Peptide Hydrogel Enhances Adipocyte Viability and Reduces Inflammatory Response in Fat Grafting: A Preclinical Study

Fat grafting is gaining traction in regenerative and aesthetic medicine because of ease of adipose tissue harvesting and potential applications in autologous soft tissue reconstructions. A key challenge remains the limited viability of lipoaspirate-derived adipocytes following the procedures of harvesting, processing, and implantation, which leads to suboptimal outcomes in graft survival.

The aim of this study was to evaluate whether a hydrogel composed of the amphiphilic and anionic β-sheet peptide Pro-Asp-(Phe-Asp)5-Pro (PFD) enhances fat graft outcomes by improving adipocyte viability, reducing inflammatory response, and facilitating tissue integration compared with conventional fat grafting.

PFD-lipoaspirate mixtures were characterized in vitro, and a lead mixture was tested in porcine models used for initial safety and efficacy assessment of subcutaneous implantation at 1 and 3 months after treatment. A single animal was used for each time point, with multiple treatment sites in each animal and a minimum of 3 sites for each of the treatment and control formulations. Histological and immunohistochemical analyses were performed.

PFD hydrogel exhibited superior injectability with smaller extrusion force than hyaluronic acid. The hydrogel could be readily mixed with lipoaspirate to form cohesive, uniform compositions that demonstrated a smoother and more consistent injection force pattern, compared with lipoaspirate only. Hydrogel-lipoaspirate formulations significantly enhanced cell viability compared with lipoaspirate. Within the lipoaspirate, the hydrogel degraded enzymatically. In vivo studies showed the hydrogel-lipoaspirate seamless integration with the surrounding adipose tissue with a 7-fold reduction in inflammatory zones compared with lipoaspirate-only treatment. Macrophage profiling indicated a transition toward predominantly M2 polarization between 1 and 3 months, supported by neovascularization and near-complete resorption by 3 months.

PFD hydrogel-lipoaspirate mixture showed favorable outcomes in this preclinical model through improved adipocyte survival, reduced inflammatory response, and seamless tissue integration. These preliminary findings suggest potential utility in fat grafting applications, although clinical validation remains necessary.