Fat Grafting for Scar Treatment
Isaac B. James
Sydney R. Coleman
J. Peter Rubin
KEY POINTS
Fat grafting is a powerful technique in scar management that functions both by replacing lost volume and remodeling tissue via its regenerative stromal constituents.
Adipose-derived stem cells are a multipotent population of mesenchymal stem cells that are generally accepted as the primary regenerative engine of fat grafting.
The Coleman method of fat grafting has been shown to minimize graft resorption and result in predictable and durable results. Key steps include gentle harvesting of fat to minimize tissue trauma, centrifugation to remove nonviable aqueous and oil fractions, and the injection of small volumes with each pass of the cannula to maximize dispersion and proximity to the blood supply.
Background
Fat grafting is a highly versatile, powerful technique that allows soft tissue augmentation across a wide range of defects and anatomy. Relatively recently, fat grafting has emerged as one of the most effective techniques for correcting scars in the surgeon’s armamentarium. However, the idea of using fat to improve scar deformity is not new. In fact, the first published account of fat grafting by Neuber in 1893 described the treatment of a depressed facial scar.1,2 Several others followed suit and advanced the technique, including the use of cannulas to inject fat under scars by both Hollander and Miller.3,4 However, it was not until 100 years later, in the 1990s, that it started to become apparent that fat might provide more than just volume replacement. In the mid-1990s, Coleman5 noticed that fat grafts were able to soften and even eliminate depressed scars in his patients. In addition to volume correction, he noted substantial rejuvenation in both injured and healthy skin. This notion was further solidified by Rigotti’s pioneering work in fat grafting sites of radiation injury.6 Volume restoration remains a pillar of fat graft efficacy, but there is clearly more to the story.
Biologic Basis for Efficacy in Scar Treatment
We now know that fat grafts improve scars by two primary functions: tissue remodeling and contour correction. Adipose-derived stem cells (ASCs) are a multipotent population of mesenchymal stem cells that reside in adipose stroma,7,8 and are now generally accepted as the primary regenerative engine of fat grafting. Coleman’s5 processing technique of centrifuging lipoaspirate can concentrate stromal regenerative cells in the remaining graft and enhance its regenerative capacity.9,10,11
Tissue Remodeling
Biology of ASCs
Our current understanding of ASC biology suggests that they play several important roles following fat transfer.
Differentiation to Adipocytes
Even when fat is transferred with meticulous technique, a large portion of the graft dies from ischemia. ASCs from the graft replace many of these dying adipocytes, and the resulting new adipocytes account for a substantial portion of the surviving adipose tissue.12 The initial success of cell-assisted lipotransfer lends support to the idea that the stromal regenerative cells are what drive volume retention.13,14,15,16,17,18,19,20
Differentiation to Other Cell Types
As a multipotent mesenchymal stem cell, ASCs are capable of differentiating into numerous tissue types when stimulated. However, the degree to which they act to replace cells other than adipocytes has not been well documented in vivo.
Paracrine Mediators
A growing body of literature suggests that ASCs direct tissue repair, remodeling, and rejuvenation primarily through complex paracrine signaling. ASCs are potent immunomodulators and mediators of angiogenesis which actively migrate to sites of injury.21,22,23,24,25,26,27,28 Moreover, ASCs residing in the hypodermis appear to play an important role in the normal wound healing cascade.29 When added to sites of injury acutely, ASCs improve wound neovascularization
and downregulate pathways responsible for excessive scarring.28,30,31 Animal studies of ASC and stromal vascular fraction (SVF) therapy in acute burn wounds have also demonstrated faster wound healing, enhanced CD31, increased collagen remodeling, decreased inflammation, and decreased fibroblast proliferation.32,33,34 When added to established scars, ASCs reduce wound size and improve color and elasticity.31 These acute and long-term effects appear to be mediated in a paracrine fashion by modulation of the transforming growth factor β and matrix metalloproteinase pathways.31,35,36,37,38,39 This is further supported by recent work from Zhou et al.40,41 that shows improvements in acne scars when ASC-conditioned media is added to conventional fractional carbon dioxide (CO2) laser resurfacing. These effects are seen both in the early phase of scarring and for mature, well-established acne scars. Because processed whole fat grafts contain a substantial number of ASCs and because those stem cells are capable of migrating to sites of injury, some of the beneficial effects of ASC therapy are likely also accessible by fat grafting alone. A number of animal and human studies have confirmed this, and fat grafts processed by Coleman’s technique do, in fact, elicit similar regenerative effects as ASCs.42,43,44,45,46
and downregulate pathways responsible for excessive scarring.28,30,31 Animal studies of ASC and stromal vascular fraction (SVF) therapy in acute burn wounds have also demonstrated faster wound healing, enhanced CD31, increased collagen remodeling, decreased inflammation, and decreased fibroblast proliferation.32,33,34 When added to established scars, ASCs reduce wound size and improve color and elasticity.31 These acute and long-term effects appear to be mediated in a paracrine fashion by modulation of the transforming growth factor β and matrix metalloproteinase pathways.31,35,36,37,38,39 This is further supported by recent work from Zhou et al.40,41 that shows improvements in acne scars when ASC-conditioned media is added to conventional fractional carbon dioxide (CO2) laser resurfacing. These effects are seen both in the early phase of scarring and for mature, well-established acne scars. Because processed whole fat grafts contain a substantial number of ASCs and because those stem cells are capable of migrating to sites of injury, some of the beneficial effects of ASC therapy are likely also accessible by fat grafting alone. A number of animal and human studies have confirmed this, and fat grafts processed by Coleman’s technique do, in fact, elicit similar regenerative effects as ASCs.42,43,44,45,46
Contour Correction
Techniques for contour correction have evolved as fat grafting has become increasingly popular. However, the general principles of successful fat grafting are the same as when Coleman described them 30 years ago. To maximize volume retention, it is important to use very small aliquots with each pass of the cannula and to disperse fat throughout the tissue. This is particularly important in scarred wound beds that have reduced vascularity and elasticity. In areas where scars are particularly adherent, subcision can help to break fibrotic bands and allow fat to fill in the defect.
