用于模拟细胞外基质的硫醇-烯水凝胶的制备

doi:10.11901/1005.3093.2021.147

材料研究学报

2021, Vol. 35

Issue (12): 903-910 DOI: 10.11901/1005.3093.2021.147

研究论文

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用于模拟细胞外基质的硫醇-烯水凝胶的制备

苏晨文¹, 张婷玥¹, 郭丽伟¹, 李乐¹, 杨苹², 刘艳秋¹(

)

^1.西南交通大学生命科学与工程学院成都 610031
^2.西南交通大学材料科学与工程学院成都 610031

Preparation of Thiol-ene Hydrogels for Extracellular Matrix Simulation

SU Chenwen¹, ZHANG Tingyue¹, GUO Liwei¹, LI Le¹, YANG Ping², LIU Yanqiu¹(

)

^1.School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
^2.School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China

引用本文:

苏晨文, 张婷玥, 郭丽伟, 李乐, 杨苹, 刘艳秋. 用于模拟细胞外基质的硫醇-烯水凝胶的制备[J]. 材料研究学报, 2021, 35(12): 903-910.
Chenwen SU, Tingyue ZHANG, Liwei GUO, Le LI, Ping YANG, Yanqiu LIU. Preparation of Thiol-ene Hydrogels for Extracellular Matrix Simulation[J]. Chinese Journal of Materials Research, 2021, 35(12): 903-910.

全文: PDF(3077 KB) HTML

摘要:

先使四臂末端羟基化的聚乙二醇(4-PEG-OH)与降冰片烯(NB)反应制备4-PEG-NB大分子单体，然后将其与二硫苏糖醇通过‘硫醇-烯点击化学方法逐步生长式’制备出硬度可调节的水凝胶并辅以REDV生物多肽修饰，用于模拟二维(2D)和三维(3D)细胞外基质(ECM)。结果表明，4-PEG-NB单体合成的接枝率为90%，制备出的硫醇-烯水凝胶具有多孔结构，发生了硫醇-烯交联反应且交联度高；改变交联比例可将杨氏模量分别调控为0.79、2.40、4.52 kPa；随着水凝胶交联比例的提高，孔隙率随之提高而溶胀率降低。这种水凝胶具有体外降解性；药物释放的前期速度较高，后期较低。2D和3D ECM模拟的细胞培养结果表明，这种水凝胶具有优异的生物相容性。

关键词 ：有机高分子材料, PEG-NB水凝胶, 硫醇-烯点击化学, ECM模拟, 硬度可调控, 生物相容性

Abstract：

The tunable stiffness step-growth hydrogels were prepared by thiol-ene click chemistry between 4 arm-polyethylene glycol-norbornene (4-PEG-NB) and dithiothreitol and supplemented with REDV biopeptide modification for 2D and 3D extracellular matrix (ECM) simulations, in which the 4-PEG-NB macromonomer was produced by the reaction of 4-PEG-OH with norbornene. The results show that the prepared thiol-ene hydrogels present a porous structure, and the thiol-ene cross-linking reaction with high cross-linking efficiency was also confirmed. The tunable Young's modulus of hydrogels could be precisely regulated to 0.79, 2.40, and 4.52 kPa by changing the thiol-ene ratio. As the crosslink ratio of the hydrogels increased, the porosity gradually increased and the swelling rate gradually decreased. The drug release of the hydrogels was faster in the early stage and then gradually slowed down. The cell culture results of 2D and 3D ECM simulations show that the hydrogel had excellent biocompatibility.

Key words： organic polymer materials PEG-NB hydrogel thiol-ene click chemistry tunable stiffness ECM simulation biocompatibility

收稿日期: 2021-02-23

ZTFLH:

R318.08

基金资助:国家自然科学基金(32071320);中央高校基本科研业务费专项(201810613085)

作者简介: 苏晨文，男，1996年生，硕士生

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https://www.cjmr.org/CN/10.11901/1005.3093.2021.147 或 https://www.cjmr.org/CN/Y2021/V35/I12/903

