Platelet-Rich Plasma and Fat Grafting: An Option?

Drs. Peter Rubin and Kacey Marra discuss the possible molecular mechanisms of PRP in fat graft survival based on a review of the current literature.

As reported by McGowan Institute for Regenerative Medicine faculty member co-authors J. Peter Rubin, MD (pictured top), Chair of the Department of Plastic Surgery, UPMC Endowed Professor of Plastic Surgery, and Professor of Bioengineering at the University of Pittsburgh, Co-Director of the Adipose Stem Cell Center, and is Founder and Director of the Center for Innovation in Restorative Medicine in the Department of Surgery at the University of Pittsburgh, and Kacey Marra, PhD (pictured bottom), Associate Professor, Department of Surgery at the University of Pittsburgh, Director of the Plastic Surgery Laboratory, and Co-Director of the Adipose Stem Cell Center, autologous fat grafting is an important treatment option for small to medium soft tissue defects derived from tumor ablation, congenital deformity, and traumatic injury. The advantages are that autologous fat is easy to obtain in large quantities and the procedure is less uncomfortable and risky to patients; the operation is of short duration, can sometimes be performed under local anesthesia, and simultaneously achieves an aesthetic result in both the donor and recipient sites. However, the disadvantages of fat grafting are an unpredictable and variable reabsorption rate of around 40%–60%, resulting in the need for repeated procedures, and microcalcifications and cyst formation due to fat necrosis. Reabsorption and fat necrosis are believed to be caused by insufficient neoangiogenesis around the fat graft, thus resulting in adipocyte apoptosis due to lack of nutrient supply and accumulation of metabolic waste.

Several strategies have been reported to enhance fat graft survival, such as adjunct therapy by adding the stromal vascular fraction (SVF), enhancing angiogenesis by addition of growth factors, or use of chemical cell-stimulating factors, such as insulin or erythropoietin. Among these, platelet-rich plasma (PRP) has recently emerged as a new matrix to enhance fat graft survival.

PRP, which is derived from whole blood through double-spin centrifugation, contains multiple growth factors and adhesion molecules in α-granules. PRP is believed to be safer and more practical in clinical adjunctive therapy than other recombinant growth factors or stem cell therapies. In addition, PRP is an economic way to obtain multiple growth factors at one time that meet the requirements for highly complex processes during tissue repair or regeneration. PRP has been demonstrated to be effective in bone regeneration, wound healing, and improvement of musculoskeletal sports injuries.

Recently, clinicians extended the scope of PRP therapy to soft tissue augmentation by combining PRP with fat grafting. Although some successful clinical results were reported, evidence supporting the application of PRP combined with fat grafts in soft tissue augmentation remains limited, as only a few basic research and preclinical studies in small animals have been conducted. Furthermore, no details on molecular mechanisms are addressed in the literature. In their review article in Tissue Engineering--Part B, Review, Drs. Rubin and Marra discuss the possible molecular mechanisms of PRP in fat graft survival based on a review of the current literature. This review discusses published in vitro, animal, and human studies and provides guidance for future research and clinical application.

The paper’s abstract follows:

Due to the natural properties of fat, fat grafting remains a popular procedure for soft tissue volume augmentation and reconstruction. However, clinical outcome varies and is technique dependent. Platelet-rich plasma (PRP) contains α-granules, from which multiple growth factors such as platelet-derived growth factor, transforming growth factor-β, vascular endothelial growth factor, and epidermal growth factor can be released after activation. In recent years, the scope of PRP therapies has extended from bone regeneration, wound healing, and healing of musculoskeletal injuries, to enhancement of fat graft survival. In this review, we focus on the definition of PRP, the different PRP preparation and activation methods, and growth factor concentrations. In addition, we discuss possible mechanisms for the role of PRP in fat grafting by reviewing in vitro studies with adipose-derived stem cells, preadipocytes, and adipocytes, and preclinical and clinical research. We also review platelet-rich fibrin, a so-called second generation PRP, and its slow-releasing biology and effects on fat grafts compared to PRP in both animal and clinical research. Finally, we provide a general foundation on which to critically evaluate earlier studies, discuss the limitations of previous research, and direct plans for future experiments to improve the optimal effects of PRP in fat grafting.

Illustration: McGowan Institute for Regenerative Medicine.

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Bio: Dr. Peter Rubin

Bio: Dr. Kacey Marra

Abstract (Application of platelet-rich plasma and platelet-rich fibrin in fat grafting: basic science and literature review. Liao HT, Marra KG, Rubin JP. Tissue Engineering. Part B, Reviews; online 12/18/13.)