Principal Investigator Alan Grodzinsky
Repair of cartilage injuries remains a tremendous challenge, despite the development of surgical treatments such as microfracture and autologous chondrocyte implantation. These surgical procedures provide symptomatic relief of joint pain, but result in fibrous tissue that degenerates within several years. One of the fundamental challenges in the engineering of musculoskeletal tissues for regenerative medicine is the design of an appropriate 3-D scaffold, combined with an appropriate cell source. Our group is studying a biologically functional 3D-microenvironment for bone marrow stromal cells within self-assembling peptide hydrogel scaffolds that can stimulate chondrogenesis and cartilage neotissue production in vivo. Collaborations with clinical veterinary laboratories enable direct testing of our approach in small and large animal models of defect repair (rabbit and horse). Equine models of cartilage repair have been recognized to have specific advantages for translation to human cartilage resurfacing. The horse provides the closest approximation to humans in terms of cartilage thickness and mechanical loading, directly relevant to pre-clinical human studies. Recent discoveries have shown that binding and tethering of chondrogenic factors (TGF-β1, IGF-1) within the self-assembling peptide gels before assembly resulted in reversible adsorption and sustained delivery to encapsulated BMSCs, which then undergo chondrogenic differentiation. In addition, the peptide gel alone showed improved filling of full-thickness osteochondral defects and improved cartilage repair in rabbits.