We are grateful to Dr. Swanson for his thoughtful comments. We are gratified that Dr. Swanson believes that decreasing scar formation is an “extraordinary claim” and that the “implications are mind-boggling.” We are confident that the body of published scientific and clinical work supporting mechanomodulation as a safe and effective approach to decrease scar formation easily meets the bar as “extraordinary evidence.”
We wholeheartedly agree with the concept of “science before marketing.” We would respectfully point out that the embrace device (Neodyne Biosciences, Inc., Menlo Park, Calif.) represents the culmination of a 20-year journey to develop scientifically based and clinically validated technologies to improve scars. This work began with the earliest human fetal surgery experience1 and initial observation of scarless fetal wound healing,2–21 extended across adult wound healing, including small- and large-animal models,22–30 and has been subjected to three clinical trials.31–33 It has been funded by grants from the National Institutes of Health, the U.S. Department of Defense, and numerous private foundations. It has been conducted at the leading academic medical centers in the world and has been published in the highest impact scientific and surgical journals, including Nature (impact factor, 38), Science (impact factor, 31), The New England Journal of Medicine (impact factor, 51), Nature Medicine (impact factor, 24), Annals of Surgery (impact factor, 6) and, of course, Plastic and Reconstructive Surgery (impact factor, 3). Possibly, even a cursory read of this substantial literature will convince Dr. Swanson that a lot of science was performed before marketing was even a glimmer in our eyes.
Dr. Swanson raises concerns about the small sample size (10 patients) and our use of photographs for analysis of the scars. The analysis was performed by three board-certified plastic surgeons evaluating the photographs in a blinded fashion. Despite our sample size of 10 patients, the observed “difference” between the half of the revised scar treated with the embrace device versus the control-treated side was highly significant (p < 0.005).
Dr. Swanson also had concerns with the scar revisions performed at different anatomical sites. Scars occur all over the body and, thus, the embrace device was tested on scars in several locations. Dr. Swanson also stated that “primary abdominoplasties would have provided a similar amount of tissue removal and similar tension from the same part of the body with symmetrical scars—ideal for side-by-side comparisons.” What Dr. Swanson could not have known is that we have performed a soon-to-be-published randomized controlled trial on primary abdominoplasties33: one side was treated with the embrace device, and the other side received the therapy that worked best in the experience of the treating surgeons. The results were again highly significant in favor of the embrace device. Furthermore, the difference in favor of the embrace-treated side was more significant at 1 year than it was near the end of the treatment, demonstrating that the results were durable. The article describing this randomized controlled trial has recently been accepted for publication by Plastic and Reconstructive Surgery.
Dr. Swanson also voiced concerns that “Patients seeking scar revisions are a selected patient group (obviously not good scar formers) that may not be comparable to first-time surgical patients.” The concerns raised about scar revisions are precisely the reasons we conducted this study. Whether or not these patients are considered “obviously not good scar-formers” is not the issue. The issue is whether a revision followed by embrace treatment can improve the scar compared with current solutions. Our data strongly support that this is true.
As to the perception of commercial bias, we would respectfully point out that there is no such thing as a free lunch. The United States currently operates under a capitalist economic system, meaning that for most endeavors, a profit motive must exist for activity to occur. To bring a novel technology from “bench to bedside” in a safe and ethical manner in the United States is an expensive proposition, even for a device as seemingly straightforward as the embrace dressing. Unlike the basic scientific discovery described above, there are no grants or funding mechanisms to support activities such as obtaining U.S. Food and Drug Administration clearance, setting up high-quality U.S. manufacturing, and establishing a distribution channel. In a capitalist economy, one must reach out to the private sector to find investors to support these expenses. In return, these investors expect some incremental return on their invested capital, which requires commercialization and sales. For better or worse, this is how innovation works in a capitalist economy. There is no question that alternative utopian systems exist that avoid the profit motive, but we would contend that the twentieth century experience with such experimental systems is not encouraging.
