| 摘要: | 在醫學工程領域中，以聚乳酸（PLA）為基礎的複合材料被當作引導骨/組織再生(GBR/GTR)材料已行之有年。因此，如何改質聚乳酸材料已成為醫學工程研究的一大課題，在許多探討聚乳酸材料的文獻中，大多集中在如何利用氫氧基磷灰石或是無機物的添加，來改變材料的物理性質和機械性質等。因為四氧化三鐵磁性奈米粒子可能具有改變純聚乳酸高分子強度及其材料性質，並擁有促進細胞增生的效果。因此本研究的目的在於製造四氧化三鐵/聚乳酸的生醫複材，並且評估其物理、化學、機械性質以及其在骨科醫學領域的應用。在方法上，本研究首先製備由奈米級四氧化三鐵與聚乳酸組成之生醫複材，利用射出成型技術將奈米級四氧化三鐵粉末以重量比0%、20%、30%、40%之比例添入聚乳酸基材中。接著複合材料的表面形態觀察、熱性質、表面親疏水性、磁性、物理性質及應力應變研究分別由掃描式電子顯微鏡(SEM)、示差掃描量熱儀(DSC)、熱重溫差同步分析儀(TGA)、動態接觸角量測儀、X光繞射(XRD)、超導量子干涉磁量儀(SQUID)、凝膠滲透層析儀(GPC)及萬能拉力試驗機等儀器進行量測，在生物功能性分析則進行血液凝血試驗、細胞毒性試驗以及細胞活性測試。在DSC分析上發現混入不同比例四氧化三鐵的複合材，其玻璃轉移溫度點(Tg)及熔點(Tm)的溫度並無差異，而當四氧化三鐵含量越高，結晶溫度點(Tc)會減少約14℃。在親疏水性研究上發現，無論添加多少比例的四氧化三鐵，水接觸角皆無明顯的差異。在XRD方面亦證實了穩定的結晶性將表現出四氧化三鐵及聚乳酸的生物效果。在TGA方面顯示添加四氧化三鐵會使聚乳酸的裂解溫度從309℃上升至317℃。在GPC方面測得此複合材料的PDI值為1.4，為分子量分布均勻的材料。由拉伸試驗結果得知添加四氧化三鐵後，應力及應變均會減少，但是彈性模數卻從1.32GPa上升至1.73GPa。在SQUID方面，隨著四氧化三鐵添加量越多，飽和磁化量會明顯上升。在SEM方面顯示其粒子排列並不規則且粒子大小皆約為400nm。在細胞毒性方面，空白組細胞存活率為100%，與陰性對照組及其他不同比例複合材之間沒有統計上的差異。在細胞活性方面，所有Fe3O4/PLA之複合材皆可支撐MG63細胞生長，細胞生長在各種不同比例之Fe3O4複合材料與生長在純聚乳酸的材料上表現出一樣的生長曲線，各觀察時間點細胞數均無統計上的差異。在血液相容性方面，與純聚乳酸比較，無論充磁與否皆表現出讓血液更快凝結的特性。
本研究結果，可以進一步作為未來動物實驗之參考資料，未來將有可能應用於生物醫學組織工程領域上，進而開發出一個新型骨材料，可作為骨釘骨板材料或其他生物醫學應用。
Polylactic acid (PLA)-based composite was used as guided bone/tissue regeneration (GBR/GTR) materials in clinical dentistry for many years. To modify the material properties of the material, inorganic substance such as nano-hydroxyapatite was used to form nanocomposites. Recent reports indicated that iron oxide magnetic nanoparticles have positive effect on the osteoblastic proliferation. The aim of this study is to develop a novel nano-magnetic biodegradable composite for bone regeneration applications. Nanoscale magnetite was incorporated into the PLA matrix with proportions of 0, 20, 30, and 40 % (w/w). Injection molding was carried out to produce the samples which were used for the following tests. X-ray diffraction (XRD), thermogravimetric analysis (TGA), gel permeation chromatography (GPC), superconducting quantum interference device (SQUID), scanning electron microscope (SEM), tensile test, differential scanning calorimetry (DSC) analysis and contact angle assess (CA) were performed to test the physical properties of the composite. In addition, cytotoxic testing, cell viability, cell activity testing and blood compatibility analysis were performed to test the biofunction of current developed composite. Our results showed that nanoscale magnetite addition significantly increase the intensity of the PLA composite. DSC analysis showed that addition of magnetite has no effect on the glass transition temperature of the PLA composite. However, the crystallization temperature of the polymer was reduced due to magnetite addition. The measured contact angle results showed no significant differences between pure PLA and magnetite-PLA composite. XRD data confirmed that the crystalline structure of the Fe3O4 and PLA were maintained during injection molding process. SEM showed that the pellets of Fe3O4 nanoparticles evenly distributed in the composites. Weak ferrimagnetic behaviors of composites were evidenced by SQUID test. Tensile test displayed that the Young’s modulus of the composites were gradually improved with the increase of Fe3O4 nanoparticles, while ultimate tensile stress and ultimate strain were decreased. MTT assay of the MG63cells seeded on the composite’s surface showed good cell adhesion and proliferation, suggesting that this magnetic biodegradable Fe3O4 / PLA nanocomposites can be one of candidate biomaterials for facilitation of osteogenesis. In the blood compatibility, no matter the composites were magnetized or not, the magnetic biodegradable Fe3O4 / PLA nanocomposites demonstrated faster blood clotting properties when compared to the pure PLA.
The nano-magnetic biodegradable composite developed in this study demonstrates good physical properties and biocompatibility. Accordingly, this newly-developed nano-magnetic composite has a potential to be a biomaterial, for bone tissue engineering in future. |
