Enhanced osteochondral repair by leukocyte-depleted platelet-rich plasma in combination with adipose-derived mesenchymal stromal cells encapsulated in a three-dimensional photocrosslinked injectable hydrogel in a rabbit model.

INTRODUCTION: Intra-articular injection of adipose-derived mesenchymal stromal cells (ASCs) and/or platelet-rich plasma (PRP) have been reported to independently and synergistically improve healing of osteochondral lesions in animal models. However, their independent and combined effects when localized to an osteochondral lesion by encapsulation within a photocrosslinkable methacrylated gelatin hydrogel (GelMA) have not been explored. Herein we investigated a unique combination of allogeneic ASCs and PRP embedded in GelMA as a single-stage treatment for osteochondral regeneration in a rabbit model. METHODS: Thirty mature rabbits were divided into six experimental groups: (1) Sham; (2) Defect; (3) GelMA; (4) GelMA + ASCs; (5) GelMA + PRP; and (6) GelMA + ASCs + PRP.At 12 weeks following surgical repair, osteochondral regeneration was assessed on the basis of gross appearance, biomechanical properties, histological and immunohistochemical characteristics, and subchondral bone volume. RESULTS: In terms of mechanical property reflecting the ability of neotissue to bear stress, PRP only group were significantly lower than the Sham group (p = 0.0098). On the other hand, ASCs only and ASCs combined with PRP groups did not exhibit significantly difference, which suggesting that incorporation of ASCs assists in restoring the ability of the neotissue to bear stresses similarly to native tissue (p = 0.346, p = 0.40, respectively). Safranin O in ASCs combined with PRP group was significantly higher than the Defect and GelMA only groups (p = 0.0009, p = 0.0017, respectively). Additionally, ASCs only and ASCs combined with PRP groups presented especially strong staining for collagen type II. Surprisingly, PRP only and PRP + ASCs groups tended to exhibit higher collagen type I and collagen type X staining compared to ASCs only group, suggesting a potential PRP-mediated hypertrophic effect. CONCLUSION: Regeneration of a focal osteochondral defect in a rabbit model was improved by a single-stage treatment of a photocrosslinked hydrogel containing allogenic ASCs and autologous PRP, with the combination of ASCs and PRP producing superior benefit than either alone. No experimental construct fully restored all properties of the native, healthy osteochondral unit, which may require longer follow-up or further modification of PRP and/or ASCs characteristics.

Minimum 10-Year Clinical Outcomes After Arthroscopic Capsulolabral Repair for Isolated Posterior Shoulder Instability.

BACKGROUND: Arthroscopic capsulolabral repair for posterior shoulder instability has been shown to improve patient-reported outcomes and return to sport at short-term and midterm follow-up, but long-term outcomes are unknown. PURPOSE: To determine the objective and subjective clinical outcomes of shoulder function after arthroscopic posterior shoulder stabilization at a minimum 10-year follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 53 patients (55 shoulders) with unidirectional recurrent posterior shoulder instability who underwent arthroscopic capsulolabral repair were evaluated at a mean follow-up of 15.4 years. Outcomes such as the American Shoulder and Elbow Surgeons (ASES) shoulder score, Kerlan-Jobe Orthopaedic Clinic shoulder and elbow score, and subjective strength, stability, range of motion, and pain were evaluated preoperatively and postoperatively at a minimum 10-year follow-up. Outcomes from the same patient cohort were previously collected at 3.0-year follow-up and were evaluated for longitudinal analysis. Subgroup analyses for sport type (contact vs noncontact), position (thrower vs nonthrower), and revision versus nonrevision were performed. Risk factors for revision surgery based on magnetic resonance imaging findings, patient characteristics, and surgical findings were investigated. RESULTS: Arthroscopic capsulolabral repair for posterior shoulder instability led to a statistically significant improvement on all outcome measures, with similar values at short-term (3.0-year) and long-term (15.4-year) follow-up. Across the total population, patients with 19 of 55 shoulders (35%) returned to sport at the same preinjury level, and patients with 33 of 55 shoulders (60%) returned to sport at some level. At long-term follow-up, patients with only 22% of shoulders were involved in the primary sport in which the injury was sustained, with patients with 28% of shoulders discontinuing sporting participation because of ongoing shoulder issues. Throwers trended toward lower Kerlan-Jobe Orthopaedic Clinic scores than nonthrowers both preoperatively (36.5 ± 22.8 vs 48.7 ± 22.9, respectively; P = .10) and postoperatively (57.4 ± 27.0 vs 73.5 ± 26.8, respectively; P = .09) but had similar improvements. Contact and noncontact athletes had similar preoperative and postoperative values, with equal improvements after surgery. With failure defined as revision surgery, an ASES score <60, or a stability value >5, 19 of 55 shoulders (35%) met failure criteria at final follow-up. Overall, 7 of 55 shoulders (13%) underwent revision surgery. At long-term follow-up, patients who underwent revision surgery had worse outcomes than those who did not undergo revision (ASES score: 53.1 ± 25.9 vs 81.8 ± 19.4, respectively; P < .001). An acute injury in the postoperative period (P < .001) and a smaller glenoid bone width on magnetic resonance imaging (P = .02) were the only identified risk factors for revision surgery. CONCLUSION: Arthroscopic capsulolabral repair for posterior shoulder instability was a durable treatment option that improved long-term shoulder pain and function and facilitated return to sport in the majority of patients at a mean follow-up of 15.4 years, although a notable proportion of patients met various criteria for failure.

