Erase the trace: new frontiers in scar prevention and skin repair

Shi Fu; Niharika  Singh; Shiffoni Sukhlal; Huiting  Luo; Divleen K. Singh; Mimi R Borrelli; Duc Bui; Sami Khan; Alexander B. Dagum; Gurtej Singh

doi:10.55092/bm20240009

Perspective

Open Access

Erase the trace: new frontiers in scar prevention and skin repair

Shi Fu ¹^,†Niharika Singh²^,†Shiffoni Sukhlal¹Huiting Luo¹Divleen K. Singh ²Mimi R Borrelli²Duc Bui²Sami Khan²Alexander B. Dagum²Gurtej Singh²^,∗

¹ Department of Materials Science and Chemical Engineering, Stony Brook University, Stony Brook, New York, USA

² Department of Surgery, Stony Brook University Hospital, Stony Brook University, Stony Brook, New York, USA

†Joint first authors.

* Gurtej.Singh@stonybrookmedicine.edu

Volume
Volume 2 Issue 2, 2024
Citation
Fu S, Singh N, Sukhlal S, Luo H, Singh DK, et al. Erase the trace: new frontiers in scar prevention and skin repair. Biofunct. Mater. 2024(2):0009, https://doi.org/10.55092/bm20240009.
DOI
10.55092/bm20240009
Copyright
Copyright2024 by the authors. Published by ELSP.

Abstract

The management of scarring continues to be significant in health care due to their ubiquity and impact on daily life. Scars include immature, mature, atrophic, hypertrophic, and keloid scars, with hypertrophic and keloid scars commonly being targeted for therapeutic interventions. Hypertrophic and keloid scars have dysregulated wound healing phases, involving higher levels of inflammatory markers, such as TGF-β, PDGF, VEGF, as well as increased type 1 collagen. Current treatments for hypertrophic scarring and keloid scars include pressure garments, corticosteroids, laser therapy, scar excision, and radiation. The next steps in therapy involve minimizing scars and eventually eliminating scars by tissue regeneration; current research is exploring the inhibition of Yes-associated protein and harnessing TGF-β3 to support tissue regeneration over scarring in humans.

