- Title
- Tissue programmed hydrogels functionalized with GDNF improve human neural grafts in Parkinson's disease
- Creator
- Hunt, Cameron; Penna, Vanessa; Gantner, Carlos; Moriarty, Niamh; Long, Benjamin
- Date
- 2021
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/179111
- Identifier
- vital:15506
- Identifier
-
https://doi.org/10.1002/adfm.202105301
- Identifier
- ISBN:1616-301X (ISSN)
- Abstract
- 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 progenitors are, however, exposed to numerous stressors prior to, and during, implantation that result in poor survival. Additionally, hPSC-derived grafts show inferior plasticity compared to fetal tissue grafts. These observations suggest that a more conducive host environment may improve graft outcomes. Here, tissue-specific support to DA progenitor grafts is provided with a fully characterized self-assembling peptide hydrogel. This biomimetic hydrogel matrix is programmed to support DA progenitors by i) including a laminin epitope within the matrix; and ii) shear encapsulating glial cell line-derived neurotrophic factor (GDNF) to ensure its sustained delivery. The biocompatible hydrogel biased a 51% increase in A9 neuron specification—a subpopulation of DA neurons critical for motor function. The sustained delivery of GDNF induced a 2.7-fold increase in DA neurons and enhanced graft plasticity, resulting in significant improvements in motor deficits at 6 months. These findings highlight the therapeutic benefit of stepwise customization of tissue-specific hydrogels to improve the physical and trophic support of human PSC-derived neural transplants, resulting in improved standardization, predictability and functional efficacy of grafts for PD. © 2021 Wiley-VCH GmbH. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Benjamin Long” is provided in this record**
- Publisher
- John Wiley and Sons Inc
- Relation
- Advanced Functional Materials Vol. 31, no. 47 (2021), p.
- Rights
- All metadata describing materials held in, or linked to, the repository is freely available under a CC0 licence
- Rights
- Copyright 2021 Wiley-VCH GmbH
- Subject
- 02 Physical Sciences; 03 Chemical Sciences; 09 Engineering; Biomaterials; Dopamine; Glial cell line-derived neurotrophic factor; Hydrogels; Laminin; Parkinson's disease; Self-assembling peptides; Stem cells; Transplantation
- Reviewed
- Funder
- Biochemical and Transcriptional Profiling Confirms Enhanced Functionality and Maturity of Grafts Supported by GDNF‐Functionalized Scaffolds
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