Highly antifouling, biocompatible and tough double network hydrogel based on carboxybetaine-type zwitterionic polymer and alginate
Graphical abstract
Introduction
Harmful adhesion of micro organisms, such as bacteria, cells, algae, is the common challenge to food packing, biosensors, medical implants, membrane separation, marine equipment and other fields (Banerjee, Pangule, & Kane, 2011). For example, non-specific protein adsorption can cause biological contamination, resulting in serious adverse biological reactions such as thrombosis, inflammatory reactions (X. Lin et al., 2019); and in the area of marine underwater facilities, the biofouling may increase the mass of the hull, which reduces the speed of navigation, increases energy consumption, and even leads to invasion of alien species (Yebra, Kiil, & Dam-Johansen, 2004). Therefore, it is urgent to develop environmentally friendly antifouling materials. Among those candidates, antifouling hydrogels have attracted broad attentions for their inherent anti-bioadhesive properties, which can be widely applied to biomedical devices (Peng et al., 2020; X. Sun et al., 2020), wound dressing (Xia et al., 2020; Zou et al., 2018), tissue scaffolds (Bonifacio et al., 2018; Madl & Heilshorn, 2018; Rogan, Ilagan, Tong, Chu, & Yang, 2020), biosensors (Chocholova et al., 2018), membrane systems (Koh et al., 2019; Tran, Ramanan, & Lin, 2017), marine coatings (Lundberg et al., 2010; Zhu et al., 2020), and so on.
In the previous studies, many antifouling hydrogels have been proposed (Sautrot-Ba et al., 2019; Wang et al., 2019; Zhang, Zeng et al., 2020; Zhang, Liu et al., 2020). Generally speaking, these hydrogels are mostly made from hydrophilic polymers, such as polyethylene glycol (PEG), polyhydroxyethyl acrylamide (PHEAA), and zwitterionic polymers. Among those hydrophilic polymers, zwitterionic polymers emerged as robust candidates for antifouling hydrogels construction, for their outstanding antifouling properties. Zhang et al. prepared a polycarboxybetaine methacrylate (PCBMA) hydrogel, which showed excellent surface resistance for both protein adsorption and cell adhesion (Zhang et al., 2009). And poly(sulfobetaine methacrylate) (PSBMA) hydrogels have also been proved to be highly resistant to non-specific protein adhesion both in vitro and in vivo (Zhang, Shen et al., 2019). However, mechanical properties of single network (SN) antifouling hydrogels are usually poor. For example, single network PSBMA hydrogel has low fracture strain which is 74.19 ± 4.27 %, and weak maximum compressive stress of 0.191 ± 0.019 MPa. The compressive stress and fracture strain of the other zwitterionic single network PCBMA hydrogel are 0.531 ± 0.058 MPa, 69.88 ± 1.93 %, respectively (Zhao et al., 2018). This cannot meet the needs of some practical applications where hydrogels are required to have excellent mechanical properties (Chang, Meng, Shao, Cui, & Yang, 2019; Dai et al., 2019), especially when they serve as a predominated biomechanical role or are subjected to external force for a long time. Thus, antifouling hydrogels with good mechanical properties need to be developed.
To date, antifouling hydrogels with high mechanical strength are rarely reported. According to literatures, DN hydrogels are famous for their excellent mechanical properties. The DN hydrogels are usually composed of a rigid network and a flexible network. The rigid network is easily broken to dissipate energy and improve strength while the flexible network can enhance the tensile properties of the hydrogels, finally the DN hydrogels will get a best balance state of stiffness and toughness (Gong, Katsuyama, Kurokawa, & Osada, 2003). For example, Liu et al. designed a dual chemically crosslinked DN hydrogel based on methacrylate-functionalized PVA (PVA-MA) and acrylamide (AM) with high compressive stress of 15.5 MPa and excellent shape recovery properties (Z. Liu et al., 2020). But purely chemically cross-linking leads to a permanent rupture of the covalent network which will cause a sharp decline of mechanical properties (Zhang, Chao, Chen, & Jiang, 2006). Differently, DN hydrogels crosslinked by reversible physical interaction acting as “sacrificial bond” can overcome the above deficiency, because they possess a recoverable energy dissipation mechanism, owing to destruction-reconstruction of the physical network (Yang, Wang, Yang, Wang, & Wu, 2018, 2020; Zhang, Zeng et al., 2020; Zhang, Liu et al., 2020).