As Dr. Swanson rightly points out, this potentially creates “conflicts of interest” and, potentially, commercial bias. The way that these sorts of conflicts are handled in an ethical manner is through complete and transparent disclosure of all potential conflicts. Despite the insinuations by Dr. Swanson, all authors provided a thorough and complete disclosure in complete compliance with the policies of Plastic and Reconstructive Surgery. Nothing was hidden or buried, and much of what Dr. Swanson is concerned about is a matter of semantics. This is important because the authors’ thorough and complete disclosure provided third-party peer reviewers an opportunity to make an independent determination of any potential commercial bias and ask for changes or reject the manuscript. In this case, our manuscript passed this impartial peer review and the data were felt to be compelling enough for publication. Although Dr. Swanson may not agree with the outcome, in this case, the system worked as designed to manage potential conflicts of interest. No amount of editorial tilting at windmills will change this fact.
More philosophically, we believe that this type of misunderstanding regarding innovation and conflict of interest is not helpful for the specialty of plastic surgery. Conflicts of interest and potential financial biases exist almost everywhere in the practice of medicine. In the current fee-for-service model, there are financial incentives to perform cases faster (to perform more cases), to treat patients insured by private payers rather than Medicaid, and to perform procedures with preferential (i.e., carved out) payments. None of these are strictly aligned with the best interests of patients. To focus exclusively on one source of conflict (commercial) while turning a blind eye to all the others strikes us as shortsighted and naive. We believe that neither the patient nor society is well served by divorcing practicing physicians from the innovation process through regulation or opprobrium.
Dr. Gurtner and Dr. Longaker are founders of, have equity positions in, and serve on the Board of Neodyne Biosciences, Inc., which provided the devices used in the study and supported the clinical trial.
Geoffrey C. Gurtner, M.D.
Michael T. Longaker, M.D., M.B.A.
Department of Surgery
Stanford University School of Medicine
1. Harrison MR, Adzick NS, Longaker MT, et al. Successful repair in utero of a fetal diaphragmatic hernia after removal of herniated viscera from the left thorax. N Engl J Med. 1990;322:1582–1584
2. Longaker MT, Harrison MR, Crombleholme TM, et al. Studies in fetal wound healing: I. A factor in fetal serum that stimulates deposition of hyaluronic acid. J Pediatr Surg. 1989;24:789–792
3. Longaker MT, Harrison MR, Langer JC, et al. Studies in fetal wound healing: II. A fetal environment accelerates fibroblast migration in vitro. J Pediatr Surg. 1989;24:793–797; discussion 798
4. Longaker MT, Whitby DJ, Ferguson MW, et al. Studies in fetal wound healing: III. Early deposition of fibronectin distinguishes fetal from adult wound healing. J Pediatr Surg. 1989;24:799–805
5. Longaker MT, Chiu ES, Harrison MR, et al. Studies in fetal wound healing: IV. Hyaluronic acid-stimulating activity distinguishes fetal wound fluid from adult wound fluid. Ann Surg. 1989;210:667–672
6. Longaker MT, Chiu ES, Adzick NS, Stern M, Harrison MR, Stern R. Studies in fetal wound healing: V. A prolonged presence of hyaluronic acid characterizes fetal wound fluid. Ann Surg. 1991;213:292–296
7. Longaker MT, Whitby DJ, Adzick NS, et al. Studies in fetal wound healing: VI. Second and early third trimester fetal wounds demonstrate rapid collagen deposition without scar formation. J Pediatr Surg. 1990;25:63–68; discussion 68
8. Longaker MT, Adzick NS, Hall JL, et al. Studies in fetal wound healing: VII. Fetal wound healing may be modulated by hyaluronic acid stimulating activity in amniotic fluid. J Pediatr Surg. 1990;25:430–433
