氫氧基磷灰石(Ca10(PO4)6(OH)2，HA)是接近人體骨骼成分的磷酸鈣鹽，因此常用於替代人體硬組織，本研究以二水磷酸氫鈣(CaHPO4‧2H2O，DCPD)為原料，於氫氧化鈉水溶液(NaOH(aq))中水解合成HA，改變製程中各項參數將其最佳化，並達成降低燒結溫度的目標。獲得以2.5 M NaOH(aq)中在75oC水解合成1 h為最佳化條件，生成奈米低結晶化HA粉末，寬50 nm，長100 nm，顯現{0 0 2n}面的異向性結晶現象。添加陽離子型介面分散劑十六烷基三甲基溴化銨(CTAB)參與反應時，在110-3 M濃度形成微胞，阻止了晶粒成長，可將HA晶粒大小降至20 nm寬，50 nm長。而當CTAB的添加與酒精水溶劑兩個條件皆參與反應而影響HA粉末生成時，會產生多孔性HA(孔徑約5 nm)。
在水解合成過程中，添加CaCO3以改變鈣磷比(Ca/P ratio=1.0~1.8)，合成之HA粉末呈現的{0 0 2n}異向性結晶現象，在高於Ca/P=1.5之後會消失，並形成寬約200 nm而長約400 nm的大顆粒。取Ca/P=1.0與1.5合成的HA粉末與Merck商用HA粉末進行萃取液體外細胞存活率研究，生物相容性為Ca/P=1.5> Ca/P=1.0>Merck，並可在短時間內促進細胞存活率。
將不同Ca/P值(1.0~1.8)水解合成之HA粉末壓胚後，在800oC進行4 h燒結，其{0 0 2n}之異向性結晶現象在Ca/P>1.5後消失，且密度趨於穩定(約2.8 g/cm3)，此乃因rhenanite相(NaCaPO4)相隨Ca/P比增加而增加，並可在晶界上觀察出非晶相的形成。Ca/P=1.5合成粉末之高溫特性可分為三階段，第一為25oC到500oC的寬化圖階段，是因升溫而轉變為缺鈣型HA以及穩定型HA的階段；第二為600oC到1250oC之間的結晶化HA階段，CaO相在升溫至700oC時出現，800oC時於晶界上出現非晶NaCaPO4相；第三階段為高溫相分解階段，在1250oC到1500oC之間逐漸轉變為α-三鈣磷酸鹽與四鈣磷酸鹽，顯示CaCO3的添加以及水解合成製程皆有助於HA高溫相的穩定化。相較於Ca/P=1.0時合成粉末以及Merck商用HA粉末，Ca/P=1.5所合成粉末之密度與硬度最高值皆較低，但其特質在於800oC即可進行燒結，並已有相當之機械性質。
將Ca/P=1.5合成之HA粉末經800oC燒結4 h的燒結體，在37oC浸漬於生理食鹽水中進行長期浸漬測試，2 週後發現隨浸漬時間而增加的焦磷酸鈣相(CPP)結晶，並因CPP的形成使燒結體表面硬度下降。另於體外以皮膜纖維母細胞3T3在37oC進行細胞培養實驗，4 d後發現周圍細胞的分裂延展以及析出的CPP結晶，顯示添加碳酸鈣所水解合成之HA粉末可在800oC的低溫燒結並有良好的生物相容性。

Hydroxyapatite (Ca10(PO4)6(OH)2, HA) has long been recognized as an important bone substitute material because of its chemical and biological similarity to the mineral phase of human bone. Using dicalcium phosphate dihydrate (CaHPO4‧2H2O, DCPD) as starting material, this study intends to optimize the synthesis parameters of nano-sized HA powders by a hydrolysis method and investigate their sintering behavior. The optimized synthesized HA powder at 75oC in 2.5M NaOH(aq) for 1h is composed of tiny crystals with a size of about 50.0 nm in thickness and 100.0 nm in length with a well one dimension alignment on the {0 0 2n} preferred orientation.
When the solvent of water is mixed with alcohol, the hydrolysis reaction becomes more intense to smash the HA aggregates into small particles. On the other hand, the HA aggregates synthesized with 110-3 M cetyltrimethyl- ammonium bromide (CTAB) as a surfactant become thinner to a size of 5-20 nm in width and 50 nm in length because of the formation of micells. The interaction between alcohol solution and CTAB induces the nano-porous HA (pore size ~ 5nm) at 50% alcohol and 110-3 M CTAB with surface area of 149.22 m2/g.
The HA powders are synthesized with Ca/P ratios from 1.0 to 1.8 by adding CaCO3 in the hydrolysis process, and the well one dimension alignment on the {0 0 2n} preferred orientation without adding CaCO3 is inhibited above Ca/P=1.5. The thickness and length of the crystals increase from 50.0 nm to 200 nm, and 100 nm to 500 nm, respectively, with the Ca/P ratio increasing from 1.0 to 1.8. The relative biocompatibility is HACa/P=1.5>HACa/P=1.0>HAMerck according to the in-vitro viability of 3T3 cells with powder immersion test.
The density of HA pellets sintered at 800oC for 4h increases with the Ca/P ratio increase of the source powder rapidly until Ca/P=1.5 and becomes stable (about 2.8 g/cm3) with the appearance of the amorphous phase identified as NaCaPO4 at the grain boundary. The thermal behavior of the HA powder with a Ca/P=1.5 between 25oC and 1500oC is divided into three stages: First, the transformation of amorphous calcium phosphate to calcium deficient HA and stoichiometric HA between 25 to 500oC. Second, the well crystallized HA stage between 600 to 1250oC with the minor CaO phase appears at 700oC and the NaCaPO4 phase at 800oC. In the last stage, HA steadily transforms to the -tricalcium phosphate (-TCP) and tetra-calcium phosphate (TTCP) between 1250 and 1500oC, revealing the stabilization of HA at high temperature after CaCO3 adding in hydrolysis process. Although the mechanical properties of sintered pellets with Ca/P=1.5 are lower than Ca/P=1.0 and commercial available HA powders from Merck, the sintering temperature is reduced to 800oC.
The HA pellets of Ca/P=1.5 sintered at 800oC for 4 h are immersed in saline at 37oC for various durations as a long term immersion test. Calcium pyro- phosphate (CPP) forms after two week immersion and increases with time until 28 deeks which induces the hardness decrease of pellet surface. In the 3T3 cell culturing test at 37oC, the living cells with CPP precipitates after 4 d are observed revealing the great biocompatibility of low temperature sintered HA pellets.

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