An Evidence-Based Assessment of Adjuvant Therapy in Autologous Fat Transfer: Ranking of the Potential Agents

Autologous fat transfer is widely used in reconstructive and aesthetic surgery; however, its efficacy is often limited by suboptimal fat graft survival. Various pharmacological adjuncts have been proposed to enhance fat graft viability. This study aims to assess and rank potential adjuvant agents based on their effectiveness, safety, Food and Drug Administration (FDA) approval for human use, and clinical applicability to identify the most promising candidate for future clinical trials.

In this targeted literature review, a weighted scoring analysis was conducted to evaluate several adjuncts proposed to improve fat graft viability. The scoring framework incorporated 6 key domains: FDA approval for human use, effectiveness in animal models, dosing optimization, safety in humans, mechanistic rationale, and cost-effectiveness. Each of the first 5 domains was scored on a 1-to-5 scale based on strength of supporting evidence, whereas cost-effectiveness was scored on a 1-to-3 scale. Total scores were calculated by summing all 6 domain scores, allowing a comparative ranking of adjuncts with the highest translational potential. The agents evaluated included deferoxamine, insulin with β-fibroblast growth factor, poloxamers, ADE4+ endothelial cells, hyaluronan hydrogel, botulinum toxin A, and a combination of prostaglandin E2 with polydeoxyribonucleotide.

Deferoxamine received the highest total score (22/28) and demonstrated robust preclinical evidence supporting its ability to promote angiogenesis, reduce oxidative stress, and enhance fat graft retention by up to 50%. Insulin combined with β-fibroblast growth factor scored 18, showing promising effectiveness but limited by lack of FDA approval. Hyaluronan hydrogel and poloxamers followed with scores of 17 and 16, respectively. Botulinum toxin A scored 15, limited by inconsistencies in efficacy data in fat grafting. Prostaglandin E2 with polydeoxyribonucleotide scored 15, and ADE4+ endothelial cells scored 14 because of limited approval and less compelling results in improving fat graft viability.

Deferoxamine emerged as the top translational candidate due to its dual role as an iron chelator and hypoxia-mimetic, reducing oxidative injury and promoting vascular regeneration. Our team is currently conducting ex vivo studies exposing human adipose grafts to deferoxamine and assessing viability with confocal microscopy. These results will inform optimal delivery and design of future clinical trials.