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In the regeneration process for new tissues, oxygen promotes re-epithelialization and healing of infected wounds, increases keratinocyte differentiation, proliferation and migration of fibroblast, and induces angiogenesis, collagen synthesis and wound contraction. Therefore, provision of oxygen to cells and tissues at an optimal level is critical for effective tissue regeneration and wound healing. In this study, we developed sustained oxygen-releasing polymeric microspheres and fabricated a sponge type dressing by embedding the microspheres into alginate-based hydrogel that can supply oxygen to wounds. We further investigated the applicability of the microspheres and hydrogel sponge to wound healing in vitro and in vivo. Oxygen-releasing microspheres (ORM) were made by incorporating hydrogen peroxide (H2O2) into poly(lactic-co-glycolic acid) (PLGA) using double emulsion method. H2O2-PLGA microspheres were embedded into alginate-based hydrogel to form a porous oxygen-releasing hydrogel sponge (ORHS). Biocompatibility was performed using cell counting kit-8. The oxygen release kinetic study was performed using a hydrogen peroxide assay kit and oxygen meter. The wound healing potential of ORHS was evaluated using the wound scratch model. In vivo studies were carried out to investigate the safety and efficacy of the ORHS for wound healing. Experimental results confirmed that oxygen released from ORMand ORHS induced neovascularization and promoted cell proliferation thereby facilitating effective wound healing. It is suggested that the ORM can be used for supplying oxygen to where cells and tissues are deprived of necessary oxygen, and ORHS is an intelligent scaffold to effectively heal wound by enhanced angiogenesis by oxygen. Conclusively, oxygen releasing polymeric microspheres and hydrogel scaffolds have potential for a variety of tissue engineering applications, where require oxygen.

Fabrication of Oxygen Releasing Scaffold by Embedding H2O2-PLGA Microspheres into Alginate-Based Hydrogel Sponge and Its Application for Wound Healing