Mechanotransduction pathways in articular chondrocytes and the emerging role of estrogen receptor-α.

In the synovial joint, mechanical force creates an important signal that influences chondrocyte behavior. The conversion of mechanical signals into biochemical cues relies on different elements in mechanotransduction pathways and culminates in changes in chondrocyte phenotype and extracellular matrix composition/structure. Recently, several mechanosensors, the first responders to mechanical force, have been discovered. However, we still have limited knowledge about the downstream molecules that enact alterations in the gene expression profile during mechanotransduction signaling. Recently, estrogen receptor α (ERα) has been shown to modulate the chondrocyte response to mechanical loading through a ligand-independent mechanism, in line with previous research showing that ERα exerts important mechanotransduction effects on other cell types, such as osteoblasts. In consideration of these recent discoveries, the goal of this review is to position ERα into the mechanotransduction pathways known to date. Specifically, we first summarize our most recent understanding of the mechanotransduction pathways in chondrocytes on the basis of three categories of actors, namely mechanosensors, mechanotransducers, and mechanoimpactors. Then, the specific roles played by ERα in mediating the chondrocyte response to mechanical loading are discussed, and the potential interactions of ERα with other molecules in mechanotransduction pathways are explored. Finally, we propose several future research directions that may advance our understanding of the roles played by ERα in mediating biomechanical cues under physiological and pathological conditions.

Freddie Fu: A Leader of Leaders.

Freddie Fu had a profound and undeniable impact on the field of orthopaedic surgery. He was a leader both personally and professionally and dedicated his career to ensuring that those around him had the opportunity to thrive. His life and career were distinguished by his exceptional leadership, boundless collaboration, and dedication to diversity. Freddie Fu's ability to train future leaders represents one of his greatest professional legacies, which will continue to permeate the field of orthopaedic surgery for decades to come. He was a giant, and those fortunate enough to train under him are better because of it.

Preoperative ultrasound predicts the intraoperative diameter of the quadriceps tendon autograft more accurately than preoperative magnetic resonance imaging for anterior cruciate ligament reconstruction.

PURPOSE: Sizing of potential autografts is essential to match the native anterior cruciate ligament (ACL) dimensions when performing ACL reconstruction (ACLR). We aimed to investigate the accuracy and reliability of the thickness and cross-sectional area (CSA) assessments for the prediction of the intraoperative diameter of the QT autograft using preoperative ultrasound and MRI. METHODS: Thirty patients (mean age ± standard deviation, 19.9 ± 5.0 years), who underwent ACLR using QT autograft, were included. The maximum thickness of the QT was assessed at 15 and 30 mm proximal using ultrasound with a long axis image, and at 15 mm proximal to the superior pole of the patella using MRI with a sagittal image. The CSA was assessed at the central 10 mm of the medial-lateral QT width at 30 mm proximal using ultrasound with a short axis image, and at 15 mm proximal to the superior pole of the patella using MRI with an axial image. Intraoperatively, QT autograft was harvested with a 10 mm width and the diameter was measured using a graft sizing device. RESULTS: Intra- and inter-observer reliabilities of all measurements using ultrasound and MRI were good (Intra-class correlation coefficient, 0.720-0.941). Correlation coefficient with the intraoperative diameter of the QT autograft was higher in ultrasound (R = 0.738-0.791, P < 0.001) than MRI (R = 0.449-0.543, P = 0.002-0.013). CONCLUSIONS: Preoperative ultrasound predicted the intraoperative diameter of the QT autograft more accurately than MRI. Ultrasound may be used clinically to assure a sufficiently large QT autograft diameter to match the diameter of the patient's native ACL. LEVEL OF EVIDENCE: Level III.

