Calcium peroxide-mediated bioactive hydrogels for enhanced angiogenic paracrine effect and osteoblast proliferation

Abstract

Polymeric hydrogels have been extensively utilized as therapeutic vehicles for delivering cells or bioactive molecules to enhance bone tissue regeneration. Among these factors, growing evidence demonstrates that oxygen (O2) and calcium ions (Ca2+) play pivotal roles in bone repair and regeneration, including cell proliferation and vascularization. Herein, we report on gelatin-based bioactive matrices as dual carriers of O2 and Ca2+ for vascularized bone tissue regeneration. Bioactive hydrogels were prepared through a calcium peroxide (CaO2)-mediated crosslinking reaction. We demonstrated that the hydrogels have controllable mechanical properties depending on the composition (G′:300–1700 Pa). We also demonstrated that the hydrogels released Ca2+ in a sustained manner for two days (2.6–2.8 mM) and released O2 (DOmax: G7C0.5, 97.9% pO2; G7C0.25, 82.7% pO2; G7C0.125, 65.5% pO2), providing transient hyperoxic conditions to cells in vitro. Notably, we found that our bioactive hydrogels enhanced the proliferation of pre-osteoblasts (MC3T3-E1) and gene expression of vascular endothelial growth factor (VEGF) from mesenchymal stem cells (MSCs). In summary, our O2- and Ca2+-releasing hydrogels show potential as bioactive hydrogels for vascularized bone tissue regeneration.