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01 Research Background
Repairing bone defects is a tough challenge in orthopedics. Autografts and allografts are limited by donor site complications and insufficient sources. Biodegradable zinc metals are promising implant materials because of their suitable degradation behavior and inherent bone-forming activity. However, their initial rapid corrosion causes a burst release of zinc ions, leading to cytotoxicity, and uneven corrosion affects mechanical integrity. Existing surface modifications mostly focus on direct interactions between the material and bone cells, overlooking the key regulatory role of nerve-bone communication in bone repair. Sensory nerves and their associated Schwann cells regulate bone formation, vascularization, and the immune microenvironment by secreting neurotrophic factors and neuropeptides. Therefore, developing a coating that combines corrosion control, ion release, and electrically active neural regulation could potentially achieve synergistic repair by coupling nerve and bone functions.
02 Main Content
The study designed a conductive hydrogel coating mediated by MOF mineralization. Using sodium alginate, dopamine-modified hyaluronic acid, and aminated gelatin as the matrix, HKUST-1 type copper-based MOF was anchored in situ, and polypyrrole nanoparticles were incorporated. This coating, through the combined action of the dense MOF layer and polypyrrole, blocks water and oxygen diffusion and competitively adsorbs phosphate, thereby inhibiting the burst release of zinc ions; at the same time, it slowly releases zinc and copper ions and provides an intrinsically electroactive interface. Electrical and ionic signals jointly activate Schwann cells, upregulating the secretion of neurotrophic factors and neuropeptides, and their conditioned medium further promotes osteogenic differentiation of mesenchymal stem cells. The coating also regulates macrophages to polarize towards a pro-repair phenotype, creating an immune microenvironment favorable for bone regeneration.
03 Research Design
The study first verified the spatial and temporal relationship between Schwann cells and bone repair in a rat femoral defect model, and confirmed through Transwell co-culture that Schwann cells promote osteogenic differentiation of mesenchymal stem cells. Next, coating materials were synthesized and systematically characterized for morphology, chemical composition, wettability, mechanical stability, conductivity, degradation and corrosion behavior, as well as ion release kinetics. In vitro, Schwann cells and mesenchymal stem cells were used to assess migration, proliferation, expression of neural markers, secretion of neurotrophic factors, and osteogenic differentiation. Transcriptome sequencing was used to analyze the molecular pathways through which the coating promotes bone formation and neural regulation. A critical-sized rat femoral defect model was established, and different coated zinc rods were implanted to evaluate biocompatibility, nerve regeneration, immune modulation, interface mechanics, and bone regeneration effects.
04 Results
The coating surface shows a porous and rough texture, increased hydrophilicity, and significantly improved interfacial adhesion and scratch resistance. Conductivity increases with higher polypyrrole content, while corrosion volume ratio and zinc ion release decrease noticeably. In vitro experiments show that the coating promotes Schwann cell migration, proliferation, and S100β and Tuj1 expression, while upregulating NGF, BDNF, GDNF, CGRP, and substance P secretion. Its conditioned medium enhances mesenchymal stem cell alkaline phosphatase activity, mineral nodule formation, and expression of osteogenic markers. In a co-culture system, Schwann cells further amplify the osteogenic effect. Transcriptomics revealed that the coating activates BMP-SMAD, PI3K-Akt, and cell adhesion pathways, and also upregulates genes related to nerve development and synaptic plasticity. In vivo results show that the coated implants have good systemic biocompatibility, recruit Schwann cells early to promote myelin formation, maintain nerve fiber maturation and sensory reinnervation later, while also promoting macrophage M2 polarization, improving interfacial shear strength and bone volume fraction, and accelerating bone integration.
05 Further Thoughts
This study introduced neuro-bone coupling into the design of zinc implant interfaces. By combining MOF mineralization with conductive nanoparticles, it achieved multifunctional integration of corrosion control, ion release, and electrically active neural regulation. In the future, it would be useful to further analyze the relative contributions and timing of electrical and ionic signals in Schwann cell activation, and clarify the specific pathways through which neurotrophic factors promote bone formation. Additionally, exploring how different combinations of conductive nanoparticles and MOFs affect neuro-bone coupling, as well as systematically evaluating the stability of coatings and the metabolic fate of their degradation products in long-term implants, would be valuable. This strategy offers an expandable model for designing implant interfaces that support both nerve regulation and bone regeneration.
Original Source:
Bioactive Materials
Pub Date: 2026-09-03
DOI:10.1016/j.bioactmat.2026.08.050
Yujia Wei, Dong Mo, Meng Pan, Tingyu Yang, Xicheng Li, Lin Ye, Jianan Li, Liping Yuan, Zhongwu Bei, Zhiyong Qian
