A Rat Model Investigation of Enhanced Facial Rejuvenation via PCL Microsphere-Induced Superior Collagen Neogenesis in the Supraperiosteal Plane

BACKGROUND: Age-related collagen loss and bone resorption leads to structural changes in the bone platform, affecting facial support. Fillers restore volume and structure, but their precise biological mechanisms remain unclear. This study aims to investigate the interaction between fillers and periosteum, and systematically compare the differential effects of supraperiosteal implantation of polycaprolactone (PCL) microspheres versus hyaluronic acid (HA) on collagen formation, elastin fiber production, as well as the recruitment of vascular and periosteal stem cells (PSCs). METHODS: Supraperiosteal implants of PCL microspheres and HA were evaluated in a rat model. Histological analyses, including Hematoxylin and Eosin (H&E) and Masson's trichrome staining, were used to assess collagen ingrowth. Immunofluorescence staining was employed to identify the presence of type I and type III collagen. Elastin van Gieson (EVG) staining was used to evaluate elastin fiber formation. Additionally, the recruitment of Emcn-positive blood vessels and LepR-positive PSCs was assessed. RESULTS: H&E and Masson's trichrome staining revealed significantly enhanced collagen ingrowth in PCL microspheres compared to HA. Immunofluorescence staining showed substantial infiltration of type I and type III collagen within the PCL microspheres, with a predominance of type I collagen. EVG staining indicated that PCL microspheres significantly promoted elastin fiber formation. Furthermore, PCL microsphere implants facilitated notable ingrowth of Emcn-positive blood vessels and LepR-positive PSCs. CONCLUSIONS: Compared to HA, PCL microspheres more effectively stimulate collagen and elastin formation and recruit vascular and periosteal stem cells. These findings suggest PCL may offer superior regenerative potential for supraperiosteal aesthetic applications. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .