孔洞在自然界有許多形形色色的應用，其中在人體植入材部分為近年來的熱門應用之一。在骨科應用材料的發展歷程中，已由實心金屬朝向多孔材料等應用趨勢，開發出更趨近人體自然骨骼之力學性質，並同時具備良好的骨質引導、誘生與形成之生物功能之多孔鈦醫材。本實驗採用傳統粉末冶金的方式製備多孔鈦，但在造孔劑移除方面，不採用傳統的燒結或超音波震盪移除，而是以水熱法來改良傳統製程。之後進行的多孔鈦的相關性質分析，在物性與化性方面，首先以ICP鑑定水熱法所闡述之證實水熱法的必要性，接著以XRD證實燒結的最佳溫度，再來為表面形貌分析的SEM與AFM、成分分析的XPS與EDS，最後以阿基米德原理來測量孔隙率。在機械性質方面，分析項目有量測整體強度(巨觀)的壓縮試驗與表面硬度(微觀)的奈米壓痕試驗，抗壓強度期望達到ISO 5833 (Implants for surgery)所規範人體植入材最低強度的70MPa；表面硬度期望與人骨硬度相符合。在生物相容性方面，為了符合ISO 10993，以培養纖維母細胞(L929)等方式來評估醫療用複合骨材細胞測試，分析項目有細胞螢光染色、MTS細胞活性測試與LDH細胞毒性測試。實驗結果證實，水熱法可確實地移除造孔劑，其效果較傳統製程顯著。多孔鈦在1100℃開始出現氧化現象，1000℃為最佳燒結溫度。壓縮強度方面，僅造孔劑添加量70%的試片未達規範強度。生物相容性方面，細胞螢光染色中僅造孔劑添加量50%與70%的試片到達規範之細胞存活率80%；MTS中顯示多孔試片的細胞活性和實心試片相比差異顯著；LDH中造孔劑添加量50%的試片，染劑從五分鐘作用至四十分鐘，細胞死亡率的顯著性從一顆星增加至兩顆星，顯示50%試片是細胞死亡的一個臨界值。綜合多孔鈦各方面性質分析，造孔劑添加量50%為較適合的參數。

Porous ceramic and polymer biomaterials are usually not suitable for load-bearing sites, but can be used for filling the cavities or regenerating the soft tissue. Porous titanium-based scaffolds are interesting, since they may have superior mechanical properties with high strength/weight ratios. Some alloying elements, e.g. ,Zr, Nb, Ta, Sn, Mo, Si, may lead to superior improvement in properties of titanium-based materials. Although its potential has been recognized for years, development of open porous structures has been hampered by limitations in production techniques. With the use of the techniques such as plasma spraying, space holder, common P/M, or sintered titanium-based fibers, it is still difficult to produce a porous structure with an expected architecture that meets both osteoconductive and mechanical requirements.
To have the effect of osteoconduction, an “open interconnected” porous structure with pores in the range of 200-500 μm is estimated, though there is no exact agreement between scientists about the perfect size of pores to stimulate cells proliferation. From a mechanical point of view, the porous structure should be stiff enough to sustain physiological loads, but should not drastically exceed the stiffness of the bone being replaced to avoid stress shielding. As a consequence, to develop P/M sintered metal porous biomaterials for biomedical applications, it is required to compromise both properties and adjust their structural stability as a function of long-term employed time. In any case, the perspective is promising to focus upon metal porous biomaterials using P/M sintering technique, in particular for orthopedic and dental applications.

[1] B. D. Ratner, A. S. Hoffman and J. E. Lemons, “An Introduction to Materials in Medicine“, Biomaterial Science, Chap. 3, 133–141, 1996.
[2] M. Hisbergues, S. Vendeville, and P. Vendeville, “Review Zirconia: Established Facts and Perspectives for a Biomaterial in Dental Implantology”, Journal of Biomedical Materials Research Part B: Applied Biomaterial, Vol. 88, 519–29, 2009.
