Osteoblast/Osteoclast and Immune Cocktail Therapy of an Exosome/Drug Delivery Multifunctional Hydrogel Accelerates Fracture Repair
Bobin Mi, Lang Chen, Yuan Xiong, Yayan Yang, Adriana C. Panayi, Hang Xue, Yiqiang Hu, Chenchen Yan, Liangcong Hu, Xudong Xie, Ze Lin, Wu Zhou, Faqi Cao, Xiufeng Xiao, Qian Feng, Guohui Liu
Abstract
High Resolution Image Download MS PowerPoint Slide The osteoblast/osteoclast and M1/M2 macrophage ratios play critical roles in delayed fracture healing. Robust osteoblast differentiation and M2 macrophage polarization can substantiality promote fracture repair; however, the combined effect of these strategies has not been previously studied. In this study, we constructed a cocktail therapy to simultaneously regulate the osteoblast/osteoclast and M1/M2 macrophage balance. The cocktail therapy composed of a natural polymer hyaluronic-acid-based hydrogel (HA hydrogel, which has a tissue-adhesive, injectable, self-healing, anti-inflammation profile), engineered endothelial cell-derived exosomes (EC-Exos miR-26a-5p ), and APY29, an IRE-1α inhibitor. This allowed for specific delivery of EC-Exos miR-26a-5p and APY29 for osteoblast/osteoclast and macrophage regulation, respectively. The results suggested that the cocktail therapy exerted pro-fracture repair effects with each of its components established as indispensable. The assessed cocktail therapy provides insight into synergistic strategies and is useful for developing more suitable pro-fracture repair therapy.