應用超臨界流體技術製備基於PLA/PBAT/PBS/nHA之生物可降解支架於組織之應用

Abstract

本研究之宗旨在於開發一種具備良好物理、機械特性，同時具備良好生物可相容性的新型生物可分解性、高分子共混材料，期望能應用於人體組織工程的領域。本研究計畫以聚乳酸（polylactic acid, PLA）、聚丁二酸丁二酯（poly(butylene succinate), PBS）與聚己二酸/對苯二甲酸丁二酯（poly(butylene adipate-co-terephthalate), PBAT）為基礎，在其中添加不同比例含量之奈米羥基磷灰石（nanohydroxyapatite, nHA），以作為功能性填料，製備PLA/PBS/PBAT/nHA共混材料，並系統性探討其物理性質、熱力學性質、力學性質與材料發泡後相關之變化。 本研究將此共混材料依照混和比例分為兩實驗組，分別為A實驗組（PLA含量70 wt%）與B實驗組（PLA含量80 wt%），各系列製備四種不同nHA添加量之樣品，均以雙螺桿擠出機，應用特殊的混練條件溫度，進行熔融混煉製程。共混材料，後續透過傅立葉轉換紅外光譜（FTIR）、X光繞射分析（XRD）確認各組成物的存在與相容性；並以示差掃描量熱儀（DSC）分析其結晶行為。後續進行拉伸與衝擊強度測試，測試的結果顯示，當適量nHA添加其中，可顯著提升共混材料所表現的機械性質。其後透過掃描式電子顯微鏡（SEM）與穿透式電子顯微鏡（TEM）進一步觀察材料表面的特性，與nHA在基材中的分散性，SEM與TEM結果均顯示nHA可作為有效成核劑，有助於在共混材料中提高結晶度與整體結構均勻性。熱重分析（TGA）驗證了，共混後的材料具備良好的熱性質與穩定性；吸水率實驗則指出，材料擁有良好的親水性，有利後續之生物應用。 本研究亦利用了超臨界二氧化碳（supercritical carbon dioxide, SC-CO₂）作為發泡的製程選項，進行PLA/PBS/PBAT/nHA共混材料之發泡處理，製作出有利細胞組織生長的多孔隙結構。本研究亦探討了不同操作策略，對孔洞結構的影響。過程中，本實驗共設計八種發泡程序，包括基本高溫高壓飽和後快速釋壓（1T-1P），以及引入中間溫度與壓力調控之策略，如中間溫度冷卻（2T-1P）、中間溫度冷卻並快速釋壓（2T-2P）與階梯式釋壓（2T-2P，stepwise ΔP）。SEM觀察發現，(2T-2P，階梯式ΔP)策略可產生雙峰孔洞的結構，其中小型泡孔尺寸為105–164 μm，大型泡孔尺寸為476–889 μm，顯示可透過操作條件有效控制泡孔分布。該結果可由經典成核理論、氣體溶解度原理與高分子熔體強度變化加以解釋。本研究最後亦評估各發泡後樣品之各項特性，包括泡孔平均尺寸、泡孔密度、膨脹比、孔隙率與開孔率等指標，並以水接觸角評估其親水性。利用動態力學分析儀（DMA）進行壓縮測試，實驗結果之應力–應變曲線顯示，發泡產品剛性與發泡策略密切相關。 綜合以上各實驗所述，本研究成功建立了製備PLA/PBS/PBAT/nHA共混材料之流程，與建立了發泡技術的加工條件。本研究亦製造了具有組織支架潛力應用的材料，並提供了不同孔洞大小之製備發泡參數，為未來生醫材料的開發，提供一定的數值參考依據。

This research aims to develop an innovative biodegradable polymer blend with excellent physical, mechanical, and biocompatible properties for potential utilization in tissue engineering. The study aimed at the fabrication of PLA/PBS/PBAT/nHA composites, using polylactic acid (PLA), poly(butylene succinate) (PBS), and poly(butylene adipate-co-terephthalate) (PBAT) as the polymer matrix, and nanohydroxyapatite (nHA) as a functional filler. The influence of nHA content on the physical, thermal, mechanical, and foaming behaviors of the blends were comprehensively analyzed. Two groups of blend formulations were designed based on PLA content: Group A with 70 wt% PLA and Group B with 80 wt% PLA. Each group consisted of four variations with different nHA concentrations. All samples were prepared using a twin-screw extruder method through a melting process. The presence and compatibility of the components were verified using FTIR and XRD, while DSC was employed to evaluate crystallization behavior. Results from tensile and impact strength tests indicated that appropriate nHA loading markedly improved the mechanical performance of the blends. SEM and TEM analyses revealed that nHA served as an effective nucleating agent, improving the crystallinity and overall structural uniformity of the composites. TGA confirmed the thermal stability of the composites, and water absorption and contact angle experiment demonstrated that nHA addition enhanced hydrophilicity, making the material suitable for biomedical applications. Furthermore, the foaming characteristics of PLA/PBS/PBAT/nHA blends were studied using supercritical carbon dioxide (SC-CO₂) as a physical foaming agent, aimed at generating porous scaffolds conducive to cell growth. Different foaming fabrication techniques were investigated, including a primary process involving saturation under conditions of saturation temperature and pressure, succeeded by rapid pressure release (1T-1P), and second strategies including intermediate steps of temperature and pressure regulation, such as cooling at an intermediate temperature (2T-1P), cooling at an intermediate temperature combined with rapid decompression (2T-2P), and stepwise decompression (2T-2P, stepwise ΔP). SEM observations revealed that the (2T-2P, stepwise ΔP) generated a bimodal cellular architecture with small cells sized between 105–164 μm and large cells from 476–889 μm, indicating that foam morphology can be precisely regulated through the adjustment of processing parameters.Key foaming characteristics such as average cell size, expansion ratio, cell density, porosity, and open-cell content were evaluated. Hydrophilicity was assessed through water contact angle measurements. Compression tests conducted using DMA revealed that foam stiffness was closely related to the foaming strategy, reflecting changes in mechanical performance. In summary, this study successfully established the processing techniques for PLA/PBS/PBAT/nHA composites and their foaming behavior, proposing material formulations and processing parameters with strong potential for tissue scaffold applications. These findings offer important insights and constitute a key reference for advancing future biomedical materials development.