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IF: 20.3 Hierarchical Gradient Mineralized Collagen Mediated Tendon-Bone Integration and Regeneration

source:material synthesis Views:38time:2026-03-20material synthesis: 1092348845

已传文件:photo/1773121782.png The extracellular matrix of the natural tendon-bone interface exhibits a hierarchical arrangement of collagen and a gradient composition of minerals. This structure is crucial for force transmission and the regulation of cell phenotypes. Replicating such complex multi-scale structures and composition gradients to achieve the integration of soft and hard tissues is a significant challenge in the field. This study has constructed a biomimetic collagen-mineral matrix that can simultaneously simulate the hierarchical structure and mineral gradient distribution of the natural tendon-bone extracellular matrix. Through specific processes, it enables the ordered assembly of collagen and the gradient mineralization. This matrix can achieve a smooth transition in the mechanical properties at the tendon-bone interface, induce specific tissue regeneration in regions such as bone, and has been verified in animal experiments to play a role in the multi-tissue reconstruction of tendon-bone. This biomimetic matrix demonstrates its research value in tissue regeneration.
This review addresses the challenges in regenerative repair caused by the heterogeneity of bone-cartilage tissues, focusing on the tissue engineering system combining mesenchymal stem cells and biomaterial scaffolds. 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 achieves precise regulation of the lineage-specific differentiation of mesenchymal stem cells. It provides theoretical support and design references for layered bone-cartilage regeneration, especially for the regeneration of subchondral bone.
01 Research Background
The tendon-bone transitional tissue has a highly specialized extracellular matrix structure, with the core feature being the hierarchical arrangement of collagen and a gradient composition of minerals. This structural system enables stable force transmission and directional guidance of the cell phenotype in the spatial organization. Currently, it is impossible to precisely reproduce the complex multi-scale structure and composition gradient of the tendon-bone interface, which has become a key bottleneck hindering the integration and regeneration of soft and hard tissues. There is an urgent need to develop a biomimetic matrix construction scheme that conforms to the characteristics of the natural structure.
The tendon-bone transitional tissue has a highly specialized extracellular matrix structure, with the core feature being the hierarchical arrangement of collagen and a gradient composition of minerals. Currently, it is impossible to precisely reproduce the complex multi-scale structure and composition gradient of the tendon-bone interface, which has become a key bottleneck hindering the integration and regeneration of soft and hard tissues. There is an urgent need to develop a biomimetic matrix construction scheme that conforms to the characteristics of the natural structure.
02 Main Content
This study aims at tendon-bone interface bone tissue regeneration and integration. It has developed a new biomimetic collagen-mineral matrix to achieve the coordinated construction of the hierarchical arrangement structure of collagen and the gradient distribution of minerals; systematically characterizes the micro-scale multi-scale structure and tensile mechanical properties of this biomimetic matrix, and explores its regulatory mechanism on the specific tissue regeneration in regions such as tendon-like tissue, fibrocartilage, and bone tissue; using animal in vivo experiments, it verifies the effect of this biomimetic matrix on the multi-tissue reconstruction of the rotator cuff tendon-bone and clarifies the application value of the bottom-up biomimetic strategy in collagen-based scaffold engineering.
03 Research Design
The research adopts a combined technical path of collaborative electro-assembly and post-treatment to guide the self-organization of collagen molecules to form a regular multi-scale fibrous matrix, replicating the morphological characteristics of the tendon side and endowing the matrix with stable tensile mechanical properties; for the matrix, it performs spatialized mineralization within and between fibers to construct a mineral gradient that conforms to the natural tendon-bone; using rabbits as the experimental model, in vivo studies are conducted to evaluate the regulatory effect of the biomimetic matrix on the multi-tissue reconstruction of tendon-bone and bone tissue regeneration.
04 Results
The constructed biomimetic collagen-mineral matrix can precisely simulate the hierarchical structure of collagen and the gradient distribution of minerals of the natural tendon-bone extracellular matrix, and has the appropriate tensile mechanical properties; the structure and composition of this matrix are continuous, achieving a smooth transition in the mechanical properties at the tendon-bone interface, and can effectively guide the specific tissue regeneration in regions such as bone, fibrocartilage, and tendon-like tissue; the in vivo experimental results confirm that this biomimetic matrix can effectively support the multi-tissue reconstruction of tendon-bone at the rotator cuff site and has a positive promoting effect on the recovery of tissue function.

05 Extension of Ideas The bottom-up collagen biomimetic assembly strategy proposed in this study can be extended to be applied in the preparation of biomimetic scaffolds for various soft and hard tissue interfaces. The core design concept centered on collagen hierarchical arrangement and gradient mineralization can provide new research ideas for the multi-scale structure design and composition gradient regulation of regenerative materials for bone-related tissue interfaces, and help deepen the research on the mechanism of material-bone tissue interaction during tissue interface regeneration.

Original source:
1. Journal: Bioactive Materials
2. Publication date: March 6, 2026
3. DOI: 10.1016/j.bioactmat.2026.03.003
4. Authors: Miao Lei, Hao Luo, Luyi Sun, Songsong Shi, Zhuangri Zhang, Chengxuan Yu, Han Gao, Jun Chen, Changsheng Liu, Xue Qu


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