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This study constructed an immune-activated gradient phase transfer lysosome/titanium dioxide nanowire composite coating and modified it onto the surface of titanium materials. Based on this system, it achieved the synergistic effect of macrophage-mediated bacterial clearance and bone integration. The study regulated the signaling pathways and phenotypic polarization of macrophages to construct an appropriate immune microenvironment to promote angiogenesis and bone formation, and screened out a composite coating formula that could balance bacterial clearance and bone tissue regeneration. The study verified the positive effect of this coating in the process of infectious bone tissue regeneration through in vivo experiments, providing a new research direction for the functional design of bone implant materials.
This review focuses on the regeneration and repair challenges caused by the heterogeneity of bone-cartilage tissue, with the tissue engineering system combining mesenchymal stem cells and biomaterial scaffolds as the core. It clarifies the regulatory mechanism of biological physical signals on the fate of stem cells, systematically summarizes the progress in the design of biomimetic microenvironment scaffolds under mechanical biology guidance, and realizes the precise regulation of mesenchymal stem cell lineage-specific differentiation, providing theoretical support and design references for layered bone-cartilage regeneration, especially the regeneration of subchondral bone.
01 Research Background
The problems of infection related to bone implants and implant loosening are important challenges in the field of bone tissue regeneration. The current clinical intervention methods involve adding antibiotics or metal ions to the implant system. These traditional strategies have obvious drawbacks, such as inducing drug resistance and causing systemic toxic reactions, ultimately having a negative impact on the normal regeneration process of bone tissue. Therefore, it is urgent to develop new research strategies centered on immune regulation to achieve anti-infection of implants while effectively promoting the completion of the bone integration process.
The tendon-bone transitional tissue has a highly specialized extracellular matrix structure, with the core feature being the hierarchical arrangement of collagen and the gradient composition of minerals. This structural system can achieve stable force transmission and guide the cell phenotype of the spatial organization. Currently, it is impossible to precisely reproduce the complex multi-scale structure and composition gradient at the tendon-bone interface, which has become a key bottleneck in the integration and regeneration of soft and hard tissues. It is urgently necessary to develop a biomimetic matrix construction scheme that conforms to the natural structure characteristics.
02 Main Content
This study proposed an immunologically driven functionalization idea for bone implant materials, constructing a gradient phase transfer lysosome (PTL) and fixed-size titanium dioxide nanowire composite coating on the surface of titanium materials, and establishing a multi-functional research platform for related mechanism exploration. It focused on analyzing the activation effect of PTL on the Toll-like receptor 4 (TLR4) signaling pathway of macrophages and the regulatory effect of nanowire structure on the polarization of macrophages, clarifying the intrinsic mechanism by which the composite coating mediates bacterial clearance and creates a pro-bone regeneration immune microenvironment, and screening out the optimal PTL dose that can balance antibacterial effect and bone tissue regeneration, and verifying the promoting effect of the composite coating on bone regeneration under infection conditions.
0 Research Design
1. Using titanium materials as the base, prepare the PTL and titanium dioxide nanowire composite coating to construct a high-throughput screening research platform;
2. Cell-level experiments: explore the activation effect of the composite coating on the TLR4 signaling pathway of macrophages, analyze the effect of nanowire on the transformation of macrophages to a healing phenotype, and the impact of this immune regulatory mode on angiogenesis and osteogenic processes;
3. Dose optimization experiments: set up different PTL experimental groups, and screen the optimal formula that can synergistically achieve bacterial clearance and bone regeneration;
4. In vivo verification experiments: evaluate the actual effect of the PTL/titanium dioxide nanowire composite coating in the process of infectious bone tissue regeneration through animal in vivo experiments.
04 Results
PTL can effectively activate the TLR4 signaling pathway of macrophages and enhance the bacterial clearance ability of macrophages; The nanowire structure in the composite coating can rapidly induce macrophages to polarize towards a pro-healing phenotype, creating an immune microenvironment conducive to angiogenesis and bone formation; specific doses of PTL can achieve a good balance between bacterial clearance and bone tissue regeneration; the results of in vivo experiments confirm that the PTL/nanowire composite coating can effectively promote the regeneration process of bone tissue in an infected environment.
05 Extension of the thinking
Based on the immune microenvironment regulation idea of this study, the gradient phase transfer lysosome and nanowire structure composite design can be further optimized, and the molecular association mechanism between macrophage phenotype polarization and bone regeneration, antibacterial behavior can be deeply analyzed; for different types of bone defects and infection models, the component ratio and structural parameters of the coating can be adjusted to improve the design system of immune-regulated bone implant materials; at the same time, the direct regulatory effect of the composite coating on osteoblast activity and bone matrix mineralization can be expanded, further enriching the functional research dimensions of bone implant materials.
Original source:
1. Journal: Bioactive Materials
2. Publication date: 2026-03-26
3. DOI: 10.1016/j.bioactmat.2026.03.044
4. Authors: Ruiyue Hang, Huanming Chen, Liwei Yang, Ruoyu Di, Yuyu Zhao, Runhua Yao, Xiaohong Yao, Huaiyu Wang, Yin Xiao, Ruiqiang Hang
