Background <p>Poly-L-lactic acid (PLLA) is a well-established facial filler recognized for its ability to stimulate collagen synthesis. While emerging evidence suggests that PLLA modulates the differentiation and lipolysis of dermal adipocytes, its role in autologous fat transplantation remains unclear.</p> Methods <p>In vitro, mature adipocytes were treated with lactate or PLLA during ceiling culture to explore the regulatory mechanisms of PLLA-mediated dedifferentiation. Subsequently, we established a murine model of PLLA and adipose tissue co-transplantation, with grafts harvested at 7, 30, and 90&#xa0;days. Graft survival was assessed via volumetric analysis, histological evaluation, and qPCR to validate the in vitro findings.</p> Results <p>PLLA-derived lactate facilitates adipocyte dedifferentiation at low-to-moderate concentrations. This phenotypic reversion was abrogated by pharmacological inhibition of monocarboxylate transporters (MCTs). Additionally, lactate-induced DFATs exhibited enhanced angiogenic potential. In vivo, co-transplantation of PLLA and adipose tissue significantly enhanced volume retention and neovascularization. PLLA implantation triggered only a transient acute inflammatory response that stabilized subsequently without inducing chronic fibrosis, ensuring long-term biocompatibility.</p> Conclusions <p>As a biocompatible synthetic material, PLLA degrades into lactate and enhances fat graft volume retention by promoting dedifferentiation of adipocytes. This finding indicates that PLLA holds broad application prospects in fat transplantation.</p> No Level Assigned <p>This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable</p>