Biphasic CK2.1-coated β-glycerophosphate chitosan/LL37-modified layered double hydroxide chitosan composite scaffolds enhance coordinated hyaline cartilage and subchondral bone regeneration

Abstract Articular osteochondral defect is commonly seen after trauma or in patients with degenerative osteoarthritis. Currently, the treatment of osteochondral lesions is still challenging due to the limited healing ability of cartilage as well as the poorly effective traditional method. In this study, we fabricated a bilayer peptide-loaded scaffold consisting of CK2.1 coated β-glycerophosphate/chitosan (CK2.1@GC) for cartilage regeneration and LL37 modified layered double hydroxide/chitosan (LL37@LC) for subchondral bone regeneration, designed in an integrated strategy involving mesenchymal stem cells (MSCs) recruitment and multifunctional therapeutic biomaterials of bone regeneration and vascularization. The lower LC scaffold is highlighted with a biomimetic lamellar structural design, providing a novel platform for the integration of newborn bone tissue and blood vessels. In vitro results showed our peptide-loaded bilayer scaffold could induce the MSCs to differentiate into chondrocytes and osteoblasts in different layers respectively. LL37@LC could also attract MSCs and promote vasculogenesis in vitro. Meanwhile, osteochondral defect could be efficiently repaired by this peptide-modified bilayered scaffold in the rabbit model. This study demonstrated that our composite scaffold could smartly enhance the repair of hyaline cartilage and subchondral bone defect, which shed light on a novel therapeutic strategy for the intervention of patients with articular osteochondral defect.