Self-Assembling Multidomain Peptide Nanofibers for Delivery of Bioactive Molecules and Tissue Regeneration

dc.citation.firstpage714
dc.citation.issueNumber4
dc.citation.journalTitleAccounts of Chemical Research
dc.citation.lastpage722
dc.citation.volumeNumber50
dc.contributor.authorMoore, Amanda N.
dc.contributor.authorHartgerink, Jeffrey D.
dc.date.accessioned2017-07-14T15:23:43Z
dc.date.available2017-07-14T15:23:43Z
dc.date.issued2017
dc.description.abstractMultidomain peptides (MDPs) are a class of self-assembling peptides that are organized in a β-sheet motif, resulting in a nanofibrous architecture. This structure is stabilized by hydrophobic packing in the fiber core and a hydrogen-bonding network down the fiber long axis. Under easily controllable conditions, regulated by electrostatic interactions between the peptides and the pH and salt composition of the solvent, the nanofiber length can be dramatically extended, resulting in fiber entanglement and hydrogel formation. One of the chief strengths of this supramolecular material is that the design criteria governing its structure and assembly are robust and permit a wide range of modifications without disruption. This allows the MDPs to be tailored to suit a wide range of applications, particularly in biomedical engineering. For example, delivery of small molecules, proteins, and cells is easily achievable. These materials can be trapped within the matrices of the hydrogel or trapped within the hydrophobic core of the nanofiber, depending on the cargo and the design of the MDP. Interactions between the nanofibers and their cargo can be tailored to alter the release profile, and in the most sophisticated cases, different cargos can be released in a cascading time-dependent fashion. The MDP hydrogel and its cargo can be targeted to specific locations, as the thixotropic nature of the hydrogel allows it to be easily aspirated into a syringe and then delivered from a narrow-bore needle. The sequence of amino acids making up the MDP can also be modified to permit cross-linking or enzymatic degradation. Selection of sequences with or without these modifications allows one to control the rate of degradation in vivo from as rapidly as 1 week to well over 6 weeks as the MDP nanofibers are degraded to their amino acid components. MDP sequences can also be modified to add biomimetic sequences derived from growth factors and other signaling proteins. These chemical signals are displayed at a very high density on the fibers’ surface, where they contribute to the modification of cellular behavior. We have used this approach to drive blood vessel formation, which is critical for tissue regeneration generally and more specifically for the treatment of diseases related to poor blood flow. MDPs represent an ideal case of bottom-up design where control of chemical structure leads to control of self-assembly and nanostructure and thereby control of material properties that collectively can control biological function.
dc.identifier.citationMoore, Amanda N. and Hartgerink, Jeffrey D.. "Self-Assembling Multidomain Peptide Nanofibers for Delivery of Bioactive Molecules and Tissue Regeneration." <i>Accounts of Chemical Research,</i> 50, no. 4 (2017) American Chemical Society and American Chemical Society: 714-722. https://doi.org/10.1021/acs.accounts.6b00553.
dc.identifier.digitalacs.accounts.6b00553
dc.identifier.doihttps://doi.org/10.1021/acs.accounts.6b00553
dc.identifier.urihttps://hdl.handle.net/1911/95194
dc.language.isoeng
dc.publisherAmerican Chemical Society
dc.publisherAmerican Chemical Society
dc.rightsThis is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes
dc.rights.urihttp://pubs.acs.org/page/policy/authorchoice_termsofuse.html
dc.titleSelf-Assembling Multidomain Peptide Nanofibers for Delivery of Bioactive Molecules and Tissue Regeneration
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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