Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People's Republic of China.
Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, 310000, People's Republic of China.
J Nanobiotechnology. 2021 Dec 14;19(1):420. doi: 10.1186/s12951-021-01173-z.
Engineering approaches for growth factor delivery have been considerably advanced for tissue regeneration, yet most of them fail to provide a complex combination of signals emulating a natural healing cascade, which substantially limits their clinical successes. Herein, we aimed to emulate the natural bone healing cascades by coupling the processes of angiogenesis and osteogenesis with a hybrid dual growth factor delivery system to achieve vascularized bone formation. Basic fibroblast growth factor (bFGF) was loaded into methacrylate gelatin (GelMA) to mimic angiogenic signalling during the inflammation and soft callus phases of the bone healing process, while bone morphogenetic protein-2 (BMP-2) was bound onto mineral coated microparticles (MCM) to mimics osteogenic signalling in the hard callus and bone remodelling phases. An Initial high concentration of bFGF accompanied by a sustainable release of BMP-2 and inorganic ions was realized to orchestrate well-coupled osteogenic and angiogenic effects for bone regeneration. In vitro experiments indicated that the hybrid hydrogel markedly enhanced the formation of vasculature in human umbilical vein endothelial cells (HUVECs), as well as the osteogenic differentiation of mesenchymal stem cells (BMSCs). In vivo results confirmed the optimal osteogenic performance of our F/G-B/M hydrogel, which was primarily attributed to the FGF-induced vascularization. This research presents a facile and potent alternative for treating bone defects by emulating natural cascades of bone healing.
工程学方法在生长因子传递方面已经得到了很大的发展，用于组织再生，然而，它们大多数都无法提供模拟自然愈合级联的复杂信号组合，这极大地限制了它们在临床上的成功。在这里，我们旨在通过将血管生成和成骨过程与混合双生长因子传递系统相结合，模拟自然骨愈合级联，从而实现血管化骨形成。碱性成纤维细胞生长因子（bFGF）被加载到甲基丙烯酰化明胶（GelMA）中，以模拟骨愈合过程中炎症和软痂阶段的血管生成信号，而骨形态发生蛋白-2（BMP-2）则结合到矿化涂层微球（MCM）上，以模拟硬痂和骨重塑阶段的成骨信号。实现了初始高浓度的 bFGF 伴随 BMP-2 和无机离子的持续释放，以协调骨再生的良好偶联的成骨和血管生成效应。体外实验表明，混合水凝胶显著增强了人脐静脉内皮细胞（HUVECs）中成血管的形成，以及间充质干细胞（BMSCs）的成骨分化。体内结果证实了我们的 F/G-B/M 水凝胶的最佳成骨性能，这主要归因于 FGF 诱导的血管生成。本研究通过模拟自然骨愈合级联，为治疗骨缺损提供了一种简便有效的方法。
