인슐린을 함유한 키토산-폴리카프로락톤 복합 나노섬유 시트형 창상피복재의 특성평가

전가영; 고영광; 김동진; 권오경; 김원일; 정호윤; 권오형; Ga Young Jun; Young-Gwang Ko; Dongjin Kim; Oh Kyoung Kwon; Won Il Kim; Ho Yun Chung; Oh Hyeong Kwon

Polymer(Korea), Vol.44, No.4, 549-558, July, 2020

DOI10.7317/pk.2020.44.4.549 Export Citation

인슐린을 함유한 키토산-폴리카프로락톤 복합 나노섬유 시트형 창상피복재의 특성평가

Characterization of Chitosan-Poly(ε-caprolactone) Hybrid Nanofiber Sheets Containing Insulin for Wound Dressings

전가영, 고영광, 김동진, 권오경¹, 김원일², 정호윤³, 권오형^†

금오공과대학교 고분자공학과
¹칠곡경북대학교병원 위암센터
²(주)원바이오젠
³경북대학교 의과대학 성형와과, 세포외기질연구소

Ga Young Jun, Young-Gwang Ko, Dongjin Kim, Oh Kyoung Kwon¹, Won Il Kim², Ho Yun Chung³, and Oh Hyeong Kwon^†

Department of Polymer Science and Engineering, Kumoh National Institute of Technology, Gumi, Gyeongbuk 39177, Korea
¹Gastric Cancer Center, Kyungpook National University Chilgok Hospital, Daegu 41404, Korea
²R&D Center, Wonbiogen Co., Ltd., Gumi, Gyeongbuk 39372, Korea
³Department of Plastic and Reconstructive Surgery, CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Korea

E-mail:

초록

창상피복용 구조체는 생체적합성과 물리적 강도가 보장되고 외부의 감염균으로부터 상처부를 보호하면서, 상피층과 진피층의 재생을 촉진할 수 있도록 설계되어야 한다. 본 연구에서는 키토산과 poly(ε-caprolactone)(PCL) 및 인슐린 혼합물의 전기방사를 통해 나노섬유 시트형 창상피복재를 제조하였다. 혼합비율에 따른 각 나노섬유 시트의 미세구조분석, 원소조성분석, 인장시험, 생분해성, in vitro 약물방출능, 항균능, 세포증식 거동, in vivo 동물실험을 통하여 물리화학적 특성분석 및 창상치유능을 평가하였다. 키토산의 비율이 증가할수록 시트의 변형률이 감소하였고, 생분해성, 약물방출능 및 항균능은 증가하는 경향을 보였다. 동물실험 및 조직분석결과에서 키토산-PCL-인슐린 나노섬유 시트는 다른 나노섬유 시트보다 촉진된 상처회복률을 보였으며 창상피복용 소재로의 활용이 기대된다.

The construct for wound dressings should be designed to promote the regeneration of the epidermal and dermal layers while ensuring biocompatibility and physical strength with protecting the wound from external infectious bacteria. In this study, nanofibrous sheet type wound dressings were prepared by electrospinning of a mixture of chitosan, poly(ε-caprolactone) (PCL) and insulin. The nanofiber sheets according to the mixing ratio were analyzed for physicochemical properties through structural analysis, elemental composition, tensile test, biodegradability, drug release behavior, antibacterial activity, cell proliferation behavior, and wound healing ability via in vivo animal testing. As the content of chitosan increased, the elongation of the nanofiber sheets decreased, and the biodegradability, drug release ability, and antibacterial activity tended to increase. In animal experiments and histological analysis, the accelerated wound healing rate of the chitosan-PCL-insulin nanofibrous sheet was verified when compared to other nanofiber sheets, and thus it is expected to be used as a wound dressing material.

