A PIWI-interacting RNA-loaded gelatin methacryloyl microneedle patch improves wound repair following cutaneous injury

Inducing cutaneous regeneration is a key strategy for significantly accelerating wound closure. A cardiac-regeneration-associated PIWI-interacting RNA (CRAPIR) has shown advantages in cardiomyocytes proliferation and cardiac repair post-myocardial infarction. However, whether it participates in regulating cutaneous wounds healing is still unclear. Here, we demonstrate that agomir-mediated overexpression of CRAPIR promotes skin fibroblasts proliferation and endothelial cell migration. Local injection of CRAPIR agomir into the injured tissue area accelerate skin wounds recovery in mouse full-thickness wound model via promoting collagen deposition and angiogenesis while inhibiting inflammatory. Furthermore, we synthesize a gelatin methacryloyl microneedle (GelMA-MN) patch with superior biocompatibility and mechanical strength for loading CRAPIR agomir, and penetrating the skin stratum corneum. Notably, this patch loaded with CRAPIR agomir show stronger angiogenesis and anti-inflammatory effects. Mechanistically, CRAPIR promotes skin fibroblasts proliferation by inhibiting p53/p21 expression while increasing CCND1 protein content. In conclusion, these findings confirm CRAPIR both act as a regulator of skin fibroblasts proliferation and as a therapeutic target for skin tissue regeneration and repair though p53/p21 signaling axis. Moveover, biomaterials-based approach better achieve wound healing and sustained release piRNAs, providing an efficient treatment strategy for skin tissue repair.