Bio-OPMATCH: A multifunctional biomimetic shape-memory scaffold for repairing osteoporotic bone defects by promoting osteogenesis and inhibiting osteoclastogenesis

Abstract

Osteoporotic bone defects, stemming from an imbalance between osteogenesis and osteoclastogenesis, are characterized by reduced bone strength, heightened brittleness, and often irregular morphology, which contribute to delayed repair and pose challenges for mechanical reconstruction. There is an urgent need for scaffolds that integrate mechanical adaptability, precise filling capability, and the capacity to regulate bone regeneration. This study introduces Bio-OPMATCH, a composite scaffold designed to integrate mechanical, structural, and functional matching for osteoporotic bone defect repair, with adaptability to irregular defect morphology. The scaffold is based on the shape-memory polymer poly(L-lactic acid-co-trimethylene carbonate-co-glycolic acid) (PTG), compounded with dopamine-modified hydroxyapatite (PHA) and integrated with a Cu-Zol metal-organic framework (CZ) formed by coordination of copper ions (Cu) with zoledronic acid (Zol). Bio-OPMATCH exhibits favorable shape-recovery properties and a controllable degradation behavior. It can be compressed for minimally invasive implantation and undergoes in situ shape restoration at physiological temperature, while its adaptive filling of irregular bone defects was demonstrated in an ex vivo model. Moreover, the scaffold demonstrates excellent cytocompatibility, promoting the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) while inhibiting osteoclast differentiation. Evaluations in a rat osteoporosis model revealed that Bio-OPMATCH promotes bone regeneration and suppresses the osteoclast differentiation signaling axis centered on Csf1/Csf1r. By leveraging mechanical adaptability and shape-memory-enabled minimally invasive filling to achieve structural matching, and by utilizing the sustained local Zol release from CZ to promote structural repair and functional regeneration of osteoporotic bone defects, Bio-OPMATCH provides a potential strategy for osteoporotic bone defect repair, particularly where complex or irregular defect morphology presents additional challenges.