Two-fragment Segond fracture validates historical descriptions of independent soft tissue attachments.

This is a case report of a 26-year-old male who sustained a Segond fracture in the context of an acute anterior cruciate ligament (ACL) rupture incurred while downhill skiing. Further work-up revealed that the Segond fracture consisted of two distinct fragments with separate soft tissue attachments, including the capsule-osseous layer of the iliotibial band and the short arm of the biceps femoris. Imaging showed interval healing of the Segond fracture between initial presentation and the performance of arthroscopic ACL reconstruction approximately 4 months later. As intraoperative evaluation demonstrated that anatomic ACL reconstruction restored translational and rotatory knee stability, surgical repair of the Segond fracture, or the anterolateral complex of the knee more broadly, was not required. Maintenance of translational and rotatory knee stability was confirmed at serial post-operative appointments up through final follow-up.Level of evidence Level V.

Superb microvascular imaging (SMI) detects increased vascularity of the torn anterior cruciate ligament.

PURPOSE: Ultrasound with superb microvascular imaging (SMI) is a novel microvascular imaging technology which may be useful to assess the vascularity of the torn anterior cruciate ligament (ACL) as a potential measure of healing potential following surgery. This study aimed to quantify the vascularity of the torn and intact ACL using ultrasound with SMI. METHODS: 23 patients (mean age ± standard deviation, 27.1 ± 12.8 years), who were diagnosed with an ACL tear with an intact contralateral ACL were enrolled (ACL injury group). Ten healthy volunteers (36.1 ± 4.9 years) who had intact ACLs in both knees were also recruited (ACL healthy controls). The vascularity of the ACL was assessed using SMI within 15 mm from the tibial insertion in both knees. The amount of the vascular signal was assessed using a semi-quantitative grading scale (vascularity grade: grade 0-3) and a quantified ratio of vascularized area with respect to total area of the region of interest (vascularity ratio). RESULTS: In the ACL injury group, a significantly higher vascularity grade and ratio were observed in the torn ACL (vascularity grade 0-3: 1, 8, 7, and 7 patients, respectively; vascularity ratio: 1.3 ± 1.4%) than the contralateral intact ACL (vascularity grade 0-3: 21, 1, 1, and 0 patients, respectively; vascularity ratio: 0.1 ± 0.5%) (P < 0.001), whereas no significant difference was observed between both ACLs in the ACL healthy control group. CONCLUSIONS: SMI was useful to assess the increased vascularity in torn ACL, which may reflect the potential for, or state of, ACL maturation following reconstruction or repair. LEVEL OF EVIDENCE: Level III.

Treatment after anterior cruciate ligament injury: Panther Symposium ACL Treatment Consensus Group.

Treatment strategies for anterior cruciate ligament (ACL) injuries continue to evolve. Evidence supporting best practice guidelines for the management of ACL injury is to a large extent based on studies with low-level evidence. An international consensus group of experts was convened to collaboratively advance towards consensus opinions regarding the best available evidence on operative versus non-operative treatment for ACL injury.The purpose of this study was to report the consensus statements on operative versus non-operative treatment of ACL injuries developed at the ACL Consensus Meeting Panther Symposium 2019. Sixty-six international experts on the management of ACL injuries, representing 18 countries, convened and participated in a process based on the Delphi method of achieving consensus. Proposed consensus statements were drafted by the Scientific Organising Committee and Session Chairs for the three working groups. Panel participants reviewed preliminary statements prior to the meeting and provided initial agreement and comments on the statement via online survey. During the meeting, discussion and debate occurred for each statement, after which a final vote was then held. Eighty per cent agreement was defined a priori as consensus. A total of 11 of 13 statements on operative veresus non-operative treatment of ACL injury reached consensus during the symposium. Nine statements achieved unanimous support; two reached strong consensus; one did not achieve consensus; and one was removed due to redundancy in the information provided.In highly active patients engaged in jumping, cutting and pivoting sports, early anatomical anterior cruciate ligament reconstruction (ACLR) is recommended due to the high risk of secondary meniscus and cartilage injuries with delayed surgery, although a period of progressive rehabilitation to resolve impairments and improve neuromuscular function is recommended. For patients who seek to return to straight plane activities, non-operative treatment with structured, progressive rehabilitation is an acceptable treatment option. However, with persistent functional instability or when episodes of giving way occur, anatomical ACLR is indicated. The consensus statements derived from international leaders in the field will assist clinicians in deciding between operative and non-operative treatment with patients after an ACL injury.Level of evidence: V.

