Engineering injectable synthetic ECM-based hydrogel as vehicles for retinal progenitor cells transplantation

Statement of Purpose: Photoreceptor loss and damage in retinal degenerative diseases, like Age-related macular degeneration (AMD) results in visual impairment. Retinal cells implanted into the subretinal space have been shown to integrate within host retina, improving visual function in models of retinal degeneration¹. One barrier to the clinical success of extremely promising cell delivery treatments is loss, through efflux and death, of the majority (>99%) of implanted cells². Recent studies have demonstrated that delivery of retinal progenitor cells (RPCs) using polymer scaffolds results in improved cell survival with associated increases in RPC integration^3-4. However, current polymer scaffolds still result in extremely limited overall integration (<2%). Decellularized extracellular matrix (ECM) has been utilized as a scaffold material with considerable success⁵. It is known that ECM provides cells with specific physical and chemical cues that drive cell behavior. Still, the major shortcomings of native ECM include compositional variation from lot to lot and undefined composition. Unlike naturally derived ECM-based biomaterials, synthetic ECMs are more favorable in terms of mechanical properties, tenability and reproducibility, since their physicochemical properties can be easily controlled. We investigated an inert hydrogel system (alginate) with retinal ECM-based components, specifically the glycosaminoglycans (GAGs): hyaluronic acid (HA) and chondroitin sulphate (CS) as a cell delivery platform to treat retinal degenerative diseases.