Multifunctional layered microneedle patches enable transdermal angiogenesis and immunomodulation for scarless healing of thermal burn injuries.

Thermal burn injuries induce substantial alterations in the immune compositions and anatomical structures in the skin, which are characterized by strong inflammatory responses and thick eschar formation on the wound surface. These traits challenge current treatment paradigms due to insufficient drug penetration into affected tissues and the unsatisfactory wound regeneration. Herein, we report a layered microneedle (MN) patch for addressing these challenges in burn injury healing. The MN patch features a core/shell structure with methacrylated gelatin (GelMA) encapsulated with human umbilical vein endothelial cell (HUVECs)-derived hypoxia-induced exosomes (EXO-H) as the bottom layer and sodium alginate (SA) containing naringin (Nar)-loaded CaCO nanoparticles (CaCO@Nar) as the top layer. Upon administration onto thermal burn injury site, the MN patches enable transdermal drug delivery by perforating the eschar. The spontaneous degradation of CaCO@Nar in the interstitial fluid triggers sustained Nar release to alleviate local inflammation and scavenge excessive reactive oxygen species (ROS). Meanwhile, EXO-H significantly promote the migration and proliferation of HUVECs and enhance their angiogenesis capacity to support scarless wound tissue regeneration. The MN patch in this work successfully promoted scarless healing of skin burn injuries on rat models, providing an approach for thermal burn treatment in the clinics.