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Sequentially releasing self-healing hydrogel fabricated with tgfβ3-microspheres and bFGF to facilitate rat alveolar bone defect repair

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Asian Journal of Pharmaceutical Sciences 2022年第3期17卷 425-434页

作者： Fenglin Yu Dezhi Geng Zhanpeng Kuang Shiyi Huang Yating Cheng Yini Chen Fang Leng Yu Bei Yueping Zhao Qingxia Tang Yadong Huang Qi Xiang Department of Cell Biology College of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Bioengineering Medicine Jinan UniversityGuangzhou 510632China Biopharmaceutical R&D Center of Jinan University Guangzhou 510632China Department of Stomatology Jinan University Medical CollegeGuangzhou 510632China

Resorption and loss of alveolar bone leads to oral dysfunction and loss of natural or implant teeth. Biomimetic delivery of growth factors based on stem cell recruitment and osteogenic differentiation, as the key steps in natural alveolar bone regenerative process, has been an area of intense research in recent years. A mesoporous self-healing hydrogel(DFH) with basic fibroblast growth factor(bFGF) entrapment and transforming growth factor β3(tgfβ3)-loaded chitosan microspheres(CMs) was developed. The formulation was optimized by multiple tests of self-healing, in-bottle inversion, SEM, rheological, swelling rate and in vitro degradation. In vitro tubule formation assays, cell migration assays, and osteogenic differentiation assays confirmed the ability of DFH to promote blood vessels, recruit stem cells, and promote osteogenic differentiation. The optimum DFH formula is 0.05 ml 4ArmPEG-DF(20%) added to 1 ml CsGlu(2%) containing bFGF(80 ng) and tgfβ3-microspheres(5 mg). The results of in vitro release studied by Elisa kit, indicated an 95% release of b FGF in7 d and long-term sustained release of tgfβ3. For alveolar defects rat models, the expression levels of CD29 and CD45, the bone volume fraction, trabecular number, and trabecular thickness of new bone monitored by Micro-CT in DFH treatment groups were significantly higher than others(*P tgfβ3 slowly released speed up the process of new bones formation to common facilitate rat alveolar defect repair. The DFH with higher regenerative efficiency dovetails nicely with great demand due to the requirement of complicated biological processes.

关键词： Self-healing hydrogel tgfβ3 microspheres bFGF Sequential release Alveolar defects

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