Bioactive scaffolds with Li and Si ions-synergistic effects for osteochondral defects regeneration

Abstract

Osteoarthritis (OA) is a common disease cause cartilage damage, which always extends into subchondral bone, thus simultaneous regeneration of these two tissues is of great importance for OA osteochondral defect reconstruction. Since cartilage and subchondral bone have different biological properties, the therapy of osteochondral defects remains great challenging. A lithium (Li) and silicon (Si)-containing biomaterial (LCS) was, for the first time, synthesized, and the bioactivity and mechanism of LCS for osteochondral defect regeneration were systematically studied. It was found that LCS extracts significantly stimulated the proliferation and maturation of chondrocytes, as well as promoted the osteogenic differentiation of rabbit mesenchymal stem cells (rBMSCs). Histological and Micro-CT analysis indicated that LCS scaffolds distinctly promoted osteochondral defect regeneration in vivo. Further study showed that the Li and Si ions released from LCS scaffolds may play a pivotal role in inducing osteochondral defects regeneration. The underlying mechanism is relating to the synergistically effect of Li and Si promoting chondrocytes maturation via activating HIF pathway, as well as protecting chondrocytes from OA environment through inhibiting the hedgehog pathway and activating autophagy. These findings suggest that LCS scaffolds possess bi-lineage bioactivities for osteochondral defect regeneration, which represent an intelligent strategy for OA therapy by harnessing the synergistic effect of multi-bioactive ions in one single scaffold, instead of traditional methods by using multi-layered scaffolds and growth factor/drug delivery.