A Bioactive 3D-Bioprinted AuNC@DHLA/GelMA Hydrogel Containing Skin Cells Promotes Burn Wound Healing and Tissue Regeneration.

Severe burn injuries are often associated with excessive and prolonged inflammation, resulting in delayed wound healing and poor tissue regeneration. Accordingly, the development of effective skin substitutes capable of modulating inflammation and promoting tissue repair remains a critical challenge in regenerative medicine. Gelatin methacryloyl (GelMA) has emerged as a promising biomaterial for tissue engineering applications. Moreover, dihydrolipoic acid-modified gold nanoclusters (AuNC@DHLA) have demonstrated anti-inflammatory and regenerative-promoting effects. In this study, we fabricated a bioactive tissue-engineered skin construct by incorporating AuNC@DHLA, fibroblasts, and keratinocytes into a 3D-bioprinted GelMA hydrogel scaffold. The therapeutic efficacy of the cell-laden AuNC@DHLA/GelMA scaffold was evaluated using a murine burn wound model. Furthermore, RNA sequencing was further conducted to explore the molecular mechanisms underlying wound repair, and the findings were subsequently validated by immunohistochemistry. The results demonstrated that the scaffold significantly attenuated local inflammatory responses and accelerated burn wound closure compared with control treatments. Transcriptomic analysis revealed the modulation of inflammation-related and tissue regeneration-associated pathways, which was further confirmed by immunohistochemical analyses. Collectively, these findings indicate that the AuNC@DHLA/GelMA bioengineered skin substitute promotes burn wound healing by regulating the inflammatory microenvironment and enhancing tissue regeneration. This strategy represents a promising therapeutic approach for the treatment of severe burn injuries.