Comparative ESEM Characterization and Collagen-Related Tissue Responses to Commercial Injectable Bioregenerative Formulations in a Murine Model.

Dermal senescence is associated with reduced fibroblast activity, decreased extracellular matrix synthesis, and impaired tissue repair. Commercial injectable formulations containing poly-L-lactic acid (PLLA), hyaluronic acid (HA), and polydeoxyribonucleotide (PDRN)-associated compounds have been proposed for dermal remodeling approaches and modulate tissue-response pathways; however, comparative studies evaluating commercially available formulations under standardized experimental conditions remain limited. This study aimed to characterize the morphology of formulations containing PLLA, HA, and PDRN, used alone or in combination, by environmental scanning electron microscopy (ESEM), and to investigate formulation-associated histological and collagen-related molecular responses in a murine model. Formulations containing PLLA, HA, HA + PDRN, and PLLA, HA and PDRN were administered into the dorsal subcutaneous tissue of 14 Mus musculus mice (Swiss strain). After 30 days, tissue response was assessed by ultrasound, histological analysis with Masson's trichrome staining, and RT-qPCR quantification of collagen-related gene expression. ESEM analysis revealed distinct morphological characteristics among the biomaterials, and the combined PLLA, HA and PDRN formulation exhibited a more complex and integrated multiphase structure. Histological analysis showed preserved tissue architecture in all groups, with no evidence of marked inflammatory response or structural disruption. RT-qPCR demonstrated significantly higher COL1A1 expression in the PLLA-only and PLLA, HA, and PDRN groups compared with controls (p < 0.05), whereas no significant differences were observed for COL2A1 or COL3A1. These findings indicate that PLLA-containing formulations were associated with selective COL1A1 upregulation under the evaluated conditions, suggesting formulation-associated collagen-related molecular responses in this short-term model.