本研究選用聚酯高分子Poly(ε-caprolactone) (PCL)、天然高分子Type II collagen及Chondroitin sulfate (CS)做為複合型支架。先以鹽粒溶濾法，將PCL製備成三維多孔性支架，利用1,6-hexandiamine進行化學改質，使表面帶有自由胺基端。之後以水溶性carbodiimd [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)]作為交聯劑，結合將PCL、Type II Collagen及Chondroitin sulfate三者，做成一類細胞外間質支架，使材料具有適當的機械性質，又具有可與細胞相結合的受器(conjugate site)，使培養出的人工組織與天然軟骨組織相似。研究中，對支架材料的基本結構鑑定、不同型態下的機械性質、親水性以及表面形態作了探討及評估。並將軟骨細胞種植入複合型支架，進行體外培養，藉由定量分析及細胞型態評估細胞在基材上生長的情形。實驗結果顯示Collagen及Chondroitin sulfate的添加對細胞生長、細胞外間質的合成、分泌及分佈都有一定程度的助益。

1.Nesic, D., et al., Cartilage tissue engineering for degenerative joint disease. Advanced Drug Delivery Reviews, 2006. 58(2): p. 300-322.
2.Temenoff, J.S. and A.G. Mikos, Review: tissue engineering for regeneration of articular cartilage. Biomaterials, 2000. 21(5): p. 431-440.
3.Aigner, T. and J. Stove, Collagens - major component of the physiological cartilage matrix, major target of cartilage degeneration, major tool in cartilage repair. Advanced Drug Delivery Reviews, 2003. 55(12): p. 1569-1593.
4.S. L. Turek, 傅., 骨科學原理及應用. 民 76: 大中國圖書公司. p. 13-281.
5.LeBaron, R.G. and K.A. Athanasiou, Ex vivo synthesis of articular cartilage. Biomaterials, 2000. 21(24): p. 2575-2587.
6.Aubin, J.E., et al., Osteoblast and Chondroblast Differentiation. Bone, 1995. 17(2): p. S77-S83.
7.Hutmacher, D.W., Scaffolds in tissue engineering bone and cartilage. Biomaterials, 2000. 21(24): p. 2529-2543.
8.Eyre, D.R., J.J. Wu, and P.E. Woods, The Cartilage Collagens - Structural and Metabolic Studies. Journal of Rheumatology, 1991. 18: p. 49-51.
9.Huber, M., S. Trattnig, and F. Lintner, Anatomy, biochemistry, and physiology of articular cartilage. Investigative Radiology, 2000. 35(10): p. 573-580.
10.Athanasiou, K.A., G.G. Niederauer, and C.M. Agrawal, Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid polyglycolic acid copolymers. Biomaterials, 1996. 17(2): p. 93-102.
11.Suh, J.K.F. and H.W.T. Matthew, Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials, 2000. 21(24): p. 2589-2598.
12.Furukawa, T., et al., Biochemical-Studies on Repair Cartilage Resurfacing Experimental Defects in the Rabbit Knee. Journal of Bone and Joint Surgery-American Volume, 1980. 62(1): p. 79-89.
13.R. P. Lanza, R.L., J. Vacanti, Principles of tissue engineering. 2nd ed. 1999, Tokyo: Academic Press. p.671-682.
14.Shin, M., H. Yoshimoto, and J.P. Vacanti, In vivo bone tissue engineering using mesenchymal stem cells on a novel electrospun nanofibrous scaffold. Tissue Engineering, 2004. 10(1-2): p. 33-41.
15.J. M. Pachence, J.K., Biodegradable Polymers. 2nd edition ed. In Principle of Tissue Engineering. 2000: Academic Press. p. 263.
16.Sung, H.J., et al., The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesis. Biomaterials, 2004. 25(26): p. 5735-5742.
17.Kirker, K.R., et al., Glycosaminoglycan hydrogel films as bio-interactive dressings for wound healing. Biomaterials, 2002. 23(17): p. 3661-3671.
18.Bali, J.P., H. Cousse, and E. Neuzil, Biochemical basis of the pharmacologic action of chondroitin sulfates on the osteoarticular system. Seminars in Arthritis and Rheumatism, 2001. 31(1): p. 58-68.
19.Pieper, J.S., et al., Preparation and characterization of porous crosslinked collagenous matrices containing bioavailable chondroitin sulphate. Biomaterials, 1999. 20(9): p. 847-858.
20.Pieper, J.S., et al., Development of tailor-made collagen-glycosaminoglycan matrices: EDC/NHS crosslinking, and ultrastructural aspects. Biomaterials, 2000. 21(6): p. 581-593.
21.Daamen, W.F., et al., Preparation and evaluation of molecularly-defined collagen-elastin-glycosaminoglycan scaffolds for tissue engineering. Biomaterials, 2003. 24(22): p. 4001-4009.
22.Ohno, T., et al., Effect of type I and type II collagen sponges as 3D scaffolds for hyaline cartilage-like tissue regeneration on phenotypic control of seeded chondrocytes in vitro. Materials Science & Engineering C-Biomimetic and Supramolecular Systems, 2004. 24(3): p. 407-411.
23.Ma, Z.W., et al., Cartilage tissue engineering PLLA scaffold with surface immobilized collagen and basic fibroblast growth factor. Biomaterials, 2005. 26(11): p. 1253-1259.
24.Zhu, Y.B., et al., Surface modification of polycaprolactone membrane via aminolysis and biomacromolecule immobilization for promoting cytocompatibility of human endothelial cells. Biomacromolecules, 2002. 3(6): p. 1312-1319.
25.Rault, I., et al., Evaluation of different chemical methods for cross-linking collagen gel, films and sponges. Journal of Materials Science-Materials in Medicine, 1996. 7(4): p. 215-221.
26.Damink, L.H.H.O., et al., Cross-linking of dermal sheep collagen using a water-soluble carbodiimide. Biomaterials, 1996. 17(8): p. 765-773.
27.Plumb, J.A., R. Milroy, and S.B. Kaye, Effects of the Ph-Dependence of 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyl-Tetrazolium Bromide-Formazan Absorption on Chemosensitivity Determined by a Novel Tetrazolium-Based Assay. Cancer Research, 1989. 49(16): p. 4435-4440.
28.L., S., Biochemistry. 1988, New York: Freeman. 50-51.
29.Kim, Y.J., et al., Fluorometric Assay of DNA in Cartilage Explants Using Hoechst-33258. Analytical Biochemistry, 1988. 174(1): p. 168-176.
30.Enobakhare, B.O., D.L. Bader, and D.A. Lee, Quantification of sulfated glycosaminoglycans in chondrocyte/alginate cultures, by use of 1,9-dimethylmethylene blue. Analytical Biochemistry, 1996. 243(1): p. 189-191.