Keywords

scars; scar prevention; skin regeneration

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References

Sen CK. Human wound and its burden: updated 2020 compendium of estimates. Adv. Wound Care. 2021, 10(5):281–292.
Amici JM, Taieb C, Le Floc’h C, Demessant AL, Seité S, et al. The impact of visible scars on well‐being and quality of life: an international epidemiological survey in adults. J. Eur. Acad. Dermatol. Venereol. 2023, 37:3–6.
Shirakami E, Yamakawa S, Hayashida K. Strategies to prevent hypertrophic scar formation: a review of therapeutic interventions based on molecular evidence. Burns trauma 2020, 8:tkz00
Khansa I, Harrison B, Janis JE. Evidence-based scar management: how to improve results with technique and technology. Plast. Reconstr. Surg. 2016, 138(3S):165S–178S.
Landén NX, Li D, Stahle M. Transition from inflammation to proliferation: a critical step during wound healing. Cell. Mol. Life Sci. 2016, 73:3861–388
Ghosh B, Mukhopadhyay M, Bhattacharya D. Biopolymer-based nanofilms for the treatment of burn wounds. In Biopolymer-Based Nano Films, Elsevier, 2021, pp. 311–33
Wolfram D, Tzankov A, Pülzl P,Piza-Katzer H. Hypertrophic scars and keloids—a review of their pathophysiology, risk factors, and therapeutic management. Dermatol. Surg. 2009, 35(2):171–181.
Darby IA, Laverdet B, Bonté F,Desmoulière A. Fibroblasts and myofibroblasts in wound healing. Clin. Cosmet. Investig. Dermatol. 2014:301–311.
Wilgus TA, Ferreira AM, Oberyszyn TM, Bergdall VK,DiPietro LA. Regulation of scar formation by vascular endothelial growth factor. Lab. Investig. 2008, 88(6):579–590.
Atiyeh B, El Khatib A, Dibo S. Pressure garment therapy (PGT) of burn scars: evidence-based efficacy. Ann. Burns Fire Disasters 2013, 26(4):205.
Monstrey S, Middelkoop E, Vranckx JJ, Bassetto F, Ziegler UE, et al. Updated scar management practical guidelines: non-invasive and invasive measures. J. Plast. Reconstr. Aesthetic Surg. 2014, 67(8):1017–1025.
Gold MH, McGuire M, Mustoe TA, Pusic A, Sachdev M, et al. Updated international clinical recommendations on scar management: part 2—algorithms for scar prevention and treatment. Dermatol. Surg. 2014, 40(8):825–831.
Ogawa R. The most current algorithms for the treatment and prevention of hypertrophic scars and keloids: a 2020 update of the algorithms published 10 years ago. Plast. Reconstr. Surg. 2022, 149(1):79e–94e.
Butler PD, Longaker MT, Yang GP. Current progress in keloid research and treatment. J. Am. Coll. Surg. 2008, 206(4):731–741.
Mascharak S, DesJardins-Park HE, Davitt MF, Griffin M, Borrelli MR, et al. Preventing Engrailed-1 activation in fibroblasts yields wound regeneration without scarring. Science 2021, 372(6540):eaba2374.
Aramaki-Hattori N, Okabe K, Hamada M, Takato T,Kishi K. Relationship between keloid formation and YAP/TAZ signaling. Plast. Reconstr. Surg. Glob. Open 2017, 5(6):e1357.
Clark RA. To scar or not to scar. N. Engl. J. Med. 2021, 385(5):469–471.
Kwak DH, Bae TH, Kim WS,Kim HK. Anti-vascular endothelial growth factor (Bevacizumab) therapy reduces hypertrophic scar formation in a rabbit ear wounding model. Arch. Plast. Surg. 2016, 43(06):491–497.
Jagadeesan J, Bayat A. Transforming growth factor beta (TGFβ) and keloid disease. Int. J. Surg. 2007, 5(4):278–285.
Durani P, Occleston N, O'Kane S,Ferguson MW. Avotermin: a novel antiscarring agent. Int. J. Low. Extrem. Wounds 2008, 7(3):160–168.
Leon MV. Is Avotermin Safe and Effective Treatment for Scar Improvement in Healthy Males and Females? 2015.
Igarashi A, Okochi H, Bradham DM,Grotendorst GR. Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair. Mol. Biol. Cell 1993, 4(6):637–645.
Mu S, Kang B, Zeng W, Sun Y,Yang F. MicroRNA-143-3p inhibits hyperplastic scar formation by targeting connective tissue growth factor CTGF/CCN2 via the Akt/mTOR pathway. Mol. Cell. Biochem. 2016, 416:99–108.
Hu ZC, Tang B, Guo D, Zhang J, Liang YY, et al. Expression of insulin‐like growth factor‐1 receptor in keloid and hypertrophic scar. Clin. Exp. Dermatol. 2014, 39(7):822–828.
Nguyen JK, Austin E, Huang A, Mamalis A,Jagdeo J. The IL-4/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets. Arch. Dermatol. Res. 2020, 312:81–92.
Zhang J, Qiao Q, Liu M, He T, Shi J, et al. IL-17 promotes scar formation by inducing macrophage infiltration. Am. J. Pathol. 2018, 188(7):1693–1702.
Shi J, Shi S, Xie W, Zhao M, Li Y, et al. IL‐10 alleviates lipopolysaccharide‐induced skin scarring via IL‐10R/STAT3 axis regulating TLR4/NF‐κB pathway in dermal fibroblasts. J. Cell. Mol. Med. 2021, 25(3):1554–1567.
Kim YS, Lew DH, Tark KC, Rah DK,Hong JP. Effect of recombinant human epidermal growth factor against cutaneous scar formation in murine full-thickness wound healing. J. Korean Med. Sci. 2010, 25(4):589.
Kao CC, Huang SY, Chiang CH, Lin CH,Chang TC. Microencapsulated rhEGF to facilitate epithelial healing and prevent scar formation of cesarean wound: a randomized controlled trial. Taiwan. J. Obstet. Gynecol. 2021, 60(3):468–473.