Development and assessment of a cutaneous tissue stretch device as a novel scar therapy

Abstract

Aim: Scar prevention and reduction is an area of therapeutic opportunity and unmet medical need. With no current effective scar therapy, patients are often disappointed in their appearance post surgery and re-present to surgeons, only to be turned away. The purpose of this study was to develop and test a device that produces intermittent parallel stretch on new scars and to analyze its potential to reduce scarring.

Methods: Mice were randomized into 5 scar stretch treatment groups: 1 control, 1 sham, and 3 stretch models (0.5×, 1×, or 2× device strength) and treated for 10 days. Scars were scored using the Vancouver Scar Scale. Scar tissue samples were compared by histology and transforming growth factor beta 1 (TGF-β1) expression between control and treatment groups.

Results: Scar scores of 0.5× and 1× groups were significantly lower than the control group (P < 0.05). Scar scores from the 1× treatment group were also significantly lower than the 0.5× group (P < 0.05). Sham, control scar and 2× groups showed more collagen deposition and a thicker dermal scar than the 0.5× and 1× groups. Unstretched scars had fewer fibroblasts with more collagen deposition than the 0.5× and 2× groups. TGF-β1 levels were significantly lower in the 0.5× (342.1 ± 9.2) and 1× (254.1 ± 3.1) groups than in the control group (P < 0.05). TGF-β1 levels in the 1× treatment group were also significantly lower than the 0.5× treatment group (P < 0.05).

Conclusion: Intermittent cutaneous tissue stretch parallel to scars during the proliferative phase of wound healing decreases fibrosis on a macroscopic, microscopic and biochemical level.

Keywords

Mechanotransduction / scar therapy / hypertrophic scar / skin stretch

References

[1] Lawrence JW,Heinberg L.Visible vs. hidden scars and their relation to body esteem..J Burn Care Rehabil2004;25:25-32

[2] Bayat A.Clinical management of skin scarring..Skinmed2005;4:165-73

[3] Newell R.Psychological difficulties amongst plastic surgery ex-patients following surgery to the face: a survey..Br J Plast Surg2000;53:386-92

[4] Valente SM.Visual disfigurement and depression..Plast Surg Nurs2009;29:10-6

[5] Rumsey N,White P.Exploring the psychosocial concerns of outpatients with disfiguring conditions..J Wound Care2003;12:247-52

[6] McGrouther DA.Facial disfigurement..BMJ1997;314:991 PMCID:PMC2126436

[7] Bragg TW,Srivastava S.Patient satisfaction following abdominoplasty: an NHS experience..J Plast Reconstr Aesthet Surg2007;60:75-8

[8] Abu-Nab Z.Satisfaction with outcome and attitudes towards scarring among women undergoing breast reconstructive surgery..Patient Educ Couns2007;66:243-9

[9] Tebble NJ,Price P.Anxiety and self-consciousness in patients with minor facial lacerations..J Adv Nurs2004;47:417-26

[10] Levine E,Pruzinsky T,Persing JA.Quality of life and facial trauma: psychological and body image effects..Ann Plast Surg2005;54:502-10

[11] Robert R,Bishop S,Murphy L.Disfiguring burn scars and adolescent self-esteem..Burns1999;25:581-5

[12] Occleston NL,Goldspink N.New therapeutics for the prevention and reduction of scarring..Drug Discov Today2008;13:973-81

[13] Stewart KJ,Coghlan B,Jones BM.Complications of 278 consecutive abdominoplasties..J Plast Reconstr Aesthet Surg2006;59:1152-5

[14] Crossland DS,Lyall R,Hasan A,O'Sullivan JJ.Patient attitudes to sternotomy and thoracotomy scars..Thorac Cardiovasc Surg2005;53:93-5

[15] Franz MG,Robson MC.Optimizing healing of the acute wound by minimizing complications..Curr Probl Surg2007;44:691-763

[16] Batra RS.Surgical techniques for scar revision..Skin Therapy Lett2005;10:4-7

[17] Meier K.Emerging new drugs for scar reduction..Expert Opin Emerg Drugs2006;11:39-47

[18] Sen CK,Roy S,Lambert L,Gottrup F,Longaker MT.Human skin wounds: a major and snowballing threat to public health and the economy..Wound Repair Regen2009;17:763-71 PMCID:PMC2810192

