Effective regeneration of critical-sized bone defects requires the integrated coordination of osteogenesis, neurogenesis, angiogenesis, and immune regulation—but most biomaterials fail to address these dimensions simultaneously. Here, we developed a norepinephrine-loaded, biomimetic mineralized electro-dense collagen scaffold (NE-MEC) that integrates structural anisotropy with sustained biochemical activity to promote bone integration and repair. NE-MEC is fabricated through isoelectric focusing, mechanical stretching, and amorphous calcium phosphate mineralization.Simulating the composition and orderly arrangement of native bone, it maintains the unique D-periodicity of collagen fibers. Mineralized dense collagen itself can promote osteogenic differentiation of rat bone marrow mesenchymal stem cells. After the addition of norepinephrine, this bone-inducing effect is further enhanced, accompanied by early upregulation of nerve growth factor, supporting peripheral nerve repair and inducing the production of calcitonin gene-related peptide (CGRP). In turn, CGRP enhances osteogenic differentiation and neovascularization.At the same time, NE-MEC also stimulates the expression of vascular endothelial growth factor A in regenerating bone tissue and regulates macrophage polarization. These effects together establish a regenerative loop, coordinating osteogenesis, neurogenesis, angiogenesis, and immune regulation, providing a promising biomaterial platform for synergistic bone repair.

Original link

Advanced Science ( IF 14.1 )

Pub Date : 2025-11-22

DOI: 10.1002/advs.202518807

Zhengyun Ren,  Zhaojun Wu,  Anhang Wu,  Hui Zhang,  Jiachen Lu,  Jiahao Zhang,  Jie Weng,  Jinhua Zhang,  Song Chen,  Huan Tan ,  Tailin Guo