In situ cross-sectional area of the quadriceps tendon using preoperative magnetic resonance imaging significantly correlates with the intraoperative diameter of the quadriceps tendon autograft.

PURPOSE: Preoperative assessment to determine the sizes of potential autografts is necessary for individualized anterior cruciate ligament reconstruction (ACLR). However, no study has investigated the prediction of the intraoperative diameter of the quadriceps tendon (QT) autograft based upon preoperative imaging. This study investigated the correlation between the intraoperative diameter of a QT autograft and in situ thickness or cross-sectional area (CSA) measured using preoperative MRI. METHODS: Thirty-one knees of 31 patients (mean age 20.9 ± 5.0 years) who underwent individualized anatomic ACLR using all soft tissue QT autograft were included retrospectively. At 15 mm proximal to the superior pole of the patella, the maximum QT thickness was assessed in the sagittal plane and the CSA was assessed at the central 10 mm of the QT in the axial plane. The angle between the axial plane and a line perpendicular to the QT longitudinal axis was used to calculate an adjusted CSA using a cosine function. Intraoperatively, each QT autograft was harvested with 10 mm width and the diameter was measured using a graft sizing device. RESULTS: Intra- and inter-observer reliabilities of all measurements using preoperative MRI were excellent (intra-class correlation coefficient, 0.833-0.970). Significant correlations were observed between the thickness, CSA, or adjusted CSA, and the intraoperative diameter (R = 0.434, 0.607, and 0.540, respectively; P < 0.05). CONCLUSIONS: The CSA correlated most strongly with the QT autograft diameter. For individualized anatomic ACLR, measuring in situ CSA can be useful for preoperative planning of appropriate graft choices prior to surgery. LEVEL OF EVIDENCE: III.

Clinical studies of single-stage combined ACL and PCL reconstruction variably report graft tensioning, fixation sequence, and knee flexion angle at time of fixation.

PURPOSE: In single-stage ACL-PCL reconstruction, there is uncertainty regarding the order of graft tensioning and fixation, as well as the optimal knee flexion angle(s) for graft fixation. A systematic review of clinical studies of single-stage combined ACL-PCL reconstruction was performed to determine whether a particular fixation sequence and/or knee flexion angle is associated with superior outcomes. METHODS: A systematic review was performed according to PRISMA guidelines. All levels of evidence were included. All outcome measures were extracted, including physical examination values, radiographic measurements, and objective and subjective outcomes. RESULTS: Of the 19 included studies, 17 tensioned and fixed the PCL before the ACL. Only four studies reported the methods/forces used for graft tensioning. Across studies, the ACL was fixed at variable knee flexion angles, from full extension to 70°. Conversely, 3 studies fixed the PCL at a knee flexion angle < 45°, while the remaining 16 studies fixed the PCL at a flexion angle > 70°. Patient-reported outcomes were qualitatively similar between groups. CONCLUSIONS: This systematic review found considerable variability in graft tension, fixation sequence, and knee flexion angle at the time of fixation, with insufficient evidence to support specific surgical practices. Most commonly, the PCL is fixed before the ACL graft, with fixation occurring at a knee flexion angle between 70° and 90° and near full extension, respectively. The methodology for quantifying the forces applied for graft tensioning is rarely described. Given this clinical equipoise, future studies should consistently report these surgical details. Furthermore, prospective, randomized studies on the treatment of multiligament knee injuries are needed to improve outcomes in patients. LEVEL OF EVIDENCE: IV.

Clinical outcomes after anterior cruciate ligament injury: panther symposium ACL injury clinical outcomes consensus group.

