Antifouling Super Water Absorbent Supramolecular Polymer Hydrogel as an Artificial Vitreous Body

Abstract

Recently, there has been a high expectation that high water absorbent hydrogels can be developed as an artificial vitreous body. However, the drawbacks associated with in vivo instability, biofouling, uncontrollable in situ reaction time, and injection‐induced precrosslinked fragmentation preclude their genuine use as vitreous substitutes. Here, a supramolecular binary copolymer hydrogel termed as PNAGA‐PCBAA by copolymerization of N‐acryloyl glycinamide (NAGA) and carboxybetaine acrylamide (CBAA) is prepared. This PNAGA‐PCBAA hydrogel physically crosslinked by dual amide hydrogen bonds of NAGA exhibits an ultralow solid content (1.6, 98.4 wt% water content), and shear‐thinning behavior, body temperature extrudability/self‐healability, rapid network recoverability, and very close key parameters (modulus, antifouling/antifibrosis, light transmittance, refractive index, ultrastability) to human vitreous body. It is demonstrated that the hydrogel can be readily injected by a 22G needle into the rabbits' eyes where the gelling network is rapidly recovered. After 16 weeks postoperation, the hydrogel acts as a very stable vitreous substitute without affecting the structure of soft tissues in eye, or eliciting adverse effects. This supramolecular binary copolymer hydrogel finds a broad application in ophthalmic fields as not only a self‐recoverable permanent vitreous substitute, but also transient intraocular filling for prevention of inner tissues in postsurgical eyes.

Macro- and Microscale Properties of the Vitreous Humor to Inform Substitute Design and Intravitreal Biotransport

“…17,34,59 Only a handful of hydrogel vitreous substitutes (n = 13) have similar storage and loss moduli to those reported for the human vitreous humor (less than 20 Pa). 34,59,[62][63][64]69,73,76,81,84,110,128,129 In contrast, a majority of the previously proposed vitreous substitutes have modulus values that are orders of magnitude higher than those of the reported human vitreous humor. While the in vivo results for some of these hydrogel vitreous substitutes were promising for short-and intermediate-term applications (less than 1 or 2 years), it is unknown whether the high modulus of these stiff gels would have long-term adverse effects on ocular tissues.…”

“…However, stiff hydrogels can be difficult to inject through a small gauge needle into the vitreous chamber. The storage and loss moduli of synthetic hydrogels 34,[59][60][61][62]69,73,74,76,[81][82][83] (G' = 1203 ± 755 Pa, n = 18 and G" = 373 ± 330 Pa, n = 12) and semisynthetic hydrogels [92][93][94]97,98,[100][101][102]104 (G' = 1330 ± 1090 Pa, n = 9 and G" = 291 ± 223 Pa, n = 9) are approximately two orders of magnitude higher, while natural hydrogels' 37,110 (G' = 99.4 ± 53.4 Pa, n = 3 and G" = 51.5 ± 48.5 Pa, n = 2) are about one order of magnitude higher compared to the human vitreous [15][16][17] (G' = 5.09 ± 1.86 Pa, n = 3 and G" = 1.81 ± 0.98 Pa, n = 3). Hydrogels with different mechanisms of injection into the eye also have a wide variation in storage and loss moduli ( Table 5 and Figure 4B).…”

“…Hydrogels with different mechanisms of injection into the eye also have a wide variation in storage and loss moduli ( Table 5 and Figure 4B). Hydrogel vitreous substitutes with direct injection mechanism 59,62,73,76,[81][82][83]94,110 (G' = 49.9 ± 31.3 Pa, n = 9 and G" = 26.3 ± 21.8 Pa, n = 9) have the closest modulus to the human vitreous, followed by thermogelling/in situ crosslinking hydrogels 37,96,100,101 (G' = 136 ± 33.1 Pa, n = 4 and G" = 28.9 ± 23.8 Pa, n = 4). The moduli of hydrogels with in situ crosslinking 34,69,93,97,98,104 (G' = 1626 ± 1031 Pa, n = 13 and G" = 338 ± 332 Pa, n = 6) or thermogelling 60,61,74,102 (G' = 2946 ± 2360 Pa, n = 4 and G" = 1206 ± 937 Pa, n = 4) mechanisms are, on average, more than two orders of magnitude higher than those of the natural human vitreous.…”

Substitutes and Colloidal System for Vitreous Replacement and Drug Delivery: Recent Progress and Future Prospective

“…High water absorbent hydrogels have gained popularity and were thought to be a good vitreous substitute. Therefore, recently in 2018, Wang et al, developed a supramolecular binary copolymer PNAGA-PCBAA hydrogel by copolymerizing N-acryloyl glycinamide (NAGA) and carboxybetaine acrylamide (CBAA) [ 82 ]. It exudes characteristics similar to native vitreous, such as antifouling, antifibrosis, refractive index, modulus, stability.…”

Light‐Induced Swelling‐Responsive Conductive, Adhesive, and Stretchable Wireless Film Hydrogel as Electronic Artificial Skin

“…The advanced design of a soft skin hydrogel matrix with controlled hydrophobic–hydrophilic surface properties has been implemented, regarding huge advantages of diffusion and exchange of substances, surface functionalization, surface patterning, and antifouling . In addition, modifications of chains with stimuli‐responsive functional groups impart dynamic surface properties, which can be stimulated using heat, light, magnetic field, chemical agents, or pH .…”