An in situ-forming polyzwitterion hydrogel: Towards vitreous substitute application

Abstract

Development of a biostable and biosafe vitreous substitute is highly desirable, but remains a grand challenge. Herein, we propose a novel strategy for constructing a readily administered vitreous substitute based on a thiol-acrylate clickable polyzwitterion macromonomer. A biocompatible multivinyl polycarboxybetaine (PCB-OAA) macromonomer is designed and synthesized, and mixed with dithiothreitol (DTT) via a Michael addition reaction to form a hydrogel in vitreous cavity. This resultant PCB-OAA hydrogel exhibits controllable gelation time, super anti-fouling ability against proteins and cells, excellent biocompatibility, and approximate key parameters to human vitreous body including equilibrium water content, density, optical properties, modulus. Remarkably, outperforming clinically used silicone oil in biocompatibility, this rapidly formed hydrogel in the vitreous cavity of rabbit eyes remains stable in vitreous cavity, showing an appealing ability to prevent significantly inflammatory response, fibrosis and complications such as raised intraocular pressure (IOP), and cataract formation. This zwitterionic polymer hydrogel holds great potential as a vitreous substitute.

Recent developments of temperature‐responsive polymers for ophthalmic applications

“…Moving towards click chemistry, He et al engineered a vitreous substitute from multivinyl polycarboxybetaine (PCB‐OAA) and dithiothreitol (DTT) based on a thiol‐acrylate click reaction 87 . The zwitterionic PCB‐OAA gave the hydrogel anti‐fouling ability; it was resistant to non‐specific protein adsorption and cell attachment.…”

“…Moving towards click chemistry, He et al engineered a vitreous substitute from multivinyl polycarboxybetaine (PCB-OAA) and dithiothreitol (DTT) based on a thiolacrylate click reaction. 87 The zwitterionic PCB-OAA gave the hydrogel anti-fouling ability; it was resistant to nonspecific protein adsorption and cell attachment. Further, a stable polyzwitterionic gel could be formed in situ rapidly upon injection of the precursor solutions via multiple crosslinks and monosulfide bonds.…”

“…The abovementioned hydrogels for vitreous replacement [86][87][88] have been investigated for their swelling behavior because swelling can exert pressure on the surrounding tissues. A low polymer concentration can reduce swelling but will require hours to gelate, which is undesirable for clinical applications.…”

Engineering Injectable Anti‐Inflammatory Hydrogels to Treat Acute Myocardial Infarction

“…To overcome these limitations and achieve potent therapeutic effects, hydrogels composed of 3D polymeric networks with an ECM-like structure and viscoelasticity can be used as an ideal matrix to locate and deliver drug molecules. [28][29][30] With the advancement of material technology, a large number of hydrogels composed of synthetic or natural polymers have been developed as carriers for the delivery of various signaling molecules. [31][32][33] By combining pharmaceutical or nanopreparations, predesignable hydrogels can be easily implanted or injected directly into the target site to allow locally controlled drug release, thereby avoiding systemic side effects caused by intravenous drug administration.…”

Antibacterial self-fused supramolecular polymer hydrogel for infected wound healing

“…Herein, we presented a self-fused supramolecular hydrogel made by N-acryloyl glycinamide (NAGA) and antimicrobial peptide Polymyxin E with good biocompatibility and antibacterial and anti-inflammatory properties for infected wound healing, as shown in figure 1. NAGA is a kind of small molecule that has a bisamide structure [18,19]. When NAGA was polymerized and formed PNAGA by chemical crosslinking, the bisamide structure among the side chains could form a hydrogen bond and thus caused the physical crosslinking and formed the supramolecular hydrogel.…”