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

Xiaoying Zhao; Ximiao Chen; Yuxin Deng; Chenyu Wu; Zihang Ruan; Chenchao Li; Yu Chen; Chaoyong Bei; Linyong Zhu; Huachen Yu; Xiaolei Zhang

doi:10.1016/j.mtbio.2023.100840

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

Mater Today Bio. 2023 Nov 2:23:100840. doi: 10.1016/j.mtbio.2023.100840. eCollection 2023 Dec.

Authors

Xiaoying Zhao^{1

2

3}, Ximiao Chen^{1

2

3}, Yuxin Deng^{1

2

3}, Chenyu Wu^{1

2

3}, Zihang Ruan^{1

2

3}, Chenchao Li^{1

2

3}, Yu Chen^{1

2

3}, Chaoyong Bei⁴, Linyong Zhu⁵, Huachen Yu^{1

2

3}, Xiaolei Zhang^{1

2

3}

Affiliations

¹ Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
² Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China.
³ The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
⁴ Department of Orthopaedics, Aﬃliated Hospital of Guilin Medical College, Guilin, Guangxi Province, China.
⁵ School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Abstract

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.

Keywords: Bone defect repair; Exosome; F127/HA-NB hydrogel; M2 macrophage; Wnt/β-catenin signaling pathway.