April 2020 HSC Section 4 - Plastic and Reconstructive Problems

Reprinted by permission of J Craniofac Surg. 2019; 30(3):644-651.

O RIGINAL A RTICLE

The Future of Facial Fat Grafting

Jack E. Brooker, MD, J. Peter Rubin, MD, yz and Kacey G. Marra, PhD yz

magnetic resonance imaging (MRI) to track the fate of facial fat grafts found that 49% of the original graft resorbed in the first 3 months, increasing to 55% by the first 6 months. 9 The first demon- stration of long-term survival in fat grafting was reported in the mid- 1990s when Coleman reported his trials in the nasolabial fold. 10,11 Unlike previous authors, Coleman did not extract the fat from the donor area at high negative pressure, break up the adipose tissue, or implant into the recipient area at high positive pressure. Instead fat was transferred in ‘‘parcels’’ such that cells had their own nutritional source upon implantation. 10 This fat grafting procedure is now used in a wide range of clinical scenarios including aesthetic surgery, cranio- facial abnormalities, posttumor resection reconstruction and trauma reconstruction. 8 Additionally, fat grafting has been used for the surgical correction of a number of congenital craniofacial anomalies, including hemifacial microsomia and Parry-Romberg syndrome. 12,13 Although initially seen as an autologous filler, interest soon grew in the apparent regenerative effects of engrafted lipoaspirate on overly- ing skin. 14,15 Tissue overlying the grafts appeared to improve in the first year postoperatively; pore size decreased, wrinkles softened, skin pigmentation changes regressed. 14 As a result the use of fat grafting has also been reported in scar resolution secondary to acne and burns. 1,16 Rigotti et al contend that radiation scarring is due to anoxia and poor vascularity and contend that tissue healing in refractory scars relies on the stem-cell populationwithin the graft secreting angiogenic factors which leads to microvascularization and oxygenation. 17 There are several key advantages which render fat grafting attractive to plastic and reconstructive surgeons. Autologous fat grafting is versa- tile, lacks immunogenicity and is readily available in most patients. 18 Patient satisfaction has generally been high with fat grafting, even when multiple procedures are required. 19 Complications are also relatively low compared to prosthetics and fillers and include hema- toma, ecchymosis, and resorption. 19 Resorption remains a major challenge even with Coleman’s improved method for harvesting and grafting; retention rates during the 1990s ranged from 20% to 90% while more recent studies report that resorption rates still vary from 20% to 60%. 8 The sheer unreliability of long-term retention is itself a significant drawback to the use of facial fat grafting. Adipose tissue is derived from the mesoderm with cellular components including endothelial cells, mesenchymal stem cells, fibroblasts, macrophages, pericytes and muscle cells which, after lipoaspiration, can be broken down (usually with collagenase) and separated by centrifuge. 20 Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSC) with many properties similar to bone-marrow-derived stem cells (BMSC) and bear the relevant immunologic cell surface markers (CD105, CD73, CD29, CD44, CD90) (25). 21 The ASCs are multipotent, like BMSCs, and can differentiate into multiple cell lines. 22 The ASCs are capable of differentiating into mesenchymal phenotypes. 22 These include mesenchymal tissue such as chondrocytes and osteocytes as well as nonmesenchymal cell phenotypes; cardiomyocytes, neurons, and endothelial cells have all been reported. 22–25 NEAR FUTURE APPLICATIONS Nanofat Grafting It has been suggested that stromal cells and preadipocytes represent the surviving population of cells in a graft as their

Abstract: Fat grafting was first described in the early 20th century but for many years remained a relatively underused technique due to the unreliability of long-term volume expansion. Significant improvements in reliability have been made in the last 2 decades and there is a large body of literature pertaining to extraction, processing and injection methods to obtain more lasting effects. However, volume loss and graft resorption remain a major challenge in the long term and lead to unpredictability in results. Enriching adipose graft with stromal vascular fraction, ex vivo cultured adipose stem cells and platelet-derived growth factor among others is one method under active investigation which may assist graft survival through a range of mechanisms including increased angiogenesis. Breaking adipose graft into smaller fragments such that engrafted cells have greater access to donor-site oxygenation and nutrition is another method which in theory may promote survival. Presently, adipose grafting in the face is usually for the addition of volume to fill defects. However, the stem-cell containing fraction of adipose graft- ing (stromal vascular fraction) appears to exert a rejuvenating effect on overlying skin and soft tissue when administered alone. The application of these low-volume injections represents a significant shift in thinking away from mere volume expansion. These techni- ques have been tested in a range of animal models and some human studies. In this review, the authors provide a broad overview of present research and highlight both limitations in previous research and current areas of investigation. A utologous fat grafting has been has been practiced for over 100 years, having first been described for the use of tuberculo- sis-induced changes to facial contours. 1 The growth of fat grafting in the area of facial reconstruction was at first slow but over time gathered new applications. The use of fat grafting in the obliteration of frontal sinus described in the 1950s remains the gold standard today. 2– 4 In the 1980s and early 1990s, the use of fat grafts in cosmetic filling was described by multiple surgeons 5–7 ; however, results often dem- onstrated a high degree of resorption and their reports garnered relatively little attention at the time. 8 One 5-year study utilizing From the Department of Plastic Surgery; y Department of Plastic Surgery, Department of Bioengineering, McGowan Institute of Regenerative Medicine; and z Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA. Received August 29, 2018. Accepted for publication September 22, 2018. Address correspondence and reprint requests to Kacey G. Marra, PhD, Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15213; E-mail: marrak@upmc.edu Key Words: Adipose, craniofacial, fat, graft, stem cell ( J Craniofac Surg 2019;30: 644–651)

The authors report no conflicts of interest. Copyright # 2019 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000005274

The Journal of Craniofacial Surgery

Volume 30, Number 3, May 2019

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