利用水熱法合成氫氧基磷灰石及其顆粒型態在mPEG-PLGA溫感性水膠流變性質的影響

Synthesis of Hydroxyapatite Using Hydrothermal Method and Effect of Its Particle Morphology on the Rheology Behavior of Poly(ethylene glycol)-Poly(lactic-co-glycolic acid) Thermosensitive Hydrogel

黃昱超(Yu-Chao Huang)

指導教授 ： 楊大毅

中原大學/工學院/化學工程研究所/碩士(2014年)

https://doi.org/10.6840/cycu201400757

摘要

人類隨著年齡的增長，由於骨質含量減少，骨頭變得疏鬆脆弱，而造成骨質疏鬆症，因此本研究合成新穎性之可注射式溫感性水膠(mPEG-PLGA)混摻氫氧基磷灰石，作為解決的方案。氫氧基磷灰石與人體骨骼成份相近，具良好的生物相容性;溫感性水膠則具有溫度敏感性，良好的生物相容性以及生物可降解之特性。將所合成之溫感性水膠混摻不同型態之氫氧基磷灰石，探討其流變性質，並增加其機械強度。
　　本實驗以水熱法合成氫氧基磷灰石，並利用酸鹼值、界面活性劑濃度、與反應時間，客製化氫氧基磷灰石的型態。此外，利用開環聚合方式，合成具生物降解性及溫度敏感性的mPEG-PLGA共聚物，並加入氫氧基磷灰石以控制其流變性質。實驗結果得到20%溫感性水膠與片狀氫氧基磷灰石比例為8:2或7:3時，在室溫下呈現自由流動的溶膠(sol)態，然而在人體體溫時，呈現不流動的凝膠(gel)態，因此適用於可注射式輸送系統，並且由於加入氫氧基磷灰石，其機械強度也隨之提升。再者，溫感性水膠酸性釋放的問題，可藉由添加氫氧基磷灰石或界面活性劑Sodium oleate，有效抑制其酸性釋放，並且可延長降解時間。
　　本實驗結果證實，利用水熱法可合成出不同型態之氫氧基磷灰石，其亦可明顯地控制溫感性水膠的流變性質。所發展出水膠之溶膠-凝膠相轉移溫度(sol-gel transition temperature)與機械強度，隨著不同比例的氫氧基磷灰石摻混而有所差異。可預期本實驗結果，將有益於以混摻氫氧基磷灰石之溫感性水膠，治療骨質疏鬆症之應用。

關鍵字

氫氧基磷灰石 ； 骨質疏鬆症 ； 水熱法 ； 溫感性水膠 ； 相轉移溫度 ； 流變學

並列摘要

The aim of this study is to develop novel temperature-sensitive hydrogels based on a biodegradable poly (ethylene glycol)-poly (lactic-co-glycolic acid) (mPEG-PLGA) copolymer for the treatment of osteoporosis. Hydroxyapatite (HA) is one of the most widely used materials that interfaces with bone for clinical application as a filler in dentistry and orthopedic for decades due to its highly biocompatibility. The rheology behavior and mechanical properties of the thermosensitive mPEG-PLGA hydrogels could be tailored by incorporating the HA fillers with specific morphology into the hydrogel.
HA was synthesized using a hydrothermal method. The experimental results exhibited that the morphologies (shape and size) of the HA were controlled by reaction time, pH values, and the addition of surfactants. The thermosensitive mPEG-PLGA block copolymers were prepared by ring opening polymerization, and their resulting properties significantly depended on the addition of surfactant-modified HA. Our results showed that the rheology behavior and mechanical properties of the mPEG-PLGA hydrogels can be controlled by adding the surfactant-modified HAs. For example, the resulting gels exhibited sol state at room temperature while they were in gel state at body temperature as the ratios of 20% thermosensitive hydrogel to HA with sheet morphology were 8:2 or 7:3. In addition, their mechanical strength also increased by adding HAs. Furthermore, the adverse effect of acid release from gel degradation was overcome by utilizing HA and sodium oleate surfactant, and the gel degradation rate was also reduced.
We have successfully demonstrated the feasibility of synthesizing surfactant-modified HA with tailored morphologies (shape and size) by a hydrothermal method. The synthesized HA could significantly change the rheology behavior of the thermosensitive mPEG-PLGA hydrogels. The sol-gel transition temperature and mechanical strength for the resultant HA/ mPEG-PLGA hydrogels could be easily adjusted. The developed thermosensitive hydrogels in this study are expected to significantly contribute to the application of treating osteoporosis.

並列關鍵字

Rheology ； Phase Transition Temperature ； Thermosensitive Hydrogel ； Hydrothermal Method ； Hydroxyapatite ； Osteoporosis

參考文獻

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