A viscoelastic PEGylated poly(glycerol sebacate)-based bilayer scaffold for cartilage regeneration in full-thickness osteochondral defect. (September 2020) - Lin, Dan
Abstract: Defects of either articular cartilage or subchondral bone would destroy the structural integrity and functionality of the joint. Reconstruction of osteochondral defects requires difunctional scaffolds that simultaneously induce cartilage and subchondral bone morphogenesis, however, high-performance cartilage reconstructive scaffolds remain a considerable challenge. In this study, a solvent-free urethane crosslinking and spontaneous pore-forming procedure under room temperature was proposed and optimized to produce PEGylated poly(glycerol sebacate) (PEGS) scaffolds with controllable crosslinking degrees and hierarchical macro-/micro-porosities. Based on the economical and feasible preparative approach, the viscoelastic PEGS-12h with low crosslinking degree was demonstrated to significantly stimulate chondrogenic differentiation, maintain chondrocyte phenotype and enhance cartilage matrix secretion compared to elastic polymer with high crosslinking degree, emphasizing the importance of matrix viscoelasticity in cartilage regeneration. On this basis, the viscoelastic low-crosslinked PEGS-12h was combined with the well-acknowledged osteoinductive mesoporous bioactive glass (MBG) to construct a difunctional PEGS/MBG bilayer scaffold, and evaluated in a full-thickness osteochondral defect model in vivo . The PEGS/MBG bilayer scaffold successfully reconstructed well-integrated articular hyaline cartilage and its subchondral bone in 12 weeks, exhibiting extraordinary regenerative efficiency. The results indicated that the viscoelastic PEGS scaffold and PEGS/MBG bilayer scaffold proposed in this study made an excellent candidate for cartilage and osteochondral regeneration, and was expected for clinical translation in the future.