Using UV-Responsive Nanoparticles to Provide In Situ Control of Growth Factor Delivery and a More Constant Release Profile from a Hydrogel Environment

Abstract

Nanoparticles are popular delivery vehicles, but their diffusional release results in inconstant drug delivery. Here, we flatten the delivery profile into a more constant, zero-order profile. Brain-derived neurotrophic factor (BDNF) is attached to photoactive titanium dioxide nanoparticles and loaded into a nanofibrous self-assembling peptide (SAP) hydrogel. Different UV exposure conditions show three distinct profiles, including a counterintuitive decrease in release after UV exposure. We propose that the adsorption of the freed growth factor onto the hydrogel nanofibers affects release. Nanoparticles diffuse from the hydrogel readily, carrying the bound growth factor, but the freed growth factor (released from the nanoparticles by UV) instead interacts withand is released less readily fromthe hydrogel. UV shifts growth factor from nanoparticles to the hydrogel, therefore changing the diffusional release. Through midpoint UV exposure, we achieve a flattened delivery profileunusual for diffusionby changing in situ the amount of growth factor bound to the diffusing nanoparticles. With nanoparticle diffusion alone, we observed an increasing release profile with 36% of release in the first 6 h and 64% in the second 6 h. With midway UV exposure, this was controlled to 49 and 51%, respectively. The release of an unbound (soluble) control growth factor, glial cell-line derived neurotrophic factor (GDNF), was not affected by UV treatment, demonstrating the potential for independent control of temporal delivery profiles in a multiagent material.

Hydrogel‐Based Growth Factor Delivery Platforms: Strategies and Recent Advances

“…In growth factor delivery hydrogels, light-controlled growth factor release can be achieved using various photosensitive chemicals. [23,24,51,306] Siebert et al achieved light-responsive growth factor release by constructing a wound patch based on a tetrapod-shaped ZnO particle (t-ZnO)-embedded GelMA hydrogel (Figure 12a). [23] The surface of t-ZnO was oxidized to ZnO 2 using H 2 O 2 and coated with VEGF to realize light-responsive VEGF release.…”

Simple Complexity: Incorporating Bioinspired Delivery Machinery within Self-Assembled Peptide Biogels

“…These drugs must be presented at a specific concentration, time and place; typically determined by the biological needs of the therapeutic or regenerative process. This presentation must ensure that the therapeutic payload is both protected from the biological environment that may degrade it, administered in a dose-dependent, safe manner [ 10 ] to minimize off-target effects, and be co-located to the site of therapeutic need [ 11 ]. Numerous strategies have been developed to achieve this, from simple injection [ 12 ], through to biologically stimulated release [ 13 ].…”

“…Cyclic peptides are able to form rigid nanotubes via hydrogen bonding and allow the molecules to present a variety of orientations that are not available in linear peptides [ 33 ]. They have been shown to have several favorable properties, such as strong binding affinity, target selectivity and low toxicity, which make them an attractive modality for the development of therapeutics [ 9 ] and nanoparticles [ 10 ]. The vast majority of clinically-approved cyclic peptides are derived from natural products [ 34 ].…”

Substance P‐Derived Extracellular‐Matrix‐Mimicking Peptide Hydrogel as a Cytocompatible Biomaterial Platform

“…However, due to the leaching effect, the use of cytotoxic solvents for hydrogelation, and the simultaneous oxidation of Fmoc functionality, such N-terminally Fmocfunctionalized peptides have some controversial harmful consequences. [48] Despite of all these finding several recent cytocompatible peptide based supramolecular assemblies reported by Nishbet et al were established with the incorporation of Fmoc in their sequences [49][50][51][52] .…”