A novel adhesive dual-sensitive hydrogel for sustained release of exosomes derived from M2 macrophages promotes repair of bone defects

• Published in: Materials today bio 2023-12, Vol.23, p.100840-100840, Article 100840
• Main Authors: Zhao, Xiaoying, Chen, Ximiao, Deng, Yuxin, Wu, Chenyu, Ruan, Zihang, Li, Chenchao, Chen, Yu, Bei, Chaoyong, Zhu, Linyong, Yu, Huachen, Zhang, Xiaolei
• Format: Article
• Language: English
• Subjects: Bone defect repair; Exosome; F127/HA-NB hydrogel; M2 macrophage; Wnt/β-catenin signaling pathway
• ISSN: 2590-0064; 2590-0064
• DOI: 10.1016/j.mtbio.2023.100840

The repair of bone defects remains a huge clinical challenge. M2 macrophage-derived exosomes (M2-Exos) can act as immunomodulators to promote fracture healing; however, how to retain the sustained release of exosomes to the target area remains a challenge. Here, we report a composite hydrogel loaded with M2-Exos aiming to accelerate bone defect healing. It was verified that the F127/HA-NB hydrogel had a dense network structure, tissue adhesiveness, and dual sensitivity to temperature and light. F127/HA-NB loaded with M2-Exos (M2-Exos@F127/HA-NB) exhibited good biocompatibility and achieved sustained release of exosomes for up to two weeks. The study showed that both M0-Exos and M2-Exos@F127/HA-NB significantly promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells. The mechanism study implied that M2-Exos activates the Wnt/β-catenin signaling pathway to promote osteogenic differentiation of BMSCs. Finally, we evaluated the osteogenetic effects of M2-Exos@F127/HA-NB in a rat cranial defect model, and the results showed that M2-Exos@F127/HA-NB had superior bone regeneration-promoting effects. This study provides a new strategy for cell-free treatment of bone defects. [Display omitted]