Keywords:chitosan;poly(ε-caprolactone);insulin;nanofiber;wound dressing

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[Referenced By]

[1] Yang S, Leong KF, Du Z, Tissue Eng., 7, 679 (2001)

[2] Helary C, Desimone MF, Curr. Pharm. Biotechnol., 16, 635 (2015)

[3] Langer R, Vacanti JP, Science, 260, 920 (1993)

[4] O'Connor N, Mulliken J, Banks-Schlegel S, Kehinde O, Green H, Lancet, 317, 75 (1981)

[5] Pearson AS, Wolford W, Prim. Care, 27, 475 (2000)

[6] Winter GD, Nature, 193, 293 (1962)

[7] Hinman CD, Maibach H, Nature, 200, 377 (1963)

[8] Szycher M, Games S, Lee FD, J. Biomater. Appl., 7, 142 (1992)

[9] Ishihara M, Nakanishi K, Ono K, Sato M, Kikuchi M, et al., Biomaterials, 23, 833 (2002)

[10] Singh DK, Ray AR, J. Macromol. Chem. Phys., C49, 69 (2000)

[11] Ishigara M, Ono K, Sato M, Nakanishi K, Saito Y, Yura H, Matsui T, Hattori H, Fujita M, Kikuchi M, Kurita A, Wound Repair Regen., 9, 513 (2001)

[12] Ehterami A, Salehi M, Farzamfar S, Vaez A, Samadian H, Sahrapeyma H, Mirzaii M, Ghorbani S, Goodarzi A, Int. J. Biol. Macromol., 117, 601 (2018)

[13] Howling GI, Dettmar PW, Goddard PA, Hampson FC, Dornish M, Wood EJ, Biomaterials, 22, 2959 (2001)

[14] Goorbandi RG, Mohammad MR, Malekzadeh K, Biomater. Res., 24, 9 (2020)

[15] Smirnova NV, Kolbe KA, Dresvyanina EN, Grebennikov SF, Dobrovolskaya IP, Yudin VE, Luxbacher T, Morganti P, Materials, 12, 11 (2019)

[16] Liu H, Wang C, Li C, Qin Y, Wang Z, Yang F, Li Z, Wang J, RSC Adv., 8, 7533 (2018)

[17] Manea LR, Hristian L, Leon AL, Popa A, Mater. Sci. Eng., 145, 032006 (2016)

[18] Ramakrishna S, Fujihara K, Teo WE, Lim TC, Ma Z, An Introduction to Electrospinning and Nanofibers, World Scientific, Singapore, p. 7 (2005).

[19] Gupta KC, Haider A, Choi YR, Kang IK, Biomater. Res., 18, 5 (2014)

[20] Mo XM, Xu CY, Kotaki M, Ramacrishna S, Biomaterials, 25, 1883 (2004)

[21] Boland ED, J. Biomed. Mater. Res., 71B, 144 (2004)

[22] Wnek GE, Carr ME, Simpson DG, Bowlin GL, Nano Lett., 3, 213 (2003)

[23] Ohkawa K, Cha DI, Kim H, Nishida A, Yamamoto H, Macromol. Rapid Commun., 25(18), 1600 (2004)

[24] Park WH, Jeong L, Yoo DI, Hudson S, Polymer, 45(21), 7151 (2004)

[25] Chen JP, Chang GY, Chen JK, Colloids Surf. A: Physicochem. Eng. Asp., 313, 183 (2007)

[26] Li L, Hsih YL, Carbohydr. Res., 341, 374 (2006)

[27] Li Z, Ramay HR, Hauch KD, Xiao D, Zhang M, Biomaterials, 26, 3919 (2005)

[28] Lee CH, Hung KC, Hsieh MJ, Chang SH, Juang JH, Hsieh IC, Wen MS, Liu SJ, Nanomed.-Nanotechnol., 24, 102123 (2020)

[29] Li WJ, Danielson KG, Alexander PG, Tuan RS, J. Biomed. Mater. Res., 67A, 1105 (2003)

[30] Li WJ, Laurencin CT, Caterson EJ, Tuan RS, Ko FK, J. Biomed. Mater. Res., 60, 613 (2002)

[31] Kidoaki S, Kwon IK, Matsuda T, Biomaterials, 26, 37 (2005)

[32] Kwon IK, Kidoaki S, Matsuda T, Biomaterials, 26, 3929 (2005)

[33] Liu Y, Zhou S, Gao Y, Zhai Y, Asian J. Pharm. Sci., 14, 130 (2019)