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Sufficient oxygenation for prevention of cellular damage remains a critical barrier to successful tissue engineering, especially in the construction of a large-sized tissue despite numerous attempts to resolve this issue in recent years. There have been a number of hypothetical solutions to this problem, including the use of artificial oxygen carriers, induction of vascularization, and fabrication of oxygen-generating biomaterials. All of these efforts have improved the efficiency of oxygen supply, but none have been able to support the large tissue mass required for clinical application. Necrosis, which often occurs during hypoxic stress, is one of the most significant limitations in large-sized tissue regeneration. In this study, we developed an oxygen producing capsule using hydrogen peroxide (H2O2), PLGA (poly (lactic-co-glycolic acid) and alginate, and also evaluated the capsule as a model of a large-sized tissue. Firstly, H2O2 was microencapsulated by PLGA, and subsequently the H2O2-PLGA microspheres were embedded into a catalase-immobilized alginate capsule of 5.0 mm in diameter. The alginate capsules of a fairly large size were characterized for their oxygenation capability to cells embedded such as human umbilical vein endothelial cells (HUVECs) by HIF-1α and VEGF expression. The results of this study confirmed that in the oxygen-releasing capsule composed of H2O2 polymeric microspheres and catalase-bound alginate, HUVEC cells successfully survived in the hypoxic state. These results demonstrated that our oxygen producing system containing H2O2-PLGA microspheres could be a useful oxygenating biomaterial for engineering large-sized tissue.

Preparation of an Oxygen-Releasing Capsule for Large-Sized Tissue Regeneration