Combinatorial mechanical gradation and growth factor biopatterning strategy for spatially controlled bone-tendon-like cell differentiation and tissue formation

Abstract Engineering scaffolds to augment the repair of hard-to-soft multitissue musculoskeletal tissue units, such as bone-tendon, simultaneously support healing and functional movement has had limited success. Overcoming this challenge will require not only precise spatial control bone- tendon-like biomechanical properties, but also consideration resultant cues, well embedded biochemical cues imparted by these scaffolds. Here, we report on effects a spatially engineered combination stiffness growth factor (GF) bone-tendon-like differentiation in vitro formation vivo. This was achieved using mechanically graded, QHM polyurethane (QHM: Q: Quadrol; H: hexamethylene diisocyanate; M: methacrylic anhydride) selectively biopatterned with osteogenic bone morphogenetic protein-2 (BMP-2) tenogenic fibroblast factor-2 (FGF-2). First, material characterization, including porosity, surface roughness, contact angle, microindentation measurements, performed. Second, studies demonstrated that increased promoted GF-mediated osteoblast reduced tenocyte differentiation. Sustained GF exposure masked effect. Third, vivo involving subcutaneous implantation graded biochemically patterned (composed tendon-promoting GFs biphasic tendon biomechanically mimicking regions) mice formation. Altogether, data provide new insights for future engineering repair.