Abstract：
Bone regeneration is a well-orchestrated process synergistically involving inflammation, angiogenesis, and osteogenesis. Therefore, an effective bone graft should be designed to target multiple molecular events and biological demands during the bone healing process. In this study, a biodegradable gelatin methacryloyl (GelMA)-based Janus microsphere delivery system containing calcium phosphate oligomer (CPO) and bone morphogenetic protein-2 (BMP-2) is developed based on natural biological events. The exceptional adjustability of GelMA facilitates the controlled release and on-demand application of biomolecules, and optimized delivery profiles of CPO and BMP-2 are explored. The sustained release of CPO during the initial healing stages contributes to early immunomodulation and promotes mineralization in the late stage. Meanwhile, the administration of BMP-2 at a relatively high concentration within the therapeutic range enhances the osteoinductive property. This delivery system, with fine-tuned release patterns, induces M2 macrophage polarization and creates a conducive immuno-microenvironment, which in turn facilitates effective bone regeneration in vivo. Collectively, this study proposes a bottom-up concept, aiming to develop a user-friendly and easily controlled delivery system targeting individual biological events, which may offer a new perspective on developing function-optimized biomaterials for clinical use.
摘要：
骨再生是一个协调良好的过程，涉及炎症，血管生成,和成骨。因此,有效的骨移植物应设计为针对骨愈合过程中的多种分子事件和生物学需求。在这项研究中,基于天然生物事件开发了一种基于明胶甲基丙烯酰（GelMA）的可生物降解Janus微球递送系统，该系统包含磷酸钙低聚物（CPO）和骨形态发生蛋白2（BMP-2）。GelMA的特殊可调性促进了生物分子的受控释放和按需应用，并探索了CPO和BMP-2的优化递送曲线。在初始愈合阶段持续释放CPO有助于早期免疫调节并促进晚期矿化。同时,在治疗范围内以相对较高的浓度施用BMP-2增强了骨诱导性质。这个传送系统，通过微调的释放模式，诱导M2巨噬细胞极化并创建有益的免疫微环境，这反过来又促进了体内有效的骨再生。总的来说，这项研究提出了一个自下而上的概念，旨在开发针对单个生物事件的用户友好且易于控制的递送系统，这可能为开发用于临床的功能优化的生物材料提供新的视角。