PURPOSE: A stringent outcome assessment is a key aspect for establishing evidence-based clinical guidelines for anterior cruciate ligament (ACL) injury treatment. The aim of this consensus statement was to establish what data should be reported when conducting an ACL outcome study, what specific outcome measurements should be used and at what follow-up time those outcomes should be assessed. METHODS: To establish a standardized approach to assessment of clinical outcome after ACL treatment, a consensus meeting including a multidisciplinary group of ACL experts was held at the ACL Consensus Meeting Panther Symposium, Pittsburgh, PA; USA, in June 2019. The group reached consensus on nine statements by using a modified Delphi method. RESULTS: In general, outcomes after ACL treatment can be divided into four robust categories-early adverse events, patient-reported outcomes, ACL graft failure/recurrent ligament disruption and clinical measures of knee function and structure. A comprehensive assessment following ACL treatment should aim to provide a complete overview of the treatment result, optimally including the various aspects of outcome categories. For most research questions, a minimum follow-up of 2 years with an optimal follow-up rate of 80% is necessary to achieve a comprehensive assessment. This should include clinical examination, any sustained re-injuries, validated knee-specific PROs and Health-Related Quality of Life questionnaires. In the mid- to long-term follow-up, the presence of osteoarthritis should be evaluated. CONCLUSION: This consensus paper provides practical guidelines for how the aforementioned entities of outcomes should be reported and suggests the preferred tools for a reliable and valid assessment of outcome after ACL treatment. LEVEL OF EVIDENCE: V.

Treatment After Anterior Cruciate Ligament Injury: Panther Symposium ACL Treatment Consensus Group.

Treatment strategies for anterior cruciate ligament (ACL) injuries continue to evolve. Evidence supporting best-practice guidelines for the management of ACL injury is to a large extent based on studies with low-level evidence. An international consensus group of experts was convened to collaboratively advance toward consensus opinions regarding the best available evidence on operative versus nonoperative treatment for ACL injury. The purpose of this study was to report the consensus statements on operative versus nonoperative treatment of ACL injuries developed at the ACL Consensus Meeting Panther Symposium 2019. There were 66 international experts on the management of ACL injuries, representing 18 countries, who were convened and participated in a process based on the Delphi method of achieving consensus. Proposed consensus statements were drafted by the scientific organizing committee and session chairs for the 3 working groups. Panel participants reviewed preliminary statements before the meeting and provided initial agreement and comments on the statement via online survey. During the meeting, discussion and debate occurred for each statement, after which a final vote was then held. Ultimately, 80% agreement was defined a priori as consensus. A total of 11 of 13 statements on operative versus nonoperative treatment of ACL injury reached consensus during the symposium. Overall, 9 statements achieved unanimous support, 2 reached strong consensus, 1 did not achieve consensus, and 1 was removed because of redundancy in the information provided. In highly active patients engaged in jumping, cutting, and pivoting sports, early anatomic ACL reconstruction is recommended because of the high risk of secondary meniscal and cartilage injuries with delayed surgery, although a period of progressive rehabilitation to resolve impairments and improve neuromuscular function is recommended. For patients who seek to return to straight-plane activities, nonoperative treatment with structured, progressive rehabilitation is an acceptable treatment option. However, with persistent functional instability, or when episodes of giving way occur, anatomic ACL reconstruction is indicated. The consensus statements derived from international leaders in the field will assist clinicians in deciding between operative and nonoperative treatment with patients after an ACL injury.

Editorial Commentary: The Segond Fracture Has Multiple Attachments: Yet Another Demonstration of the Anatomical Complexity of the Anterolateral Complex of the Knee.

The anterolateral complex (ALC) of the knee comprises multiple layers, with continued debate on the identity and function of the structures of the ALC. The Segond fracture, long considered pathognomonic of an anterior cruciate ligament injury, has now been shown to have several attachments to soft tissues of the ALC. To the extent that a Segond fracture, or injury to the ALC more broadly, increases knee rotatory instability in vivo is a question of ongoing investigation. By extension, it remains uncertain whether an untreated Segond fracture adversely affects outcomes and therefore warrants consideration for operative intervention. Prospective randomized studies of anatomic anterior cruciate ligament reconstruction with or without concomitant treatment of Segond fractures are needed to more definitively answer these questions.

Decellularized bone extracellular matrix in skeletal tissue engineering.

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms - whole organ, particles, hydrogels - has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

Treatment after anterior cruciate ligament injury: Panther Symposium ACL Treatment Consensus Group.

