Tranilast-delivery surgical sutures to ameliorate wound healing by reducing scar formation through regulation of TGF-β expression and fibroblast recruitment

Sung Yoon Choi; Byung Hwi Kim; Beom Kang Huh; Woong Jeong; Min Park; Hyo Jin Park; Ji-Ho Park; Chan Yeong Heo; Young Bin Choy

Journal of Industrial and Engineering Chemistry, Vol.67, 469-477, November, 2018

DOI10.1016/j.jiec.2018.07.021 Export Citation

Tranilast-delivery surgical sutures to ameliorate wound healing by reducing scar formation through regulation of TGF-β expression and fibroblast recruitment

Sung Yoon Choi¹, Byung Hwi Kim², Beom Kang Huh¹, Woong Jeong³, Min Park¹, Hyo Jin Park⁴, Ji-Ho Park⁵, Chan Yeong Heo^{3, 6, †}, and Young Bin Choy^{1, 2, †}

¹Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 08826, Republic of Korea
²Department of Biomedical Engineering, College of Medicine and Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul 03080, Republic of Korea
³Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea
⁴Department of Pathology, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea
⁵Department of Bio and Brain Engineering and KAIST Institute of Health Science and Technology, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea
⁶Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul 03080, Republic of Korea

E-mail:,

We describe surgical sutures enabled with the local, sustained delivery of a TGF-β inhibitory drug, tranilast. To fabricate drug-delivery sutures, we separately prepared a tranilast-loaded strand using poly (lactic-co-glycolic acid), which was then physically braided with a surgical suture already in clinical use. By this method, the drug-delivery sutures maintained the mechanical strength and allowed the modulation of drug release profiles by simply altering the tranilast-loaded strand. The drug-delivery sutures herein released tranilast for up to 14 days. When applied to animal models, scarring was indeed reduced with diminished TGF-β expression and fibroblast numbers during the entire 21 day testing period.

Keywords:Fibroblasts;Scar reduction;Surgical suture;Sustained drug delivery;TGF-β

[References]

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Witte MB, Barbul A, Surg. Clin. North Am., 77, 509 (1997)
Clark RA, The Molecular and Cellular Biology of Wound Repair, Springer Science & Business Media, 2013.
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Beanes SR, Dang C, Soo C, Ting K, Expert Rev. Mol. Med., 5, 1 (2003)
Leask A, Abraham DJ, Faseb J., 18, 816 (2004)
Darakhshan S, Pour AB, Pharmacol. Res., 91, 15 (2015)
Varga J, Pasche B, Curr. Opin. Rheumatol., 20, 720 (2008)
Hu H, Yang S, Zheng J, Mao G, Chem. Biol. Drug Des., 90, 345 (2017)
See F, Watanabe M, Kompa AR, Wang BH, Boyle AJ, Kelly DJ, Gilbert RE, Krum H, Heart Lung Circ., 22, 122 (2013)
Tamai H, Katoh O, Suzuki S, Fujii K, Aizawa T, Takase SI, Kurogane H, Nishikawa H, Sone T, Sakai K, Am. Heart J., 138, 968 (1999)
Nair LS, Laurencin CT, Prog. Polym. Sci, 32, 762 (2007)
Gupta B, Jain R, Singh H, Polym. Adv. Technol., 19, 1698 (2008)
Janiga P, Elayarajah B, Rajendran R, Rammohan R, Venkatrajah B, Asa S, J. Ind. Text., 42, 176 (2012)
Lee JE, Park S, Park M, Kim MH, Park CG, Lee SH, Choi SY, Kim BH, Park HJ, Park JH, Acta Biomater., 8318 (2013).
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McMullen C, Bauza E, Gondran C, Oberto G, Domloge N, Farra CD, Moore D, Int. J. Cosmet. Sci., 32, 143 (2010)
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Sporn MB, Roberts AB, J. Clin. Invest., 92, 2565 (1993)
Zhang KAI, Garner W, Cohen L, Rodriguez J, Phan SEM, J. Invest. Dermatol., 104, 750 (1995)
Park S, Park M, Kim BH, Lee JE, Park HJ, Lee SH, Park CG, Kim MH, Kim R, Kim EH, J. Control. Release, 200, 125 (2015)

[Referenced By]

[1] Bayat A, McGrouther DA, Ferguson MWJ, BMJ, 326, 88 (2003)

[2] Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG, Mol. Med., 17, 113 (2011)

[3] Witte MB, Barbul A, Surg. Clin. North Am., 77, 509 (1997)

[4] Clark RA, The Molecular and Cellular Biology of Wound Repair, Springer Science & Business Media, 2013.

