Engineering an Injectable and Tunable Hydrogel as a Potential Vitreous Substitute

Abstract

Retinal detachment, proliferative diabetic retinopathy, and ocular trauma are major causes of blindness, and their treatment often relies on intraocular endotamponades following vitrectomy. However, many existing endotamponades tend to disperse or fragment during injection, making it difficult to form a stable structure within the vitreous cavity and thereby severely limiting their functional performance and clinical applicability. Consequently, the development of injectable endotamponades with precisely controlled viscosity and in situ gelation remains a critical challenge. In this study, we present an injectable polyethylene glycol (PEG) hydrogel incorporating highmolecular-weight hyaluronic acid (HA), designed to mimic key physicochemical features of the human vitreous. The hydrogel forms a three-dimensional network via covalent crosslinking between eight-arm PEG-thiol (8sPEG-SH) and eight-arm PEGmaleimide (8sPEG-MAL), while the incorporation of high-molecular-weight HA enables precise viscosity regulation and imparts vitreous-like mechanical properties.The hydrogel exhibits a storage modulus of 8-15 Pa and an adjustable in situ gelation time of approximately 3 minutes, together with excellent optical transparency, appropriate surface tension, and a low swelling ratio. In vivo studies in rabbit eyes further demonstrate that the hydrogel can be smoothly injected and subsequently form a stable structure within the vitreous cavity, confirming its practical operability for intraocular application. Notably, this work introduces a tunable PEG hydrogel system with controllable in situ gelation enabled by a double-chamber syringe, providing a new strategy for the development of long-term stable vitreous substitutes.