An injectable and self-healing hydrogel with dual physical crosslinking for in-situ bone formation

Tao Yu; Yunping Hu; Wenbao He; Yong Xu; Anqi Zhan; Kai Chen; Mingxiang Liu; Xiufeng Xiao; Xiangyang Xu; Qian Feng; Liangfu Jiang

doi:10.1016/j.mtbio.2023.100558

An injectable and self-healing hydrogel with dual physical crosslinking for in-situ bone formation

Mater Today Bio. 2023 Jan 24:19:100558. doi: 10.1016/j.mtbio.2023.100558. eCollection 2023 Apr.

Authors

Tao Yu¹, Yunping Hu², Wenbao He³, Yong Xu⁴, Anqi Zhan⁴, Kai Chen², Mingxiang Liu², Xiufeng Xiao², Xiangyang Xu¹, Qian Feng⁵, Liangfu Jiang⁶

Affiliations

¹ Department of Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, College of Chemistry and Materials Science, Fujian Normal University, Fuzhou, China.
³ Department of Orthopedics, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
⁴ Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
⁵ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
⁶ Department of Orthopedics (Division of Wound Repair), The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Abstract

Although hydrogels have been widely studied because of their satisfactory biocompatibility and plasticity, their application is limited in bone tissue engineering (BTE) owing to their inadequate mechanical properties and absence of osteogenic activity. To address this issue, we developed an updated alendronate (ALN)-Ca²⁺/Mg²⁺-doped supramolecular (CMS) hydrogel based on our previously developed mechanically resilient "host-guest macromer" (HGM) hydrogel to improve the hydrogel's mechanical properties and osteogenic activity. The CMS hydrogel was prepared by introducing a new physical crosslinking comprising the strong chelation of the comonomer acrylate alendronate (Ac-ALN) and Ca²⁺/Mg²⁺ in the HGM hydrogel. Compared with the previously developed HGM hydrogel, the upgraded CMS hydrogel presented better mechanical properties because of the additional physical crosslinking, while possessing injectable and self-healing properties like the HGM hydrogel. Moreover, the addition of Ac-ALN and Ca²⁺/Mg²⁺ also effectively promoted the in vitro proliferation, migration, and osteogenic differentiation of bone marrow-derived stem cells. The healing effect of a rat cranial defect further proved that the in vivo bone regeneration ability of CMS hydrogel was better than that of HGM hydrogel. The updated CMS hydrogel shows significant potential for BTE application.

Keywords: Hydrogel; Mechanical properties; Osteogenesis; Physical crosslinking; Self-healing.