Human Clinical Data
Fat Grafting for Surgical or Traumatic Scars
Appearance
Scar appearance and contour is commonly rated using the Patient Observer Scar Assessment Score (POSAS).47 This well-validated metric consists of both patient- and observer-reported assessments of vascularization, pigmentation, thickness, relief, pliability, and an overall score, each rated on a 10-point scale. In addition to the POSAS score, a durometer is often used as an objective measure of scar hardness (see Chapter 28).
To date, two prospective cohort studies have assessed scar appearance and contour in a nonburn population. Sardesai42 followed 14 patients with facial scars for 1 year after subdermal fat grafting and found improved dermal elasticity, reduced scar thickness, and reduced stiffness. Klinger et al.43 followed 20 patients for 1 year and found improvements in scar hardness by durometer as well as POSAS improvements for all measures except itch.
An observational study by Maione et al.48 used fat grafting to treat problematic scars after limb lengthening for short-limb deformity in 36 children. After grafting, patients had better skin pliability as measured by durometer and improvement on nearly all measures of POSAS. Other case reports and smaller studies have found fat grafting to be an effective treatment for tracheostomy scars,49 cicatricial ectropion,50,51 and reversing atrophic alopecia in a scar across the eyebrow.52
Pain
Fascinating work by Huang et al.53,54 shows at least one mechanism by which fat grafts reduce neuropathic pain in burn wounds. They found that animals receiving fat grafts following burn injury to a limb experienced less neural inflammation and apoptosis in areas associated with neuropathic pain in the spinal cord. A variety of other groups have also found improvements in pain following fat grafting. Ulrich55 reported improved pain scores when fat grafting was conducted on 20 episiotomy scars. Fredman et al.56 found that two sessions of fat grafting into the burn scars of seven patients with chronic, refractory neuropathic pain provided some relief to six of them, evidenced by reductions in their neuropharmacologic regimen (see Chapter 11). A number of other studies of traumatic scars and surgical scars have shown similar improvements.42,43,49,57,58,59 Similarly, several other studies have shown improvements in itching.42,43,49
Fat Grafting in Burn Scars
To date, 11 human clinical studies have assessed the impact of fat grafting targeted specifically at burn scars.20,43,51,60,61,62,63,64,65,66 Most were cohort studies, and only one had a control group. All reported some level of functional and aesthetic improvement with fat grafting. Improvements in texture, contour, color, elasticity, mobility, patient satisfaction, and softness by durometer were reported. Histology revealed improved vascularization, dermal thickening, and deposition of organized neocollagen.
Scars from Radiation Injury
Rigotti was the first to report using fat grafts to treat severe radiation injury (LENT-SOMA grade 3-4). He treated 20 consecutive patients and saw major improvements in all but one case.6 Panettier67 followed 61 patients with irradiated prosthetic breast reconstructions, 20 of which received multiple rounds of lipofilling. Three months after the final grafting session, he found improvements on all objective LENT-SOMA measures as well as improvements in the aesthetic rating. Akita has also reported improvement from chronic radiation injury in 10 patients when treated with ASCs.68,69
Keloids and Severe Hypertrophic Scars
To date, no robust trials have addressed fat grafting for the management of keloids. Klinger et al.61 published a report of three patients with hypertrophic scars and keloids from severe burns and found improved texture, softness, thickness, and elasticity compared to their pretreatment baseline. Given the limited treatment options currently available and the relative success of ASCs in animal models of hypertrophic scarring, ongoing trials will be of great interest.
Capsular Contracture
Fat grafts have been used to treat the complications of capsular contracture since 2007 when their regenerative properties were beginning to be fully realized.5,6,70 Missana, Yoshimura, and others have published techniques using fat grafts and cell-enriched fat grafts as a rescue procedure for capsular contracture necessitating implant removal or downsizing.70,71,72,73,74 However, this phenomenon has not been studied systematically in the context of fat grafting.
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