Improved control over spatiotemporal delivery of growth factors is needed to enhance tissue repair. Current methods are limited-requiring invasive procedures, poor tissue targeting, and/or limited control over dosage and duration. Incorporation into implantable biomaterials enables stabilized delivery and avoids burst release/fluctuating doses. Here, the physical forces of fibrils formed by self-assembly of epitope-containing peptides are exploited. This biomimetic hydrogel is loaded with neurotrophic factor BDNF via a shear-induced gel-solution transition, unique to noncovalent hydrogels. This results in a biomaterial with three desirable features: a nanofibrillar scaffold, presentation of a laminin epitope, and slow release of BDNF. In a stroke-injury model, synergistic actions of this trimodal strategy on the integration of transplanted human neural progenitor cells, and protection of peri-infarct tissue are identified. These BDNF-functionalized hydrogels promote the integration of transplanted human embryonic stem cell-derived neural progenitors-resulting in larger grafts with greater cortical differentiation, appropriate for neuronal replacement. Furthermore, BDNF promotes the infiltration of host endothelial cells into the graft to augment vascularization of the graft, and adjacent penumbra tissue. These findings demonstrate the benefits of multifaceted tissue-specific hydrogels to provide biomimetics of the host tissue, while sustain protein delivery, to promote endogenous and graft-derived tissue repair. Self-Assembling PeptidesThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.
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 172 hr after gel loading. This represents a significant advance in drug delivery, because its lifetime in phosphate buffered saline was less than 1 hr. 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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