Injectable and Biodegradable Vitreous Substitute

Abstract

Purpose : Current clinical vitreous substitutes carry major drawbacks during patient recovery from vitreoretinal surgery including blurred vision, risk of glaucoma, face-down posturing for gas substitutes, and a second removal surgery for non-resorbable fluid substitutes. There is an unmet need for a new biomimetic vitreous substitute to improve patient recovery following vitreoretinal surgery. We developed a novel hydrogel vitreous substitute composed of hyaluronan crosslinked with poly(ethylene glycol) using oxime chemistry. Our hydrogel was designed to overcome the limitations of current clinical substitutes by being biomimetic and biodegradable.

Methods : Three candidate hydrogel formulations were autoclave-sterilized and characterized for biocompatibility and biomimicry by measuring gelation time, stiffness, injectability, swelling mass, transparency, refractive index, density, and surface tension. Injection force through 25G and 27G needles was measured over 2 h. Hydrolytic stability was monitored by measuring swelling mass after incubation in BSS over 28 d. Spectral transmittance was measured over 10 d during which in vitro hyaluronidase treatment was used to simulate accelerated biodegradation.

Results : Candidate hydrogel formulations had tunable gelation time between 7.6 ± 0.1 and 12.9 ± 2.3 min (n = 3) and tunable Young’s modulus between 2.6 ± 0.8 and 5.0 ± 0.2 kPa (n = 3). Injection force through 25G and 27G needles was well below the 30 N injection threshold for 2 h (n = 3). The hydrogels were hydrolytically stable and exhibited minimal swelling over 28 d incubation in BSS (n = 5). Hydrogels were transparent as they degraded over the course of the 10 d in vitro hyaluronidase treatment (n = 3) and had a refractive index of 1.337 ± 0.000 (n = 3). Surface tension was measured to be between 37 ± 3 and 56 ± 4 mN/m (n = 3). The density was measured to be between 1.014 ± 0.012 and 1.017 ± 0.007 g/mL (n = 4). The refractive index, surface tension, and density are much closer to that of the native vitreous compared to a silicone oil control.

Conclusions : Our novel hydrogel vitreous substitute is injectable, biodegradable, low swelling, and possesses similar physical properties to the native vitreous including transparency, refractive index, and density. These results combined with previously reported in vivo biocompatibility studies demonstrate that our novel hydrogel is a promising candidate as a vitreous substitute for vitreoretinal surgery.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.