Three-Dimensional-Printed Lithium-Doped Conductive Carbon@Hydroxyapatite Scaffolds for Coordinated Neurovascular-Osseous Regeneration

The repair of critical-sized bone defects remains a formidable clinical challenge, where coordinated neurovascular reconstruction is important for effective bone regeneration. Accordingly, this study aimed to develop a three-dimensional (3D)-printed hydroxyapatite (HAp) scaffold integrating a polydopamine (PDA)-derived conductive carbon interface with Li+ release, and to evaluate its neural-, vascular-, and osteogenic-related effects in vitro and its bone-regenerative performance in vivo. A lithium-containing, hydrothermally carbonized HAp scaffold (HAp@C/Li) was fabricated through 3D printing, Li+-assisted dopamine coating, and hydrothermal carbonization. Material characterization confirmed a PDA-derived carbon coating with measurable local surface conductivity and Li+ release characterized by an early release phase followed by a gradual plateau. In vitro experimental results revealed that HAp@C/Li possessed excellent cytocompatibility. It effectively promoted neurite outgrowth of dorsal root ganglion (DRG) neurons, migration and tube formation of human umbilical vein endothelial cells (HUVECs), as well as osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In vivo evaluation in a rat femoral condyle defect model showed favorable bone repair, collagen deposition, vascular remodeling, and neural-associated tissue responses, with significantly higher BMD at 8 weeks, whereas BV/TV did not differ significantly from that of the HAp group. Collectively, these results indicate that the HAp@C/Li scaffold provides a promising therapeutic strategy for the clinical repair of critical-sized bone defects.