In-situ forming PEG-engineering hydrogels with anti-fouling characteristics as an artificial vitreous body

Abstract

Endotamponade is in huge demand for vitrectomy, while current vitreous substitutes exhibit instability and foreign body reactions that impede long-term implantation. Herein, we report an in-situ forming hydrogel (PEGBAA) with prominent stability and anti-fouling properties as a long-term vitreous substitute consisting of two main components: functional-modified multi-arm poly(ethylene glycol) (8sPEG-SH/Mal) and zwitterionic poly(carboxybetaine) (pCBAA). The former is bioinert to provide long-term stability via the thiol-ene Michael addition reaction. The latter possesses anti-fouling characteristics to prevent adsorption of protein and cells due to its strong hydrophilicity. The PEGBAA hydrogel formed fast in situ exhibits reduced protein adsorption and cell adhesion compared to pure PEG-based hydrogels, good in vitro biocompatibility, and very similar critical parameters (i.e., light transmittance, refractive index, water content, modulus, high stability) to the natural vitreous humor. After a 180-day implantation through injection with a double syringe via standard vitrectomy procedures in rabbit models, the hydrogels acts as a very stable vitreous substitute without abnormal complications. Therefore, the strategy of in-situ forming hydrogels with anti-fouling properties offers a new avenue to improve the in vivo stability of long-term vitreous endotamponades.