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Central to ocular health is the vitreous body, a complex, gelatinous tissue filling the space between the lens and retina. It is a natural polymeric hydrogel whose delicate architecture of collagen and hyaluronic acid loses its mechanical structure under the influence of degeneration or destruction, leaving the retina vulnerable to injury and disease. Since World War II, combat ocular trauma has increased six-fold while the population of aging veterans continues to grow in tandem. Compared to injuries in the civilian sector, injuries in theaters of combat operations are sustained in dirty, dusty, high-stress environments under hostile fire. These penetrating and perforating ocular injuries have predicable consequences, cascading into scarring on or under the retina (known as proliferative vitreoretinopathy or PVR). The growing population of aging veterans also faces a multitude of vitreous-related and vision-threatening pathologies. Current standards of care call for the removal and replacement of the vitreous, but contemporary substitutes are ill suited for long-term use. As such, there is critical need for development of a successful, long-term vitreous substitute. A biomimetic in situ forming hydrogel has been developed that utilizes a reversible disulfide cross-linker, enabling easy injection into the vitreous cavity. Recently, a copolymer has been introduced with this new formulation that possesses a unique comb-like structure whose characteristic bristles inhibit protein adsorption and cellular adherence, perfectly suited for the inhibition of PVR. The objective of this dissertation was to evaluate select formulations of this unique in situ forming hydrogel as potential vitreous substitutes. This was accomplished through rigorous in vivo rabbit modeled testing of long-term biocompatibility and bioperformance utilizing electroretinography, clinical examination, and histopathological assessment. We hypothesized that the in situ forming hydrogels would serve as a substantial improvement over the current gold standard, silicone oil, in terms of biocompatibility and the ability to inhibit PVR. / Bioengineering