A novel magnesium ion-incorporating dual-crosslinked hydrogel to improve bone scaffold-mediated osteogenesis and angiogenesis

Abstract

Osteogenesis is closely complemented by angiogenesis during the bone regeneration process. The development of functional hydrogel bone substitutes that mimic the extracellular matrix is a promising strategy for bone tissue engineering. However, the development of scaffold materials tailored to exhibit sufficient biomechanics, biodegradability, and favorable osteogenic and angiogenic activity continue to present a great challenge. Herein, we prepared a novel magnesium ion-incorporating dual-crosslinked hydrogel through the photocrosslinking of gelatin methacryloyl (GelMA), thiolated chitosan (TCS) and modified polyhedral oligomeric silsesquioxane (POSS) nanoparticles, and active Mg²⁺ ions were then introduced into system via coordination bonds of MgS, which can be tailored to possess superior mechanical strength, a stable network structure and more suitable pore size and degradation properties. The fabricated GelMA/TCS/POSS-Mg hydrogels effectively promoted cell adhesion, spreading, and proliferation, demonstrating that the introduction of POSS and Mg²⁺ not only stimulates the osteogenic differentiation of BMSCs but also promotes angiogenesis both in vitro and in vivo, thereby facilitating subsequent bone regeneration in calvarial defects of rats. Taken together, the results of this study indicate that the GelMA/TCS/POSS-Mg hydrogel has promising potential for repairing bone defects by promoting cell adhesion, osteogenesis and vascularization.

Keywords: Bone regeneration; Magnesium ion-incorporating dual-crosslinked hydrogel; Osteogenesis and angiogenesis; POSS.