Injectable, Self-Contained, Subaqueously Cross-Linking Laminous Adhesives for Biophysical-Chemical Modulation of Osteochondral Microenvironment

Current osteochondral (OC) defect repair approaches using premade scaffolds face clinical limitations due to invasiveness, weak integrity, and/or insufficient interfacial bonding. An injectable hydrophobic laminous adhesive is developed that rapidly photocross-link subaqueously and forms robust bi-layered structure that orchestrates biophysical-chemical cues for stimulating OC repair. Liquid hydrophobic photo-cross-linkable poly (lactide-co-propylene glycol-co-lactide) dimethacrylates (P(m)L(n)DMA) are adopted as cartilage phase and P(m)L(n)DMA encapsulating methacrylated hydroxyapatite nanoparticles (P(m)L(n)DMA/MH) as the mineralized subchondral bone phase. Both phases exhibit strong interfacial bonding due to the presence of "C(sic)C". Mechanotransduction and growth factor-mediated signaling pathways are enchanced by matching the mechanical properties of two phases to native cartilage and bone via systematical modulation of the adhesives' composition and encapsulated growth factors' release profile. This enhances mesenchymal stem cells' commitment to corresponding chondrocytes and osteoblasts to augment OC repair in vitro and in vivo, and ultimately benefits patients suffering from OC fracture, osteoarthritis, and osteoporosis.