Optimizing Autologous Fat Grafting: A Systematic Review of Enhancement Strategies and Graft Survival.

Autologous fat grafting has become an important tool in reconstructive and aesthetic surgery, particularly for breast reconstruction and soft tissue augmentation. Despite its promise, long-term outcomes remain unpredictable. To address this, research has increasingly focused on optimizing graft survival by enriching the lipoaspirate with additional substances. A systematic search of PubMed (National Institutes of Health, Bethesda, MD) and Web of Science (Clarivate, Philadelphia, PA) identified studies on enhancement methods of autologous fat grafting in both animal models and clinical settings, published up to February 2025. In vitro trials, case reports, and studies comparing techniques without specific enhancement of the lipoaspirate were excluded. Twenty-seven studies fulfilled the criteria, including 15 animal studies and 12 clinical studies, most of which investigated applications in breast reconstruction and augmentation. The included studies showed substantial heterogeneity in enhancement strategies, case numbers, follow-up duration, and outcome measures. The most frequently examined approaches involved enrichment with stromal vascular fraction (SVF) and/or adipose-derived stem cells (ADSCs). Both methods demonstrated favourable results in many trials, though statistical significance was not always achieved. Other strategies included the use of Vitamin D3, Botulinum toxin A, platelet-rich plasma (PRP), and less frequently studied agents such as N-acetylcysteine and Salvia miltiorrhiza. Overall, enrichment of lipoaspirate appears to enhance graft survival, with SVF/ADSC-based methods and PRP emerging as the most promising approaches. Nevertheless, marked variability in protocols and outcome measures hampers comparability between studies. Larger randomized controlled trials employing standardized methodologies are essential to confirm clinical feasibility and provide a basis for evidence-based guidelines. Level of Evidence: 3 (Therapeutic)  For image description, please refer to the figure legend and surrounding text.