新型生物引導性骨修復材料的製備與應用評估

Manufacturing processes and specifications of novel bone restorative biomaterials

柯嘉泠(Chia-Ling Ko)

指導教授 ： 王震乾

共同指導教授 ： 陳文正 ； 田英俊(Yin-Chun Tien)

高雄醫學大學/口腔醫學院/牙醫學研究所/博士(2013年)

摘要

鈣磷系骨水泥由於其本身良好的生物相容性與骨傳導性，所以此類材料在骨科與牙科被大量的用來做為骨填補材料。鈣磷系骨水泥的優勢在於可針對骨科、牙科、整形外科等不同填補區域調整陶瓷的黏滯性，使其成為便於操作、流動性佳又能符合骨缺損形狀之泥狀材料，再加上鈣磷系骨水泥具有可注射性，在手術過程中，不用製造過大的手術傷口即可使用注射器將骨水泥注射到填補處。然而鈣磷系骨水泥在硬化初期，接觸血液及水溶液會有崩解的現象，無法維持理想的機械強度，而目前傳統的鈣磷系骨水泥因為其最終產物為穩定的氫氧基磷灰石，所以植入後吸收率不佳，也限制了臨床應用的可能性。
本研究主要目的為製作一新型鈣磷系骨水泥，合成具有雙相產物相的新型鈣磷系骨水泥，釐清其機械性質與動物體內實際植入之效果。
本研究將探討實驗室自製的新型鈣磷系骨水泥，對其機械性質的影響。我們測試不同比例的鈣磷系骨水泥的抗壓強度與抗崩解性，並利用X-光繞射分析儀(X-ray diffraction, XRD)與掃瞄式電子顯微鏡(scanning electron microscope, SEM)觀察其顯微結構與晶體的變化。
在體外細胞反應部分，測試前驅骨母細胞與骨水泥試片接觸培養後，細胞活性與鹼性磷酸酶生成量；在動物體內植入部分，則會分析植入材殘餘量與新骨生成率。
結果發現在機械性質部分，新型骨水泥在浸泡人工體液不同時間，測試其濕壓抗壓強度，不論時間為何，皆可發現其抗壓強度超過30MPa，符合臨床應用之要求，且此一富二鈣磷酸鹽相新型骨水泥不僅擁有可注射性，也具有良好的抗崩解性。在細胞與動物相關試驗部分，前驅骨母細胞與骨水泥試片接觸培養後，細胞活性與鹼性磷酸酶生成量皆優於傳統型鈣磷系骨水泥；新型骨水泥也擁有較好的植入材吸收率與新骨生成率。
此一新型鈣磷系骨水泥不僅擁有良好的機械強度，且具有可調整其產品比例的優點，未來可依據臨床上植入位置的需求，調控組成成份比例，調控自然骨重建速率與材料吸收速率，以提高骨組織的重建(osteo regeneration)及材料的吸收率(bioresorption rate)，此一新型鈣磷系骨水泥為一良好的骨填補材。

關鍵字

鈣磷系骨水泥 ； 二鈣磷酸鹽 ； 奈米晶體 ； 吸收率

並列摘要

Calcium phosphate cement (CPC) is widely used as a filling material in dental and orthopedic applications because of its superior biocompatibility and osteoconductivity. CPC presents several advantages because its paste can be easily shaped during operation and injected into cavities using a syringe without requiring an open portal through the tissues. The viscosity of the cement can be adjusted depending on its applications in orthopedic, craniofacial, and periodontal operations.
However, CPC is characterized by low strength, easy dispersion when in contact with body fluids and the application of CPCs is limited by poor bioresorption attributed to the stable product, apatite.
These study aim to compare the mechanical properties in vitro and biological performance in vivo of a newly developed CPC (New CPC) which has multiphasic product phase is evaluated and conventional CPC (c-CPC).
The pH values and dispersive properties of CPC during the early setting reactions were investigated as well as the compressive strength of New CPC after different immersion time. The composition and morphology of several bone cement samples during setting were analyzed using X-ray diffraction and transmission electron microscopy coupled with an energy dispersive spectroscopy system.
Cell adhesion, morphology, viability, and alkaline phosphatase (ALP) activity in the two CPCs were examined using progenitor bone cell D1 cultured in vitro. After CPC implantation in vivo, the residual implant ratio and new bone formation rate were analyzed by micro-CT analysis, and the image was obtained.
The compressive strength of New CPCs was greater than 30 MPa after different immersion time in vitro. The reaction of the CPCs produced steady final biphasic products of DCPs with apatite. Composite bone cements derived from tetracalcium phosphate mixed with surface-modified DCPA exhibited excellent mechanical properties, injectability, and interlocking forces between particles and featured nondispersive behavior when immersed in physiological solution. D1 cells cultured on the surfaces of New CPC exhibited higher cell viability, ALP activity, and ALP quantity than c-CPC. Histological evaluation indicated that New CPC showed better adhesion with bone tissues, less residual implant, and higher new bone formation rate than did c-CPC.
New CPC not only has great mechanical properties but also improve bioresorption.
In addition, New CPC can adjust the product phase to control the biological to improve the bone regeneration rate and bioresorption rate of implant in connection with different bone defect area.The newly developed New CPC exhibits potential therapeutic applications for bone reconstruction.

並列關鍵字

Calcium Phosphate Cement (CPC) ； Dicalcium Phosphate ； Nanocrystal ； bioresorption rate

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