Article Cite This: Macromolecules XXXX, XXX, XXX−XXX
CO2‑Switchable Self-Healing Host−Guest Hydrogels Yong-Guang Jia, Meng Zhang, and X. X. Zhu* Département de Chimie, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montréal, QC H3C 3J7, Canada S Supporting Information *
ABSTRACT: The use of natural compounds to construct reversible networks is an attractive strategy in biomaterials design. Our design is based on a host−guest pair of natural compounds β-cyclodextrin and cholic acid through the use of a cholic acid dimer tethered with a poly(ethylene glycol) spacer, which subsequently served as a guest cross-linker to afford a hydrogel with copolymers bearing β-cyclodextrin pendants. The hydrogel after incision self-heals rapidly under ambient atmosphere as observed and confirmed by rheological measurements. To endow the hydrogels with reversibility and responsiveness, the addition of a CO2-switchable guest of benzimidazole followed by alternating treatments with CO2 and N2 leads to a reversible sol−gel transition due to the dynamic complexation between the cholic acid and β-cyclodextrin units. The CO2 responsiveness and the natural origin of the constituents make these self-healing hydrogels attractive as smart biomaterials.
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INTRODUCTION Hydrogels bear some similarities to biological tissues; both are soft and highly hydrated. Hence, they attract much attention as synthetic equivalents for use in biological systems, such as tissue engineering.1−4 Any given application, however, requires a combination of mechanical properties and self-healing5 along with biocompatibility.6,7 To date, such a combination is rarely realized.8 Host−guest interactions have been used in the construction of self-healing hydrogels9−11 because the combination of multiple noncovalent interactions between two complementary compounds renders the material a good binding affinity and a complexation with fixed host−guest geometry and directionality.12−14 Unlike the other synthetic host molecules, such as crown ethers,15 calixarenes,16 cucurbiturils,17 and pillar[n]arenes,18−20 cyclodextrins (CDs) are water-soluble cyclic oligomers of D-(+)-glucose units bound to each other through α-1,4-glucose bonding and are produced from enzymatic processing of starch, ensuring their biocompatibility and availability. The CDs can be easily functionalized for the preparation of hydrogels.21−23 Improved biocompatibility may be achieved by designing materials from natural compounds or biocompatible constituents.24 Bile acids are biocompounds that exist in large quantities in the gallbladder of humans and most animals.25 We previously attached bile acids guest and β-CD host as pendant groups onto poly(N,N′-dimethylacrylamide) separately, making each a copolymer. When they were mixed, a rapidly ( β-CD/CA > β-CD/BzI+, as shown in Table 1, as confirmed by the 2D NOESY 1H NMR spectroscopy (Figure S9) and the reversible sol−gel transitions (Figure 3B). The viscosity of the hydrogel system decreases significantly to form a viscous solution as shown in Figure 3B, for which G″ is larger than G′, indicating that the BzI-A replaces the CA units and is included inside the cavity of CD units. After 2 min of CO2 treatment of this solution, BzI-A is converted to the charged BzI+-A which is excluded from the CD cavities. The CA units can complex with CD again to re-form a hydrogel, for which G′ becomes higher than G″ and reaches 89% of its original value (Figure 3B), indicating a CO2-switchable dissociation between CD and BzI moieties (Figure 1C). Purging with N2 displaces the CO2 in the system, yielding a solution again with G″ > G′, which indicates the recovery of BzI+-A to its BzI-A form which can then form a complex with CD (Figure 3B). Such a reversible gel−sol transition based on the competing host−guest interactions is also confirmed by 2D NOESY NMR experiments (red rectangles in Figure S9). After BzI-A was added into the mixture of PDMA-CD7% and PEGCA2, the strong NOE correlation of protons from BzI-A with the interior H3/H5 of β-CD disappeared upon purging with CO2 (Figure S9B) but reappeared after purging with N2 (Figure S9C).
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CONCLUSION In summary, we introduced a water-soluble cholic acid dimer as a cross-linker to prepare hydrogels with polymers bearing β-CD pendant groups. In addition to the self-healing capabilities through host−guest complexation, these gels possess the merits of simple molecular design with the choice of host−guest pair of natural compounds as starting materials. In contrast to previously reported self-healing hydrogels, this represents the first example of self-healing hydrogel made by a simple guest dimer. Furthermore, the reversible gel−sol capability is achieved through alternating treatment with CO2 and N2 after the addition of a CO2-responsive BzI-A guest due to the protonation and deprotonation of BzI units. These unique features are attributed to the formation of dynamically reversible inclusion complexation. Because of the natural origin of both cholic acid and β-CD as well as the responsiveness toward CO2, a gas of physiological relevance, we anticipate that these hydrogels will find uses as smart soft materials in biomedical and pharmaceutical applications where reversibility, responsiveness, and self-healing behavior are useful and necessary.
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EXPERIMENTAL SECTION
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Materials. Acryloyl chloride, p-nitrophenol, β-cyclodextrin, ptoluenesulfonyl chloride, ethylenediamine, cholic acid, poly(ethylene glycol)-2000, p-nitrophenyl chloroformate, pyridine, 3-(1Hbenzimidazolyl)propan-1-amine (BzI-A), and triethylamine were purchased from Aldrich and used without further purification unless otherwise stated. 2,2′-Azoisobutyronitrile (AIBN) was recrystallized twice from methanol. N,N′-Dimethylacrylamide (DMA) was distilled
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.7b02163. D
DOI: 10.1021/acs.macromol.7b02163 Macromolecules XXXX, XXX, XXX−XXX
Article
Macromolecules
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Characterization of the dimer and polymers, inverted vial tests, temperature sweep, frequency sweep and strain sweep, 2D NOESY 1H NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected] (X.X.Z.). ORCID
Yong-Guang Jia: 0000-0001-8924-2820 X. X. Zhu: 0000-0003-0828-299X Present Address
Y.-G.J.: School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510641, China. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS Financial support from NSERC of Canada and FQRNT of Quebec is gratefully acknowledged. Authors are members of CSACS funded by FQRNT and GRSTB funded by FRSQ.
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DOI: 10.1021/acs.macromol.7b02163 Macromolecules XXXX, XXX, XXX−XXX
