Polymer(Korea), Vol.30, No.3, 196-201, May, 2006
온도감응성 수화젤을 이용한 골수간엽줄기세포의 골분화 유도
Osteogenic Differentiation of Bone Marrow Stem Cells Using Thermo-Sensitive Hydrogels
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초록
온도감응성 고분자인 폴리(에틸렌 글리콜)을 기본으로 하는 다이블록 및 트리블록 폴리에스테르 공중합체들은 비독성과 생체적합성 그리고 생분해성 특징 때문에 조직공학 분야 및 주사제형의 약물전달체에서 많은 응용이 이루어지고 있다. 본 연구에서는 다이블록 공중합체를 이용한 솔-젤 전이 현상을 갖는 고분자를 평균분자량 750 g/mole의 메톡시 폴리(에틸렌 글리콜)과 카프로락톤을 실온에서 HClㆍEt2O 존재 하에서 개환중합을 통하여 합성하였다. 이 공중합체를 이용하여 in vivo 상에서 골수간엽줄기세포와 골유도물질인 덱사메타손의 존재 여부에 따라 골분화의 가능성을 조사하였다. 조직을 파라핀으로 고정시켜 슬라이드를 제조한 후 hematoxylin & eosin, 본쿠사 및 오스테오칼신 염색을 통하여 골형성 정도를 확인하였다. 결론적으로 덱사메타손이 함유된 젤이 골형성에 도움을 주지만 젤만으로는 강한 골형성을 유도할 수 없으므로 줄기세포나 다른 골형성 유도재료를 사용하면 우수하게 골형성 효과를 가져올 것이라고 판단되었다.
Poly(ethylene glycol)-based diblock and triblock thermo-sensitive polyester copolymers were investigated for application on tissue engineering and injectable biomaterials in drug delivery system due to their nontoxicity, biocompatibility and biodegradability. We synthesized the diblock copolymers consisting of methoxy poly(ethylene glycol)(MPEG)(Mn=750 g/mole) and poly(ε-caprolactone)(PCL) by ring opening polymerization of ε-CL with MPEG as an initiator in the presence of HClㆍEt2O. The effect of diblock copolymers on in vivo osteogenic differentiation of rat bone marrow stromal cells (BMSCs) with and without the presence of osteogenic supplements (dexamethasone) was investigated. Thin sections were cut from paraffin embedded tissues and histological sections were stained by H&E, von Kossa, and immunohistochemical staining for osteocalcin. In conclusion, dexamethasone containing thermo-sensitive hydrogel might be improved osteogenic differentiation of BMSCs. We expect the osteoinduction effect to be excellent when it uses stem cell or other osteogenic materials.
- Khang G, Lee HB, in Methods of Tissue Engineering, A. Atala, and R. Lanza, Editors, Academic Press, p.771 (2001)
- Khang G, Lee I, Rhee JM, Lee HB, Polym. Sci. Technol., 12(2), 239 (2001)
- Khang G, Lee SJ, Han CW, Rhee JM, Lee HB, in Advances in Experimental Medicine and Biology, M. Elcin, Editor, Kluwer-Plenum Press, London, Vol. 657, p.235 (2003)
- Khang G, Lee I, Lee HB, Lee SJ, Polym. Sci. Technol., 13(1), 4 (2002)
- Khang G, Kim MS, Cho SH, Lee IW, Rhee JM, Lee HB, Tissue Eng. Regen. Med., 1, 9 (2004)
- Khang G, Kim MS, Lee HB, Chem. World, 45, 24 (2005)
- Khang G, Kim SK, Hong KD, Jang WY, Kim MS, Han CW, Lee IW, Lee HB, Tissue Eng. Regen. Med., 1, 136 (2004)
- Kim HS, Lee IW, Lee JM, Han CW, Sung JH, Park MY, Khang G, Lee HB, J. Korea Soc. Endocrinology, 17, 206 (2002)
