已传文件：photo/1773121782.png
Large-sized bone defects encounter significant repair obstacles due to the inability to coordinate the continuous regeneration process of inflammatory response, angiogenesis, and bone formation. The paracrine signals from mesenchymal stromal cells are important regulatory factors for bone regeneration, but their effects are limited by the early inflammatory microenvironment and the characteristics of the cells themselves. In this study, a three-dimensional radial arrangement of nanofiber composite scaffolds was constructed, integrating hydroxyapatite fibers and GelMA hydrogels loaded with bone marrow-derived mesenchymal stromal cells. Through the synergistic enhancement of structural and material functions to strengthen the paracrine signals of cells, the orderly transformation of immune-angiogenesis-bone formation was driven. Combined with in vitro molecular biological analysis and animal model experiments, the regulatory mechanism of the scaffolds and the promotion effect of bone regeneration were clarified, achieving the temporal coordinated regulation of the entire process of bone regeneration.
Large-sized bone defects encounter significant repair obstacles due to the inability to coordinate the continuous regeneration process of inflammatory response, angiogenesis, and bone formation. The paracrine signals from mesenchymal stromal cells are important regulatory factors for bone regeneration, but their effects are limited by the early inflammatory microenvironment and the characteristics of the cells themselves. In this study, a three-dimensional radial arrangement of nanofiber composite scaffolds was constructed, integrating hydroxyapatite fibers and GelMA hydrogels loaded with bone marrow-derived mesenchymal stromal cells. Through the synergistic enhancement of structural and material functions to strengthen the paracrine signals of cells, the orderly transformation of immune-angiogenesis-bone formation was driven. Combined with in vitro molecular biological analysis and animal model experiments, the regulatory mechanism of the scaffolds and the promotion effect of bone regeneration were clarified, achieving the temporal coordinated regulation of the entire process of bone regeneration.
01Research Background
Large-sized bone defects lack the physiological basis for autonomous healing and are difficult to orderly complete the continuous physiological processes necessary for bone regeneration, such as inflammatory regulation, angiogenesis, and bone formation. These are the core challenges in the field of bone repair. Mesenchymal stromal cells can participate in bone regeneration regulation through paracrine signal transmission, but these cells have a low survival rate in the early inflammatory environment and their own plasticity leads to a decrease in paracrine activity after inflammation subsides, unable to provide continuous signal support for the entire bone regeneration cycle, thereby limiting the overall effect of bone regeneration.
Large-sized bone defects lack the physiological basis for autonomous healing and are difficult to orderly complete the continuous physiological processes necessary for bone regeneration, such as inflammatory regulation, angiogenesis, and bone formation. These are the core challenges in the field of bone repair. Mesenchymal stromal cells can participate in bone regeneration regulation through paracrine signal transmission, but these cells have a low survival rate in the early inflammatory environment and their own plasticity leads to a decrease in paracrine activity after inflammation subsides, unable to provide continuous signal support for the entire bone regeneration cycle, thereby limiting the overall effect of bone regeneration.
02 Main Content
This study developed a three-dimensional radial arrangement nanofiber composite scaffold loaded with bone marrow-derived mesenchymal stromal cells, to explore the regulatory effects of scaffold topological structure and material composition on cell activity, residence, and paracrine function; analyze the regulatory effect of the scaffold on the immune-angiogenesis-bone formation transformation process; through in vitro metabolomics and transcriptomics detection, clarify the molecular pathways regulating cell proliferation and osteogenic differentiation of the scaffold; using animal models to verify the alleviation effect of the composite scaffold on early inflammation and the promotion effect of bone regeneration.
03 Research Design
A three-dimensional radial arrangement nanofiber platform was constructed, and hydroxyapatite fibers were combined with GelMA hydrogel encapsulating bone marrow-derived mesenchymal stromal cells to prepare a multifunctional bone regeneration scaffold; the radial topological structure was used to promote early centripetal infiltration of cells, GelMA hydrogel was used to maintain cell activity and residence ability, and hydroxyapatite was used to enhance cell paracrine output and provide continuous bone conduction signals; using metabolomics and transcriptomics analysis, clarify the regulatory role of glycerophospholipid metabolism and PI3K/Akt signaling pathway; construct rat subcutaneous implantation models and critical cranial bone defect models to evaluate the inflammatory regulation and bone regeneration ability of the scaffold.
04 Results
The radial structure of the three-dimensional radial composite scaffold can effectively promote early centripetal infiltration of cells, GelMA hydrogel can maintain the activity and residence ability of bone marrow-derived mesenchymal stromal cells, prolong the paracrine signal release cycle, and hydroxyapatite can enhance cell paracrine output and provide continuous bone conduction signals, and the three work together to accelerate the transformation process of immune-angiogenesis-bone formation. In vitro molecular detection shows that the upregulation of glycerophospholipid metabolism can support early cell proliferation, and the activation of PI3K/Akt signaling pathway can drive cell osteogenic directional differentiation. Animal model experiments confirmed that this scaffold can effectively alleviate early inflammatory response and significantly improve bone regeneration effect, achieving the coordinated regulation of the temporal sequence of bone regeneration process.
05 Extension of Thoughts
Based on the scaffold design strategy of topological structure, biomaterials and cell function synergy, it provides experimental and theoretical support for the research and development of functional scaffolds in bone tissue engineering; with cell paracrine regulation as the core and combined with the research idea of coordinated regeneration sequence, it can be extended to the optimization of bone regeneration microenvironment and the directional regulation of cell functions; for the coordinated regulatory mode of the continuous physiological process of bone regeneration, it provides new research ideas for the functional design of bone repair materials.
Original Source:
1. Journal: Bioactive Materials
2. Publication Date: 2026-03-06
3. DOI: 10.1016/j.bioactmat.2026.02.059 4. Authors: Lei Fang, Min He, Tao Zhang, Bowen Gong, Li Ruan, Jichuan Qiu, Jiajia Xue, Feng Tian
