A Self-Oxygenating Wound-Adaptive Stem Cell Encapsulation Platform for Chronic Wound Repair.

Abstract

Stem cell-based therapies hold substantial promise for the treatment of chronic wounds. However, limited clinical efficacy has frequently arisen not from inadequate cell potency, but from failure of current delivery paradigms to sustain cell survival and function within hostile host microenvironments. Here, we report a wound-adaptive, self-oxygenating stem cell encapsulation platform designed to overcome this delivery paradigm failure. The device embeds living stem cells within an immunoisolating hydrogel matrix conformally shaped to individual wound geometries and converts locally accumulated CO₂ into molecular O₂, thereby providing an oxygen supply that preserves cellular metabolic activity in situ. Importantly, oxygenation in this system functions primarily to sustain cell viability rather than to directly oxygenate host tissue. Compared with conventional local or systemic delivery strategies, encapsulated cells exhibit markedly enhanced survival, persistence, and therapeutic function. Evaluation in diabetic rat and porcine wound models demonstrates accelerated resolution of inflammation, improved vascular maturation, and robust tissue regeneration. By reframing cell therapy as a problem of environment-cell compatibility, this platform establishes a clinically translatable delivery paradigm for precision stem cell therapy in chronic wound repair.