- Khang G, Kim EJ, Kim SH, Park KS, Han CW, Yang YS, Kim MS, Lee HB, Tissue Eng. Regen. Med., 2, 20 (2005)
- Lee SJ, Lee DH, Khang G, Lee YM, Lee HB, Macromol. Chem. Symp., 15, 201 (2002)
- Jang JW, Lee B, Han CW, Lee IW, Lee HB, Khang G, Polym.(Korea), 27(3), 226 (2003)
- Lee SJ, Lee IW, Lee YM, Lee HB, Khang G, J. Biomater. Sci.-Polym. Ed., 15, 1003 (2004)
- Jang JW, Lee B, Han CW, Kim MS, Cho SH, Lee HB, Khang G, Polym.(Korea), 28(5), 382 (2004)
- Jang JW, Park KS, Kim SH, Park CS, Kim MS, Han CW, Rhee JM, Khang G, Lee HB, Tissue Eng. Regen. Med., 2, 34 (2005)
- Seo KS, Park CS, Kim MS, Cho SH, Lee HB, Khang G, Polym.(Korea), 28(3), 211 (2004)
- Seo KS, Chon SK, Kim MS, Cho SH, Lee HB, Khang G, Polym.(Korea), 28(3), 232 (2004)
- Kim MS, Seo KS, Khang G, Cho SH, Lee HB, J. Biomed. Mater. Res., 70A, 154 (2004)
- Seo KS, Kim MS, Kim K, Cho SH, Lee HB, Khang G, Polym.(Korea), 28(4), 328 (2004)
- Seo KS, Park CS, Kim MS, Cho SH, Lee HB, Khang G, Polym.(Korea), 28(4), 344 (2004)
- Kim MS, Seo KS, Jeong SY, Khang G, Cho SH, Lee HB, Polym. Prepr, 45, 1054 (2004)
- Kim MS, Seo KS, Khang G, Cho SH, Lee HB, J. Polym. Sci. A: Polym. Chem., 42(22), 5784 (2004)
- Seo KS, Kim MS, Khang G, Cho SH, Lee HB, Polym. Prepr, 46, 820 (2005)
- Kim MS, Seo KS, Khang G, Lee HB, Macromol. Rapid Commun., 26, 643 (2005)
- Kim MS, Seong HS, Cho SH, Lee HB, Chae KS, Lee JS, Khang G, Bio-Med. Mater. Eng., 15, 229 (2005)
- Bae YH, Okano T, Hsu R, Kim SW, Makromol. Chem. Rapid Common., 8, 481 (1994)
- Feil H, Bae YH, Feijen J, Kim SW, Macromolecules, 25, 5440 (1992)
- Yoshida R, Uchida K, Kaneko Y, Sakai K, Kikuchi A, Sakurai Y, Okano T, Nature, 372, 240 (1995)
- Brazel CS, Peppas NA, Macromolecules, 28(24), 8016 (1995)
- Park SR, Min BH, Park SH, Lee HJ, Tissue Eng. Regen. Med., 2, 77 (2005)
- Chen GH, Hoffman AS, Nature, 373(6509), 49 (1995)
- Thomas JL, You H, Tirrell DA, J. Am. Chem. Soc., 117(10), 2949 (1995)
- Yang J, Pickard S, Deng NJ, Barlow RJ, Attwood D, Booth C, Macromolecules, 24, 670 (1994)
- Jeong B, Bae YH, Lee DS, Kim SW, Nature, 388(6645), 860 (1997)
- Bhardwaj R, Blanchard J, J. Pharm. Sci., 85, 915 (1996)
- Kim YJ, Choi S, Koh JJ, Lee M, Ko KS, Kim SW, Pharm. Res., 18, 548 (2001)
- Jeong B, Bae YH, Kim SW, J. Biomed. Mater. Res., 50, 171 (2000)
- Berglund F, Acta Physiol. Scand, 73, 20 (1968)
- Temenoff JS, Steinbis ES, Mikos AG, Orthopaedic Tissue Engineering: Basic Science and Practice, New York, Marcel Dekker, p.77 (2004)
- Bellow CG, Heersch JNM, Dev. Biol., 140, 132 (1990)
- Benayahu D, Fred A, Zipori D, Wientroub S, Calcif. Tissue Int., 49, 202 (1991)