these progenitor cells to define the pathways that regulate zonal tendon-to-bone repair in the adult. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:105-116, 2020.

Transection of the medial meniscus anterior horn results in cartilage degeneration and meniscus remodeling in a large animal model.

The meniscus plays a central load-bearing role in the knee joint. Unfortunately, meniscus injury is common and can lead to joint degeneration and osteoarthritis (OA). In small animal models, progressive degenerative changes occur with the unloading of the meniscus via destabilization of the medial meniscus (DMM). However, few large animal models of DMM exist and the joint-wide initiation of the disease has not yet been defined in these models. Thus, the goal of this study is to develop and validate a large animal model of surgically induced DMM and to use multimodal (mechanical, histological, and magnetic resonance imaging) and multiscale (joint to tissue level) quantitative measures to evaluate degeneration in both the meniscus and cartilage. DMM was achieved using an arthroscopic approach in 13 Yucatan minipigs. One month after DMM, joint contact area decreased and peak pressure increased, indicating altered load transmission as a result of meniscus destabilization. By 3 months, the joint had adapted to the injury and load transmission patterns were restored to baseline, likely due to the formation and maturation of a fibrovascular scar at the anterior aspect of the meniscus. Despite this, we found a decrease in the indentation modulus of the tibial cartilage and an increase in cartilage histopathology scores at 1 month compared to sham-operated animals; these deleterious changes persisted through 3 months. Over this same time course, meniscus remodeling was evident through decreased proteoglycan staining in DMM compared to sham menisci at both 1 and 3 months. These findings support that arthroscopic DMM results in joint degeneration in the Yucatan minipig and provide a new large animal testbed in which to evaluate therapeutics and interventions to treat post-traumatic OA that originates from a meniscal injury.

Streamlining the evaluation of low back pain in children.

UNLABELLED: The workup of low back pain in children often results in overimaging so as not to miss organic back pain. The primary goal of this study was to identify which combination of imaging modalities provides the most sensitive and specific screening protocol for children with low back pain. Medical records from 100 consecutive patients between 2 and 18 years of age presenting with low back pain, without night pain or constitutional symptoms, were evaluated. A hyperextension test combined with a radiograph showed a negative predictive value of 0.81 and sensitivity of 0.90. The addition of a bone scan was highly effective in achieving good negative predictive value and sensitivity. Bone scans had perfect negative predictive value and sensitivity when symptom duration was less than 6 weeks. We identified a set of factors that is highly predictive for distinguishing organic back pain from mechanical back pain. Painless hyperextension combined with negative anteroposterior, lateral, and oblique lumbar radiographs and magnetic resonance images predicts mechanical back pain. For patients with nonneurologic back pain of less than 6 weeks duration, bone scan is the most useful screening test because it is accurate, accessible, inexpensive, and unlikely to require sedation. LEVEL OF EVIDENCE: Level III, diagnostic study.

Effect of interleukin-10 overexpression on the properties of healing tendon in a murine patellar tendon model.

PURPOSE: Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine shown to inhibit scar formation in fetal wound healing. The role of IL-10 in adult tendon healing and scar formation, however, remains unknown. The objective of this study is to investigate the effect of IL-10 overexpression on the properties of adult healing tendon using a well-established murine model of tendon injury and a lentiviral-mediated method of IL-10 overexpression. METHODS: A murine model of patellar tendon injury was used and animals divided into 3 groups. Mice received bilateral patellar tendon injections with a lentiviral vector containing an IL-10 transgene (n = 34) or no transgene (n = 34). Control mice (n = 34) received injections of sterile saline. All animals then were subjected to bilateral, central patellar tendon injuries 2 days after injection and were killed at 5, 10, 21, and 42 days after injury. IL-10 content was analyzed by immunohistochemistry (n = 4/group). Tendon healing was evaluated by histology (n = 4/group) and biomechanical analysis (n = 10/group). RESULTS: Overexpression of IL-10 in patellar tendon was confirmed after injection of the lentiviral vector. IL-10 immunostaining was increased at day 10 in the IL-10 group relative to that in controls. Histologically, there was no significant difference in angular deviation between groups at day 21, but a trend toward decreased angular deviation in controls relative to that in empty vector group mice was seen at day 42. Biomechanically, the IL-10 group showed significantly increased maximum stress at day 42 relative to that in controls. Percent relaxation showed a trend toward an increase at day 10 and a significant increase at day 42 in the IL-10 group relative to that in controls. CONCLUSIONS: This study demonstrates successful gene transfer of IL-10 into adult murine patellar tendon using a lentiviral vector. Although the effects of overexpression of IL-10 on adult tendon healing have not yet been fully elucidated, the current study may help to further clarify the mechanisms of tendon injury and repair.