9. Burd DA, Longaker MT, Adzick NS, Harrison MR, Ehrlich HP. Foetal wound healing in a large animal model: The deposition of collagen is confirmed. Br J Plast Surg. 1990;43:571–577
10. Longaker MT, Whitby DJ, Jennings RW, et al. Fetal diaphragmatic wounds heal with scar formation. J Surg Res. 1991;50:375–385
11. Longaker MT, Adzick NS. The biology of fetal wound healing: A review. Plast Reconstr Surg. 1991;87:788–798
12. Lorenz HP, Longaker MT, Perkocha LA, Jennings RW, Harrison MR, Adzick NS. Scarless wound repair: A human fetal skin model. Development. 1992;114:253–259
13. Lorenz HP, Whitby DJ, Longaker MT, Adzick NS. Fetal wound healing: The ontogeny of scar formation in the non-human primate. Ann Surg. 1993;217:391–396
14. Stern M, Dodson TB, Longaker MT, Lorenz HP, Harrison MR, Kaban LB. Fetal cleft lip repair in lambs: Histologic characteristics of the healing wound. Int J Oral Maxillofac Surg. 1993;22:371–374
15. Longaker MT, Whitby DJ, Ferguson MW, Lorenz HP, Harrison MR, Adzick NS. Adult skin wounds in the fetal environment heal with scar formation. Ann Surg. 1994;219:65–72
16. Longaker MT, Bouhana KS, Harrison MR, Danielpour D, Roberts AB, Banda MJ. Wound healing in the fetus: Possible role for inflammatory macrophages and transforming growth factor-beta isoforms. Wound Repair Regen. 1994;2:104–112
17. Lorenz HP, Lin RY, Longaker MT, Whitby DJ, Adzick NS. The fetal fibroblast: The effector cell of scarless fetal skin repair. Plast Reconstr Surg. 1995;96:1251–1259; discussion 1260
18. West DC, Shaw DM, Lorenz P, Adzick NS, Longaker MT. Fibrotic healing of adult and late gestation fetal wounds correlates with increased hyaluronidase activity and removal of hyaluronan. Int J Biochem Cell Biol. 1997;29:201–210
19. Cass DL, Bullard KM, Sylvester KG, Yang EY, Longaker MT, Adzick NS. Wound size and gestational age modulate scar formation in fetal wound repair. J Pediatr Surg. 1997;32:411–415
20. Mackool RJ, Gittes GK, Longaker MT. Scarless healing: The fetal wound. Clin Plast Surg. 1998;25:357–365
21. Larson BJ, Longaker MT, Lorenz HP. Scarless fetal wound healing: A basic science review. Plast Reconstr Surg. 2010;126:1172–1180
22. Werner S, Smola H, Liao X, et al. The function of KGF in morphogenesis of epithelium and reepithelialization of wounds. Science. 1994;266:819–822
23. Wong VW, Rustad KC, Akaishi S, et al. Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling. Nat Med. 2012;18:148–152
24. Wong VW, Akaishi S, Longaker MT, Gurtner GC. Pushing back: Wound mechanotransduction in repair and regeneration. J Invest Dermatol. 2011;131:2186–2196
25. Aarabi S, Longaker MT, Gurtner GC. Hypertrophic scar formation following burns and trauma: New approaches to treatment. PLoS Med. 2007;4:e234
26. Wong VW, Paterno J, Sorkin M, et al. Mechanical force prolongs acute inflammation via T-cell-dependent pathways during scar formation. FASEB J. 2011;25:4498–4510
27. Aarabi S, Bhatt KA, Shi Y, et al. Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis. FASEB J. 2007;21:3250–3261
28. Wang Z, Fong KD, Phan TT, Lim IJ, Longaker MT, Yang GP. Increased transcriptional response to mechanical strain in keloid fibroblasts due to increased focal adhesion complex formation. J Cell Physiol. 2006;206:510–517
29. Wong VW, Longaker MT, Gurtner GC. Soft tissue mechanotransduction in wound healing and fibrosis. Semin Cell Dev Biol. 2012;23:981–986
30. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453:314–321
31. Gurtner GC, Dauskardt RH, Wong VW, et al. Improving cutaneous scar formation by controlling the mechanical environment: Large animal and phase I studies. Ann Surg. 2011;254:217–225
32. Lim AF, Weintraub J, Kaplan EN, et al. The embrace device significantly decreases scarring following scar revision surgery in a randomized controlled trial. Plast Reconstr Surg. 2014;133:398–405
33. Longaker MT, Rohrich RJ, Greenberg L, et al. A randomized controlled trial of the embrace device to reduce incisional scar formation. Plast Reconstr Surg. Accepted for publication
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