Comparative Morphological Characterization of Skin after Subcutaneous Application of Hyaluronic Acid and Polycaprolactone in Rats: Establishment of an Experimental Model

Abstract Injectable facial fillers are excellent options for treating facial aging, wrinkles, and contour defects. Both polycaprolactone (PCL) and hyaluronic acid (HA) have been used to restore lost tissue volume and improve facial contour. However, the mechanisms involved in the effect of these biomaterials still need to be fully understood. The present work aims to establish an experimental model to investigate cellular and morphological changes in the skin of Wistar rats in response to HA and PCL to understand the mechanisms associated with these effects. The subcutaneous tissue of the back of Wistar rats was used as a reception area for biomaterials, represented by the commercial products Ellansé®, containing polycaprolactone (PCL) and Juvederm Voluma®, containing hyaluronic acid (HA). Animals were euthanized afetr 30 or 60 days, and skin samples were collected from treated and untreated animals (CONTROL) for histological and immunohistochemical evaluation for IBA-1, TGF-β, and FGF. Analysis of type I and type III collagen deposition, neovascularization, and adipose tissue was performed. On histological examination, HA appeared as an amorphous, basophilic material interspersed with connective tissue bundles. The skin fragments with PCL showed intense cell proliferation, with foreign body giant cells and a higher capillary proliferation than the HA group. More vessels were observed in the HA and PCL groups compared to the CONTROL group. A significant increase in fibroblasts and fibrocytes was observed in skin fragments inoculated with HA and PCL, associated with increased FGF expression. The number of fibroblasts was significantly higher in the PCL group than HA. The PCL group showed higher immunostaining for IBA-1 and TGF-β than the CONTROL and HA groups. Collagen deposition was observed in the treated groups, especially type III collagen in the PCL group, when compared to HA. Our morphological results demonstrated stimulation of fibroblastic activity and active-related tissue regeneration, with increased vascular proliferation and expression of markers related to tissue proliferation, mainly associated with the PCL group. We also observed increased adipose tissue, although further studies are needed to confirm these findings.