Predicting severity of cartilage damage in a post-traumatic porcine model: Synovial fluid and gait in a support vector machine.

The inflammatory response to joint injury has been thought to play a key role in the development of osteoarthritis. In this preclinical study, we hypothesized that synovial fluid presence of inflammatory cytokines, as well as altered loading on the injured leg, would be associated with greater development of macroscopic cartilage damage after an ACL injury. Thirty-six Yucatan minipigs underwent ACL transection and were randomized to: 1) no further treatment, 2) ACL reconstruction, or 3) scaffold-enhanced ACL restoration.

Articular cartilage and synovium may be important sources of post-surgical synovial fluid inflammatory mediators.

The primary source of synovial fluid inflammatory mediators is currently unknown and may include different tissues comprising the joint, including the synovium and articular cartilage. Prior work in a porcine model has demonstrated that anterior cruciate ligament (ACL) surgery leads to significant changes in early gene expression in the synovium and articular cartilage, which are the same whether concomitant ligament restoration is performed or not. In this study, 36 Yucatan minipigs underwent ACL surgery, and a custom multiplex assay was used to measure synovial fluid protein levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-12, MMP-13, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, GM-CSF, and TNFα in 18 animals at 1 and 4 weeks after surgery.

Peripheral shift in the viable chondrocyte population of the medial femoral condyle after anterior cruciate ligament injury in the porcine knee.

Anterior cruciate ligament injuries result in posttraumatic osteoarthritis in the medial compartment of the knee, even after surgical treatment. How the chondrocyte distribution within the articular cartilage changes early in this process is currently unknown. The study objective was to investigate the chondrocyte distribution within the medial femoral condyle after an anterior cruciate ligament transection in a preclinical model.

Enrichment of inflammatory mediators in the synovial fluid is associated with slower progression of mild to moderate osteoarthritis in the porcine knee.

The roles that cytokines and matrix metalloproteinases play in the onset and progression of posttraumatic osteoarthritis (PTOA) remain a topic of debate. The study objective was to evaluate the concentrations of these inflammatory mediators during the development of mild to moderate PTOA in the porcine anterior cruciate ligament (ACL) surgical model. We hypothesized that there would be more animals with detectable mediators in the pigs that develop moderate PTOA (those receiving ACL reconstruction or untreated ACL transection) compared to those that develop mild PTOA (those receiving scaffold-enhanced ACL repair).

Terminal sterilization influences the efficacy of an extracellular matrix-blood composite for treating posttraumatic osteoarthritis in the rat model.

The objective was to determine if an intra-articular injection of an extracellular matrix (ECM) powder and blood composite (ECM-B) after anterior cruciate ligament (ACL) injury would have a mitigating effect on posttraumatic osteoarthritis and if that effect would be different with terminal sterilization of the ECM powder before use. Eighty Lewis rats underwent ACL transection and were divided into four groups: (1) intra-articular injection with phosphate-buffered saline (PBS; n = 20), (2) intra-articular injection of ECM-B using aseptically processed ECM (ASEPTIC; n = 20), (3) intra-articular injection of the ECM-busing ECM powder sterilized with 15 kGy electron beam irradiation (EBEAM; n = 20), and (4) intra-articular injection of the ECM-B using ECM powder sterilized with ethylene oxide (EO; n = 20). Twenty additional animals received capsulotomy only (SHAM).

Bridge-Enhanced Anterior Cruciate Ligament Repair Leads to Greater Limb Asymmetry and Less Cartilage Damage Than Untreated ACL Transection or ACL Reconstruction in the Porcine Model.

Background: The extent of posttraumatic osteoarthritis (PTOA) in the porcine anterior cruciate ligament (ACL) transection model is dependent on the surgical treatment selected. In a previous study, animals treated with bridge-enhanced ACL repair using a tissue-engineered implant developed less PTOA than those treated with ACL reconstruction (ACLR). Alterations in gait, including asymmetric weightbearing and shorter stance times, have been noted in clinical studies of subjects with osteoarthritis.

Neuromuscular function in anterior cruciate ligament reconstructed patients at long-term follow-up.

Background: The permanence of neuromuscular adaptations following anterior cruciate ligament reconstruction is not known. The aim of this study was to compare bilateral muscle co-contraction indices, time to peak ground reaction force, and timing of muscle onset between anterior cruciate ligament reconstruction subjects 10-15 years post reconstruction with those of matched uninjured controls during a one-leg hop landing.

Methods: Nine healthy controls and 9 reconstruction subjects were recruited.

Evaluation of Graft Tensioning Effects in Anterior Cruciate Ligament Reconstruction between Hamstring and Bone-Patellar Tendon Bone Autografts.

This article investigates the clinical, functional, and radiographic outcomes in anterior cruciate ligament (ACL) reconstruction patients over 7 years to determine the effects of initial graft tension on outcomes when using patellar tendon (bone-tendon-bone [BTB]) and hamstring tendon (HS) autografts. Ninety patients, reconstructed with BTB or HS, were randomized using two initial graft tension protocols: (1) normal anteroposterior (AP) laxity ("low-tension";  = 46) and (2) AP laxity overconstrained by 2 mm ("high-tension";  = 44). Seventy-two patients had data available at 7 years, with 9 excluded for graft failure.

SDF-1 preconditioned HPC scaffolds mobilize cartilage-derived progenitors and stimulate meniscal fibrocartilage repair in human explant tissue culture.

: The purpose of this study was to characterize the influence of SDF-1 on cell migration/adhesion and temporal gene expression of human cartilage mesenchymal progenitor cells (C-PCs); and to utilize SDF-1 conditioned mesenchymal progenitors to stimulate reintegration of human meniscus fibrocartilage breaks.: Characterization of SDF-1-induced cell migration was achieved using hydroxypropyl cellulose (HPC) scaffolds pretreated with SDF-1. Fluorescence microscopy and cell counting were used to visualize and quantify the extent of cell migration into scaffolds, respectively.

