Please wait a minute...
Chinese Journal of Materials Research  2021, Vol. 35 Issue (12): 903-910    DOI: 10.11901/1005.3093.2021.147
ARTICLES Current Issue | Archive | Adv Search |
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
Cite this article: 

SU Chenwen, ZHANG Tingyue, GUO Liwei, LI Le, YANG Ping, LIU Yanqiu. Preparation of Thiol-ene Hydrogels for Extracellular Matrix Simulation. Chinese Journal of Materials Research, 2021, 35(12): 903-910.

Download:  HTML  PDF(3077KB) 
Export:  BibTeX | EndNote (RIS)      
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     
Received:  23 February 2021     
ZTFLH:  R318.08  
Fund: National Natural Science Foundation of China(32071320);the Fundamental Research Funds for the Central Universities(201810613085)
About author:  LIU Yanqiu, Tel: 13980462692, E-mail: yqliu@home.swjtu.edu.cn

URL: 

https://www.cjmr.org/EN/10.11901/1005.3093.2021.147     OR     https://www.cjmr.org/EN/Y2021/V35/I12/903

Fig.1  1H NMR spectrum of 4-PEG-NB
Fig.2  Preparation process of 4-PEG-NB hydrogel (a) and hydrogel prepared (b)
Fig.3  Cross-sectional SEM images of hydrogels with thiol-ene ratio 0.5 (a), 0.75 (b) and 1 (c)
Fig.4  Porosity of three hydrogels with different thiol-ene ratio
Fig.5  FTIR spectra (a) and cross-linkage (b) of three thiol-ene ratio hydrogels
Fig.6  Storage modulus (G') and loss modulus (G'') of hydrogels with different stiffness (a) and conversion to Young's modulus (b)
Fig.7  Swelling kinetic curves of soft (a), med (b), stiff (c) hydrogels in DI water, medium and PBS
Fig.8  Degradation curves of soft (a), med (b), stiff (c) hydrogels in DI water, medium and PBS
Fig.9  SEM images of soft (a), med (b), stiff (c) hydrogels degradation in DI water for 7 d
Fig.10  Encapsulation efficiency (a) and cumulative release curves (b) of different stiffness hydrogels loaded with metronidazole
Fig.11  2D (a) and 3D (b) cell viability of hydrogels with different stiffness in 5 d
Fig.12  Schematic diagram of thiol-ene click chemistry mechanism (a) photocleavage of photoinitiator LAP into radicals and (b) schematics of a radical-mediated step-growth thiol-ene photoclick reaction between 4-PEG-NB and DTT
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
[1] YE Jiaofeng, WANG Fei, ZUO Yang, ZHANG Junxiang, LUO Xiaoxiao, FENG Libang. Epoxy Resin-modified Thermo-reversible Polyurethane with High Strength, Toughness, and Self-healing Performance[J]. 材料研究学报, 2023, 37(4): 257-263.
[2] LI Hanlou, JIAO Xiaoguang, ZHU Huanhuan, ZHAO Xiaohuan, JIAO Qingze, FENG Caihong, ZHAO Yun. Synthesis of Branched Fluorine-containing Polyesters and their Properties[J]. 材料研究学报, 2023, 37(4): 315-320.
[3] MA Yizhou, ZHAO Qiuying, YANG Lu, QIU Jinhao. Preparation and Dielectric Energy Storage Properties of Thermoplastic Polyimide/Polyvinylidene Fluoride Composite Film[J]. 材料研究学报, 2023, 37(2): 89-94.
[4] SHEN Yanlong, LI Beigang. Preparation of Magnetic Amino Acid-Functionalized Aluminum Alginate Gel Polymer and its Super Adsorption on Azo Dyes[J]. 材料研究学报, 2022, 36(3): 220-230.
[5] LONG Qing, WANG Chuanyang. Thermal Degradation Behavior and Kinetics Analysis of PMMA with Different Carbon Black Contents[J]. 材料研究学报, 2022, 36(11): 837-844.
[6] LI Jianzhong, ZHU Boxuan, WANG Zhenyu, ZHAO Jing, FAN Lianhui, YANG Ke. Preparation and Properties of Copper-carrying Polydopamine Coating on Ureteral Stent[J]. 材料研究学报, 2022, 36(10): 721-729.
[7] JIANG Ping, WU Lihua, LV Taiyong, Pérez-Rigueiro José, WANG Anping. Repetitive Stretching Tensile Behavior and Properties of Spider Major Ampullate Gland Silk[J]. 材料研究学报, 2022, 36(10): 747-759.
[8] YAN Jun, YANG Jin, WANG Tao, XU Guilong, LI Zhaohui. Preparation and Properties of Aqueous Phenolic Resin Modified by Organosilicone Oil[J]. 材料研究学报, 2021, 35(9): 651-656.
[9] ZHANG Hao, LI Fan, CHANG Na, WANG Haitao, CHENG Bowen, WANG Panlei. Preparation of Carboxylic Acid Grafted Starch Adsorption Resin and Its Dye Removal Performance[J]. 材料研究学报, 2021, 35(6): 419-432.
[10] SUN Liying, QIAN Jianhua, ZHAO Yongfang. Preparation and Performance of AgNWs -TPU/PVDF Flexible Film Capacitance Sensors[J]. 材料研究学报, 2021, 35(6): 441-448.
[11] TANG Kaiyuan, HUANG Yang, HUANG Xiangzhou, GE Ying, LI Pinting, YUAN Fanshu, ZHANG Weiwei, SUN Dongping. Physicochemical Properties of Carbonized Bacterial Cellulose and Its Application in Methanol Electrocatalysis[J]. 材料研究学报, 2021, 35(4): 259-270.
[12] ZHANG Xiangyang, ZHANG Qiyang, ZHENG Tao, TANG Tao, LIU Hao, LIU Guojin, ZHU Hailin, ZHU Haifeng. Fabrication of Composite Material Based on MOFs and its Adsorption Properties for Methylene Blue Dyes[J]. 材料研究学报, 2021, 35(11): 866-872.
[13] YU Jiaying, YANG Xixiang, ZHAN Desong, YANG Ke, REN Ling, WANG Jingren, XU Jiawei. Antibacterial Property and in vitro Biocompatibility of a Ti-Zr-Cu Alloy[J]. 材料研究学报, 2021, 35(11): 873-880.
[14] WAN Liying, XIAO Yang, ZHANG Lunliang. Preparation and Properties of PU-DA System Based on Thermoreversible Diels-Alder Dynamic Covalent Bond[J]. 材料研究学报, 2021, 35(10): 752-760.
[15] ZHANG Cuige, HU Liang, LU Zuxin, ZHOU Jiahui. Preparation and Emulsification Properties of Self-assembled Colloidal Particles Based on Alginic Acid[J]. 材料研究学报, 2021, 35(10): 761-768.
No Suggested Reading articles found!