효소촉매 가교반응을 이용한 스프레이형 젤라틴 하이드로젤 창상피복제의 개발

김귀재; 고영광; 이혜영; 정호윤; 권오형; Gwijae Kim; Young-Gwang Ko; Hyeyoung Lee; Ho Yun Chung; Hyeong Kwon

Polymer(Korea), Vol.45, No.4, 610-619, July, 2021

DOI10.7317/pk.2021.45.4.610 Export Citation

효소촉매 가교반응을 이용한 스프레이형 젤라틴 하이드로젤 창상피복제의 개발

Development of Sprayable Gelatin Hydrogel Wound Dressings Using Enzymatic Crosslinking Reaction

김귀재, 고영광, 이혜영, 정호윤¹, 권오형^†

금오공과대학교 고분자공학과
¹경북대학교 의과대학 성형외과 세포기질연구소

Gwijae Kim, Young-Gwang Ko, Hyeyoung Lee, Ho Yun Chung¹, and Hyeong Kwon^†

Department of Polymer Science and Engineering, Kumoh National Institute of Technology, Gumi, Gyeongbuk 39177, Korea
¹Department of Plastic and Reconstructive Surgery, CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Korea

E-mail:

초록

생체적합성, 창상치유능 및 피부밀착성을 가지는 동시에 광범위하고 굴곡진 창상부에 간편하고 위생적으로 적용할 수 있는 스프레이형 창상피복제를 개발하고자 효소촉매 가교반응을 이용하여 티라민으로 개질된 젤라틴(Gel-Tyr) 하이드로젤을 제조하였다. Gel-Tyr의 개질률은 1H NMR을 통해 산출하였고 젤라틴, horseradish peroxidase (HRP) 및 H2O2의 농도에 따른 하이드로젤의 젤화시간, 유변학적 특성, 팽윤도, 생분해도, in vitro 세포독성, 세포생존거동을 평가하였다. 신속한 젤화속도와 창상피복제로서의 최적성능 조건의 하이드로젤은 배합농도 Gel-Tyr 3 wt%, HRP 3.50 units/mL 및 H2O2 0.2 μL/mL로 제조된 시료로 선정하였다. In vivo 전층창상모델 동물실험 및 조직학적 평가에서 Gel-Tyr 하이드로젤은 대조군보다 촉진된 창상회복속도와 진피재생능을 보여주었으며, 의료현장에서 편리하게 사용할 수 있는 스프레이형 창상피복제로의 활용이 기대된다.

The gelatin hydrogel modified with tyramine (Gel-Tyr) was prepared an enzymatic crosslinking reaction to develop a sprayable wound dressing that is easy to use and hygienic on broad and complicate wound area with biocompatibility, wound healing ability, and comfortable wearing. The substitution rate of Gel-Tyr was calculated through 1H NMR. And the gelation time according to the concentration of gelatin, horseradish peroxidase (HRP) and H2O2, rheological properties, swelling ratio, biodegradation behavior, in vitro cytotoxicity, cell viability was evaluated. The hydrogel with rapid gelation rate and optimum performance as a wound dressing was selected as a sample prepared with a compound concentration of Gel-Tyr 3 wt%, HRP 3.50 units/mL, and H2O2 0.2 μL/mL. In the in vivo full-thickness wound model animal experiment and histological evaluation, the Gel-Tyr hydrogel showed an accelerated wound healing rate and dermal regeneration compared to the control group. It is expected to be used as a sprayable wound dressing in medical treatment, conveniently.

Keywords:gelatin;tyramine;sprayable hydrogel;enzymatic crosslinking;wound dressing

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

[2] Hollister SJ, Nat. Mater., 4, 518 (2006)

[3] Hubbell JA, Nat. Biotechnol., 13, 565 (1995)

[4] Hanna JR, Giacopelli JA, J. Foot Ankle Surg., 36, 2 (1997)

[5] Zeng D, Shen S, Fan D, Chin. J. Chem. Eng., 30, 308 (2021)

[6] Zhang M, Zhao X, Int. J. Biol. Macromol., 162, 1414 (2020)

[7] Ngece K, Aderibigbe BA, Ndinteh DT, Fonkui YT, Kumar P, Int. J. Biol. Macromol., 172, 350 (2021)

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

[9] Cheng H, Shi Z, Yue K, Huang X, Xu Y, Gao C, Yao Z, Zhang YS, Wang J, Acta Biomater., 124, 219 (2021)

[10] Amirsadeghi A, Jafari A, Hashemi SS, Kazemi A, et al., Mater. Today Commun., 27, 102225 (2021)

[11] Dauton C, Kothari S, Smith L, Steele DA, Wound Practice and Research, 20, 174 2012.

[12] Varaprasad K, Raghavendra GM, Jayaramudu TA, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 79, 958 (2017)

[13] Ullah F, Othman MBH. Javed F, Ahmad Z, Akil HM, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 57, 414 (2015)

[14] Bang S, Lee E, Ko YG, Kim WI, Kwon OH, Int. J. Biol. Macromol., 87, 155 (2016)

[15] Lee F, Chung JE, Kurisawa M, Soft Matter, 4, 880 (2008)

[16] Bang S, Ko YG, Kim WI, Cho D, Park WH, Kwon OH, Int. J. Biol. Macromol., 105, 886 (2017)

[17] Martinez-Diaz GJ, Nelson D, Crone WJ, Kao WJ, Macromol. Chem. Phys., 204, 1898 (2003)

[18] Kim YH, Cho CS, Kang IK, Kim SY, Kwon OH, Key Eng. Mater., 342, 169 (2007)

[19] Zhao X, Lang Q, Yildirimer L, Lin ZY, Cui W, et al., Adv. Healthc. Mater., 5, 108 (2016)

[20] Sakai S, Hirose K, Taguchi K, Qgushi , Kawakami K, Biomaterials, 30, 3371 (2009)

[21] Akkara JA, Senecal KJ, Kaplan DL, J. Polym. Sci. A: Polym. Chem., 29, 1561 (1991)

[22] Ghasempur S, Torabi SF, Siadat SOR, Heravi MJ, Ghami N, Khajeh K, Environ. Sci. Technol., 41, 7073 (2007)

[23] Linh NTB, Abueva CDG, Lee BT, Biomed. Mater, 12, 015026 (2017)

[24] Kiselioviene S, Baniukaitiene O, Harkavenko V, Babenko NA, Liesiene J, Cellulose Chem. Technol., 50, 915 (2016)