5-ALA-loaded GelMA hydrogel for antibacterial and healing-promoting photodynamic therapy of infected wounds

Photodynamic therapy is widely applied in dermatology, and 5-aminolevulinic acid (5-ALA), as a classic photosensitizer, has the advantages of excellent targeting specificity, low biotoxicity, and high conversion efficiency. Nevertheless, conventional topical preparations suffer from short drug retention time, insufficient moisture retention, and lack of physical protection. In this study, a gelatin methacryloyl (GelMA) hydrogel dressing loaded with 5-ALA was fabricated. The dressing forms a three-dimensional network structure via photocrosslinking, enabling it to maintain a moist microenvironment for wounds, prolong the drug residence time, and provide a physical barrier. The loaded 5-ALA can be excited by both a 635 nm laser and natural light to generate reactive oxygen species and exert antibacterial effects, making the system suitable for clinical laser treatment and home care under natural light. The composite hydrogel has antibacterial rates greater than 99% against Staphylococcus aureus (including methicillin-resistant S. aureus , MRSA), Escherichia coli , and Pseudomonas aeruginosa . It also promotes tissue repair and regeneration in preclinical rodent models by regulating immune responses, enhancing angiogenesis, and facilitating collagen deposition. This study not only provides a novel and efficient therapeutic strategy for bacterially infected wounds but also lays an experimental foundation for expanding the clinical applications of photodynamic therapy.