Year 3

Cell replacement therapies (CRTs) have considerable promise for addressing unmet medical needs, including incurable neurodegerative diseases. However, several bottlenecks hinder CRTs, especially the needs for improved cell manufacturing processes and enhanced cell survival and integration after implantation. Engineering synthetic biomaterials that present biological signals to support cell expansion, differentiation, survival, and/or integration can help overcome these bottlenecks. We had previously generated successful synthetic biomaterial platforms for the long-term expansion of human pluripotent stem cells (hPSCs) at large scale, efficient differentiation of hPSCs into dopaminergic progenitors and neurons for treating Parkinson’s Disease, and modulation of stem cell function to promote neuronal differentiation within the brain. Here, we have substantially advanced this work by further engineering this biomaterial system for scalable hPSC differentiation into dopaminergic neurons, then by engineering a second biomaterial system as a biocompatible delivery vehicle to enhance the survival and engraftment of dopaminergic in an animal model of Parkinson’s disease, leading to substantial behavioral recovery. In addition, we made progress in adapting the biomaterial manufacturing platform for generation of photoreceptor neurons, with implications for retinitis pigmentosa (RP). These modular, tunable platforms will have broad implications PD, RP, and other cell replacement therapies to treat human disease.