PA-PEG-PA光交聯水膠之合成分析與應用

Synthesis, Characterization, and Application of Photo-Crosslinkable PA-PEG-PA Hydrogel

龔珮慈(Kung, Pei Tzu)

指導教授 ： 朱一民

國立清華大學/工學院/化學工程學系/碩士(2016年)

摘要

本研究利用丙胺酸(L-alanine)和poly(ethylene glycol)(PEG)共聚合成一同時具有溫度敏感性和可進行光交聯的高分子。先在PEG以開環反應在兩末端接上poly(L-alanine)(L-PA)形成一三嵌段共聚物PA-PEG-PA(PEA)，並將其末端接上丙烯醯基(acryloyl group)，此過程稱為「diacrylation」。然後利用紫外光(UV light)對此材料進行照射，藉此引發聚合反應形成光交聯水膠。在本研究中，首先利用PEG與L-PA合成之高分子原本即具有溫度敏感之成膠特性，希望透過光交聯的步驟能增強其水膠的機械強度，此外由於alanine為一種生體具備的胺基酸，其作為共聚物的疏水鏈段相信比傳統聚酯類高分子(polyester)更有好的生物相容性(biocompatibility)。在本研究中證實，不論在水膠表面進行細胞培養，抑或是利用水膠包埋細胞，PEA水膠均相較PEG水膠有提升細胞相對存活率之功效；另外於PEA水膠中混摻人體骨骼主要成分磷酸鈣(β-TCP)，發現有助於細胞增生及骨分化能力。綜合以上之研究結果，PEA高分子材料對於未來組織工程上的應用有很大的發展空間，例如生物黏著劑和軟骨、硬骨修復等。

關鍵字

水膠 ； 光交聯 ； 組織工程 ； 丙胺酸

並列摘要

The synthesis of photocrosslinked and thermosensitive hydrogels are performed by copolymerization of poly(L-alanine)(L-PA) and poly(ethylene glycol)(PEG). Both ends of PEG were conjugated with L-PA to form a PA-PEG-PA(PEA) tri-block. Then, the terminal ends of PA-PEG-PA were modified by acroyloyl groups, which was called “diacrylation”. Exposing this material to UV-light, photo-crosslinking would begin. As photoinitiator attacked C=C double bond of vinyl groups and induced photopolymerized to form the gel. First, we want to use the thermosensitive property of the tri-block to form the hydrogel, and let it expose UV to begin photocrosslinking. This step we hope can increase mechanical strength of the hydrogel. Besides, alanine is an amino acid, it is more suitable to culture cell than polyester hydrogels. We think the hydrogel we made that can increase not only strength but with good biocompatibility. In this study, we prove that PEA hydrogel can enhance cell proliferation whether cell seeded on hydrogel surface or encapsulated into hydrogel. Comparing with PEG hydrogel, PEA hydrogel has better performance on cell viability than PEG hydrogel. In addition, we study that PEA incorporated with β-TCP which is main component of bone can promote cell proliferation and also induce osteogenic differentiation. In summary, this copolymer “PEA” has wide range of the development in the tissue engineering field, such as bioadhesive, cartilage or bone regeneration.

並列關鍵字

hydrogel ； photocrosslink ； tissue engineering ； alanine

參考文獻

[1] Hoare, T. R., and Kohane, D. S. (2008) Hydrogels in drug delivery: Progress and challenges, Polymer 49, 1993-2007.

[2] Wichterle, O., and Lim, D. (1960) Hydrophilic Gels for Biological Use, Nature 185, 117-118.

[3] Dušek, K., and Patterson, D. (1968) Transition in swollen polymer networks induced by intramolecular condensation, Journal of Polymer Science Part A-2: Polymer Physics 6, 1209-1216.

[4] Nuttelman, C. R., Rice, M. A., Rydholm, A. E., Salinas, C. N., Shah, D. N., and Anseth, K. S. (2008) Macromolecular monomers for the synthesis of hydrogel niches and their application in cell encapsulation and tissue engineering, Progress in Polymer Science 33, 167-179.

[5] Yang, J., Han, C.-R., Duan, J.-F., Xu, F., and Sun, R.-C. (2013) Mechanical and Viscoelastic Properties of Cellulose Nanocrystals Reinforced Poly(ethylene glycol) Nanocomposite Hydrogels, ACS Applied Materials & Interfaces 5, 3199-3207.