In vivo and in vitro evaluation of an ECM-based OA therapy

Abstract

Osteoarthritis (OA) is a disease estimated to affect 10-12% of the adult US population and there are currently no clinically proven disease modifying therapies. Micronized dehydrated human amnion/chorion membrane (μ-dHACM) is an extracellular matrix (ECM)-based therapy that has been shown to attenuate OA progression in rats but many of the underlying mechanisms and design variables involved with μ-dHACM are not well understood. The primary objective of this proposed research is to investigate factors that influence the therapeutic benefit of potential disease modifying OA therapies. Specifically this work (i) developed a technological platform using contrast enhanced µCT to quantify cartilage surface roughness and utilized this platform to characterize early articular joint tissue changes in a rat OA model (Chapter 3), (ii) used contrast enhanced µCT and near-infrared fluorescent tracking to evaluate the effect of μ-dHACM particle size on the intra-articular residence time and therapeutic efficacy in a rat OA model (Chapter 4), and (iii) characterized and utilized synoviocyte and cartilage co-culture models to investigate the effect of interactions between synovium and μ-dHACM on OA disease progression (Chapter 5). This work increased the scientific community’s understanding of the factors influencing the efficacy of μ-dHACM treatment for OA. It also increased the characterization and understanding of the in vivo and in vitro models used to investigate these factors.