以有機添加物調控氟基磷灰石晶態之研究

Abstract

氟基磷灰石(Fluorine-substituted hydroxyapatite, FHAp)的研究在近幾年成為熱門課題，原因是其化學成分和晶體結構甚為接近人體中骨骼和牙齒的組成，且具有很好的生物相容性，在水中的溶解度非常小，植入體內不會引起身體的免疫反應，因此被認為是理想的硬骨組織替代品。然而，經過幾十年的研究，我們對磷灰石礦化機制的了解仍在初級階段，像是對於有機物質和無機礦物的結合、自我組裝的行為都存在許多疑問，需要更多研究才可了解這複雜過程。不過一旦能了解礦化過程，那麼對生物材料的發展，將是一大突破，人造骨骼或人造牙齒的生物相容性勢必大幅提升而失效率也會下降。本研究工作即是藉由調控氟基磷灰石的晶體生長形態，推測合理的生長機制以便能了解自然界生物礦化(Biomineralization)的過程。 在第三章中，我們運用水熱法並加入檸檬酸去調控氟基磷灰石的晶體生長。有趣的是，合成出的晶體具有複雜的球狀結構並存在自我組裝的行為。我們亦觀察到中間相氟化鈣的存在並提出檸檬酸可能的調控機制，實驗結果證明即使是有機小分子也能大幅影響晶體生長並產生複雜的氟基磷灰石晶體形態。 第四章主要探討檸檬酸和氟基磷灰石表面的微觀作用方式。我們透過固態核磁共振的技術證實檸檬酸的氫氧基以及磷灰石表面的磷酸根基團存在著氫鍵作用力，在此作用模式下，檸檬酸能穩定地附著在磷灰石表面並抑制磷灰石晶體生長，進而促使奈米晶體的存在。實驗結果對骨頭生物礦化過程以及有機無機的結合行為提供新穎的觀點。 論文第五章則討論手性胺基酸對氟基磷灰石晶體的影響。經一系列實驗觀察及調控，我們得知添加物的手性性質決定晶體非對稱成長的行為。另外，立體選擇作用(Stereospecific interaction)以及非完美取向生長機制(Imperfect oriented attachment)在此生長模式下扮演重要角色。非對稱生長模式的發現對於了解生物礦化的成核和長晶過程具有重要意義。

Fluorine-substituted hydroxyapatite (FHAp, Ca10(PO4)6Fx(OH)2-x, x ≤ 2) is structurally very similar to the major inorganic species of teeth and bone. Because of its low solubility and excellent biocompatibility, FHAp has been suggested for various biomedical applications. However, the formation mechanism of the complex apatite materials remains poorly known. A better understanding of the issues such as morphology control of FHAp crystallites would be very helpful to develop the FHAp-based biomaterials and realize the biomineralization mechanism. In Chapter 3, spherical hierarchical structures of FHAp are successfully prepared by using citric acid as the crystal modifier. Under the hydrothermal conditions at 120 degrees C, the formation of calcium fluoride is kinetically favored and for thermodynamic reasons CaF2 would slowly transform to FHAp. Measurements of scanning electron microscope show that the morphology of FHAp crystallites would change from dumbbell-like to spherical as the amount of citrate ions increases. Contrary to the common believe that crystal morphology control of biominerals is generally achieved by macromolecules, we suggest that small molecules may also play an important role in the biomineralization process. In Chapter 4, we have carried out a series of solid-state NMR experiments, which provide important insights into the structural environment of the citric acid. We show that the hydrogen bonding between the hydroxyl group of citrate ions and the orthophosphate ions of apatite may also help to stabilize nanosized apatite crystallites. Our experimental results may help unravel the interaction mode of other organic molecules on apatite surface. In Chapter 5, apatite crystallites with asymmetric morphology are successfully prepared by using L- or D-form of glutamic acid and aspartic acid as additives. The findings reveal that the chirality of the additives is a key factor for the asymmetric crystal growth. Moreover, imperfect oriented attachment and the stereospecific interaction between the additives and the crystal surface steps are used to rationalize the observed morphologies of the apatite crystallites. This work may shed light on the adsorption-nucleation process in biomineralization.