Oxygen-Supplying Containers to Fabricate Immunomodulatory Hydrogels for Expediting Wound Healing via Acute Oxidative Stress.

Abstract

Chronic wounds impose severe health and economic burdens due to persistent inflammation and complications. Immunomodulatory hydrogels have emerged as promising therapies that modulate inflammatory responses for wound healing. Oxygen plays a crucial role in immune modulation and tissue regeneration; however, current oxygen-delivering biomaterials are limited by the mandatory incorporation of oxygen-generating agents and cytotoxic byproducts. Herein, we develop an oxygen-supplying container (Oxygener) via dopamine-mediated catalase immobilization to create oxygen-delivering and immunomodulatory hydrogels. Oxygener supplies oxygen in various solutions by hydrogen peroxide decomposition, producing cytocompatible, oxygen-enriched media for fabricating implantable oxygen-delivering hydrogels. These oxygenated systems facilitate the transition from pro-inflammatory to anti-inflammatory states by reducing macrophage recruitment while improving cellular proliferation and tissue remodeling at the gene and tissue levels in vivo. Our findings establish the minimum oxygen tension and supply duration required for effective wound healing. In summary, Oxygener holds great potential for developing various oxygen-delivering formulations for advanced wound care.