Comparative Evaluation of Hypoxia Preconditioned Serum (HPS) and Platelet-rich Plasma (PRP) on Preadipocyte Survival and Adipogenic Differentiation

Jun Jiang^1,2*Michael Martin²Lynn Röper²Samuel Knoedler²Vincent Steinbacher³Sarah Alageel⁴Marc Hanschen⁵Haydar Kükrek²Ulf Dornseifer⁶Arndt Schilling⁷Hans-Guenther Machens²Philipp Moog²

• ¹Technical University of Munich, Munich, Germany
• ²Experimental Plastic Surgery, Clinic for Plastic, Reconstructive and Hand Surgery, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany, Munich, Germany
• ³Institute of Molecular Immunology and Experimental Oncology, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany, Munich, Germany
• ⁴King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
• ⁵Klinikum rechts der Isar der Technischen Universitat Munchen, Munich, Germany
• ⁶Department of Plastic, Reconstructive and Aesthetic Surgery, Isar Klinikum, 80331 Munich, Germany, Munich, Germany
• ⁷Universitatsmedizin Gottingen, Göttingen, Germany

Lipofilling is a widely used technique in plastic and reconstructive surgery, but its long-term success is often limited by unpredictable fat graft resorption. Optimizing the adipogenic environment through bioactive factors may enhance graft survival and volume retention. This study investigates the adipogenic potential of Hypoxia Preconditioned Serum (HPS) and Platelet-Rich Plasma (PRP), in comparison to normal serum (NS). HPS demonstrated significantly higher levels of Adiponectin, IGF-1, bFGF, VEGF-A, and PDGF-BB compared to PRP and NS, while Leptin levels were lower in HPS and PRP than in NS. To assess adipogenic effects, human preadipocytes were stimulated with these secretomes at low (10%) and high (40%) concentrations. All conditions increased proliferation on day 4, with the highest cell count observed in NS-40%. Treatment-induced cytotoxicity was absent in all groups, as indicated by Lactate Dehydrogenase (LDH) assay. On day 4, HPS-40% promoted most significant adipogenic differentiation, as indicated by enhanced lipid droplet formation. This was further supported by gene expression data, which revealed an upregulation of adipogenic markers, including PPARgamma, CEBP-alpha, FABP4, Adiponectin, and LPL, in the HPS-40% treated preadipocyte group by day 4. These findings suggest that HPS enhance the proliferation, survival, and terminal differentiation of preadipocytes. Validation in in vivo models and clinical studies will be necessary to confirm its potential efficacy in enhancing graft survival and volume retention.