Abstract
The harsh microenvironment characterized by avascularity and hypoxia presents a significant challenge for bone regeneration following refractory bone defects. Tissue engineering combined with electrotherapy has emerged as a promising alternative for repairing bone defects, offering advantages such as accelerated healing and the restoration of physiological functions in regenerated bone. In this study, we propose a strategy for constructing tissue-engineered cartilage derived from bone marrow stem cells (BMSCs) for bone regeneration, utilizing 3D-printed triboelectric scaffolds (TES). The TES scaffold is fabricated from biodegradable bioelastomer and conductive biomaterial, featuring excellent biomimetic elasticity and hydrophobicity. The TES contains numerous hydrophobic microporous units, enabling in situ self-powered stimulation in vivo. The conductivity of the TES has been shown to enhance the chondrogenic differentiation potential of BMSCs during in vitro induction into tissue-engineered cartilage. Notably, the TES scaffold was more effective in promoting endochondral ossification of tissue-engineered cartilage in vivo. The in vivo osteogenesis mechanism of the TES group was further analyzed through proteomics, revealing that TES facilitated actin cytoskeleton remodeling, activated the PI3K-Akt pathway, provided metabolic support, and enhanced intercellular communication to drive the endochondral ossification process. Finally, in situ skull defect repair in rabbits successfully demonstrated the efficacy of TES electrical stimulation in promoting tissue-engineered endochondral ossification, thereby achieving bone defect regeneration and providing an effective biological strategy for the repair of refractory bone defects.