A Facile and Versatile Approach to Construct Photoactivated Peptide Hydrogels by Regulating Electrostatic Repulsion.

Short peptides that can respond to external stimuli have been considered as the preferred building blocks to construct hydrogels for biomedical applications. In particular, photoresponsive peptides that are capable of triggering the formation of hydrogels upon light irradiation allow the properties of hydrogels to be changed remotely by precise and localized actuation. Here, we used the photochemical reaction of the 2-nitrobenzyl ester group (NB) to develop a facile and versatile strategy for constructing photoactivated peptide hydrogels. The peptides with high aggregation propensity were designed as hydrogelators, which were photocaged by a positively charged dipeptide (KK) to provide strong charge repulsion and prevent self-assembly in water. Light irradiation led to the removal of KK and triggered the self-assembly of peptides and the formation of hydrogel. Light stimulation endows spatial and temporal control, which enables the formation of hydrogel with precisely tunable structure and mechanical properties. Cell culture and behavior study indicated that the optimized photoactivated hydrogel was suitable for 2D and 3D cell culture, and its photocontrollable mechanical strength could regulate the spreading of stem cells on its surface. Therefore, our strategy provides an alternative way to construct photoactivated peptide hydrogels with wide applications in biomedical areas.

Highly Tough, Stretchable, and Enzymatically Degradable Hydrogels Modulated by Bioinspired Hydrophobic ß-Sheet Peptides.

Peptide-based supramolecular hydrogels have attracted great attention due to their good biocompatibility and biodegradability and have become promising candidates for biomedical applications. The bottom-up self-assembly endows the peptides with a highly ordered secondary structure, which has proven to be an effective strategy to improve the mechanical properties of hydrogels through strong physical interactions and energy dissipation. Inspired by the excellent mechanical properties of spider-silk, which can be attributed to the rich ß-sheet crystal formation by the hydrophobic peptide fragment, a hydrophobic peptide (HP) that can form a ß-sheet assembly was designed and introduced into a poly(vinyl alcohol) (PVA) scaffold to improve mechanical properties of hydrogels by the cooperative intermolecular physical interactions. Compared with hydrogels without peptide grafting (P-HP0), the strong ß-sheet self-assembly domain endows the hybrid hydrogels (P-HP20, P-HP29, and P-HP37) with high strength and toughness. The fracture tensile strength increased from 0.3 to 2.1 MPa (7 times), the toughness increased from 0.4 to 21.6 MJ m-3 (54 times), and the compressive strength increased from 0.33 to 10.43 MPa (31 times) at 75% strain. Moreover, the hybrid hydrogels are enzymatically degradable due to the dominant contribution of the ß-sheet assembly for network cross-linking. Combining the good biocompatibility and sustained drug release of the constructed hydrogels, this hydrophobic ß-sheet peptide represents a promising candidate for the rational design of hydrogels for biomedical applications.

Photo and Reduction Dual-Responsive Hydrogel for Regulating Cell Adhesion and Cell Sheet Harvest.

Regulating cell-surface interactions plays a key role for biomaterials and their applications in cell-based therapies. In this paper, we demonstrated a dual-responsive hydrogel platform to achieve phototriggered protein immobilization and reduction-induced protein release. By o-nitrobenzyl photochemistry, including sequential aldehyde generation upon light irradiation and imine ligation with amine compounds, adhesive proteins can be effectively immobilized on the hydrogel with spatial and quantitative control, thus mediating cell adhesion in designed areas. By reduction chemistry of the disulfide bond, the patterned proteins can be released from the hydrogel, thus detaching cells in a noninvasive manner. Finally, the dynamic adsorption-dissociation of proteins enables the hydrogel to be tactfully used for cell sheet harvesting in an enzyme-free mode with light-defined shapes. This work not only provides an efficient strategy for recovery of cells and cell sheets but also provides insights into cell-material interactions mediated by proteins.