图1 4-PEG-NB的1H NMR谱

图2 4-PEG-NB水凝胶的制备流程和制备出的水凝胶照片

图3 硫醇-烯比例为0.5、0.75和1的水凝胶的截面SEM照片

图4 三种不同硫醇-烯比例水凝胶的孔隙率

图5 三种不同硫醇-烯比例水凝胶的FTIR谱和交联度

图6 不同硬度水凝胶的储能模量(G')、损失模量(G'')和转换后的杨氏模量

图7 软、中、硬3种水凝胶在去离子水、含血清培养基和磷酸盐缓冲溶液中的溶胀动力学曲线

图8 软、中、硬3种水凝胶在去离子水、含血清培养基和磷酸盐缓冲溶液中的降解曲线

图9 软、中、硬3种水凝胶在去离子水中降解7 d的SEM照片

图10 不同硬度水凝胶负载甲硝唑药物的包封率和累计释放曲线

图11 不同硬度的水凝胶的在5 d内的2D、3D细胞培养活性

图12 光引发剂通过光裂解生成自由基和4-PEG-NB与DTT之间自由基介导逐步式生长的硫醇-烯光点击反应示意图

1	Naahidi S, Jafari M, Logan M, et al. Biocompatibility of hydrogel-based scaffolds for tissue engineering applications [J]. Biotechnol. Adv., 2017, 35: 530
2	Ding L R, Li J W, Wu C R, et al. A self-assembled RNA-triple helix hydrogel drug delivery system targeting triple-negative breast cancer [J]. J. Mater. Chem., 2020, 8B: 3527
3	Zhang A D, Liu Y, Qin D, et al. Research status of self-healing hydrogel for wound management: A review [J]. Int. J. Biol. Macromol., 2020, 164: 2108
4	Sackett S D, Tremmel D M, Ma F F, et al. Extracellular matrix scaffold and hydrogel derived from decellularized and delipidized human pancreas [J]. Sci. Rep., 2018, 8: 10452
5	Giobbe G G, Crowley C, Luni C, et al. Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture [J]. Nat. Commun., 2019, 10: 5658
6	Unal A Z, West J L. Synthetic ECM: Bioactive synthetic hydrogels for 3D tissue engineering [J]. Bioconjug. Chem., 2020, 31: 2253
7	Viji Babu P K, Rianna C, Mirastschijski U, et al. Nano-mechanical mapping of interdependent cell and ECM mechanics by AFM force spectroscopy [J]. Sci. Rep., 2019, 9: 12317
8	Buxboim A, Ivanovska I L, Discher D E. Matrix elasticity, cytoskeletal forces and physics of the nucleus: how deeply do cells 'feel' outside and in? [J]. J. Cell. Sci., 2010, 123: 297
9	Duval K, Grover H, Han L H, et al. Modeling physiological events in 2D vs. 3D cell culture [J]. Physiology, 2017, 32: 266
10	Padhi A, Nain A S. ECM in differentiation: A review of matrix structure, composition and mechanical properties [J]. Ann. Biomed. Eng., 2020, 48: 1071
11	Xia T T, Liu W Q, Yang L. A review of gradient stiffness hydrogels used in tissue engineering and regenerative medicine [J]. J. Biomed. Mater. Res., 2017, 105A: 1799
12	Ding X C, Wang Y D. Weak bond-based injectable and stimuli responsive hydrogels for biomedical applications [J]. J. Mater. Chem., 2017, 5B: 887
13	Vats K, Marsh G, Harding K, et al. Nanoscale physicochemical properties of chain- and step-growth polymerized PEG hydrogels affect cell-material interactions [J]. J. Biomed. Mater. Res., 2017, 105A: 1112
14	Xu Z H, Bratlie K M. Click chemistry and material selection for in situ fabrication of hydrogels in tissue engineering applications [J]. ACS Biomater. Sci. Eng., 2018, 4: 2276
15	Devalliere J, Chen Y B, Dooley K, et al. Improving functional re-endothelialization of acellular liver scaffold using REDV cell-binding domain [J]. Acta Biomater., 2018, 78: 151
16	Jivan F, Yegappan R, Pearce H, et al. Sequential thiol–ene and tetrazine click reactions for the polymerization and functionalization of hydrogel microparticles [J]. Biomacromolecules, 2016, 17: 3516
17	Masood N, Ahmed R, Tariq M, et al. Silver nanoparticle impregnated chitosan-PEG hydrogel enhances wound healing in diabetes induced rabbits [J]. Int. J. Pharm., 2019, 559: 23
18	Liu Y Y, Cai Z X, Sheng L, et al. Structure-property of crosslinked chitosan/silica composite films modified by genipin and glutaraldehyde under alkaline conditions [J]. Carbohydr. Polym., 2019, 215: 348
19	Ding Y H, Floren M, Tan W. High-throughput screening of vascular endothelium-destructive or protective microenvironments: Cooperative actions of extracellular matrix composition, stiffness, and structure [J]. Adv. Healthc. Mater., 2017, 6: 1601426
20	Wang Y M, Wang J, Yuan Z Y, et al. Chitosan cross-linked poly(acrylic acid) hydrogels: Drug release control and mechanism [J]. Colloids Surf., 2017, 152B: 252
21	Shih H, Liu H Y, Lin C C. Improving gelation efficiency and cytocompatibility of visible light polymerized thiol-norbornene hydrogels via addition of soluble tyrosine [J]. Biomater. Sci., 2017, 5: 589

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