Abstract Background Fat grafting is gaining traction in regenerative and aesthetic medicine due to 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. Objectives 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 to conventional fat grafting. Methods 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. Results 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 to lipoaspirate-only. Hydrogel-lipoaspirate formulations significantly enhanced cell viability compared to lipoaspirate. Within lipoaspirate the hydrogel degraded enzymatically. In vivo studies showed the hydrogel-lipoaspirate seamless integration with the surrounding adipose tissue with a seven-fold reduction in inflammatory zones compare to lipoaspirate-only treatment. Macrophage profiling indicated a transition towards predominantly M2 polarization between one and three months, supported by neovascularization and near-complete resorption by three months. Conclusions 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, though clinical validation remains necessary.
Wiser et al. (Wed,) studied this question.