Immunomodulatory 3D-printed conductive scaffold combined with electrostimulation: a dual-strategy approach to enhance bone regeneration.

Abstract

Conventional conductive scaffolds lack the capacity to dynamically coordinate the immuno-osteogenic coupling that is critical for effective bone repair. In this study, we developed a three-dimensional (3D) printed immunomodulatory conductive scaffold that integrates anti-inflammatory macrophage induction with electrical signal transmission. This scaffold achieves a combination of available electrical conductivity and immunomodulatory function through poly(3,4-ethylenedioxythiophene) (PEDOT) doping and controlled ion release. In vitro experiments demonstrated that the scaffold enhanced M2 macrophage polarization by potential regulation of the NF-κB signaling pathway mediated by bioactive ions, even under conditions of electrical stimulation (ES). Furthermore, it synergistically promoted the osteogenic differentiation of bone marrow stromal cells (BMSCs) in the presence of ES. In vivo evaluation using a rat cranial defect model revealed that the scaffold combined with ES accelerated bone regeneration via the convergence of immunomodulation and electrical cues, as evidenced by coordinated M2 macrophage infiltration and early angiogenesis. This study provides a promising strategy that integrates conductive network and bioactive ion release to establish an electrostimulation and immunoregulation microenvironment for the treatment of bone defect.