A peptide-based hydrogelation strategy has been developed that allows homogenous encapsulation and subsequent delivery of C3H10t1/2 mesenchymal stem cells. Structure-based peptide design afforded MAX8, a 20-residue peptide that folds and selfassembles in response to DMEM resulting in mechanically rigid hydrogels. The folding and self-assembly kinetics of MAX8 have been tuned so that when hydrogelation is triggered in the presence of cells, the cells become homogeneously impregnated within the gel. A unique characteristic of these gel-cell constructs is that when an appropriate shear stress is applied, the hydrogel will shear-thin resulting in a low-viscosity gel. However, after the application of shear has stopped, the gel quickly resets and recovers its initial mechanical rigidity in a near quantitative fashion. This property allows gel/cell constructs to be delivered via syringe with precision to target sites. Homogenous cellular distribution and cell viability are unaffected by the shear thinning process and gel/cell constructs stay fixed at the point of introduction, suggesting that these gels may be useful for the delivery of cells to target biological sites in tissue regeneration efforts.hydrogel ͉ self-assembly ͉ stem cell

A de novo designed three-stranded beta-sheet (TSS1) has been prepared that undergoes temperature-induced folding and self-assembly to afford a network of beta-sheet rich fibrils that constitutes a mechanically rigid hydrogel. Circular dichroism and infrared spectroscopies show that TSS1 folds and self-assembles into a beta-sheet secondary structure in response to temperature. Rheological measurements show that the resulting hydrogels are mechanically rigid [at pH 9, G' = 1750-9000 Pa, and at pH 7.4, G' = 8500 Pa] and that the storage modulus can be modulated by temperature and peptide concentration. Nanoscale structure analysis by transmission electron microscopy and small angle neutron scattering indicate that the hydrogel network is comprised of fibrils that are about 3 nm in width, consistent with the width of TSS1 in the folded state. A unique property of the TSS1 hydrogel is its ability to shear-thin into a low viscosity gel upon application of shear stress and immediately recover its mechanical rigidity upon termination of stress. This attribute allows the hydrogel to be delivered via syringe to a target site with spatial and temporal resolution. Finally, experiments employing C3H10t1/2 mesenchymal stem cells seeded onto the hydrogel and incubated for 24 h indicate that the TSS1 hydrogel surface is noncytotoxic, supports cell adhesion, and allows cell migration.

Self-assembled materials composed of beta-sheet forming peptides hold promise as therapeutics and novel biomaterials. This article focuses on the design and engineering of amphiphilic peptide sequences, especially beta-hairpins. Peptides can be designed to intramolecularly fold and then self-assemble on cue, affording hydrogels rich in beta-sheet structure. Hydrogels having distinct material properties can be designed at the molecular level by modulating either the peptide's sequence or the environmental stimulus used to trigger folding and assembly, leading to gelation.

A de novo designed peptide-based gel has been prepared whose mechanical rigidity can be modulated after shear-thin recovery. The photopolymerizable β-hairpin peptide named MLD undergoes temperature-induced folding and self-assembly to afford a network of β-sheet-rich fibrils that constitutes a moderately rigid hydrogel (G 0 = 220 ( 50 Pa, 1 wt %). The MLD hydrogel can be shear-thinned into a lowviscosity gel upon application of shear stress and immediately recovers its mechanical rigidity upon termination of stress. MLD peptides contain non-natural sorbamide derivatives of lysine that allow the mechanical rigidity of its hydrogels to be enhanced through polymerization of dienes displayed along the surface of the fibrils constituting the gel. Irradiation of the gel network increases its mechanical rigidity ∼2.5-fold. Circular dichroism (CD) spectroscopy shows that MLD folds and self-assembles into β-sheet-rich fibrils and that photo-cross-linking does not influence the secondary structure contained within the assembly. The MLD hydrogel shows potential as an injectable material whose mechanical properties can be modulated after delivery.