Yanbin Huang

Evaluation of an in situ chemically crosslinked hydrogel as a long-term vitreous substitute material

Currently there is no material that can be used as a long-term vitreous substitute, and this remains an unmet clinical need in ophthalmology. In this study, we developed an injectable, in situ chemically crosslinked hydrogel system and evaluated it in a rabbit model. The system consisted of two components, both based on multi-functional poly(ethylene glycol) (PEG) but with complementarily reactive end groups of thiol and active vinyl groups, respectively. The two components are mixed and injected as a solution mixture, react in vivo via the Michael addition route and form a chemically crosslinked hydrogel in situ. The linkages between the end groups and the backbone PEG chains are specially designed to ensure that the final network structure is hydrolysis-resistant. In the rabbit study and with an optimized operation protocol, we demonstrated that the hydrogel indeed formed in situ after injection, and remained transparent and stable during the study period of 9 months without significant adverse reactions. In addition, the hydrogel formed in situ showed rheological properties very similar to the natural vitreous. Therefore, our study demonstrated that this in situ chemically crosslinked PEG gel system is suitable as a potential long-term vitreous substitute.

An in situ-forming zwitterionic hydrogel as vitreous substitute

Zwitterionic polymers have shown ultra-low biofouling properties at surfaces and excellent biocompatibility as implant. In this study, an in situ-forming zwitterionic hydrogel was designed and evaluated, both in vitro and in vivo, as a long-term vitreous substitute. The zwitterionic polymer poly(MPDSA-co-AC) was designed as a copolymer of the sulfobetaine methacrylamide and acryloyl cystamine monomers, providing the zwitterionic components and the thiol functional groups, respectively. The in situ gelation was via the thiol-ene Michael addition reaction with α-PEG-MA as the crosslinker. The gelation time, rheological properties, swelling profiles, and the transparency of zwitterionic hydrogels were studied in detail. Two systems with different crosslinker concentrations were tested in a rabbit model, and the one with the thiol-ene ratio of 2u2009:u20091 showed excellent biocompatibility in vivo, formed space-filling hydrogels and remained transparent in the vitreous cavity for the 2 month implantation period. Therefore, in situ-forming zwitterionic hydrogels represent a promising material system as a vitreous substitute and possibly for other soft tissue replacements.

A method to accelerate the gelation of disulfide-crosslinked hydrogels

A glutathione-disulfide-ended poly(ethylene glycol) (GSSG-PEG-GSSG) was designed. It is a much more efficient accelerator than glutathione disulfide (GSSG) for the gelation of an 8arm-PEG-SH polymer solution, and the gelation time can be tuned from hours to minutes at the physiological pH and temperature. A mechanism was proposed to explain the different behaviors of the GSSG and GSSG-PEG-GSSG gelation systems. Due to the ever-going thiol-disulfide exchange reaction, the thiol-disulfide hydrogels also showed interesting swelling behavior.

Disulfide-crosslinked albumin hydrogels

With its clinically-demonstrated safety profile and huge potential for functionalization, albumin should be an ideal biomaterial. In this study, we obtained disulfide-crosslinked albumin hydrogels using the proteins own thiol groups. In the water solutions with denaturants such as urea and guanidinium, the disulfide-crosslinked albumin hydrogels showed a normal swelling profile. However, in water solutions without denaturants, the same hydrogels showed erosion behavior similar to the physical gels. We explained these rich swelling behaviors by proposing that an inter-to-intramolecular disulfide exchange occurred in the eroding hydrogel. The albumin hydrogels are injectable through narrow needles and a doxorubicin-releasing study was used to demonstrate their potential applications.