[3] S. Kashefa, A. Asgarib, T. B. Hilditchb, W. Yanc, V. K. Goeld and P. D. Hodgsona, ”Fracture toughness of titanium foams for medical applications”, Materials Science and Engineering A, Vol. 527, 7689–7693, 2010.
[4] Nouri, Alireza, Hodgson, D. Peter and Wen, ”Biomimetic porous titanium scaffolds for orthopaedic and dental applications”, Biomimetics learning from nature, Chap. 21, 415–450, 2010.
[5] J. D. Bobyn, G. J. Stackpool, S. A. Hacking, M. Tanzer and J. J. Krygier, ”Characteristics of bone ingrowth and interface mechanics of a new porous tantalum biomaterial”, The Journal of Bone & Joint Surgery, Vol. 81, 907–914, 1999.
[6] L. D. Zardiackas, D. E. Parsell, L. D. Dillon, D. W. Mitchell, L. A. Nunnery and R. Poggie, ”Structure, metallurgy, and mechanical properties of a porous tantalum foam”, Journal of Biomedical Materials Research Part A ,Vol. 58, 180–187, 2001.
[7] M. Assad, P. Jarzem, M. A. Leroux, C. Coillard, A. V. Chernyshov, S. Charette and C. H. Rivard, ”Porous titanium-nickel for intervertebral fusion in a sheep model : Part 1. Histomorphometric and radiological analysis”, Journey of Biomedical Material Research Part B, Vol. 64, 107–120, 2003.
[8] M. Assad, A. V. Chernyshov, P. Jarzem, M. A. Leroux, C. Coillard, S. Charette and C. H. Rivard, ”Porous titanium–nickel for intervertebral fusion in a sheep model : Part 2. Surface analysis and nickel release assessmen”, Journal of Biomedical Materials Research Part B , Vol. 64, 121–129, 2003.
[9] Y. H. Li, L. J. Rong and Y. Y. Li, ”Pore characteristics of porous NiTi alloy fabricated by combustion synthesis”, Journal of Alloys and Compounds, Vol. 325, 259–262, 2001.
[10] S. Fujibayashi, M. Neo, H. M. Kim, T. Kokubo and T. Nakamura, ”Osteoinduction of porous bioactive titanium metal”, Biomaterials, Vol. 25, 443–450, 2004.
[11] K. Hoshijima, R. W. Nightingale, J. R. Yu, W. J. Richardson, K. D. Harper, H. Yamamoto and B. S. Myers, ”Strength and stability of posterior lumbar interbody fusion”, Comparison of titanium fiber mesh implant and tricortical bone graft. Spine, Vol. 22, 1181–1188, 1997.
[12] H. J. Rack and J. I. Qazi, ”Titanium alloys for biomedical applications”, Materials Science and Engineering: C, Vol. 26, 1269–1277, 2006.
[13] R. Khalifehzadeh, S. Forouzan, H. Arami and S. K. Sadrnezhaad, “Prediction of the effect of vacuum sintering conditions on porosity and hardness of porous NiTi shape memory alloy using ANFIS”, Computational Materials Science, Vol. 40, 359–365, 2007.
[14] G. E. Ryan, A. S. Pandit and D. P. Apatsidis, “Porous titanium scaffolds fabricated using a rapid prototyping and powder metallurgy technique”, Biomaterials, Vol. 29, 3625–3635, 2008.
[15] M. C. Kruyt, S. M. van Gaalen, F. C. Oner, A. J. Verbout, J. D. de Bruijnb and W. J. A. Dhert, “Bone tissue engineering and spinal fusion: the potential of hybrid constructs by combining osteoprogenitor cells and scaffolds”, Biomaterials, Vol. 25, 1463–1473, 2004.
[16] H. C. Chuang, D. Y. Cho, C. S. Chang, W. Y. Lee, C. J. Chung, H. C. Lee and C. C. Chen, “Efficacy and safety of the use of titanium mesh cages and anterior cervical plates for interbody fusion after anterior cervical corpectomy”, Surgical Neurology, Vol. 65, 464–471, 2006.
