A highly transparent tri-polymer complex in situ hydrogel of HA, collagen and four-arm-PEG as potential vitreous substitute

Abstract

There is a requirement of removal and replacement of vitreous for various ophthalmic diseases, e.g. retinopathy and retinal detachment. Clinical tamponades, e.g. silicone oil and fluorinated gases are used but limited due to their toxicity and some complications. A lot of polymer-based materials have been tested and proposed as vitreous substitute, but till date, there is no ideal vitreous substitute available. Thus, it requires to develop an improved vitreous substitute which will be highly suitable for vitreous replacement. We have developed tri-polymer complex in situ hydrogels by crosslinking among hyaluronic acid (HA), collagen (Coll) and four-arm-polyethylene glycol (PEG). All the developed hydrogels are biocompatible with NIH 3T3 mouse fibroblast cells, having pH in the range 7-7.44 and refractive index in the range 1.333-1.345. The developed hydrogels are highly transparent, showing transmittance >97%. FTIR study shows that the hydrogel was crosslinked by amide bond formation between HA and PEG, and between Coll and PEG. The rheological study shows that all the developed hydrogels exhibit viscoelastic behavior and all the hydrogels have storage modulus values (>100 pa) which is greater than loss modulus values-indicating sufficient elasticity for vitreous application. The elastic nature of the hydrogel increases with the increase in PEG concentration. The gel is formed in between 2 and 3 min-indicating its application in situ. The viscosity of the developed hydrogels shows shear thinning behavior. The pre-gel solution of the hydrogel is injectable through a 22 G needle-indicating its application in situ through vitrectomy surgery. All the hydrogels are hydrophilic and have water content of 96% approximately. Thus, the results show the positive properties for its application as a potential vitreous substitute.