콘드로이틴설페이트가 함유된 젤란검 하이드로젤에서의 연골재생연구

최일남; 김창현; 송정은; 백종선; 전성현; 전하얀; 이순영; 강길선; Ilnam Choi; Changhyun Kim; Jeong Eun Song; Jongseon Baek; Sung Hyun Jeon; HaYan Jeon; Soon Young Lee; Gilson Khang

Polymer(Korea), Vol.41, No.6, 962-966, November, 2017

DOI10.7317/pk.2017.41.6.962 Export Citation

콘드로이틴설페이트가 함유된 젤란검 하이드로젤에서의 연골재생연구

A Comprehensive Study on Cartilage Regeneration Using Gellan-gum/Chondroitin Sulfate Hybrid Hydrogels

최일남, 김창현, 송정은 , 백종선, 전성현, 전하얀, 이순영, 강길선 ^†

전북대학교 BIN융합공학과, 고분자나노공학과, 고분자융합소재연구소

Ilnam Choi, Changhyun Kim, Jeong Eun Song , Jongseon Baek, Sung Hyun Jeon, HaYan Jeon, Soon Young Lee, and Gilson Khang^†

Department of BIN Convergence Tech & Dept. of PolymerNanoSci Tech, Chonbuk National University, 567 Baekje-daero, Jeonju 54898, Korea

E-mail:

초록

젤란검(Gellan gum, GG)은 람노오스, 글루콘산 및 포도당으로 구성된 헤테로다당류로서 에로디속의 수초로부터 추출하며, 무색의 무미, 무취한 분말로서 생체적합성이 좋아 현대 조직공학에 주로 이용되는 생체재료이다. 콘드로이틴설페이트(CS)는 골관절염(OA)의 임상증상을 천천히 완화를 유도시키고, 이런 효과들은 치료 후에도 장기간 지속시킨다고 알려져 있다. 실질적으로, 동물실험과 임상시험에서 관절염증을 회복, 지연 혹은 안정화할 수 있어서 장기치료에서 증상완화를 제공하는 구조개선 관절염 약으로 CS의 효능이 입증되고 있다. 따라서 본 연구에서는 연골재생에 있어, CS를 함유한 GG 하이드로젤의 효과를 확인하고자 in vitro 환경에서 실험을 진행하였다. CS의 함량은 젤란검 중량의 10, 20, 30 wt%로 설정하여 하이드로젤 형태로 제조하였고, 지지체의 특성분석을 위해 압축강도, SEM을 평가하였다. 세포부착과 증식률은 MTT, 유전자발현은 RT-PCR을 통해 확인하였다. 그 결과, 20%의 CS/GG가 세포부착 및 증식률, 유전자발현이 다른 군에 비해 가장 높았다. 그에 따라 20% CS/GG는 연골재생을 위한 하이드로젤로 응용가능성이 기대된다.

Gellan gum is a heterosaccharide composed of rhamnoose, glucuronic acid and glucose. It is a colorless tasteless odorless powder extracted from aquatic plants in Erodium. It is a biomaterial mainly used in modern tissue engineering. The chondroitin sulfate (CS) has been found to induce slow, sustained relief for osteoarthritis (OA) patients worldwide. It has been also proven a structurally improved arthritis drug that can relieve, delay or stabilize joint inflammation in many animal experiments and clinical trials, thus providing symptom relief in long-term. In this study, we investigated the effect of gellan gum scaffolds containing chondroitin for treating osteoarthritis in vitro. The content of chondroitin hybride in the scaffolds was set to 10, 20 and 30%, and scaffolds was prepared by hydrogel type. SEM was performed to characterize the scaffolds. The cell adhesion and proliferation rate were confirmed by MTT assay and gene expression by RT-PCR. In addition, the compressive strength test were perfomed to confirm mechanical strength. Overall results showed that 20% CS/GG scaffolds was best suitable for adhesion, proliferation rate and gene expression and can be potentially applied for cartilage regeneration.

Keywords:chondroitin sulfate;gellan gum;hydrogel;scaffold

[References]

