Tissue Programmed Hydrogels Functionalized with GDNF Improve Human Neural Grafts in Parkinson's Disease

The survival and synaptic integration of transplanted dopaminergic (DA) progenitors are essential for ameliorating motor symptoms in Parkinson's disease (PD). Human pluripotent stem cell (hPSC)-derived DA are, however, exposed to numerous stressors prior to, during, implantation that result poor survival. Additionally, hPSC-derived grafts show inferior plasticity compared fetal tissue grafts. These observations suggest a more conducive host environment may improve graft outcomes. Here, tissue-specific support progenitor is provided with fully characterized self-assembling peptide hydrogel. This biomimetic hydrogel matrix programmed by i) including laminin epitope within the matrix; ii) shear encapsulating glial line-derived neurotrophic factor (GDNF) ensure its sustained delivery. biocompatible biased 51% increase A9 neuron specification—a subpopulation neurons critical function. delivery GDNF induced 2.7-fold enhanced plasticity, resulting significant improvements deficits at 6 months. findings highlight therapeutic benefit stepwise customization hydrogels physical trophic human PSC-derived neural transplants, improved standardization, predictability functional efficacy PD.