In our previous study, we introduced chitosan into PHEAA and PSBMA hydrogels to fabricate DN hydrogels (Zhang, Chen, Shen, Chen, & Feng, 2019; Zhang, Shen et al., 2019). The ionic cross-linked chitosan network serves as sacrificed network which will firstly break to dissipate energy when the hydrogels bear external force. And the reversible cross-linkage enables the chitosan network to reconstruct fast. Therefore, the PHEAA/Chitosan and PSBMA/Chitosan DN hydrogels show excellent mechanical properties, for instance, the maximum tensile stress is 3.8 MPa for PHEAA/chitosan (Zhang, Chen et al., 2019) DN hydrogel and 2.0 MPa for PSBMA/chitosan (Zhang, Shen et al., 2019) DN hydrogel. Furthermore, as expected, both kinds of hydrogels can effectively resist the adsorption of cells, bacteria and non-specific proteins. From the results of inflammation response in vivo, we found that the PSBMA/Chitosan DN hydrogel based on zwitterionic polymer shows much superior biocompatibility to the PHEAA/Chitosan DN hydrogel, which is also due to the less bioadhesion of PSBMA/Chitosan DN hydrogel (Zhang, Shen et al., 2019).
As reported, carboxybetaine type zwitterionic polymers show more excellent nonfouling properties than sulfobetaine type zwitterionic polymers, because the binding affinity between carboxybetaine moieties and water molecules is stronger than that between sulfobetaine moieties and water molecules (Shao & Jiang, 2015). Therefore, PCBAA is expected to further improve the antifouling performance and in vivo biocompatibility of the hydrogels. To enhance the mechanical properties of PCBAA hydrogel, DN mechanism was applied. Since sodium alginate (SA) is a polysaccharide and extremely biocompatible, which has been widely used in biomedical field (Dragan, 2014), we prepared DN hydrogel based on PCBAA and SA. The PCBAA/SA DN hydrogel was prepared by a simple “one-pot” method. SA was cross-linked by Ca2+ ions (Fan, Shi, Lian, Li, & Yin, 2013; Gao, He, Fu, Liu, & Ma, 2015) and served as rigid network whereas PCBAA was covalently crosslinked and served as flexible network. Excellent antifouling effect to bacteria, cells, non-specific proteins, and algae and good mechanical properties were achieved. This study provides a new strategy to prepare antifouling DN hydrogels with good mechanical properties to meet various needs, which can broaden their application in biomedical field, food packing, and marine coating and so on.
Section snippets
Materials
Sodium alginate (molecular weight: 32000–250000, M/G ratio: 1:1, viscosity: 200 ± 20 mPa·s), ethyl bromoacetate, N,N-dimethylaminopropyl acrylamide, OH type anionic exchange resin (IRA-400), N,N-methylene-bis-acrylamide (MBAA), α-ketoglutaric acid were purchased from Aladdin. HRP-IgG protease, Roswell Park Memorial Institute (RPMI) 1640 medium medium, fetal bovine serum (FBS) and sterile phosphate buffered saline (PBS) were purchased from Invitrogen Corp. Other reagents and solvents in the
Preparation of the DN hydrogel
Scheme 1A shows a general process to prepare the PCBAA/SA-Ca2+ DN hydrogel containing ionically crosslinked alginate network and covalently crosslinked PCBAA network. The 1H NMR spectrum shown in the Fig. S1 proves the successful synthesis of CBAA monomer. To prepare the DN hydrogel, first, all of the reactants (CBAA, SA, α-ketoglutaric acid, MBAA) were completely dissolved in DI water and then polymerized under UV to produce the semi-interpenetrated PCBAA/SA composite hydrogel. In this step,
Conclusions
In summary, a novel hybrid ionic-covalent crosslinked PCBAA/SA-Ca2+ DN hydrogel has been successfully prepared. The DN structure endows the hydrogel with an efficient energy dissipation mechanism, which achieves a high tensile strength and strong elastic modulus of the DN hydrogel. And owing to the reversible SA ionic network, the DN hydrogel shows fast self-recovery ability, and good anti-fatigue capacity. More importantly, the DN hydrogel has excellent antifouling properties, which can resist
CRediT authorship contribution statement
Jing Zhang: Supervision, Conceptualization, Methodology, Writing - review & editing. Lingdong Chen: Validation, Software, Writing - original draft. Liqun Chen: Investigation. Sunxiang Qian: Investigation. Xiaozhou Mou: Writing - review & editing. Jie Feng: Supervision.
Declaration of Competing Interest
There are no conflicts of interest to declare.
Acknowledgements
This work was funded by the National Natural Science Foundation of China (Grants 52073256, 21404091 and 21404089) and the Natural Science Foundation of Zhejiang Province (LBY21E030001).
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