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This content will become publicly available on November 14, 2024

Title: Transient Competitors to Modulate Dynamic Covalent Cross-Linking of Recombinant Hydrogels
Hydrogels cross-linked by dynamic covalent chemistry (DCC) are stiff and remodelable, making them ideal biomimetics for tissue engineering applications. Due to the reversibility of DCC cross-links, the opportunity exists to transiently control hydrogel network formation through the use of small molecule competitors. Specifically, we incorporate low molecular weight competitors that reversibly disrupt the formation of hydrazone cross-links as they diffuse through a recombinant hydrogel. Using complementary experimental, computational, and theoretical polymer physics approaches, we present a family of competitors that predictably alter hydrogel gelation time and mechanics. By changing the competitor chemistry, we connect key reaction parameters (forward and reverse reactions rates and thermodynamic equilibrium constants) to the delayed onset of a percolated network, increased hydrogel gelation time, and transient control of hydrogel stiffness. Using human intestinal organoids as a model system, we demonstrate the ability to tune gelation kinetics of a recombinant hydrogel for uniform encapsulation of individual, patient-derived stem cells and their proliferation into three-dimensional structures. Taken together, our data establish a validated framework to relate molecular-level parameters of transient competitors to predicted macromolecular-network properties. As interest in biomimetic, DCC-cross-linked hydrogels continues to grow, these results will enable the rationale design of bespoke, dynamic biomaterials for tissue engineering.  more » « less
Award ID(s):
Author(s) / Creator(s):
; ; ; ; ;
Publisher / Repository:
American Chemical Society
Date Published:
Journal Name:
Chemistry of Materials
Page Range / eLocation ID:
8969 to 8983
Medium: X
Sponsoring Org:
National Science Foundation
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