G.J.C. Braithwaite, M. Xheka
Cambridge Polymer Group, Inc.,
United States
Keywords: hydrogel, degradable, biomedical, tamponade, ocular, chromatography
Summary:
The retina is a delicate tissue in the back of the eye that converts the light to signals and transmits these signals to the brain. To function properly, it must be well-attached to the back of the eye. In a young adult, the bulk of the eye is filled with the vitreous humor, a collagenous hydrogel composed of 98-99% water that is completely transparent and transmits light to the retina from the lens. In some cases, the retina can detach from the eye, which results in serious vision issues. If caught early enough, this detachment can generally be treated successfully, but the treatment has weaknesses. Repair of the retina is relatively simple, involving reattaching the retina using a variation of techniques. This reattachment must be supported as the repair heals, generally through the use of a “tamponade”, a material that pushes against the retina to hold it in place as it heals. Today, both gases and liquids are used. However, both have weaknesses, because of their poor density and refractive index match with the physiological fluids, requiring substantial patient behavior modification during the healing process, or because they need removal upon healing. The ideal supports the healing process without requiring the patient to modify their behavior, and then safely degrades and is replaced by the body’s natural fluid turnover after the retina has healed. Here we describe the development of poly(vinyl alcohol)-based hydrogel (“Thiogel”) funded with an NIH SBIR grant (2R44EY027635-02A1). This hydrogel is refractive index-matched, has a tunable swelling pressure, and has an adjustable short-term degradation of the order of weeks. Click chemistry is utilized to avoid toxic biproducts and reaction exotherms. We present data from a pilot rabbit study (New Zealand White (NZW) Rabbits) designed to examine safety and degradation kinetics of the material in vivo. Animals received a vitrectomy using a conventional three port vitrectomy with either the Thiogel tamponade or an air tamponade (control) in the right eye while the left eye was left as the non-surgical control. Full ophthalmic exams, gross ocular exams, Intraocular pressure (IOP), and fundus images were performed to document the response at timepoints out to 8 weeks. Both test and controls exhibited expected intraocular pressure (IOP) reductions immediately following surgery, with the IOP levels returning close to baseline by 3 weeks and thereafter statistically similar. We also discuss a chromatographic assay to track the constituents of the hydrogel within the tissue and allow validation of the degradation and clearance kinetics from the eye. This assay involves extraction, digestion and separation of the tissue to isolate the hydrogel components and proves almost complete clearance by 28 days. The conclusion of the study is validation of the potential of this material, and that it meets the design requirements, mimicking the properties of the native vitreous for long enough to allow healing to occur.