Orchestrating Chemical and Physical Cross-Linking in Protein Hydrogels to Regulate Embryonic Stem Cell Growth

Abstract

Protein hydrogels are ideal candidates for nextgeneration biomaterials due to their genetically programmable properties. Herein, we report an entirely protein-based hydrogel as an artificial extracellular matrix (ECM) for regulating the embryonic stem cell growth. A synergy between chemical and physical cross-linking was achieved in one step by SpyTag/ SpyCatcher reaction and P zipper association at 37 °C. The hydrogels' stress relaxation behaviors can be tuned across a broad spectrum by single-point mutation on a P zipper. It has been found that faster relaxation can promote the growth of HeLa tumor spheroids and embryonic stem cells, and mechanical regulation of embryonic stem cells occurs via retention of the cells at the G1 phase. The results highlight the promise of genetically encoded protein materials as a platform of artificial ECM for understanding and controlling the complex cell−matrix interactions in a 3D cell culture.

Antioxidant Hydrogels: Antioxidant Mechanisms, Design Strategies, and Applications in the Treatment of Oxidative Stress‐Related Diseases

“…using the Hantzsch reaction. [87] The resulting antioxidant PVA exhibited superior therapeutic effects in mucosal repair and wound healing when incorporated into composite hydrogels. Additionally, the Biginelli reaction was employed in the synthesis of innovative antioxidant polymers.…”

Polymer-Based Hydrogels Applied in Drug Delivery: An Overview

“…The crosslinking mechanism is crucial in determining the structure, properties, and performance of the hydrogel. The two main types of crosslinking in polymer-based hydrogels are physical crosslinking [58,227,228] and chemical crosslinking [23,58,173,228].…”

“…Chemical crosslinking involves the formation of covalent bonds between the polymer chains, resulting in a three-dimensional network structure [23,228]. Chemical crosslinking methods include radical polymerization, Michael addition, Schiff base reaction, and epoxy crosslinking, among others [58,173].…”

Catcher/Tag Toolbox: Biomolecular Click‐Reactions For Protein Engineering Beyond Genetics

“…A current limitation of the Spy network hydrogels is their weak mechanical properties owing to the low crosslink density. A potential strategy to overcome this is to introduce other cross-linked networks into Spy network to construct double-network hydrogels, such as chemical-physical double-networks, [92] covalent doublenetworks, [93] or coordination-covalent double-networks. [88,94]…”