No abstract

The recent description of resident stem/progenitor cells in degenerated intervertebral discs (IVDs) supports the notion that their regenerative capacities could be harnessed to stimulate endogenous repair of the nucleus pulposus (NP). In this study, we developed a delivery system based on pullulan microbeads (PMBs) for sequential release of the chemokine CCL-5 to recruit these disc stem/progenitor cells to the NP tissue, followed by the release of the growth factors TGF-β1 and GDF-5 to induce the synthesis of a collagen type II-and aggrecan-rich extracellular matrix (ECM). Bioactivity of released CCL5 on human adipose-derived stem cells (hASCs), selected to mimic disc stem/progenitors, was demonstrated using a Transwell® chemotaxis assay. The regenerative effects of loaded PMBs were investigated in ex vivo spontaneously degenerated ovine IVDs. Fluorescent hASCs were seeded on the top cartilaginous endplates (CEPs); the degenerated NPs were injected with PMBs loaded with CCL5, TGF-β1, and GDF-5; and the IVDs were then cultured for 3, 7, and 28 days to allow for cell migration and disc regeneration. The PMBs exhibited sustained release of biological factors for 21 days. Ex vivo migration of seeded hASCs from the CEP toward the NP was demonstrated, with the cells migrating a significantly greater distance when loaded PMBs were injected (5.8 ± 1.3 mm vs. 3.5 ± 1.8 mm with no injection of PMBs). In ovine IVDs, the overall NP cellularity, the collagen type II and the aggrecan staining intensities, and the Tie2+ progenitor cell density in the NP were increased at day 28 compared to the control groups. Considered together, PMBs loaded with CCL5/TGF-β1/GDF-5 constitute an innovative and promising strategy for controlled release of growth factors to promote cell recruitment and extracellular matrix remodelling.

The knee laxity were compared between OA side and non-OA side using paired t-test at a¼0.05. Results: We found that the laxity of OA side is significantly higher (4.902 þ/-2.734 mm) than non-OA side (3.530 þ/-2.170 mm) at the 30lbs load condition (P<0.05). Conclusions: This pilot study is designed to use wearable sensors to measure knee laxity objectively in knee OA. Our results are consistent with previous studies in a similar range. We believe our pilot study results suggest that the wearable system can be a portable solution to monitor knee joint function of knee OA patients in various clinical settings and their responses to different types of clinical treatments.