Cartilage Damage Is Related to ACL Stiffness in a Porcine Model of ACL Repair.

Inferior anterior cruciate ligament (ACL) structural properties may inadequately restrain tibiofemoral joint motion following surgery, contributing to the increased risk of post-traumatic osteoarthritis. Using both a direct measure of ACL linear stiffness and an in vivo magnetic resonance imaging (MRI) T *-based prediction model, we hypothesized that cartilage damage and ACL stiffness would increase over time, and that an inverse relationship between cartilage damage and ACL stiffness would emerge at a later stage of healing. After either 6, 12, or 24 weeks (w) of healing after ACL repair, ACL linear stiffness was determined from the force-displacement relationship during tensile testing ex vivo and predicted in vivo from the MRI T *-based multiple linear regression model in 24 Yucatan minipigs.

Anatomic Features of the Tibial Plateau Predict Outcomes of ACL Reconstruction Within 7 Years After Surgery.

Background: Multiple anatomic features of the femoral condyles and tibial plateau have been shown to influence knee biomechanics and risk of anterior cruciate ligament (ACL) injury. However, it remains unclear how these anatomic factors affect the midterm outcomes of ACL reconstruction.

Hypothesis: Decreased femoral notch width, increased posterior and coronal slopes, and decreased concavity of the tibial plateau are associated with inferior clinical, patient-reported, and osteoarthritis-related outcomes 7 years after ACL reconstruction.

Tibial tunnel widening following anterior cruciate ligament reconstruction: A retrospective seven-year study evaluating the effects of initial graft tensioning and graft selection.

Purpose: To investigate tibial tunnel widening in ACL reconstruction patients over seven years to establish the effects of initial graft tension on tibial widening and clinical outcomes when using both patellar tendon (BTB) and hamstring tendon (HS) grafts.

Methods: Ninety patients, who were reconstructed with BTB or HS autografts, were randomized using one of two initial graft tension protocols; 1) tensioned to restore normal anteroposterior laxity ("low-tension"; n = 46) and 2) tensioned to over-constrain anteroposterior (AP) laxity by two millimeters ("high-tension"; n = 44). Seventy patients had post-surgical data with 45 available for review at seven years.

Transcriptional profiling of synovium in a porcine model of early post-traumatic osteoarthritis.

To determine the transcriptional profile of synovium during the molecular phase of post-traumatic osteoarthritis, anterior cruciate ligament transections (ACL) were performed in 36 Yucatan minipigs. Equal numbers were randomly assigned to no further treatment, ACL reconstruction or repair. Perimeniscal synovium for histopathology and RNA-sequencing was harvested at 1 and 4 weeks post-operatively and from six healthy control animals.

Magnetic resonance measurements of tissue quantity and quality using T * relaxometry predict temporal changes in the biomechanical properties of the healing ACL.

Unlabelled: The purpose of this study was to develop a magnetic resonance T * relaxometry-based multiple linear regression model to predict the structural properties of the healing anterior cruciate ligament (ACL) over a 24-week healing period following ACL repair in Yucatan minipigs. Two hypotheses were tested: (i) that a regression model based on ACL sub-volumes containing short and long T * relaxation times would outperform a competing model based on sub-volumes of short T * relaxation times only; and (ii) that an optimized regression model would be capable of predicting ACL structural properties between 6 and 24 weeks post-repair. ACLs were imaged in 24 minipigs (8/group) at either 6, 12, or 24 weeks after ACL repair.

Transcriptional profiling of articular cartilage in a porcine model of early post-traumatic osteoarthritis.

To identify the molecular pathophysiology present in early post-traumatic osteoarthritis (PTOA), the transcriptional profile of articular cartilage and its response to surgical PTOA induction were determined. Thirty six Yucatan minipigs underwent anterior cruciate ligament (ACL) transection and were randomly assigned in equal numbers to no further treatment, reconstruction or ligament repair. Cartilage was harvested at 1 and 4 weeks post-operatively and histology and RNA-sequencing were performed and compared to controls.

Comparison of micro-CT post-processing methods for evaluating the trabecular bone volume fraction in a rat ACL-transection model.

Trabecular bone volume fraction assessments are likely sensitive to the analysis method and selection of the region of interest. Currently, there are several methods for selecting the region of interest to analyze trabecular bone in animal models of post-traumatic osteoarthritis. The objective of this study was to compare three published methods for determining the trabecular bone volume fraction of the medial tibial epiphyses in ACL transected and contralateral ACL intact knees.

Arthroscopic irrigation of the bovine stifle joint increases cartilage surface friction and decreases superficial zone lubricin.

The purpose of this study was to determine the effects of arthroscopic irrigation on cartilage superficial zone lubricin and surface friction. Arthroscopic partial meniscectomy is one of the most commonly performed orthopedic surgeries in the United States, but rates of osteoarthritis progression following this procedure are high. The effect of arthroscopic irrigation on articular surface lubrication has not been previously considered as a contributing factor in outcomes after arthroscopy.

Superficial zone cellularity is deficient in mice lacking lubricin: a stereoscopic analysis.

Background: Lubricin, a mucinous glycoprotein secreted by synoviocytes and chondrocytes plays an important role in reducing the coefficient of friction in mammalian joints. Elevated cartilage surface friction is thought to cause chondrocyte loss; however, its quantification and methodological approaches have not been reported. We adapted a stereological method and incorporated vital cell staining to assess cellular loss in superficial and upper intermediate zones in lubricin deficient mouse cartilage.