Treatment strategies for anterior cruciate ligament (ACL) injuries continue to evolve. Evidence supporting best practice guidelines for the management of ACL injury is to a large extent based on studies with low-level evidence. An international consensus group of experts was convened to collaboratively advance toward consensus opinions regarding the best available evidence on operative vs. non-operative treatment for ACL injury. The purpose of this study is to report the consensus statements on operative vs. non-operative treatment of ACL injuries developed at the ACL Consensus Meeting Panther Symposium 2019. Sixty-six international experts on the management of ACL injuries, representing 18 countries, were convened and participated in a process based on the Delphi method of achieving consensus. Proposed consensus statements were drafted by the Scientific Organizing Committee and Session Chairs for the three working groups. Panel participants reviewed preliminary statements prior to the meeting and provided the initial agreement and comments on the statement via an online survey. During the meeting, discussion and debate occurred for each statement, after which a final vote was then held. Eighty percent agreement was defined a-priori as consensus. A total of 11 of 13 statements on operative v. non-operative treatment of ACL injury reached the consensus during the Symposium. Nine statements achieved unanimous support, two reached strong consensus, one did not achieve consensus, and one was removed due to redundancy in the information provided. In highly active patients engaged in jumping, cutting, and pivoting sports, early anatomic ACL reconstruction is recommended due to the high risk of secondary meniscus and cartilage injuries with delayed surgery, although a period of progressive rehabilitation to resolve impairments and improve neuromuscular function is recommended. For patients who seek to return to straight plane activities, non-operative treatment with structured, progressive rehabilitation is an acceptable treatment option. However, with persistent functional instability, or when episodes of giving way occur, anatomic ACL reconstruction is indicated. The consensus statements derived from international leaders in the field will assist clinicians in deciding between operative and non-operative treatments with patients after an ACL injury.Level of evidence V.

Tendon-derived extracellular matrix induces mesenchymal stem cell tenogenesis via an integrin/transforming growth factor-ß crosstalk-mediated mechanism.

Treatment of tendon injuries is challenging. To develop means to augment tendon regeneration, we have previously prepared a soluble, low immunogenic (DNA-free), tendon extracellular matrix fraction (tECM) by urea extraction of juvenile bovine tendons, which is capable of enhancing transforming growth factor-ß (TGF-ß) mediated tenogenesis in human adipose-derived stem cells (hASCs). Here, we aimed to elucidate the mechanism of tECM-driven hASC tenogenic differentiation in vitro, focusing on the integrin and TGF-ß/SMAD pathways. Our results showed that tECM promoted hASC proliferation and tenogenic differentiation in vitro based on tenogenesis-associated markers. tECM also induced higher expression of several integrin subunits and TGF-ß receptors, and nuclear translocation of p-SMAD2 in hASCs. Pharmacological inhibition of integrin-ECM binding, focal adhesion kinase (FAK) signaling, or TGF-ß signaling independently led to compromised pro-tenogenic effects of tECM and actin fiber polymerization. Additionally, integrin blockade inhibited tECM-driven TGFBR2 expression, while inhibiting TGF-ß signaling decreased tECM-mediated expression of integrin α1, α2, and ß1 in hASCs. Together, these findings suggest that the strong pro-tenogenic bioactivity of tECM is regulated via integrin/TGF-ß signaling crosstalk. Understanding how integrins interact with signaling by TGF-ß and/or other growth factors (GFs) within the tendon ECM microenvironment will provide a rational basis for an ECM-based approach for tendon repair.

Return to sport after anterior cruciate ligament injury: Panther Symposium ACL Injury Return to Sport Consensus Group.

PURPOSE: A precise and consistent definition of return to sport (RTS) after anterior cruciate ligament (ACL) injury is lacking, and there is controversy surrounding the process of returning patients to sports and their previous activity level. The aim of the Panther Symposium ACL Injury RTS Consensus Group was to provide a clear definition of RTS and description of the RTS continuum, as well as to provide clinical guidance on RTS testing and decision-making. METHODS: An international, multidisciplinary group of ACL experts convened as part of a consensus meeting. Consensus statements were developed using a modified Delphi method. Literature review was performed to report the supporting evidence. RESULTS: Key points include that RTS is characterized by achievement of the pre-injury level of sport and involves a criteria-based progression from return to participation to return to sport, and ultimately return to performance. Purely time-based RTS decision-making should be abandoned. Progression occurs along a RTS continuum with decision-making by a multidisciplinary group that incorporates objective physical examination data and validated and peer-reviewed RTS tests, which should involve functional assessment as well as psychological readiness. Consideration should be given to biological healing, contextual factors and concomitant injuries. CONCLUSION: The resultant consensus statements and scientific rationale aim to inform the reader of the complex process of RTS after ACL injury that occurs along a dynamic continuum. Research is needed to determine the ideal RTS test battery, the best implementation of psychological readiness testing and methods for the biologic assessment of healing and recovery. LEVEL OF EVIDENCE: IV.