Preclinical Histologic and Morphometric Comparison of Poly-L-Lactic Acid Fillers Formulated With Carboxymethyl Cellulose or Non-crosslinked Hyaluronic Acid in a Porcine Model

BACKGROUND: Poly-L-lactic acid (PLLA)-based injectable fillers are used as biostimulatory materials in aesthetic practice. Carrier components may influence particle distribution, hydration behavior, and tissue integration. Comparative preclinical data on PLLA formulations incorporating carboxymethyl cellulose (CMC) versus non-crosslinked hyaluronic acid (HA) remain limited. OBJECTIVE: To compare the longitudinal histologic and morphometric tissue response to PLLA fillers containing CMC or non-crosslinked HA in a porcine model. METHODS: In this paired preclinical study, 10 hybrid female pigs received bilateral subcutaneous injections of PLLA + CMC (Ellure CMC) and PLLA + HA (Ellure HA) at matched abdominal sites. Animals were euthanized at 7, 14, 30, 90, and 180 days post-injection (two animals per time point). Full-thickness skin and subcutaneous adipose tissue (SAT) were harvested from the injection sites. Histologic evaluation was performed using hematoxylin and eosin, Weigert-Van Gieson, and Sirius Red staining. Morphometric assessment included dermal thickness, fibroblast/fibrocyte-associated cellularity, vascular parameters, and collagen type I, collagen type III, and elastin content. RESULTS: Across all time points, neither formulation was associated with macroscopic inflammation or histopathologic evidence of overt adverse tissue reaction. Both formulations showed progressive tissue integration characterized by fibroblast/fibrocyte-associated cellular infiltration, neovascular remodeling, and changes in dermal thickness. Mean dermal thickness increased over time in both groups, from 928.6 ± 196.0 µm to 1590.1 ± 125.1 µm for Ellure CMC and from 1231.5 ± 267.8 µm to 1993.4 ± 149.5 µm for Ellure HA between days 7 and 180, with intermediate fluctuation. Collagen and elastin profiles showed broadly similar temporal patterns in skin and SAT in the two groups. Given the limited sample size and the exploratory design, these comparisons should be interpreted descriptively. CONCLUSION: In this porcine model, PLLA fillers incorporating either CMC or non-crosslinked HA showed comparable descriptive histologic biocompatibility and tissue-remodeling profiles over 180 days. The findings support further controlled studies to determine whether carrier composition influences clinically relevant performance in cosmetic applications.