(651d) Peptide-Amphiphile Hydrogels Formed by Mechanical Shear for Use As Injectable Tissue Engineering Matrices

Shear induced, self assembly has been extensively studied using model surfactant systems which form long extended micelles at a critical shear rate.  These polymer based extended micelles are able to entangle, giving the system viscoelastic properties.  Here we present a peptide amphiphile, a short peptide sequence attached to a fatty acid tail, which transforms into extended worm-like micelles under shear force.  Peptide amphiphiles are easily synthesized and modular in design, allowing a range of bioactive peptides to be introduced into the system.  The particular peptide sequence used in this study is alanine (A) rich with interspersed lysine (K) residues, which gives it a strongly alpha helical secondary structure. The peptide amphiphile initially forms spherical micelles in aqueous solution and then undergoes a switch to form long cylindrical micelles when the correct shear force is applied. The cylindrical micelles entangle and create a gel with viscoelastic mechanical properties. The physical transition from spherical to worm-like micelle coincides with a secondary structure transition from alpha helix to beta sheet which is monitored using circular dichroism.  As in the surfactant system, our peptide amphiphile solution initially behaves as a Newtonian fluid and then transitions to a shear thinning gel once a critical shear rate is surpassed.  The resulting gel is self healing, and stable at 4°C on the order of weeks to months.  The material properties can also be tuned to achieve the modulus of various biological tissues based on the environmental conditions such as salt concentration and content.  Additionally we have shown that bioactive peptides, such as RGDS, can be added to the end of the base peptide group without affecting the modulus of the material.  This material was tested for biocompatibility using a fibroblast cell line and was shown to support cell growth in 3D over a 3 day time period.  The versatile nature of this system makes it an attractive material for use as an injectable tissue engineering matrix.