Maturation State and Matrix Microstructure Regulate Interstitial Cell Migration in Dense Connective Tissues.

Few regenerative approaches exist for the treatment of injuries to adult dense connective tissues. Compared to fetal tissues, adult connective tissues are hypocellular and show limited healing after injury. We hypothesized that robust repair can occur in fetal tissues with an immature extracellular matrix (ECM) that is conducive to cell migration, and that this process fails in adults due to the biophysical barriers imposed by the mature ECM. Using the knee meniscus as a platform, we evaluated the evolving micromechanics and microstructure of fetal and adult tissues, and interrogated the interstitial migratory capacity of adult meniscal cells through fetal and adult tissue microenvironments with or without partial enzymatic digestion. To integrate our findings, a computational model was implemented to determine how changing biophysical parameters impact cell migration through these dense networks. Our results show that the micromechanics and microstructure of the adult meniscus ECM sterically hinder cell mobility, and that modulation of these ECM attributes via an exogenous matrix-degrading enzyme permits migration through this otherwise impenetrable network. By addressing the inherent limitations to repair imposed by the mature ECM, these studies may define new clinical strategies to promote repair of damaged dense connective tissues in adults.

Prevention and Management of Post-operative Complications Following ACL Reconstruction.

PURPOSE OF REVIEW: The goal of this paper is to review the current management and prevention of post-operative complications after anterior cruciate ligament (ACL) reconstruction. Trends in rehabilitation techniques will be presented, in addition to suggestions for interventions and expected milestones in ACL reconstruction recovery. RECENT FINDINGS: ACL reconstruction protocols have evolved to more of a criterion-based progression rather than a tissue-healing time frame. Given the evolution of ACL surgical reconstruction techniques and rehabilitation protocols, the risk of post-operative complications can arise both early and late in the recovery process. This paper will discuss the role of preventative measures as it applies to the post-operative patient with ACL reconstruction. Short-term complications following ACL reconstruction include infection and deficits to knee motion and strength, whereas long-term complications include secondary ACL injury to either the involved or contralateral knee and lack of ability to return to high-level sports following this procedure. Future research should continue to address the multifactorial causes of secondary ACL injury and limited ability of patients to return to high level activities.

Mechanical function near defects in an aligned nanofiber composite is preserved by inclusion of disorganized layers: Insight into meniscus structure and function.

The meniscus is comprised of circumferentially aligned fibers that resist the tensile forces within the meniscus (i.e., hoop stress) that develop during loading of the knee. Although these circumferential fibers are severed by radial meniscal tears, tibial contact stresses do not increase until the tear reaches ∼90% of the meniscus width, suggesting that the severed circumferential fibers still bear load and maintain the mechanical functionality of the meniscus. Recent data demonstrates that the interfibrillar matrix can transfer strain energy to disconnected fibrils in tendon fascicles. In the meniscus, interdigitating radial tie fibers, which function to stabilize and bind the circumferential fibers together, are hypothesized to function in a similar manner by transmitting load to severed circumferential fibers near a radial tear. To test this hypothesis, we developed an engineered fibrous analog of the knee meniscus using poly(ε-caprolactone) to create aligned scaffolds with variable amounts of non-aligned elements embedded within the scaffold. We show that the tensile properties of these scaffolds are a function of the ratio of aligned to non-aligned elements, and change in a predictable fashion following a simple mixture model. When measuring the loss of mechanical function in scaffolds with a radial tear, compared to intact scaffolds, the decrease in apparent linear modulus was reduced in scaffolds containing non-aligned layers compared to purely aligned scaffolds. Increased strains in areas adjacent to the defect were also noted in composite scaffolds. These findings indicate that non-aligned (disorganized) elements interspersed within an aligned network can improve overall mechanical function by promoting strain transfer to nearby disconnected fibers. This finding supports the notion that radial tie fibers may similarly promote tear tolerance in the knee meniscus, and will direct changes in clinical practice and provide guidance for tissue engineering strategies. STATEMENT OF SIGNIFICANCE: The meniscus is a complex fibrous tissue, whose architecture includes radial tie fibers that run perpendicular to and interdigitate with the predominant circumferential fibers. We hypothesized that these radial elements function to preserve mechanical function in the context of interruption of circumferential bundles, as would be the case in a meniscal tear. To test this hypothesis, we developed a biomaterial analog containing disorganized layers enmeshed regularly throughout an otherwise aligned network. Using this material formulation, we showed that strain transmission is improved in the vicinity of defects when disorganized fiber layers were present. This supports the idea that radial elements within the meniscus improve function near a tear, and will guide future clinical interventions and the development of engineered replacements.

