Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital of Nanjing Medical University; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases; Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Department of Oral and Maxillofacial Surgery, Zaozhuang Stomatological Hospital, Zaozhuang, Shandong 277100, China.
ACS Biomater Sci Eng. 2024 Sep 9;10(9):5764-5773. doi: 10.1021/acsbiomaterials.4c00269. Epub 2024 Aug 27.
Alveolar bone defect reconstruction is a common challenge in stomatology. To address this, a thermosensitive/photosensitive gelatin methacrylate (GelMA) gel was developed based on various air solubilities and light-curing technologies. The gel was synthesized by using a freeze-ultraviolet (FUV) method to form a porous and quickly (within 15 min) solidifying modified network structure. Unlike other gel scaffolds limited by complex preparation procedures and residual products, this FUV-GelMA gel shows favorable manufacturing ability, promising biocompatibility, and adjustable macroporous structures. The results from a rat model suggested that this gel scaffold creates a conducive microenvironment for mandible reconstruction and vascularization. In vitro experiments further confirmed that the FUV-GelMA gel promotes osteogenic differentiation of human bone marrow mesenchymal stem cells and angiogenesis of human umbilical vein endothelial cells. Investigation of the underlying mechanism focused on the p38 mitogen-activated protein kinase (MAPK) pathway. We found that SB203580, a specific inhibitor of p38 MAPK, abolished the therapeutic effects of the FUV-GelMA gel on osteogenesis and angiogenesis, both in vitro and in vivo. These findings introduced a novel approach for scaffold-based tissue regeneration in future clinical applications.
牙槽骨缺损重建是口腔医学中的常见挑战。为了解决这个问题，我们开发了一种基于不同空气溶解度和光固化技术的温敏/光敏感明胶甲基丙烯酸酯（GelMA）凝胶。该凝胶通过使用冷冻-紫外（FUV）方法合成，形成多孔且快速（在 15 分钟内）固化的改性网络结构。与其他受复杂制备程序和残留产物限制的凝胶支架不同，这种 FUV-GelMA 凝胶表现出良好的制造能力、有前途的生物相容性和可调节的大孔结构。大鼠模型的结果表明，这种凝胶支架为下颌骨重建和血管化创造了有利的微环境。体外实验进一步证实，FUV-GelMA 凝胶促进人骨髓间充质干细胞的成骨分化和人脐静脉内皮细胞的血管生成。对潜在机制的研究集中在 p38 丝裂原活化蛋白激酶（MAPK）途径上。我们发现，p38 MAPK 的特异性抑制剂 SB203580 消除了 FUV-GelMA 凝胶在体外和体内对成骨和血管生成的治疗作用。这些发现为未来临床应用中的基于支架的组织再生引入了一种新方法。
