Affiliation:
1. Department of Orthopedics the First Affiliated Hospital of Soochow University 188 Shizi Road, Gusu District Suzhou Jiangsu 215006 P. R. China
2. Department of Orthopedics Beijing Friendship Hospital Capital Medical University No. 95, Yong An Road, XiCheng District Beijing 100050 P. R. China
Abstract
AbstractTargeting macrophages can facilitate the site‐specific repair of critical bone defects. Herein, a composite hydrogel, gelatin‐Bletilla striata polysaccharide‐mesoporous bioactive glass hydrogel (GBMgel), is constructed via the self‐assembly of mesoporous bioactive glass on polysaccharide structures, through the Schiff base reaction. GBMgel can efficiently capture macrophages and drive the recruitment of seed stem cells and vascular budding required for regeneration in the early stages of bone injury, and the observed sustained release of inorganic silicon ions further enhances bone matrix deposition, mineralization, and vascular maturation. Moreover, the use of macrophage‐depleted rat calvarial defect models further confirms that GBMgel, with ligand‐selective macrophage targeting, increases the bone regeneration area and the proportion of mature bone. Mechanistic studies reveal that GBMgel upregulates the TLR4/NF‐κB and MAPK macrophage pathways in the early stages and the JAK/STAT3 pathway in the later stages; thus initiating macrophage polarization at different time points. In conclusion, this study is based on the endogenous self‐healing properties of bone macrophages, which enhances stem cell homing, and provides a research and theoretical basis upon which bone tissue can be reshaped and regenerated using the body's immune power, providing a new strategy for the treatment of critical bone defects.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province
Natural Science Foundation of Beijing Municipality
Project 333 of Jiangsu Province
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials