Fat Graft Enrichment Strategies: A Systematic Review.

Abstract

Sir: We read with great interest the recent systematic review by Vyas et al.1 in Plastic and Reconstructive Surgery that provides surgeons with some strategies for fat graft enrichment. We compliment the authors on the excellent results shown, and would also like to express some considerations regarding the strategies of platelet-rich plasma and growth factors. Actually, platelet concentrates, mostly represented by platelet-rich plasma, platelet-rich fibrin, and concentrated growth factor, have been known as autologous blood-derived therapeutic strategies for regenerative medicine. Platelet-rich plasma preparation is complicated with a two-step centrifugation and are not standardized because of variability in blood sample collection, centrifugation tube materials, centrifuges, and centrifugation force/time. Animal-derived thrombin additives are required in platelet-rich plasma preparation. However, without any additives, the preparation of platelet-rich fibrin or concentrated growth factor is simplified with one step and is standardized. Different from platelet-rich plasma, both platelet-rich fibrin and concentrated growth factor contain porous fibrin scaffolds that provide temporal nesting matrix for platelets and leukocytes. Fibrin scaffolds also protect growth factors from proteolysis and ultimately prolong bioactive duration, helping deliver growth factors “on demand” and reducing risks of inflammatory responses. Furthermore, platelet-rich fibrin or concentrated growth factor might contain higher levels of growth factors than platelet-rich plasma.2 Some preclinical and clinical studies3,4 have also demonstrated that both platelet-rich fibrin and concentrated growth factor were more effective for improving fat graft survival compared with platelet-rich plasma. Considering the merits listed above, both platelet-rich fibrin and concentrated growth factor are potential strategies for fat graft enrichment. Therefore, we recommend that platelet-rich fibrin and concentrated growth factor should also be included to achieve a thorough review and to popularize use of platelet concentrates. Second, the authors thought platelet-rich plasma had the strongest evidence to support efficacy, possibly by means of a dose-dependent effect. However, in this review, there were two studies reporting conflicting results. We are concerned that the management of platelet-rich plasma use might be difficult. The functions of recombinant growth factors are clear and their concentration is controllable and manageable in clinical practice, avoiding side effects caused by supraphysiologic concentration. Platelet-rich plasma is just a concentrated pool combining various growth factors with platelets and leukocytes. The concentration of each growth factor within platelet-rich plasma is little known. Excessive platelet concentration might cause desensitization and down-regulation of growth factor receptors and apoptosis. Leukocytes are known to stimulate proinflammatory and catabolic effects by releasing inflammatory factors.5 We want to know whether the function of platelet-rich plasma listed in Table 1 is the simple sum of each function of growth factors, platelets, and leukocytes. Besides, the studies included in the review had some variabilities in platelet-rich plasma preparation protocols, which consequently caused heterogeneity in the components of platelet-rich plasma. It is doubtful whether the conflicting results of platelet-rich plasma use demonstrated in this review were attributable to adverse functions of leukocytes and excessive platelet concentration or the heterogeneity in the components of platelet-rich plasma. We thank the authors for summarizing some strategies for fat graft enrichment. To make best use of platelet concentrates, we anticipate that both platelet-rich fibrin and concentrated growth factor will also be considered as enrichment strategies. The integrated functions of platelet-rich plasma and the reasons for conflicting results are worth further investigation. DISCLOSURE None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this communication.