Injectable, oxygen-releasing, thermosensitive hydrogel promotes vascularized bone formation with prolonged oxygen delivery and improved osteoinductivity
Yixin Xu, Shaowei Zheng, Zinan Tang, Qiang Zhong, Rong Chen, Pinkai Wang, Jinlang Fu, Jiajun Xie, Yanhong Ning, Mingyuan Lei, Ding Wang, Huaming Mai, Hao Li, Chunhan Sun, Zhanjun Shi, Hao Cheng, Zhe Shi
Abstract
The failure or delay in healing of critical bone defects is primarily due to early local anoxic conditions and reduced osteogenic activity. In this research, we integrated calcium peroxide (CPO) embedded polycaprolactone (PCL) microspheres and osteoinductive nanoparticles (Hydroxyapatite/Laponite) into a thermosensitive hydrogel (Pluronic F127), thereby formulating an injectable oxygen-releasing osteogenic thermosensitive hydrogel. Notably, the oxygen-releasing microspheres (ORMs) within the composite hydrogel provide stable oxygen release for up to 21 days, ensuring the survival, migration, and bioactivity of both mesenchymal stem cells and endothelial cells under anoxic conditions. Additionally, the composite hydrogel significantly augments the osteogenic potential of bone marrow mesenchymal stem cells by providing a biomimetic microenvironment with the incorporation of nano-hydroxyapatite/laponite. Ultimately, the injectable composite hydrogel successfully stimulated bone regeneration within a cranial defect in a rat model after 8 weeks, with enhanced vascularization and bone quality. The engineered hydrogel provides a minimally invasive approach to stimulate bone regeneration with a sustained oxygen supply and osteogenic microenvironment provision, underlining its potential for treating critical bone defects. Utilizing the double emulsion method, we fabricate oxygen-releasing microspheres (ORMs) which, when combined with HAP and SN into the Pluronic F127 (PF-127) thermosensitive hydrogel, thereby constructing an injectable oxygen-releasing osteogenic thermosensitive hydrogel. Upon injection into critical bone defects, it effectively mitigated the hypoxic environment through a 21-day controlled oxygen release, reconstructed the osteogenic microenvironment, and finally fostered vascularized bone regeneration. • The composite hydrogel has been shown to consistently supply oxygen for 21 days. • The composite hydrogel reestablishes the osteogenic microenvironment, markedly amplifying the osteogenic potential of BMSCs. • The novel injectable, oxygen-releasing, osteogenic hydrogel offers a unique solution for critical bone defect repair.