Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.
Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai 200011, China.
J Control Release. 2024 Oct;374:154-170. doi: 10.1016/j.jconrel.2024.08.011. Epub 2024 Aug 14.
To realize high-quality vascularized bone regeneration, we developed a multifunctional hydrogel (SHPP-ZB) by incorporating BMP-2@ZIF-8/PEG-NH nanoparticles (NPs) into a sodium alginate/hydroxyapatite/polyvinyl alcohol hydrogel loaded with PDGF-BB, allowing for the sequential release of angiogenic and osteogenic growth factors (GFs) during bone repair. ZIF-8 served as a protective host for BMP-2 from degradation, ensuring high encapsulation efficiency and long-term bioactivity. The SHPP-ZB hydrogel exhibited enhanced mechanical strength and injectability, making it suitable for complex bone defects. It provided a swelling interface for tissue interlocking and the early release of Zn and tannin acid (TA) to exert antioxidant and antibacterial effects, followed by the sequential release of angiogenic and osteogenic GFs to promote high-quality vascularized bone regeneration. In vitro experiments demonstrated the superior angiogenic and osteogenic properties of SHPP-ZB compared to other groups. In vivo experiments indicated that the sequential delivery of GFs via SHPP-ZB hydrogel could improve vascularized bone regeneration. Further, RNA sequencing analysis of regenerative bone tissue revealed that SHPP-ZB hydrogel promoted vascularized bone regeneration by regulating JUN, MAPK, Wnt, and calcium signaling pathways in vivo. This study presented a promising approach for efficient vascularized bone regeneration in large-scale bone defects.
为实现高质量的血管化骨再生，我们开发了一种多功能水凝胶（SHPP-ZB），通过将 BMP-2@ZIF-8/PEG-NH 纳米颗粒（NPs）纳入载有 PDGF-BB 的海藻酸钠/羟基磷灰石/聚乙烯醇水凝胶中，允许在骨修复过程中顺序释放血管生成和成骨生长因子（GFs）。ZIF-8 作为 BMP-2 的保护宿主，防止其降解，确保了高封装效率和长期生物活性。SHPP-ZB 水凝胶具有增强的机械强度和可注射性，适用于复杂的骨缺损。它提供了一个用于组织互锁的肿胀界面，并早期释放 Zn 和鞣酸（TA）以发挥抗氧化和抗菌作用，随后顺序释放血管生成和成骨 GFs 以促进高质量的血管化骨再生。体外实验表明，SHPP-ZB 比其他组具有优越的血管生成和成骨性能。体内实验表明，通过 SHPP-ZB 水凝胶顺序递呈 GFs 可以改善血管化骨再生。此外，对再生骨组织的 RNA 测序分析表明，SHPP-ZB 水凝胶通过调节体内 JUN、MAPK、Wnt 和钙信号通路促进血管化骨再生。这项研究为大规模骨缺损中高效血管化骨再生提供了一种有前途的方法。
