三維多孔性生物可降解支架已被廣泛應用於組織工程的骨頭修復與再生，支架的主要功能為提供結構讓細胞附著及增生。本研究選用生醫高分子材料聚己內酯Poly-ε-caprolactone (PCL)、致孔劑為氯化鈉Sodium Chloride (NaCl)及碳酸氫銨Ammonium bicarbonate ((NH4)HCO3)與生醫陶瓷氫氧基磷灰石nano-hydroxyapatite (n-HA)或磷酸三鈣β-tricalcium diphosphate (β-TCP)混合，經由溶液澆鑄/粒子析出去得到生物多孔性支架。
本研究以生醫高分子材料(PCL)針對純PCL, 不同比例之PCL/nHA及不同比例PCL/β-TCP所製成支架並且探討生物多孔性支架之機械特性(壓縮試驗)、物理特性(孔隙率測試、接觸角測試)，爾後以降解實驗來觀察生物多孔性支架之重量損失百分比及pH值變化。細胞測試選擇類骨母細胞(MG63)培養於支架並且進行細胞毒性試驗(MTT) 及鹼性磷脂酶檢測(ALP)。根據結果顯示，HA與β-TCP能夠有效的改善材料的親水性質，PCL/nHA(3:2)有較佳的機械性質。降解實驗結果指出添加nHA或β-TCP可加快降解速率。另外，PCL/nHA及PCL/β-TCP支架在體外實驗有較好的生物相容性。

Three-dimensional porous biodegradable polymer scaffolds have been widely used for tissue engineering of bone repair or regeneration. The primary function of scaffolds is to provide structure support for the cells adhesion and proliferation. This study selects the Poly-ε-caprolactone (PCL) as material, NaCl and (NH4)HCO3 mixed with nano-hydroxyapatite (n-HA) or β-tricalcium diphosphate (β-TCP). In addition, this study uses the solution casting/particulate leaching method to fabricate the porous scaffold. This study discusses the compression mechanical properties, physical properties (porosity, contact angle) of a pure PCL, PCL/nHA, PCL/β-TCP in different ratio of the scaffolds. Subsequence, this study discusses the weight loss and pH values change for degradable experiment on scaffolds. The in vitro cell culture is used for osteoblast cell (MG63) and the Microculture Tetrazolium Test (MTT), alkaline phosphatase (ALP) activity is undertaken in the scaffold.
The experimental results indicate that n-HA and β-TCP can improve the hydrophilic property. The PCL/nHA(3:2) scaffolds have excellent mechanical properties. Results of degradation test reveal that the degradation rate of the scaffolds is accelerated by adding nHA or β-TCP. Results of the MTT and alkaline phosphatase (ALP) activity test indicate that the PCL/nHA scaffolds have excellent in vitro biocompatibility.

1.Mikos, A.G., Thorsen, A.J., Czerwonka, L.A., Bao, Y., and Langer, R., “Preparation and characterization of poly(L-lactic acid) foams”, Polymer, Vol. 35, pp. 1068-1077 (1994)
2.Yu, H., Matthew, H.M., Wooley, P.H., Yang, S.Y., “Effect of porosity and pore size on microstructures and mechanical properties of poly-ε-caprolactone-hydroxyapatite composites”, Journal of Biomedical Materials Research Part B: Applied Biomaterials, Vol. 86B, pp. 541-547 (2008)
3.Wu, H., Wan, Y., Cao, X.Y., Dalai, S.Q., Wang, S., Zhang, S.M., “Fabrication of chitosan-g-polycaprolactone copolymer scaffolds with gradient porous microstructures”, Materials Letters, Vol. 62, pp. 2733-2736 (2008)
4.Fabbri, P., Bondioli, F., Messori, M., Bartoli, C., Dinucci, D., Chiellini, F., “Porous scaffolds of polycaprolactone reinforced with in situ generated hydroxyapatite for bone tissue engineering”, Journal of Material Science: Materials in Medicine, Vol. 21, pp. 343-351 (2010)
5.Shyh-Yu Shaw, Jiun-YuWu. Tissue engineering of bone: PLGA-based materials as scaffold. The Thesis of National Cheng Kung University. (2003)
6.Causa, F., Netti, P.A., Ambrosio, L., Ciapetti, G., Baldini, N., Pagani, S., Martini, D., Giunti, A., “Poly-ε-caprolactone/hydroxyapatite composites for bone regeneration: in vitro characterization and human osteoblast response”, Journal of Biomedical Materials Research Part A, Vol. 76A, pp. 151-162 (2006)
7.Shor, L., Guceri, S., Wen, X., Gandhi, M., Sun, W., “Fabrication of three-dimensional polycaprolactone/hydroxyapatite tissue scaffolds and osteoblast-scaffold interactions in vitro”, Biomaterials, Vol. 28, pp. 5291-5297 (2007)