[17] Y. Shikinami and M. Okuno, “Mechanical evaluation of novel spinal interbody fusion cages made of bioactive, resorbable composites”, Biomaterials, Vol. 24, 3161–3170, 2003.
[18] A. S. Kanter, A. R. Asthagiri and C. I. Shaffrey, “Aging Spine: Challenges and Emerging Techniques”, Clinical Neurosurgery , Vol. 54, 10–18, 2007.
[19] H. Kienapfel, C. Sprey, A. Wilke and P. Griss, ”Implant fixation by bone ingrowth”, The Journal of Arthroplasty, Vol.14, 355–368, 1999.
[20] H. U. Cameron, ”Six-year results with a microporous-coated metal hip prosthesis”, Clinical Orthopaedics and Related Research, Vol. 208, 81–83, 1986.
[21] S. H. Huo, M. Qian, G. B. Schaffer and E. Crossin, “Chapter 21：Aluminium powder metallurgy”, Fundamentals of Aluminium metallurgy, 655–701, 2011.
[22] X. Li, C. T. Wang, W. G. Zhang and Y. C. Li, ”Properties of a porous Ti--6Al--4V implant with a low stiffness for biomedical application”, Proceedings of the Institution of Mechanical Engineers Part H: Journal of Engineering in Medicine, Vol. 223, 173–178, 2009.
[23] K. Nishiyabu, S. Matsuzaki, K. Okubo, M. Ishida and S. Tanaka, ”Porous graded materials by stacked metal powder hot-press moulding”, Material Science Forum, Vol. 492–493, 765, 2005.
[24] S. W. Lee, A. Seokyoung, C. J. Whang, S. J. Park, S. V. Atre, K. Jookwon and R. M. German, ”Effects of process parameters in plastic, metal, and ceramic injection molding processes”, Korea-Australia Rheology Journal , Vol. 23, 127–138, 2011.
[25] D. C. Dunand, ”Processing of titanium foams”, Advance Engineering Material, Vol. 6, 369–376, 2004.
[26] C. Gaillard, L. F. Despois and A. Mortensen, ”Processing of NaCl powders of controlled size and shape for the microstructural tailoring of aluminum foams”, Material Science Engineering A, Vol. 374, 250–262, 2004.
[27] B. Q. Li, C. Y. Wang and X. Lu, “Effect of pore structure on the compressive property of porous Ti produced by powder metallurgy technique”, Materials and Design, Vol. 50, 613–619, 2013.
[28] N. Jha, D. P. Mondal, J. D. Majumdar, A. Badkul, A. K. Jha and A. K. Khare, “Highly porous open cell Ti-foam using NaCl as temporary space holder through powder metallurgy route”, Materials and Design, Vol. 47, 810–819, 2013.
[29] Z. Esen and S. Bor, ”Processing of titanium foams using magnesium spacer particles”, Scripta Materialia , Vol. 56, 341–344, 2007.
[30] X. Zhang, X. W. Li, J. G. Li and X. D. Sun, “Preparation and mechanical property of a novel 3D porous magnesium scaffold for bone tissue engineering”, Materials Science and Engineering C, Vol. 42, 362–367, 2014.
[31] B. Ye and D. C. Dunand, “Titanium foams produced by solid-state replication of NaCl powders”, Materials Science and Engineering A, Vol. 528, 691–697, 2010.
[32] G. Engin, B. Aydemir, and H. Ö. Gülsoy, “Injection molding of micro-porous titanium alloy with space holder technique”, Rare Metals, Vol. 30, 565–571, 2011.
[33] K. Nishiyabu, K. Matsuzaki and S. Tanaka, ”Net-shape manufacturing of micro porous metal components by powder injection molding”, Material Science Forum, Vol. 534–536, 2007.
[34] A. K. Gain, H. Y. Song and B. T. Lee, ”Microstructure and mechanical properties of porous yttria stabilized zirconia ceramic using poly methyl methacrylate powder”, Scripta Materialia, Vol. 54, 2081–2085, 2006.
