A reversible thermoresponsive sealant for temporary closure of ocular trauma

Abstract

Open globe injuries are full-thickness injuries sustained to the eye wall (cornea or sclera), which cause immediate drops in intraocular pressure that may lead to retinal detachment and permanent vision loss if not treated rapidly after injury. The current standard of care for open globe injuries consists of suturing the margins closed, but the technique can be time-consuming, requires specialized training and equipment, and can lead to patient discomfort, abrasion, and infection from eye rubbing. We engineered an injectable, thermoresponsive sealant (TRS) and a custom tool to occlude open globe injuries. The smart hydrogel sealant consists of physically cross-linked -isopropylacrylamide copolymerized with butylacrylate. At low temperatures, it can be injected as a liquid, and when raised to body temperature, a heat-induced gelation converts the hydrogel into a solidified occlusion. The sealant can be repositioned or removed without causing additional trauma via exposure to cold water. In vitro and ex vivo assessments of mechanical adhesion to eye tissue revealed maintenance of intraocular pressure that is five times greater than the physiological range with reversible seal strength comparable to cyanoacrylate (super glue). In vivo assessment in a rabbit model of ocular trauma demonstrated ease of use for TRS deployment, statistically significant improvement in wound sealing, and no evidence of neurotoxicity, retinal tissue degradation, or significant chronic inflammatory response after 30 days of exposure. Given the advantages of body heat-induced gelation, rapid reversible occlusion, and in vivo safety and efficacy, shape-adaptable TRSs have translational potential as smart wound sealants for temporary occlusion of surgical incisions or traumatic injuries.

Inside-Out 3D Reversible Ion-Triggered Shape-Morphing Hydrogels

“…Hydrogels are a class of three-dimensional (3D) networks formed by hydrophilic polymer chains embedded in a water-abundant environment, which can swell and shrink in response to certain stimuli, for example, light, pH, temperature, biochemical processes, and electric and magnetic fields. With the abilities to change their volumes sizably and reversibly, together with structures and functionalities comparable to biological systems, hydrogels favor competent applications in traumatic injuries, tissue engineering, and biosensors [13][14][15][16][17].…”

Reversible Bioadhesives Using Tannic Acid Primed Thermally‐Responsive Polymers

“…In contrast, the TAPTRA patch withstood a much higher pressure at an environmental temperature of 32–35 °C. Leakage from the incision was only observed at pressures of 44–45 mmHg, which is far beyond the normal IOP ranges in 12–22 mmHg . Rinsing with cold water quickly transformed the gel to a transparent state with a compromised cohesive strength, causing leakage at a much lower pressure (≈12 mmHg on both the cornea and sclera tissues).…”

Safety and Biocompatibility of Aflibercept-Loaded Microsphere Thermo-Responsive Hydrogel Drug Delivery System in a Nonhuman Primate Model

“… 50 – 52 Reversible thermo-responsive sealants have been applied for temporary closure of surgical incisions or traumatic injuries of the sclera and cornea. 53 Moreover, intrascleral delivery of in situ thermo-responsive implants have been tested with a microneedle injection system. 54 However, most currently available IVT devices are in solid form.…”