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Biological and Environmental Phenomena at the Interface
A Simple Thermal Pretreatment Strategy to Tune Mechanical and Antifouling Properties of Zwitterionic Hydrogels Huacheng He, Xuan Xuan, Cuiyun Zhang, Yi Song, Shengfu Chen, Xiong Gong, Baiping Ren, Jiang Wu, and Jie Zheng Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.8b01755 • Publication Date (Web): 23 Jul 2018 Downloaded from http://pubs.acs.org on July 26, 2018
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Langmuir
A Simple Thermal Pretreatment Strategy to Tune Mechanical and Antifouling Properties of Zwitterionic Hydrogels Huacheng He1, Xuan Xuan2, Cuiyun Zhang2, Yi Song2, Shengfu Chen3, Xiong Gong4, Baiping Ren5, Jiang Wu2*, Jie Zheng5* 1
College of Chemistry and Materials Engineering Wenzhou University, Wenzhou, Zhejiang 325027, P.R. China 2
School of Pharmaceutical Sciences Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China 3
College of Chemical and Biological Engineering Zhejiang University, Hangzhou, Zhejiang 310027, P.R. China 4
Department of Polymer Engineering College of Polymer Science and Polymer Engineering The University of Akron, Akron, Ohio 44325, United States 5
Department of Chemical and Biomolecular Engineering The University of Akron, Akron, OH 44325, USA
*Corresponding Author: JW:
[email protected] and JZ:
[email protected] Graphic Abstract
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Abstract Zwitterionic hydrogels are promising biomaterials due to their high water content, three-dimensional network structure, and antifouling property. However, it still remains unclear about how mechanical properties of zwitterionic hydrogels affect their antifouling property. In this work, we propose a simple, thermal-pretreatment method to fabricate poly(sulfobetaine methacrylate) (pSBMA) hydrogels with varied mechanical properties that can be readily tuned by thermal pretreatment time and crosslinker density, as well as to correlate their mechanical property with antifouling property. The resulting thermaltreated pSBMA hydrogels show significantly enhanced mechanical properties with tunable compressive modulus and elastic modulus as compared to the untreated hydrogels. A combination of ELISA investigations and short-term cell adhesion assays also confirm that pSBMA hydrogels exhibit superior antifouling properties to resist protein adsorption and cell adhesion. Further analysis shows a linear inversion correlation between elastic modulus and protein adsorption of pSBMA hydrogels, i.e. the hydrogel with the higher elastic modulus exhibits the lower protein adsorption (the better antifouling property). This work not only provides a simple thermal-pretreatment strategy for fabricating pSBMA hydrogels, but also demonstrates multifunctional properties of the pSBMA hydrogels, which possess a great potential to fulfill some biomedical applications. Key words: Zwitterionic Hydrogels, Non-fouling, Elastic Modulus, Protein adsorption, Thermal pre-treatment
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Langmuir
1. Introduction Polymer hydrogels as soft-wet materials contain a large amount of water in a threedimensional porous network, mimicking physiological tissues, thus they are considered one of the most promising biomaterials, which have been extensively used for biomedical applications including implants1-3, biosensors4, 5, wound healing dressings6, 7, tissue scaffolds8,
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and drug delivery systems10-12. However, almost all blood- or tissue-
contacted hydrogels are vulnerable to unwanted protein and cell adsorption, which would lead to a well-known biofouling problem. For instance, nonspecific protein adsorption often causes foreign-body reaction and results in the failure of implanted devices13; protein deposited to nanomedicine carriers not only block the release of encapsulated drugs, but also shorten their circulation time, leading to the low therapeutic efficacy and possible inflammatory response14. To address this biofouling issue, a general strategy is to fabricate nonfouling hydrogels by using highly protein/cell resistant and biocompatible polymers, such as poly(ethylene glycol) (PEG) and zwitterionic polymers such as poly(sulfobetaine methacrylate) (pSBMA) and poly(carboxybetaine methacrylate) (pCBMA). It is well known that PEG and zwitterionic polymers can form a stable hydration layer around themselves as the physical barrier to prevent protein adsorption1519
. Both PEG- and zwitterionic-based hydrogels have been proved to resist the adhesion
of proteins, cells, and bacteria20-22. However, PEG-based hydrogels are susceptible to oxidization in most of biochemical media containing transition metal ions, which severely limits their utilization in the biomedical applications23, 24. Zwitterionic hydrogels exhibit great superiority over PEG-based hydrogels because of their long-term stability, ease of pre- and post-functionalization, reduced in vivo cytotoxicity25.
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To meet different needs in biomedical applications, zwitterionic hydrogels have been used as surface coating26,
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, contact lens28, cell culture matrix29-31, medical
implants32, and both soft tissues (e.g. skins)33, 34 and stiff tissues (e.g. bones)35. However, zwitterionic hydrogels are often mechanically weak and brittle, thus can not sustain large mechanical forces from gel deformation or even damage14, 36. In addition, it is equally important for zwitterionic hydrogels to accommodate different mechanical forces for practical applications especially as load-bearing materials. Thus, a common strategy to improve and regulate mechanical strength is to adjust crosslinker density and/or introduce the more rigid polymers with stiff backbones. However, simply changing crosslinking density would also likely compromise the antifouling function of hydrogels because most of crosslinkers are fouling materials, which present rich hotspots for binding proteins. Bao and co-workers reported that even at low crosslinking levels (
