Spatiotemporal 4D-printed shape-memory scaffold with a triple-acting liposomal strategy for the treatment of infectious bone defects.

Abstract

Infectious bone defects (IBD) are complex bone tissue injuries caused by pathogenic bacterial invasion, characterized by delayed bone healing due to bacterial infection and chronic inflammation. In this study, we developed an adaptive filling shape memory scaffold (PTC@PS-EGCG) with temporal and spatial sequence regulation capabilities, integrating multiple functions including antibacterial, immune modulation, and osteogenic induction. The shape memory scaffold (PT) was fabricated using low-temperature 4D printing technology, and a pH-responsive chitosan hydrogel (CS) was used to load phosphatidylserine-modified epigallocatechin gallate liposomes (PS-EGCG) on the scaffold surface to form a coating. The PTC@PS-EGCG scaffold can achieve adaptive filling and integration of irregular defect interfaces at body temperature (37 °C) while providing mechanical support. In the early stages of infection, PS-EGCG is released in response to the infection, clearing bacteria and being phagocytosed by macrophages. Subsequently, PS-EGCG promotes metabolic reprogramming by regulating macrophage oxidative phosphorylation, achieving a "triple effect." In the middle and late stages, the internal scaffold continues to sustain bone formation. In a rat model of IBD, the PTC@PS-EGCG significantly reduced the expression of inflammatory cytokines and bacterial load, promoted bone regeneration, and improved gait function. This integrated scaffold provides a promising and reliable solution for the clinical treatment of IBD.