Large Animal Models of Meniscus Repair and Regeneration: A Systematic Review of the State of the Field.

Injury to the meniscus is common, but few viable strategies exist for its repair or regeneration. To address this, animal models have been developed to translate new treatment strategies toward the clinic. However, there is not yet a regulatory document guiding such studies. The purpose of this study was to carry out a systematic review of the literature on meniscus treatment methods and outcomes to define the state of the field. Public databases were queried by using search terms related to animal models and meniscus injury and/or repair over the years 1980-2015. Identified peer-reviewed manuscripts were screened by using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. One of nine reviewers read each manuscript and scored them based on whether the publication described a series of predefined study descriptors and outcome measures. Additional data were extracted to identify common assays used. A total of 128 full-length peer-reviewed manuscripts were identified. The number of publications increased over the time frame analyzed, with 48% focused on augmented repair. Rabbit was, by far, the most prevalent species utilized (46%), with dog (21%) and sheep (20%) being the next most common. Analysis of study descriptors revealed that most studies appropriately documented details of the animal used, the surgical approach, and defect and implant characteristics (e.g., 63% of studies identified clearly the defect size). In terms of outcome parameters, most studies carried out macroscopic (85%), histologic (90%), and healing/integration (83%) analyses of the meniscus. However, many studies did not provide further analysis beyond these fundamental measures, and less than 40% reported on the adjacent cartilage and synovium, as well as joint function. There is intense interest in the field of meniscus repair. However, given the current lack of guidance documentation in this area, preclinical animal models are not performed in a standardized fashion. The development of a "Best Practices" document would increase reproducibility and external validity of experiments, while accelerating advancements in translational research. Advancement is of paramount importance given the high prevalence of meniscal injuries and the paucity of effective repair or regenerative strategies.

Interposition Dermal Matrix Xenografts: A Successful Alternative to Traditional Treatment of Massive Rotator Cuff Tears.

BACKGROUND: Management of massive rotator cuff tears in shoulders without glenohumeral arthritis remains problematic for surgeons. Repairs of massive rotator cuff tears have failure rates of 20% to 94% at 1 to 2 years postoperatively as demonstrated with arthrography, ultrasound, and magnetic resonance imaging. Additionally, inconsistent outcomes have been reported with debridement alone of massive rotator cuff tears, and limitations have been seen with other current methods of operative intervention, including arthroplasty and tendon transfers. HYPOTHESIS: The use of interposition porcine acellular dermal matrix xenograft in patients with massive rotator cuff tears will result in improved subjective outcomes, postoperative pain, function, range of motion, and strength. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Sixty patients (61 shoulders) were prospectively observed for a mean of 50.3 months (range, 24-63 months) after repair of massive rotator cuff tears with porcine acellular dermal matrix xenograft as an interposition graft. Subjective outcome data were obtained with visual analog scale for pain score (0-10, 0 = no pain) and Modified American Shoulder and Elbow Surgeons (MASES) score. Active range of motion in flexion, external rotation, and internal rotation were recorded. Strength in the supraspinatus and infraspinatus muscles was assessed manually on a 10-point scale and by handheld dynamometer. Ultrasound was used to assess the integrity of the repair during latest follow-up. RESULTS: Mean visual analog scale pain score decreased from 4.0 preoperatively to 1.0 postoperatively ( P < .001). Mean active forward flexion improved from 140.7° to 160.4° ( P < .001), external rotation at 0° of abduction from 55.6° to 70.1° ( P = .001), and internal rotation at 90° of abduction from 52.0° to 76.2° ( P < .001). Supraspinatus manual strength increased from 7.7 to 8.8 ( P < .001) and infraspinatus manual strength from 7.7 to 9.3 ( P < .001). Mean dynamometric strength in forward flexion was 77.7 N in nonoperative shoulders (shoulder that did not undergo surgery) and 67.8 N ( P < .001) in operative shoulders (shoulder that underwent rotator cuff repair with interposition porcine dermal matrix xenograft). Mean dynamometric strength in external rotation was 54.5 N in nonoperative shoulders and 50.1 N in operative shoulders ( P = .04). Average postoperative MASES score was 87.8. Musculoskeletal ultrasound showed that 91.8% (56 of 61) of repairs were fully intact; 3.3% (2 of 61), partially intact; and 4.9% (3 of 61), not intact. CONCLUSION: Patients who underwent repair of massive rotator cuff tears with interposition porcine acellular dermal matrix graft have good subjective function as assessed by the MASES score. Patients have significant improvement in pain, range of motion, and manual muscle strength. Postoperative ultrasound demonstrated that the repair was completely intact in 91.8% of patients, a vast improvement compared with results previously reported for primary repairs of massive rotator cuff tears.