A near-infrared regulated programmable multi-mode periosteum scaffold for sequential healing of infected bone defects.

Abstract

Infected bone defects present a major clinical challenge, requiring precise sequential therapy that transitions from antibacterial activity to bone regeneration. Piezoelectric materials can transduce external stimulation into bioelectrical cues, providing a promising controllable handle to regulate antibacterial and osteogenic processes. However, conventional piezoelectric scaffolds often lack the capacity to distinctly separate these multifunctional roles, making it difficult to meet the therapeutic needs of different stages in the treatment of infected bone defects. Here, we develop a programmable NIR-responsive periosteum scaffold featuring a Janus bilayer architecture, in which a PDA-rich photothermal side and a non-photothermal piezoelectric side enable spatially separated antibacterial and osteogenic functions. This system integrates a thermoresponsive hydrogel with a piezoelectric polyvinylidene fluoride/barium titanate (PVDF/BT) electrospun membrane, achieving three switchable functional modes: continuous NIR irradiation for antibacterial therapy, intermittent irradiation for immunomodulation, and no irradiation for mechanical support and Ca²⁺ release to facilitate mineralization. <i>In vitro</i> studies demonstrated effective antibacterial efficacy and enhanced pro-healing M2 macrophage polarization, while comprehensive <i>in vivo</i> studies in rat models of 8 mm infected bone defect models achieved over 60% bone healing rate through programmable sequential therapy at 4 weeks. This programmable multi-mode periosteum scaffold provides a promising strategy for temporally orchestrating complex microenvironments, advancing the regenerative medicine for infected bone repair.