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

摘要

Current osteochondral (OC) defect repair approaches using premade scaffoldsface clinical limitations due to invasiveness, weak integrity, and/or insufficient interfacial bonding. An injectable hydrophobic laminousadhesive is developed that rapidly photocross-link subaqueously and formsrobust bi-layered structure that orchestrates biophysical-chemical cues forstimulating OC repair. Liquid hydrophobic photo-cross-linkable poly (lactideco-propylene glycol-co-lactide) dimethacrylates (P_mL_nDMA) are adopted ascartilage phase and P_mL_nDMA encapsulating methacrylated hydroxyapatitenanoparticles (P_mL_nDMA/MH) as the mineralized subchondral bonephase. Both phases exhibit strong interfacial bonding due to the presence of“C=C”. Mechanotransduction and growth factor-mediated signaling pathwaysare enchanced by matching the mechanical properties of two phasesto native cartilage and bone via systematical modulation of the adhesives’composition and encapsulated growth factors’ release profile. This enhancesmesenchymal stem cells’ commitment to corresponding chondrocytes andosteoblasts to augment OC repair in vitro and in vivo, and ultimately benefitspatients suffering from OC fracture, osteoarthritis, and osteoporosis.