Synthesis and characterization of <i>in situ</i>
 forming anionic hydrogel as vitreous substitutes

Liang, Jue; Struckhoff, Jessica J.; Du, Hongwei; Hamilton, Paul D.; Ravi, Nathan

doi:10.1002/jbm.b.33632

Cited by 25 publications

(39 citation statements)

References 26 publications

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“…The thiol content of the poly(MAM-co-MAA-co-BMAC) copolymer was 2% (mol) from NTSB assay and 1 HNMR. Liang et al [17] showed that the poly(MAM-co-MAA-co-BMAC) with 2% (mol) thiol cross-linker and a methacrylate content of 20% (mol) was biocompatible on ocular epithelial cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…The poly (MAM-co-MAA-co-BMAC) (CoP) was synthesized by free radical polymerization of MAM, MAA and BMAC as described in detail by Liang et al [17]. The disulfide and thiol content in the copolymer was determined by the NTSB assay as used for gellan.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, it is used in ophthalmic applications [8, 16]. On the other hand, the poly(methacrylamide-co-methacrylate-co- N′,N′ -bis(methylacryloyl-cystamine)) (poly(MAM-co-MAA-co-BMAC) is a random coil, ionic polyelectrolyte, that allows for variation in the swelling (osmotic pressure) and gelling properties of the hydrogels [17], analogues to HA at a mesoscopic level. Nakagawa [18] observed that a simple combination of collagen and HA does not last long as a vitreous substitute as they diffuse out of the vitreous cavity.…”

Section: Introductionmentioning

confidence: 99%

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Biomimetic hydrogel with tunable mechanical properties for vitreous substitutes

et al. 2016

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The vitreous humor of the eye is a biological hydrogel principally composed of collagen fibers interspersed with hyaluronic acid. Certain pathological conditions necessitate its removal and replacement. Current substitutes, like silicone oils and perfluorocarbons, are not biomimetic and have known complications. In this study, we have developed an in situ forming two-component biomimetic hydrogel with tunable mechanical and osmotic properties. The components are gellan, an analogue of collagen, and poly(methacrylamide-co-methacrylate), an analogue of hyaluronic acid; both endowed with thiol side groups. We used response surface methodology to consider seventeen possible hydrogels to determine how each component affects the optical, mechanical, sol-gel transition temperature and swelling properties. The optical and physical properties of the hydrogels were similar to vitreous. The shear storage moduli ranged from 3 to 358 Pa at 1Hz and sol-gel transition temperatures from 35.5 to 43 °C. The hydrogel had the ability to remain swollen without degradation for four weeks in vitro. Three hydrogels were tested for biocompatibility on primary porcine retinal pigment epithelial cells, human retinal pigment epithelial cells, and fibroblast (3T3/NIH) cells, by electric cell-substrate impedance sensing system. The two-component hydrogels allowed for the tuning and optimizing of mechanical, swelling, and transition temperature to obtain three biocompatible hydrogels with properties similar to vitreous. Future studies include testing of the optimized hydrogels in animal models for use as a long-term substitute, whose preliminary results are mentioned.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biomimetic hydrogel with tunable mechanical properties for vitreous substitutes

et al. 2016

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“…By using the conventional free-radical polymerization, we were able to obtain copolymers with a molecular weight ( M n = 194 kDa) that, according to our previous work, is suitable for making hydrogels. 37 The thiol content (5.0–5.1 mol %), which was measured by a 2-nitro-5-thiosulobenzoate (NTSB) assay, was very close to the feed ratio (5.0 mol %), suggesting stoichiometric incorporation of thiol groups into the copolymer. The content of AMPS (20.6 mol %) was also close to the feed ratio (20 mol %), as determined by 1 H NMR.…”

Section: Resultsmentioning

confidence: 84%

Synthesis and Characterization of Injectable Sulfonate-Containing Hydrogels

et al. 2016

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Sulfonate-containing hydrogels are of particular interest because of their tunable mechanical and swelling properties, as well as their biological effects. Polysulfonate copolymers were synthesized by reacting 2-acrylamido-2-methylpropanesulfonic acid (AMPS), acrylamide (AM), and acrylic acid (AA). We found that the incorporation rate of sulfonate-containing monomer and the molecular weight of the copolymer were significantly enhanced by increasing the ionic strength of the solution. We introduced thiol groups by modifying the pendant carboxylates or copolymerizing along with a disulfide-containing monomer. The thiol-containing copolymers were reacted with a 4-arm acrylamide-terminated poly(ethylene glycol) via a thiol–ene click reaction, which was mediated by a photoinitiator, a redox initiator, or a base-catalyzed Michael-Addition. We were able to tailor the storage modulus (33–1800 Pa) and swelling capacity (1–91 wt %) of the hydrogel by varying the concentration of the copolymers. We determined that the injectable sulfonate-containing hydrogels were biocompatible up to 20 mg/mL, as observed by an electric cell–substrate impedance sensing (ECIS) technique, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using three different cell lines: human retinal pigment epithelial cells (ARPE-19), fibroblasts (NIH 3T3), and Chinese hamster ovary cells (CHO).

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“…The use of redox-active cross-links in this system facilitates injectability. 24 Using swelling equilibrium, rheology, and dynamic light scattering, we show that this combination, inspired by the major components of the natural vitreous, leads to synthetic materials which closely resemble the polymer volume fraction, shear modulus, elastic diffusion, and friction coefficient of the natural tissue.…”

Section: ■ Results and Discussionmentioning

confidence: 97%

Development of a Vitreous Substitute: Incorporating Charges and Fibrous Structures in Synthetic Hydrogel Materials

et al. 2016

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Synthetic hydrogel systems are promising long-term candidates for therapeutic use as vitreous substitutes. To improve the swelling and mechanical properties of existing synthetic substitutes for the natural vitreous, we incorporate charges and fibrous structures. Using dynamic light scattering, rheology, and swelling techniques we show in vitro that synthetic copolymers of methacrylic acid (MAA), methylacrylamide (MAm), and bismethacryloylcystamine (BMAC) cross-linked with gellan match the water content, transport properties, and dynamic response of the natural vitreous better than previously proposed synthetic substitutes.

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Synthesis and characterization of in situ forming anionic hydrogel as vitreous substitutes

Cited by 25 publications

References 26 publications

Biomimetic hydrogel with tunable mechanical properties for vitreous substitutes

Biomimetic hydrogel with tunable mechanical properties for vitreous substitutes

Synthesis and Characterization of Injectable Sulfonate-Containing Hydrogels

Development of a Vitreous Substitute: Incorporating Charges and Fibrous Structures in Synthetic Hydrogel Materials

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