Engineering microalgae-based oxygenators for hypoxia relief and enhanced photodynamic therapy against biofilms in...

Diabetic wounds present complex therapeutic challenges due to bacterial infection, persistent inflammation, microvascular hypoxia, and biofilm formation. Although photodynamic therapy (PDT) enables antibacterial activity in deep tissues, its efficacy is limited under hypoxic conditions and within biofilms. To address this, we developed an engineered microalgae-based oxygen-generating system capable of sustained in situ oxygen production to alleviate hypoxia, enhance PDT effectiveness, and disrupt biofilms. Specifically, these oxygenators comprise Chlorella vulgaris (Cv) was encapsulated within a bioactive metal-phenolic network formed by epigallocatechin gallate (EGCG) and Fe³⁺ ions via layer-by-layer assembly, followed by loading with the photosensitizer tetra-(4-carboxyphenyl) porphyrin (TCPP), resulting in a multifunctional system designated as Cv@EFe-TCPP. The embedded Cv continuously produces oxygen through photosynthesis, a process modulated by the thickness of the coating. Meanwhile, the metal-phenolic coating and TCPP generate reactive oxygen species upon light irradiation. The endogenous oxygen supply significantly improves PDT efficiency by mitigating hypoxia, thereby enhancing antibacterial and anti-inflammatory outcomes. In addition, under light exposure, Cv@EFe-TCPP promotes cell migration, reduces inflammatory responses, and stimulates angiogenesis and tissue regeneration, without inducing detectable side effects in normal tissues. This study extends the scope of PDT-based antibacterial strategies by integrating photosynthetic oxygen production, offering a promising therapeutic platform for diabetic wound healing.