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This study focuses on the core issues of the decline in the regenerative and reconstructive ability of bone marrow mesenchymal stem cells during the aging process of the skeleton, as well as the obstruction of bone integration caused by immune aging. Through special techniques, eco-structured multi-scale porous titanium implants were prepared to conduct in vitro cell experiments and in vivo animal experiments to explore their effects. The study confirmed that the porous structure can regulate the osteogenic differentiation ability of bone marrow mesenchymal stem cells in situ, and also regulate the immune aging state of macrophages in the bone defect area. Through the synergistic effect of stem cell regeneration and immune regulation, it effectively restores the repair ability of aging bones and improves the bone integration effect. This provides a new experimental basis and mechanism idea for the research on bone reconstruction under the condition of aging, and also expands new possibilities for the research direction of macrophage immune phenotype remodeling.
This review focuses on the regeneration and repair dilemma caused by the heterogeneity of bone and 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 the guidance of mechanical biology, and realizes the precise regulation of lineage-specific differentiation of mesenchymal stem cells. It provides theoretical support and design references for layered bone and cartilage regeneration, especially for the regeneration and repair of subchondral bone.
01 Research Background
As the body ages, the bone repair ability of bone marrow mesenchymal stem cells will significantly decline, making it difficult to effectively complete the repair and integration of bone defects. This becomes an important cause of impaired bone healing in the elderly population. In the microenvironment of aging bones, the depletion of ARG1+ macrophages will further aggravate the damage to the reconstructive function of bone marrow mesenchymal stem cells. This abnormal immune cell function state, triggered by immune aging, becomes a key limiting factor that hinders the effective integration and completion of repair in aging bones. Current research on the remodeling of the regenerative ability of aging bone marrow mesenchymal stem cells is insufficient. It is urgent to focus on the interaction between stem cells and immune cells in the bone microenvironment, develop targeted research strategies, and solve the problem of impaired bone repair in aging bones.
The transitional tendon-bone 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 structure system can achieve stable force transmission and guide the cell phenotype of 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 tissue interfaces. It is necessary to develop a biomimetic matrix construction scheme that conforms to the characteristics of the natural structure.
02 Main Content
This study focuses on the core obstacles in aging bone repair, with the interaction regulation between bone marrow mesenchymal stem cells and macrophages in the bone microenvironment as the core entry point. Using the gas-assisted alloy-dealloying technology, multi-scale porous titanium implants that simulate the ecological niche were prepared. This technology can construct a porous surface layer on the complex commercial titanium implants with geometrically complex shapes. The study compared conventional commercial titanium implants as the control group and systematically explored the regulatory effect of the eco-structured multi-scale porous titanium implants on the function of aging bone marrow mesenchymal stem cells, as well as the alleviation effect on the immune aging of macrophages during bone reconstruction. The study focused on analyzing the internal mechanism by which the porous structure regulates the immune microenvironment, activates the osteogenic potential of stem cells, and thereby realizes the recovery of aging bone repair. It clarified the application value of this biomimetic porous structure in bone defect repair and bone integration.
03 Research Design
This study adopts the research design of control experiments, setting conventional commercial titanium implants as the blank control group, and the eco-structured multi-scale porous titanium implants prepared by the gas-assisted alloy-dealloying technology as the experimental group. The experimental system is divided into two levels: in vitro cell experiments and in vivo animal experiments. Rat and rabbit were selected as experimental animals to build bone defect-related models, fully simulating the repair scenarios of aging bones. During the research process, the focus was on detecting the formation of the osteogenic phenotype of bone marrow mesenchymal stem cells, as well as the osteogenic differentiation level of bone marrow mesenchymal stem cells at the bone-implant interface. At the same time, the phenotypic changes of ARG1+ macrophages in the bone defect area, the immune aging status, and the repair effect of bone defects, as well as the integration degree of the bone-implant interface were monitored. Through multi-dimensional and multi-level index detection, the mechanism and repair effect of the porous titanium implant in the experimental group were systematically verified.
04 Results
The results of in vitro cell experiments and in vivo experiments in rats and rabbits all indicated that compared with conventional commercial titanium implants, the ecological-scale multi-scale porous titanium implants could effectively act on bone marrow mesenchymal stem cells, promoting their formation of the osteogenic phenotype, and precisely regulating the microenvironment in the bone defect area, creating favorable conditions for bone repair. The porous structure could exert regulatory effects at the bone-implant interface, promoting the directional differentiation of bone marrow mesenchymal stem cells towards the osteogenic direction, and inducing the production of ARG1+ macrophages with regenerative potential, effectively alleviating the immune aging phenomenon during bone reconstruction. The osteogenic differentiation of bone marrow mesenchymal stem cells and the immune regulation of macrophages formed a synergistic effect, significantly improving the bone integration effect in aging organisms and successfully restoring the repair ability of aged bones. The study also confirmed that macrophages could be reformed into a younger state through the regulation of this porous structure, thereby maintaining the immune homeostasis during bone repair, providing a reversible experimental research idea for the reconstruction of aging bones.
05 Extension of the Thought
This research broke through the previous limitation of aging bone repair studies that only focused on the functions of bone marrow mesenchymal stem cells themselves. It was the first to clarify the core mechanism of ecological-scale porous structure through regulating macrophage immune aging and coordinating stem cell osteogenic differentiation to achieve the recovery of aging bone repair, providing a new paradigm for cross-disciplinary research in bone regeneration and bone immunity. The design concept of this biomimetic porous structure and the core logic of immune-stem cell interaction regulation can not only be deeply applied to the basic research of bone reconstruction in the elderly but also be extended to the mechanism exploration of other aging-related bone diseases. At the same time, it provides a reference technical direction and theoretical basis for the repair research of other tissue organ aging-related injuries, expanding the research boundaries of the regulation of biological materials for aging-related diseases in the field.
