Smartly Engineered Casein Manganese Oxide Nanobiomaterials and Its Potential Therapeutic Angiogenesis Applications for Wound Healing and Limb Ischemia

Abstract Recent research offers several approaches for the advancement of manganese‐based nanomaterials for its therapeutic use. The present research paper reports the development of smartly engineered casein manganese oxide nanobiomaterials (CMnNP) using manganese chloride and casein under alkaline condition at room temperature. The CMnNP are systematically characterized by various analytical techniques. The biocompatibility of these nanomaterials is observed by in vitro cell viability and in vivo hemolysis assay. The nanomaterials (CMnNP) exhibit the pro‐angiogenic properties, established through various in vitro assays in endothelial cells and in vivo experiments. The interaction of manganese with different enzymes and angiogenic proteins is identified through in silico analysis that is further validated through in vitro western blot studies. This study also demonstrates the application of therapeutic angiogenesis of CMnNP for wound healing as well as hindlimb ischemia in C57BL/6J and BALB/c mouse model, respectively. The formation of redox signaling molecules (especially H 2 O 2 , O 2 ˙ − , and NO) in endothelial cells may be one of the plausible mechanisms for CMnNP‐mediated angiogenesis. Considering the results, the current study offers a nanomedical perspective for the therapy of various ischemic diseases as well as wound healing where angiogenesis involves is a crucial step.