[5] Branton MH, Kopp JB, Microbes Infect., 1, 1349 (1999)

[6] Beanes SR, Dang C, Soo C, Ting K, Expert Rev. Mol. Med., 5, 1 (2003)

[7] Leask A, Abraham DJ, Faseb J., 18, 816 (2004)

[8] Darakhshan S, Pour AB, Pharmacol. Res., 91, 15 (2015)

[9] Varga J, Pasche B, Curr. Opin. Rheumatol., 20, 720 (2008)

[10] Hu H, Yang S, Zheng J, Mao G, Chem. Biol. Drug Des., 90, 345 (2017)

[11] See F, Watanabe M, Kompa AR, Wang BH, Boyle AJ, Kelly DJ, Gilbert RE, Krum H, Heart Lung Circ., 22, 122 (2013)

[12] Tamai H, Katoh O, Suzuki S, Fujii K, Aizawa T, Takase SI, Kurogane H, Nishikawa H, Sone T, Sakai K, Am. Heart J., 138, 968 (1999)

[13] Nair LS, Laurencin CT, Prog. Polym. Sci, 32, 762 (2007)

[14] Gupta B, Jain R, Singh H, Polym. Adv. Technol., 19, 1698 (2008)

[15] Janiga P, Elayarajah B, Rajendran R, Rammohan R, Venkatrajah B, Asa S, J. Ind. Text., 42, 176 (2012)

[16] Lee JE, Park S, Park M, Kim MH, Park CG, Lee SH, Choi SY, Kim BH, Park HJ, Park JH, Acta Biomater., 8318 (2013).

[17] Yamagami N, Mori R, Yotsumoto T, Hatanaka H, Takao M, Uchio Y, J. Orthop. Sci., 11, 614 (2006)

[18] Shanmugasundaram O, Gowda RM, Saravanan D, Int. J. Biotechnol. Mol. Biol. Res., 2, 80 (2011)

[19] Aksoy MH, Vargel I, Canter IH, Erk Y, Sargon M, Pinar A, Tezel GG, Aesthet. Surg. J., 26, 388 (2002)

[20] Dorsett-Martin WA, Wound Repair Regen., 12, 591 (2004)

[21] United States Pharmacophia; General chapter: <881> Tensile strength in USP 29. http://www.pharmacopeia.cn/v29240/usp29nf24s0_c881.html.

[22] Hardy MA, Phys. Ther., 69, 1014 (1989)

[23] English RS, Shenefelt PD, Dermatol. Surg., 25, 631 (1999)

[24] McMullen C, Bauza E, Gondran C, Oberto G, Domloge N, Farra CD, Moore D, Int. J. Cosmet. Sci., 32, 143 (2010)

[25] Vogt FG, Cohen DE, Bowman JD, Spoors GP, Zuber GE, Trescher GA, Dell’Orco PC, Katrincic LM, Debrosse CW, Haltiwanger RC, . Pharm. Sci. Exp. Pharmacol., 94, 651 (2005)

[26] Choi HS, Seo SA, Khang G, Rhee JM, Lee HB, Int. J. Pharm., 234, 195 (2002)

[27] Kawashima Y, Niwa T, Takeuchi H, Hino T, Itoh Y, Furuyama S, J. Pharm. Sci. Exp. Pharmacol., 80, 472 (1991)

[28] Khalil KA, Fouad H, Elsarnagawy T, Almajhdi FN, Int. J. Electrochem. Sci., 8, 3483 (2013)

[29] Carantino I, Florescu IP, Carantino A, J. Med. Life, 3, 122 (2010)

[30] Thareja S, Kundu RV, Keloids and Hypertrophic Scarring, Springer International Publishing, Cham, pp.233 2017.

[31] Darby IA, Hewitson TD, Int. Rev. Cytol., 257, 143 (2007)

[32] Mutalik S, Indian J. Dermatol. Venereol. Leprol., 71, 3 (2005)

[33] Lee MJ, Jin SE, Kim CK, Choung HK, Jeoung JW, Kim HJ, Choe G, Hwang JM, Invest. Ophthalmol. Vis. Sci., 48, 699 (2007)

[34] Cui H, Gensini M, Kataria R, Twaddle T, Zhang J, Wadsworth S, Petrilli J, Rodgers K, Cooper K, Biomed. Mater., 4 (2008)

[35] Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M, Wound Repair Regen., 16, 585 (2008)

[36] Verrecchia F, Mauviel A, J. Invest. Dermatol., 118, 211 (2002)

[37] Sporn MB, Roberts AB, J. Clin. Invest., 92, 2565 (1993)

[38] Zhang KAI, Garner W, Cohen L, Rodriguez J, Phan SEM, J. Invest. Dermatol., 104, 750 (1995)

[39] Park S, Park M, Kim BH, Lee JE, Park HJ, Lee SH, Park CG, Kim MH, Kim R, Kim EH, J. Control. Release, 200, 125 (2015)