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

Abstract

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 β-sheet crystal formation by the hydrophobic peptide fragment, a hydrophobic peptide (HP) that can form a β-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 β-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 β-sheet assembly for network cross-linking. Combining the good biocompatibility and sustained drug release of the constructed hydrogels, this hydrophobic β-sheet peptide represents a promising candidate for the rational design of hydrogels for biomedical applications.

High Mechanical Strength and Multifunctional Microphase‐Separated Supramolecular Hydrogels Fabricated by Liquid‐Crystalline Block Copolymer

“…The crystallization domain expanded with the increase of Azobenzene content, then the rigidity of P(AM-G)-b-PAzo hydrogels was enhanced, which strengthen the fracture strength and weaken the fracture elongation [47] (Figure 2f). P(AM-G)-b-PAzo 15 [8] hydrogel, [35] P-HP hydrogel, [48] PAM-CS-A hydrogel, [13] DFT hydrogel, [49] Tetra-PVA hydrogel, [50] 𝛽CD-VC hydrogel, [51] APVA/HTCC hydrogel, [52] CNH hydrogel [53] ).…”

Naturally sourced hydrogels: emerging fundamental materials for next-generation healthcare sensing

“…Different from the rod-shaped a-helical polypeptide, b-sheets are thin sheets arranged parallelly or antiparallelly formed by the hydrogen bond force between N-H and CQO. 146 The internal force is mainly the hydrogen bond between the peptide bonds and the polypeptide chain segments. 147 Intermolecular and intramolecular forces, such as electrostatic and hydrophobic interactions, drive the b-sheet self-assembly.…”

Noncovalently Cross-Linked Polymeric Materials Reinforced by Well-Designed In Situ-Formed Nanofillers

“…The construction of in situ-formed rigid and dynamic nanofillers capable of enzyme dissociation could endow PVA-based supramolecular hydrogels with excellent biodegradability. As shown in Figure c, Bao et al grafted hydrophobic short peptide chains on PVA chains and fabricated high-strength and biodegradable medical hydrogels . The hydrogels were reinforced by dynamically cross-linked localized β-sheet domains, which were formed by the assembly of peptide chains.…”

“…(d) Degradation of PVA-based hydrogels in enzymatic environments. Reprinted with permission from ref . Copyright 2021, American Chemical Society.…”

“…As shown in Figure 5c, Bao et al grafted hydrophobic short peptide chains on PVA chains and fabricated high-strength and biodegradable medical hydrogels. 64 The hydrogels were reinforced by dynamically cross-linked localized β-sheet domains, which were formed by the assembly of peptide chains. The β-sheet domains could dissociate under the action of enzymes, leading to hydrogel degradation in enzymatic environments (Figure 5d).…”