8.Wan, Y., Wu, H., Cao, X.Y., Dalai, S.Q., “Compressive mechanical properties and biodegradability of porous poly(caprolactone)/chitosan scaffolds”, Polymer Degradation and Stability, Vol. 93, pp. 1736-1741 (2008)
9.Yuanyuan Wang, Li Liu, Shengrong Guo, “Characterization of biodegradable and cytocompatible nano-hydroxyapatite/polycaprolactone porous scaffolds in degradation in vitro”, Polymer Degradation and Stability, Vol. 95, pp. 207-213 (2010)
10.Ang, K.C., Leong, K.F., Chua, C.K., Chandrasekaran, M., “Compressive properties and degradability of poly(e-caprolatone)/hydroxyapatite composites under accelerated hydrolytic degradation”, Journal of Biomedical Materials Research Part A, Vol. 80A, pp. 655-660 (2007)
11.Oh, S.H., Park, I.K., Kim, J.M., Lee, J.H., “In vitro and in vivo characteristics of PCL scaffolds with pore size gradient fabricated by a centrifugation method”, Biomaterials, Vol. 28 pp. 1664-1671 (2007)
12.Yang, S., Leong, K., and Chua, C., “The design of scaffold for use in tissue engineering part I. traditional factors”, Tissue Engineering, Vol. 7, pp. 1-12 (2001)
13.Kim, S.E., Yun, H.S., Hyun, Y.T., Shin, J.W., Song, J.J., “Nano-hydroxyapatite/poly ε-caprolactone composite 3D scaffolds for mastoid obliteration”, Journal of Physics: Conference Series, Vol. 165, 012083 (2009)
14.Yang, J., Shi, G.X., Bei, J.H., Wang, S.G., Cao, Y.L., Shang, Q.X., Yang, G.H., Wang, W.J., “Fabrication and surface modification of macroporous poly(L-lactic acid) and poly(L-lactic-co-glycolic acid) (70/30) cell scaffolds for human skin fibroblast cell culture”, Journal of Biomedical Materials Research, Vol. 62, pp. 438-446 (2002)
15.Heo, S.J., Kim, S.E., Wei, J., Hyun, Y.T., Yun, H.S., Kim, D.H., Shin, J.W., and Shin, J.W., “Fabrication and characterization of novel nano- and micro-HA/PCL composite scaffolds using a modified rapid prototyping process”, Journal of Biomedical Materials Research, Vol. 89 A, pp. 108-116 (2009)
16.Smejkal GB, Kaul CA. “Stability of nitroblue tetrazolium-based alkaline phosphatase substrates”, Journal of Histochem Cytochem, Vol. 49, pp. 1189–1190(2001)
17.Jia-Hsiang Hung, Ming-Jyh Chern, Yung-Kang Shen. Analysis on oseto tissue regeneration of PCL combined biomedical ceramic materials. The Thesis of National Taiwan University of Science and Technology. (2011)
18.Lien, S.M., Ko, L.Y., and Huang, T.J., “Effect of pore size on ECM secretion and cell growth in gelatin scaffold for articular cartilage tissue engineering”, Acta Biomaterialia, Vol. 5, pp. 670-679 (2009)
19.Huang, F.L., Wang, Q.Q., Wei, Q.F., Gao, W.D., Shou, H.Y., Jiang, S.D., “Dynamic wettability and contact angles of poly(vinylidene fluoride) nanofiber membranes grafted with acrylic acid”, eXPRESS Polymer Letters, Vol. 4, pp. 551-558 (2010)
20.Li, Y., Cheah, C.M., Chang, H., Leonard, L., Kum, A., “Preparation and characterization of bioactive composites of PCL/bioactive fillers”, International Journal of Modern Physics B, Vol. 24, pp. 128-135 (2010)
21.Loher, S., Reboul, V., Brunner, T.J., Simonet, M., Dora, C., Neuenschwander, P., and Stark, W.J., “Improved degradation and bioactivity of amorphous aerosol derived tricalcium phosphate nanoparticles in poly(lactide-co-glycolide) ”, Nanotechnology, Vol. 17, pp. 2054-2061 (2006)
22.Vollenweider, M., Brunner, T.J., Knecht, S., Grass, R.N., Zehnder, M., Imfeld, T., and Stark, W.J., “Remineralization of human dentin using ultrafine bioactive glass particles”, Acta Biomaterialia, Vol. 3, pp. 936-943 (2007)