Kim IG, Ko J, Lee HR, Do SH, Park K, Biomaterials, 85, 18 (2016)
Kuo YC, Wang CC, Biointerfaces, 93, 235 (2012)
Cheng Z, Teoh SH, Biomaterials, 25, 1991 (2004)
Daamen WF, Veerkamp JH, van Hest JCM, van Kuppevelt TH, Biomaterials, 28, 4378 (2007)
Augst AD, Kong HJ, Mooney DJ, Macromol. Biosci., 6, 623 (2006)
Segura T, Anderson BC, Chung PH, Webber RE, Shull KR, Shea LD, Biomaterials, 26, 359 (2005)
Khang G, Lee SK, Kim HN, Silva-Correia J, Gomes ME, Viegas CA, Dias IR, Oliveira JM, Reis RL, J. Tissue Eng. Regen. Med., 9, 265 (2015)
Park H, Kim HY, Kwon SY, Khang G, Kim YS, Polym. Korea, 39(1), 144 (2015)
Oliveira JT, Martins L, Picciochi R, Malafaya IB, Sousa RA, Neves NM, Mano JF, Reis RL, J. Biomed. Mater. Res., 93A, 852 (2010)
Nadanaka S, Sugahara K, Glycobiology, 7, 253 (1997)
Ohtsuka Y, Nakae H, Ade H, Obinata T, Zool. Sci., 11, 409 (1994)
Caliari SR, Ramirez MA, Harely BAC, Biomaterials, 32, 8990 (2011)
Song T, Ma J, Guo L, Yang P, Cell Physiol., 10, 1002 (2017)
Song JE, Kim R, Lee JH, Kim HM, Kim CM, Lee D, Khang G, Inter. J. Tissue Regen., 4, 17 (2013)
Brinckmann J, Top. Curr. Chem., 247, 1 (2005)
Hong HK, Lee SK, Song YS, Kim DS, Eom S, Kim HE, Khang GS, Polym. Korea, 10, 1 (2010)
Han KS, Ko HA, Jang NK, Song JE, Khang G, Macromol. Res., 22(12), 1253 (2014)
Einbinder J, Schubert M, J. Biol. Chem., 85, 725 (1950)
Sakloetsakun D, Drug Dev. Ind. Pharm., 14, 10 (2016)
Mandal BB, Kundu SC, Biomaterials, 30, 2956 (2009)
Gu BK, Kim MS, Park SJ, Kim CH, Inter. J. Tissue Regen.., 2, 833 (2011)
Sahoo S, Toh SL, Goh JC, Biomaterials, 31, 2990 (2010)
Rutgers M, Saris DB, Vonk LA, Van Rijen MH, Akrum V, Tissue Eng., 19, 59 (2013)
Perugini V, Guildford AL, Silva-Correia J, J. Tissue Eng. Regen. Med., 10, 1002 (2016)
Mahdi MH, Conway BR, Int. J. Pharm., 30, 515 (2016)
Mobini S, Hoyer B, Solati-Hashjin M, Lode A, Nosoudi N, Samadikuchaksaraei A, Gelinsky M, J. Biomed. Mater. Res., 101, 2392 (2013)
Ha HJ, Song JE, Kang Y, Kim EY, Yoon SJ, Yang YI, Lee D, Khang G, Biomed. Eng. Appl. Basis Commun., 26, 1 (2014)
Kim JC, Song HJ, Jang E, Kim SH, Park HW, Polym. Korea, 39, 1 (2015)

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[2] Kuo YC, Wang CC, Biointerfaces, 93, 235 (2012)

[3] Cheng Z, Teoh SH, Biomaterials, 25, 1991 (2004)

[4] Daamen WF, Veerkamp JH, van Hest JCM, van Kuppevelt TH, Biomaterials, 28, 4378 (2007)

[5] Augst AD, Kong HJ, Mooney DJ, Macromol. Biosci., 6, 623 (2006)

[6] Segura T, Anderson BC, Chung PH, Webber RE, Shull KR, Shea LD, Biomaterials, 26, 359 (2005)

[7] Khang G, Lee SK, Kim HN, Silva-Correia J, Gomes ME, Viegas CA, Dias IR, Oliveira JM, Reis RL, J. Tissue Eng. Regen. Med., 9, 265 (2015)

[8] Park H, Kim HY, Kwon SY, Khang G, Kim YS, Polym. Korea, 39(1), 144 (2015)

[9] Oliveira JT, Martins L, Picciochi R, Malafaya IB, Sousa RA, Neves NM, Mano JF, Reis RL, J. Biomed. Mater. Res., 93A, 852 (2010)

[10] Nadanaka S, Sugahara K, Glycobiology, 7, 253 (1997)

[11] Ohtsuka Y, Nakae H, Ade H, Obinata T, Zool. Sci., 11, 409 (1994)

[12] Caliari SR, Ramirez MA, Harely BAC, Biomaterials, 32, 8990 (2011)

[13] Song T, Ma J, Guo L, Yang P, Cell Physiol., 10, 1002 (2017)

[14] Song JE, Kim R, Lee JH, Kim HM, Kim CM, Lee D, Khang G, Inter. J. Tissue Regen., 4, 17 (2013)

[15] Brinckmann J, Top. Curr. Chem., 247, 1 (2005)

[16] Hong HK, Lee SK, Song YS, Kim DS, Eom S, Kim HE, Khang GS, Polym. Korea, 10, 1 (2010)

[17] Han KS, Ko HA, Jang NK, Song JE, Khang G, Macromol. Res., 22(12), 1253 (2014)

[18] Einbinder J, Schubert M, J. Biol. Chem., 85, 725 (1950)

[19] Sakloetsakun D, Drug Dev. Ind. Pharm., 14, 10 (2016)

[20] Mandal BB, Kundu SC, Biomaterials, 30, 2956 (2009)

[21] Gu BK, Kim MS, Park SJ, Kim CH, Inter. J. Tissue Regen.., 2, 833 (2011)

[22] Sahoo S, Toh SL, Goh JC, Biomaterials, 31, 2990 (2010)

[23] Rutgers M, Saris DB, Vonk LA, Van Rijen MH, Akrum V, Tissue Eng., 19, 59 (2013)

[24] Perugini V, Guildford AL, Silva-Correia J, J. Tissue Eng. Regen. Med., 10, 1002 (2016)

[25] Mahdi MH, Conway BR, Int. J. Pharm., 30, 515 (2016)

[26] Mobini S, Hoyer B, Solati-Hashjin M, Lode A, Nosoudi N, Samadikuchaksaraei A, Gelinsky M, J. Biomed. Mater. Res., 101, 2392 (2013)

[27] Ha HJ, Song JE, Kang Y, Kim EY, Yoon SJ, Yang YI, Lee D, Khang G, Biomed. Eng. Appl. Basis Commun., 26, 1 (2014)

[28] Kim JC, Song HJ, Jang E, Kim SH, Park HW, Polym. Korea, 39, 1 (2015)