Photoregulated Hydrazone-Based Hydrogel Formation for Biochemically Patterning 3D Cellular Microenvironments

Abstract

Photodriven click reactions have emerged as versatile tools for biomaterial synthesis that can recapitulate critical spatial and temporal changes of extracellular matrix (ECM) microenvironments in vitro. In this article, we report on the synthesis of poly(ethylene glycol) (PEG) hydrogels using photodriven step-growth polymerization, where one of the reactive functionalities is formed by a photocleavage reaction. Upon photocleavage, an aldehyde functionality is generated that rapidly reacts with hydrazinefunctionalized PEGs; the gelation kinetics and final material modulus are distinctly controlled by variations in the light intensity. This light-driven aldehyde generation is further exploited to install biochemical ligands in the hydrazone-based hydrogels with precise spatial control. We expect that userdirected spatial and temporal control over both biophysical and biochemical gel properties through photochemical reactions and photopatterning, respectively, should provide newfound opportunities to probe and understand dynamic cell−matrix interactions.

Spatiotemporal hydrogel biomaterials for regenerative medicine

“…Conveniently, the product of o -NB uncaging is a nitrosobenzaldehyde (Figure 12b), the generation of which can result in the formation of oxime or hydrazone bonds in the presence of alkoxyamines 97,98 or hydrazines, 99 respectively. Hydrazone-based hydrogel networks have been formed in such a manner, and used for cell encapsulation, while modulating the temporal network evolution with light dose and the spatial chemistry with controlled illumination.…”

“…Hydrazone-based hydrogel networks have been formed in such a manner, and used for cell encapsulation, while modulating the temporal network evolution with light dose and the spatial chemistry with controlled illumination. 99 Alternative approaches involve caging the alkoxyamine substrate for subsequent reaction with a carbonyl species. 2-(2-nitrophenyl)propoxycarbonyl (NPPOC) is an appropriate photocage for this purpose because its uncaging does not form a carbonyl group that would undergo condensation with the liberated alkoxyamine (Figure 12c).…”

Light to Shape the Future: From Photolithography to 4D Printing

“…Such a functional group is capable of reacting in aqueous media at neutral pH with hydrazine derivatives to generate hydrazones. This concept was employed to produce patterned hydrogel structures by exposing a mixture of caged aldehyde and hydrazine‐terminated poly(ethylene glycol) star‐shaped polymers to a light pattern …”

Cell‐Surface Engineering for Advanced Cell Therapy

“…[182,[190][191][192] In addition to cycloaddition reactions, other organic reactions have also been used for cell encapsulation in covalent cross-linked hydrogels, including Staudinger ligation, [193] oxime/hydrazone formation, [194,195] phenylboronic acid-polyol reaction, [196] urea bond formation, [197] and KATl igation (amide bond formation of hydroxylamines and potassium acyltrifluoroborates). [198] From the standpoint of control of degradation, severalc ovalenth ydrogels whose degradation is triggered by light, [199,200] enzymes, [147,201] or natural hydrolysis [197] have been developed. In addition to alginate-based ionotropich ydrogels and covalently cross-linked hydrogels, other chemical interac- tions have been introduced to encapsulate cells.…”