Ceria‐Nanoparticle‐Entangled Reticulation for Angiogenic and Therapeutic Embrocation for Multifactorial Approach to Treat Diabetic Wound

Ceria-nanoparticle-entangled reticulation for angiogenic and therapeutic embrocation (CERATE) is engineered for topical treatment of diabetic excisional wounds. The as-synthesized ceria nanoparticles and levofloxacin internally cross-link hyaluronic acid through a mild synthesis, resulting in a clinically synergistic nanocomplex. CERATE effectively repairs diabetic wounds by tackling various pathological factors throughout the wound healing stages, with a primary focus on boosting angiogenesis.

Abstract

The therapeutic efficacy of a nanomedicine or a natural biomaterial can vary in different disorders due to their complex pathophysiology. A nanomedicine that is capable of not only targeting specific pathological cues through functional ligands but also optimizing the therapeutic efficacy of its components throughout the intricate pathways involved in complex disorders is highly desired. Here, ceria-nanoparticle-entangled reticulation for angiogenic and therapeutic embrocation (CERATE), composed of hyaluronic acid, levofloxacin, and the as-synthesized ceria nanoparticles is developed. CERATE is formulated in situ as a rigid nanoparticle-based network that integrates its components intimately using highly diluted concentrations, thereby augmenting the therapeutic efficiency of its individual components. The physical states of CERATE can be altered freely while retaining its integrity, by adjusting the water proportion to accommodate diverse clinical needs. This physically robust CERATE can withstand enzymatical degradation, display antibacterial activity, scavenge reactive oxygen species, and improve the migration and proliferation of fibroblasts by activating the proangiogenic factors. CERATE accelerates the repair of diabetic wounds by promoting both the angiogenesis and the synthesis of collagen. The results demonstrate the effectiveness of a multifactorial approach involving the recruitment of minimally modified biofunctional ligands and nanomaterials altogether with synergistic efficacy in treating complex disorders.