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標題: | 雙刺激敏感型可生物降解聚胺酯軟質水凝膠之合成與表徵於細胞共列印應用 Synthesis and characterization of dual stimuli–sensitive biodegradable polyurethane soft hydrogels for 3D cell-laden bioprinting |
作者: | Shih-Hsiang Hsiao 蕭士翔 |
指導教授: | 徐善慧(Shan-hui Hsu) |
關鍵字: | 3D生物列印,可生物降解聚胺酯,雙重刺激響應性,蠕變性,軟質水凝膠, 3D bioprinting,biodegradable polyurethane,dual stimuli-responsiveness,creep,soft hydrogel, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 3D生物列印技術在組織工程與再生醫學領域帶來了革新,經由生物材料與細胞的結合能客製化出組織工程替代物,以達到修復或替換受損組織和器官為目的,因此成為一個相當有吸引力的平台。目前,由於大部分可生物降解的聚合物水凝膠機械穩定性能差,使得在列印的過程中結構傾向於塌陷,因此在開發生物材料上仍然是具有挑戰性。在本研究中,經由環保水性製程的技術,合成出具有雙敏感刺激響應性的可生物降解聚胺酯 (polyurethane, PU) 分散液。製備方法是在PU主鏈的末端引入能紫外線誘導交聯的丙烯酸酯基團,目的是藉由光敏感基團的引入能大幅改善列印性能;在軟鏈段的部分仍然選用混合低聚二醇為熱敏感性的組分。合成出雙刺激性PU分散液通過動態光散射 (dynamic light scattering)、小角X射線散射 (small-angle X-ray scattering) 和流變學測量來驗證PU奈米顆粒的光/熱誘導形態學之變化。結果顯示,這些PU奈米顆粒在經過UV的處理後,顆粒型態多數轉變成棒狀,並且之後在進一步加熱時會形成緻密堆積的結構。藉由其熱敏感性能,固化的PU分散液在接近體溫時能快速的熱凝膠化,並且凝膠模數在0.5–2 kPa範圍內。固化PU水凝膠的流變性能包括動態粘彈性 (dynamic viscoelasticity),蠕變恢復 (creep recovery) 和剪切變稀行為 (shear thinning behavior) 在37°C下能有利於在列印之前與細胞共混合,並且通過微擠壓的3D列印程序以製造含細胞的建構體。雙刺激型水凝膠建構體顯示出比單刺激型 (熱敏感性) 對照組有更高的列印分辨率、形狀保真度以及有更好的細胞存活率和增殖。此外,具有較低模數 (< 1 kPa) 的軟質水凝膠 (PUA3) 可以提供神經幹細胞具有類似 '豆腐' 和穩定的3D微環境,以利於細胞增殖和分化。我們期望此光/熱敏感可生物降解PU墨水可以提供獨特的流變性質,有助於客製化生物列印軟組織。 3D bioprinting serves as an attractive platform to fabricate customized tissue-engineered substitutes from biomaterials and cells for the repair or replacement of injured tissues and organs. A common challenge for 3D bioprinting materials is that the structures printed from the biodegradable polymer hydrogels tend to collapse because of the poor mechanical stability. In this study, dual stimuli-responsive biodegradable polyurethane (PU) dispersions (PUA2 and PUA3) were synthesized from an eco-friendly waterborne process. Acrylate group was introduced in the PU chain end to serve as a photo-sensitive moiety for UV-induced crosslinking and improvement of the printability, while mixed oligodiols in the soft segment remained to be the thermo-sensitive moiety. The photo-/thermal-induced morphological changes of PU nanoparticles were verified by dynamic light scattering, small-angle X-ray scattering, and rheological measurement of the dispersions. It was observed that these PU nanoparticles became more rod-like in shape after UV treatment and formed compact packing structures upon further heating. With the thermo-sensitive properties, these UV cured PU dispersions underwent rapid thermal gelation with gel moduli in the range 0.5−2 kPa near body temperature. The rheological properties of the PU hydrogels including dynamic viscoelasticity, creep recovery, and shear thinning behavior at 37°C were favorable for processing by microextrusion-based 3D printing and could be easily mixed with cells before printing to produce cell-laden constructs. The dual-responsive hydrogel constructs demonstrated higher resolution and shape fidelity as well as better cell viability and proliferation than the thermo-responsive control. Moreover, the softer hydrogel (PUA3) with a low modulus (< 1 kPa) could offer neural stem cells a tofu-like, stable, and inductive 3D microenvironment to proliferate and differentiate. We expect that the photo-/thermo-responsive biodegradable polyurethane ink may offer unique rheological properties to contribute toward the custom-made bioprinting of soft tissues. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72122 |
DOI: | 10.6342/NTU201803853 |
全文授權: | 有償授權 |
顯示於系所單位: | 高分子科學與工程學研究所 |
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