Journal
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
Volume 12, Issue 3, Pages E1571-E1579Publisher
WILEY
DOI: 10.1002/term.2582
Keywords
biomaterials; cell transplantation; drug delivery; GDNF; Parkinson's disease; self-assembling peptide; tissue engineering
Categories
Funding
- National Health and Medical Research Council [GNT1135657]
- Victorian Government's Operational Infrastructure Support Grant
- NHMRC Dementia Research Leadership Fellowship [GNT1135657]
- Senior Medical Research Fellowship
- Alfred Deakin Research Fellowship
- Australian Research Council [DP130103131]
- Australian Microscopy and Microanalysis Research Facility (AMMRF)
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Neurotrophic growth factors are effective in slowing progressive degeneration and/or promoting neural repair through the support of residual host and/or transplanted neurons. However, limitations including short half-life and enzyme susceptibility of growth factors highlight the need for alternative strategies to prolong localised delivery at a site of injury. Here, we establish the utility of minimalist N-fluorenylmethyloxycarbonyl (Fmoc) self-assembling peptides (SAPs) as growth factor delivery vehicle, targeted at supporting neural transplants in an animal model of Parkinson's disease. The neural tissue-specific SAP, Fmoc-DIKVAV, demonstrated sustained release of glial cell line derived neurotrophic factor, up to 172hr after gel loading. This represents a significant advance in drug delivery, because its lifetime in phosphate buffered saline was less than 1hr. In vivo transplantation of neural progenitor cells, together with our growth factor-loaded material, into the injured brain improved graft survival compared with cell transplants alone. We show for the first time the use of minimalist Fmoc-SAP in an in vivo disease model for sustaining the delivery of neurotrophic growth factors, facilitating their spatial and temporal delivery in vivo, whilst also providing an enhanced niche environment for transplanted cells.
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