title: Mixed α/β-Peptides as a Class of Short Amphipathic Peptide Hydrogelators with Enhanced Proteolytic Stability.
abstract: Peptide hydrogels are a highly promising class of materials for biomedical application, albeit facing many challenges with regard to stability and tunability. Here, we report a new class of amphipathic peptide hydrogelators, namely mixed α/β-peptide hydrogelators. These mixed α/β-gelators possess good rheological properties (high storage moduli) and form transparent self-supporting gels with shear-thinning behavior. Infrared spectroscopy indicates the presence of β-sheets as the underlying secondary structure. Interestingly, self-assembled nanofibers of the mixed α/β-peptides display unique structural morphologies with alteration of the C-terminus (acid vs amide) playing a key role in the fiber formation and gelation properties of the resulting hydrogels. The incorporation of β3-homoamino acid residues within the mixed α/β-peptide gelators led to an increase in proteolytic stability of the peptides under nongelating conditions (in solution) as well as gelating conditions (as hydrogel). Under diluted conditions, degradation of mixed α/β-peptides in the presence of elastase was slowed down 120-fold compared to that of an α-peptide, thereby demonstrating beneficial enzymatic resistance for hydrogel applications in vivo. In addition, increased half-life values were obtained for the mixed α/β-peptides in human blood plasma, as compared to corresponding α-peptides. It was also found that the mixed α/β-peptides were amenable to injection via needles used for subcutaneous administrations. The preformed peptide gels could be sheared upon injection and were found to quickly reform to a state close to that of the original hydrogel. The shown properties of enhanced proteolytic stability and injectability hold great promise for the use of these novel mixed α/β-peptide hydrogels for applications in the areas of tissue engineering and drug delivery.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Mangelschots
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bibian
authors.affiliation: CSIRO Manufacturing Flagship, Bayview Avenue, Clayton, VIC 3169, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Gardiner
authors.affiliation: CSIRO Manufacturing Flagship, Bayview Avenue, Clayton, VIC 3169, Australia.
authors.forename: Lynne
authors.initials: L
authors.lastname: Waddington
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel , Laarbeeklaan 103, B-1090 Brussels, Belgium.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Van Wanseele
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussel , Laarbeeklaan 103, B-1090 Brussels, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Van Eeckhaut
authors.forename: Maria M Diaz
authors.initials: MM
authors.lastname: Acevedo
authors.forename: Bruno
authors.initials: B
authors.lastname: Van Mele
authors.forename: Annemieke
authors.initials: A
authors.lastname: Madder
authors.forename: Richard
authors.initials: R
authors.lastname: Hoogenboom
authors.forename: Steven
authors.initials: S
authors.lastname: Ballet
mesh_terms: D000595:Amino Acid Sequence; D006207:Half-Life; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D009842:Oligopeptides / Q000737:chemistry*; D010196:Pancreatic Elastase / Q000737:chemistry; D058105:Polymerization; D017433:Protein Structure, Secondary; D059748:Proteolysis
chemical_list: D020100:Hydrogels; D009842:Oligopeptides; D010196:Pancreatic Elastase