Transdermal delivery of Protocatechuic aldehyde using hyaluronic acid/gelatin-based microneedles for the prevention and treatment of hypertrophic scars

Abstract

The formation of hypertrophic scar (HS) involves many pathological processes, such as reduced apoptosis in fibroblasts, excessive collagen deposition by fibroblasts, over-abundant angiogenesis, etc. The therapeutic effects of current treatments targeting one single pathological process are limited. Due to their diverse biological activities, natural products offer a potential solution to this issue. In this study reported herein, we investigated the effects of Protocatechuic aldehyde (PA) on both hypertrophic scar-derived fibroblasts (HSF) and vascular endothelial growth factor (VEGF)-stimulated human umbilical vein endothelial cells (HUVECs). Microneedles (MN) containing PA and hyaluronic acid (HA) or containing PA, HA, and gelatin were prepared by mixing PA stock solution with HA or HA/gelatin at a ratio of 1:10. The HS prevention and treatment outcomes of these HA-PA-MN and HA/gelatin-PA-MN were tested using a rabbit ear HS model. Our data indicate that PA induces apoptosis and reduces collagen deposition in HSF. In addition, PA attenuates VEGF-stimulated angiogenesis of HUVECs. Furthermore, HA-PA-MN or HA/gelatin-PA-MN are able to effectively penetrate the epidermis of the HS tissues and then quickly dissolve, enabling the fast release of PA directly into the dermis of the HS tissues. HA-PA-MN or HA/Gelatin-PA-MN have also been found to effectively prevent or alleviate HS in a rabbit ear HS model. In conclusion, this study demonstrates that PA can be used to prevent and treat HS by simultaneously regulating HSF and HUVECs, which offers a potential novel reagent for HS management.