Adipose-derived exosomes as a preventative strategy against complications in hyaluronic acid filler applications: A comprehensive in vivo analysis.

Abstract

The aim of this study was to investigate the impact of exosomes derived from adipose-derived stem cells (ASCs) on complications arising from hyaluronic acid (HA) filler injections. An HA hydrogel blended with adipose stem cell-derived exosomes was prepared and administered to the inguinal fat pads of 16 C57BL/6J mice. The control group received only HA filler (HA group), and the study group was treated with a combination of HA filler and exosomes (exoHA group). Biopsy was performed 1 week and 1, 2, 3, and 6 months after the injections. The effects were assessed using hematoxylin and eosin and Masson's trichrome staining for histological examination, immunohistochemistry for collagen type I and Vascular Endothelial Growth Factor (VEGF), RNA sequencing, and quantitative real-time polymerase chain reaction (PCR) (Il6, Ifng, Hif1a, Acta2, Col1a1). RNA sequencing revealed significant downregulation of the hypoxia (false discovery rate [FDR] q = 0.007), inflammatory response (FDR q = 0.009), TNFα signaling via NFκB (FDR q = 0.007), and IL6 JAK-STAT signaling (FDR q = 0.009) gene sets in the exoHA group. Quantitative PCR demonstrated a decrease in expression of proinflammatory cytokines (Il6, P < 0.05; Hif1a, P < 0.05) and fibrosis markers (Acta2, P < 0.05; Col1a1, P < 0.05) within the exoHA group, indicating reduced inflammation and fibrosis. Compared to the exoHA group, the HA group exhibited a thicker and more irregular capsules surrounding the HA filler after 6 months. The addition of ASC-derived exosomes to HA fillers significantly reduces inflammation and accelerates collagen capsule maturation, indicating a promising strategy to mitigate the formation of HA filler-related nodules.