3D-printed nHA/PA66 porous scaffold: Regulating immune balance and vascularization synergistically promotes bone regeneration

Abstract

3D-printed porous scaffolds have emerged as a potential solution for treating critical-sized bone defects, yet localized inflammatory imbalance leads to suboptimal therapeutic outcomes. This study utilized nHA/PA66 composite material as the foundation, employing APF additive manufacturing technology to fabricate a three-dimensional porous scaffold (HP) suitable for local bone filling, and functionalized the porous scaffold through modification with polydopamine and magnesium ions (Mg²⁺) (HPDM). First, the physicochemical properties and biosafety of the HPDM scaffold were verified, followed by a comparative analysis of its effects on macrophage phenotype transformation, vascular endothelial cell differentiation, and pre-osteoblast differentiation differences. The HPDM scaffold achieves coordinated balance in the transformation between M1 and M2 macrophages through sustained release of polydopamine and Mg²⁺. Mg²⁺ plays a crucial role in inflammatory regulation by downregulating the NF-κB signaling pathway. Furthermore, several experiments demonstrated that the HPDM scaffold regulates orderly inflammatory responses to promote intercellular interactions, stimulating angiogenesis and osteogenic regeneration. In New Zealand rabbits' femoral condyle bone defect model, the HPDM porous scaffold achieved significant vascularized bone regeneration. This study confirms that the functionalized HPDM porous scaffold prepared using nHA/PA66 as the base material has significant potential in regulating immune responses and enhancing vascularized bone regeneration.