Biomimetic electroactive nano-heterojunction for vascularized bone regeneration in large segmental load-bearing bone defects via temporal regulation of endogenous functional ions.

Abstract

The repair and functional reconstruction of large segmental bone defects in load-bearing regions are extremely difficult, mainly because the body's capacity to recruit endogenous functional ions such as Ca2+, Cu2+, and Mg2+ to facilitate mineralization and vascularization is compromised. Herein, inspired by the bioelectric field-mediated ion regulation in native bone, a biomimetic carbon fiber reinforced polyetherketoneketone (CF/PEEK) scaffold incorporated with a bio-heterojunction was fabricated via 3D printing, liquid-phase chemistry and hydrothermal treatment. The heterojunction composed of 2D nano-MXene and in-situ ZnS quantum dots enriches functional ions on the scaffold surface through an endogenous electric field, thereby remarkably improving its bioactivity. In vitro cell experiments demonstrated that the CF/PEEK biomimetic scaffold promotes cells' osteogenic and angiogenic differentiation through the epidermal growth factor receptor (EGFR)-mediated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. In vivo investigations via non-load-bearing lacunar and load-bearing segmental bone defect models verified that the CF/PEEK biomimetic scaffold possesses superior bone and vascular regeneration capacity, enabling rapid vascularized bone regeneration under complex stress conditions through a bone-vessel coupling mechanism. This work offers a novel strategy for repairing load-bearing large segmental bone defects and new insights into designing bioelectric field-guided biomimetic materials.