Osteoarthritis (OA) is the most common inflammatory and degenerative joint disease. Mesenchymal Stromal Cells (MSCs), with their chondro-protective and immune-regulatory properties, have been considered as a new approach to treat OA. Considering the risk of cell leakage outside the articular space and the poor survival rate after intra-articular (IA) injection, we hypothesized that cell encapsulation in cytoprotective hydrogels could overcome these limitations and provide cells with a suitable 3D microenvironment supporting their biological activity. We previously generated micromolded alginate particles (diameter 150 μm) and demonstrated the long-term viability of microencapsulated MSCs isolated from human adipose tissue (hASCs). Encapsulated cells maintained their in vitro ability to sense and respond to a pro-inflammatory environment (IFN-γ/TNF-α or synovial fluids from OA patients) by secreting PGE2, IDO, HGF and TGF-β. In this study, we evaluated the anti-OA efficacy of these microencapsulated hASCs in a post-traumatic OA model in rabbits. OA was surgically induced by anterior cruciate ligament transection (ACLT)-mediated destabilization of the right knee in rabbits (n=24). Eight weeks after surgery, destabilized joints were injected (IA, 26G needle) with 200 μL of either PBS, blank microparticles, non-encapsulated or microencapsulated cells (5×105 cells). Six weeks after injection, rabbits were euthanized and all destabilized (right) and sham-operated (left contralateral) joints were dissected and analyzed for OA severity. Tibial subchondral bone histomorphometric parameters were measured by quantitative micro-computed tomography (micro-CT). Histological sections of samples were analyzed after Safranin-O staining and quantitatively assessed according to a modified Osteoarthritis Research Society International (OARSI) scoring system. Immunohistochemical detection of NITEGE was performed to assess the extracellular matrix degradation.Introduction and Objective
Materials and Methods
The aim of an anterior cruciate ligament (ACL) reconstruction is to regain functional stability of the knee following ACL injury, ideally allowing patients to return to their pre-injury level of activity. The purpose of this study was to assess clinical, functional and patient-reported outcomes following primary ACL reconstruction with hamstring autograft. A prospective case-series design (n=1610) was used to gather data on post-operative ACL graft laxity, functional testing performance and scores on the ACL quality of life (ACL-QOL) questionnaire. Demographic data were collected for all patients. Post-operative ACL laxity assessment using the Lachman and Pivot-shift tests was completed independently on each patient by a physiotherapist and an orthopaedic surgeon at the 6-, 12- and 24-months post-operative appointments. A battery of functional tests was also assessed including single leg Bosu balance, and 4 single-leg hop tests. The hop tests provided a comparative assessment of limb-to-limb function. Patients completed the ACL-QOL at all time points. The degree and frequency of post-operative laxity was calculated. A Spearman's rank correlation matrix was undertaken to assess for relationships between post-operative laxity, functional test performance, and the ACL-QOL scores. A linear regression model was used to assess for relationships between the ACL-QOL scores, as well as the functional testing results, and patient demographic factors. ACLR patients were 55% male, with a mean age of 29.7 years (SD=10.4), mean BMI of 25 (SD=3.9), and mean Beighton score of 3.3 (SD=2.5). At clinical assessment 2-years post-operatively, 20.6% of patients demonstrated a positive Lachman test and 7.7% of patients demonstrated a positive Pivot-shift test. The mean ACL-QOL score was 28.6/100 (SD=13.4) pre-operatively, 58.2/100 (SD=17.6) at 6-months, 71.8/100 (SD=18.1) at 12-months, and 77.4/100 (SD=19.2) at 24-months post-operative. Functional tests assessing operative to non-operative limb performance demonstrated that patients were continuing to improve up to the 24-month mark, with limb symmetry indices ranging from 96.6–103.1 for the single-leg hop tests. Spearman's correlation coefficient demonstrated a significant relationship between the presence of ACL graft laxity and ACL-QOL score at 12- and 24-months post-operative (p < 0 .05). Functional performance on the single leg balance and single-leg hop tests demonstrated significant correlations to the 6-, 12- and 24-month ACL-QOL scores (p < 0 .05). There was no statistically significant correlation between the functional testing results and the presence of ACL graft laxity. This study demonstrated that up to 20.6% of patients had clinically measurable graft laxity 2-years after ACLR. In this cohort, patients with graft laxity demonstrated lower ACL-QOL scores, but did not demonstrate lower functional testing performance. Patient-reported ACL-QOL scores improved significantly at each time point following ACLR, and functional performance continued to improve up to 2-years after surgery. The ACL-QOL score was strongly correlated to the patient's ability to perform single-limb functional tests, indicating that the ACL-QOL score accurately predicted level of function.