[35] M. Köhl, T. Habijan, M. Bram, H. P. Buchkremer, D. Stover and M. Koller, ”Powder metallurgical near-net-shape fabrication of porous NiTi shape memory alloys for use as long-term implants by the combination of the metal injection molding process with the space-holder technique”, Advance Engineering Materials, Vol. 11, 959–968, 2009.
[36] I. H. Oh, N. Nomura and S. Hanada, ” Microstructures and mechanical properties of porous Titanium compacts prepared by powder sintering”, Materials Transcations, Vol. 43, 443–446, 2002.
[37] Y. Torres, S. Lascano, J. Bris, J. Pavón and J. A. Rodriguez, ”Development of porous titanium for biomedical applications: A comparison between loose sintering and space-holder techniques”, Materials Science and Engineering C, Vol. 37, 148–155, 2014.
[38] 黃坤祥, 第六章：粉末冶金學, 中華民國粉末冶金協會, 2001.
[39] J. L. Shi, “Solid state sintering of ceramics: pore microstructure models, densification equations and applications”, Journal of Materials Science, Vol. 34, 3801–3812, 1999.
[40] P. W. Voorhees, “Ostwald Ripening of Two-Phase Mixtures”, Annual Review of Materials Science, Vol. 22, 197–215, 1992.
[41] Z. Brytan, L. A. Dobrzański, M. A. Grande and M. Rosso, “Characteristic of vacuum sintered stainless steels”, Journal of Achievements in Materials and Manufacturing Engineering, Vol. 33, 126–134, 2009.
[42] Zhigang Zak Fang, “Vacuum Sintering”, Sintering of Advanced Materials - Fundamentals and Processes, Chap. 8, 189–220, 2011.
[43] K. Byrappa and M. Yoshimura, “Hydrothermal Technology for Nanotechnology—Processing of Advanced Materials’, Handbook of Hydrothermal Technology, Chap. 10, 754–768, 2001.
[44] M. T. Reagan, J. G. Harris and J. W. Tester, “Molecular Simulations of Dense Hydrothermal NaCl-H2O Solutions from Subcritical to Supercritical Conditions”, Journey of Physical Chemistry B, Vol. 103, 7935–7941, 1999.
[45] T. Onoki, “Porous Apatite Coating on Various Titanium Metallic Materials via Low Temperature Processing”, Biomaterials Science and Engineering, Chap. 3, 67–98, 2011.
[46] M. C. Andrade, M. R. T. Filgueiras and T. Ogasawara, “Hydrothermal nucleation of hydroxyapatite on titanium surface”, Journal of the European Ceramic Society, Vol. 22, 505–510, 2002.
[47] S. Danwittayakul and J. Dutta, “Controlled growth of zinc oxide microrods by hydrothermal process on porous ceramic supports for catalytic application”, Journal of Alloys and Compounds, Vol. 586, 169–175, 2014.
[48] A. Moradi, S. Pramanik, F. Ataollahi, T. Kamarul and P. M. Belinda, “Archimedes revisited: computer assisted microvolumetric modification of the liquid displacement method for porosity measurement of highly porous light materials”, Analytical Methods, Vol. 6, 4396–4401, 2014.
[49] Y. Oshida, “Introduction”, Bioscience and Bioengineering of Titanium Materials 1st Edition, Chap. 1, 1-7, 2006.
[50] W. M. Haynes, CRC Handbook of Chemistry and Physics, 94th Edition, 2013.
[51] J. Jia, K. Zhang and S. Jiang, “Microstructure and mechanical properties of Ti–22Al–25Nb alloy fabricated by vacuum hot pressing sintering”, Materials Science and Engineering A, Vol. 616, 93–98, 2014.

[52] A. C. T. North,” X-Ray Crystallography of Macromolecules, Theory and Methods”, Encyclopedia of Spectroscopy and Spectrometry (Second Edition), 2968–2975, 2010.