[19] Field T,Scd,Krugman S,Ozment-Schenck L.Postburn itching, pain, and psychological symptoms are reduced with massage therapy..J Burn Care Rehabil2000;21:189-93

[20] Field T,Krugman S,Schanberg S,Burman I.Burn injuries benefit from massage therapy..J Burn Care Rehabil1998;19:241-4

[21] Foo CW.Topical modalities for treatment and prevention of postsurgical hypertrophic scars..Facial Plast Surg Clin North Am2011;19:551-7

[22] Huang C,Ogawa R.Mechanosignaling pathways in cutaneous scarring..Arch Dermatol Res2012;304:589-97

[23] Ogawa R,Tokumura F,Ohmori Y,Hyakusoku H.The relationship between skin stretching/contraction and pathologic scarring: the important role of mechanical forces in keloid generation..Wound Repair Regen2012;20:149-57

[24] Yagmur C,Ogawa R.Mechanical receptor-related mechanisms in scar management: a review and hypothesis..Plast Reconstr Surg2010;126:426-34

[25] Wong VW,Akaishi S,Glotzbach JP,Nelson ER,Paterno J,Kuang AA,Gurtner GC.Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling..Nat Med2012;18:148-52 PMCID:PMC4457506

[26] Langevin HM,Badger GJ,Howe AK.Dynamic fibroblast cytoskeletal response to subcutaneous tissue stretch ex vivo and in vivo..Am J Physiol Cell Physiol2005;288:C747-56

[27] Langevin HM,Cipolla MJ,Buttolph TR.Fibroblast spreading induced by connective tissue stretch involves intracellular redistribution of alpha- and beta-actin..Histochem Cell Biol2006;125:487-95

[28] Langevin HM,Badger GJ,Howe AK.Subcutaneous tissue fibroblast cytoskeletal remodeling induced by acupuncture: evidence for a mechanotransduction-based mechanism..J Cell Physiol2006;207:767-74

[29] Bouffard NA,Badger GJ,Buttolph TR,Stevens-Tuttle D.Tissue stretch decreases soluble TGF-beta1 and type-1 procollagen in mouse subcutaneous connective tissue: evidence from ex vivo and in vivo models..J Cell Physiol2008;214:389-95 PMCID:PMC3065715

[30] Alenghat FJ.Mechanotransduction: all signals point to cytoskeleton, matrix, and integrins..Sci STKE2002;2002:pe6

[31] Von Offenberg Sweeney N,Cotter EJ,Birney YA,Cahill PA.Cyclic strain- mediated regulation of vascular endothelial cell migration and tube formation..Biochem Biophys Res Commun2005;329:573-82

[32] Aarabi S,Shi Y,Chang EI,Holmes JW,Yee H.Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis..FASEB J2007;21:3250-61

[33] Gurtner GC,Wong VW,Wu K,Padois K,Longaker MT.Improving cutaneous scar formation by controlling the mechanical environment: large animal and phase I studies..Ann Surg2011;254:217-25

[34] Gurtner GC.Reply: tension shielding with the embrace device: does it really improve scars?.Plast Reconstr Surg2014;134:e664-6

[35] Langevin HM,Snapp RR,Badger GJ,Taatjes DJ.Tissue stretch induces nuclear remodeling in connective tissue fibroblasts..Histochem Cell Biol2010;133:405-15 PMCID:PMC2880391

[36] Baryza MJ.The Vancouver Scar Scale: an administration tool and its interrater reliability..J Burn Care Rehabil1995;16:535-8

[37] Suarez E,Alonso-Rasgado T,Bayat A.Up-regulation of tension-related proteins in keloids: knockdown of Hsp27, alpha2beta1- integrin, and PAI-2 shows convincing reduction of extracellular matrix production..Plast Reconstr Surg2013;131:e158-73

[38] Chin MS,Helm DL,Prsa MJ,Akaishi S,Ogawa R.Analysis of neuropeptides in stretched skin..Plast Reconstr Surg2009;124:102-13

[39] Lim AF,Kaplan EN,Cowley C,Beasley B,Longaker MT.The embrace device significantly decreases scarring following scar revision surgery in a randomized controlled trial..Plast Reconstr Surg2014;133:398-405 PMCID:PMC4874339