[53] M. F. C. Ladd and R. A. Palmer, “Intensities and Intensity Statistics”, Structure determination by X-ray crystallography, Chap. 4, 161–186, 1985.
[54] W. B. Amos and G. McConnell, “Electron Microscopic Measurement of the Size of the Optical Focus in Laser Scanning Microscopy”, Microscopy and Microanalysis, Vol. 18, 596–602, 2012.
[55] G. E. Lloyd, “Atomic Number and Crystallographic Contrast Images with the SEM: A Review of Backscattered Electron Techniques”, Mineralogical Magazine, Vol. 51, 3–19, 1987.
[56] S. Hengsberger, A. Kulik, and P. H. Zysset, “Nanoindentation Discriminates the Elastic Properties of Individual Human Bone Lamellae Under Dry and Physiological Conditions”, Bone, Vol. 30, 178–184, 2002.
[57] P. Majumdar, S. B. Singh and M. Chakraborty , “Elastic modulus of biomedical titanium alloys by nano-indentation and ultrasonic techniques—A comparative study”, Materials Science and Engineering A, Vol. 489, 419–425, 2008.
[58] W. C. Oliver and G. M. Pharr, “An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments”, Journal of Materials Research, Vol. 7,1564–1583, 1992.
[59] 陳俊生, 張柳春, 楊子毅, 簡仁德, “第七章：機械性質”, 材料科學與工程, 157–165, 2002.
[60] C. E. B. Marino, P. A. P. Nascente, S. R. Biaggio, R. C. R. Filho and N. Bocchi, “XPS characterization of anodic titanium oxide films grown in phosphate buffer solutions”, Thin Solid Films, Vol. 468, 109–112, 2004.
[61] V. V. Atuchin, V. G. Kesler, N. V. Pervukhina and Z. Zhang, “Ti 2p and O 1s core levels and chemical bonding in titanium-bearing oxides”, Journal of Electron Spectroscopy and Related Phenomena, Vol. 152, 18–24, 2006.
[62] J. Li, X. Wang, R. Hu and H. C. Kou “Structure, composition and morphology of bioactive titanate layer on porous titanium surfaces”, Applied Surface Science, Vol. 308, 1–9, 2014.
[63] C. Xiang, Y. Zhang, Z. Li, H. Zhang, Y. Huang and H. Tang, “Preparation and compressive behavior of porous titanium prepared by space holder sintering process”, Procedia Engineering, Vol. 27, 768–774, 2012.
[64] H. Giambini, H. J. Wang, C. Zhao, Q. Chen, A. Nassr and K. N. An “Anterior and posterior variations in mechanical properties of human vertebrae measured by nanoindentation”, Journal of Biomechanics, Vol. 46, 456–461, 2013.
[65] L. Feng, M. Chittenden, J. Schirer, M. Dickinson and I. Jasiuk, “Mechanical properties of porcine femoral cortical bone measured by nanoindentation”, Journal of Biomechanics, Vol. 45, 1775–1782, 2012.
[66] U. O. Hafeli, J. Aue and J. Damani, “The biocompatibility and toxicity of magnetic particles”, Laboratory Techniques in Biochemistry and Molecular Biology, Vol. 32, 2007.
[67] G. M. Peppo, A. Palmquist, P. Borchardt, M. Lenner, J. Hyllner, A. Snis, J. Lausmaa, P. Thomsen, and C. Karlsson1, “Free-Form-Fabricated Commercially Pure Ti and Ti6Al4V Porous Scaffolds Support the Growth of Human Embryonic Stem Cell-Derived Mesodermal Progenitors” The Scientific World Journal, Vol. 2012, 1–14, 2012.
[68] C. D. Cole, T. D. McCall, M. H. Schmidt, A. T. Dailey, “Comparison of low back fusion techniques: transforaminal lumbar interbody fusion (TLIF) or posterior lumbar interbody fusion (PLIF) approaches”, Current Reviews in Musculoskeletal Medicine, Vol. 2, 118–126, 2009.