Editorial pubs.acs.org/accounts
Stimuli-Controlled Hydrogels and Their Applications Guest Editorial for the Accounts of Chemical Research special issue on “Stimuli-Responsive Hydrogels”.
H
as sealants, adhesives, or dressings for wounds, injuries, or surgical intervention is discussed. Similarly, the preparation of “intelligent” hydrogels responding to analytes, biomarkers, or environmental disease conditions and their applications for biosensing and drug delivery are addressed in the Account of Peppas and colleagues. They report on the synthesis of molecularly imprinted, biomolecule-containing, and enzymatically responsive hydrogels and their analytical and therapeutic applications. Improved sensitivities and specificities are demonstrated by the imprinted hydrogel sensing matrices, and the biomarker-induced dissolution of drugs, encapsulated in the hydrogels, is used to treat diseases, such as cancer, diabetes, or the irritable bowel syndrome. The preparation of hydrogels based on the self-assembly of multidomain β-sheet peptide nanofibers is discussed by Hartgerink and Moore. The incorporation of low-molecular-weight substrates, proteins, or cells in the hydrogel matrices or the hydrophophic cores of the nanofibers provides versatile carriers for controlled drug release via the enzymatic degradation of the peptides networks. By the further modification of the nanofiber networks with growth factors or signaling proteins, the formation of blood vessels was stimulated. Artzi and co-workers report on the development of disease-responsive hydrogels based on an amino-functionalized dextran aldhyde dedendrimer. The hydrogel reveals localized and sustained release of drugs, and the delivery of a range of anticancer therapeutics, including nucleic acids, low-molecularweight substrates and antibody drugs, is demonstrated. Eelkema and colleagues introduce in their Account the application of synthetic catalysts for the kinetic control of the properties of supramolecular hydrogels. Specifically, they demonstrate different appearance, shapes, and mechanical properties of hydrogels formed under kinetic control conditions. The importance of “colloidal” microgels as stimuli-responsive microstructures is introduced by Richtering and Plamper. By the modification of the microgels with surface functionalities, the shape and volume responses of the particles are controlled by external stimuli, such as temperature, pH, pressure, light, or electrochemical triggers. The applications of the microgels as sensors, catalysts, or separation matrices are evaluated. The reversible stimuliresponsive control over the shapes and adhesion properties of materials is addressed by Ko and Javey by discussing the reversible reconfiguration of porous or structured hydrogel materials by enhanced solvent diffusion, electrostatic repulsions between electrolyte nanosheets, and photothermal actuation. They discuss the development of “smart” adhesives as functional ingredients to maintain robust reconfiguration of shapes and reversible “on−off” switching of the binding between components. A set of Accounts introduces DNA or nucleic acids as a functional material to assemble hydrogels. The synthesis of DNA-cross-linked hydrogels, responsive to pH, temperature,
ydrogels are hydrophilic polymer networks of natural or synthetic origin. The polymers exhibit high water absorbent capacities (over 90% weight of water in the composite). Hydrogels have been studied for decades, and over the years, they were applied as scaffolds in tissue engineering, drug delivery carriers, sensors, and glues, and were used as functional materials to produce contact lenses, disposable diapers, implants, and moist pads for healing wounds or burns. Stimuli-responsive hydrogels represent a broad class of hydrogels undergoing switchable gel-to-solution or gel-to-solid transitions upon application of external triggers. Different physical or chemical external stimuli can be applied to induce reversible or single-cycle phase transitions of the hydrogels. These include thermal, magnetic, ultrasonic, electrochemical, or light stimuli as physical triggers, and pH, redox reactions, supramolecular complexes, and biocatalytically driven reactions as chemical triggers. Numerous applications of stimuliresponsive hydrogels were suggested, including their use as functional matrices for sensing, actuators, and biomedical applications, such as controlled drug release, tissue engineering, and imaging. Also, stimuli-triggered hydrogels were used to construct catalytic switches, logic-gate operations, surfaces for controlled growth of cells, and more. Methods to immobilize and pattern stimuli-responsive hydrogels on surfaces were developed, and the fabrication of surfaces revealing signaltriggered stiffness and switchable interfacial electron transfer properties was demonstrated. The synthetic advances in preparing nanometer- and micrometer-sized inorganic particles enable the incorporation of the micro- or nanoparticles into stimuli-responsive hydrogels to yield hybrid materials for electronic and optical applications. Additionally, methods to prepare stimuli-responsive nano- or microhydrogels introduced new concepts for controlled and targeted drug release. Not surprisingly, the rapid progress in developing stimuliresponsive hydrogels and their broad applications attracted substantial recent research efforts in the field. This thematic special issue on “Stimuli-Responsive Hydrogels” aims to provide a series of Accounts formulated by experts in the field, summarizing recent developments and future challenges in the area. The series of Accounts represent a blend of different synthetic methodologies to prepare stimuli-responsive hydrogels and address the diverse applications of the signaltriggered materials. The articles highlight the overlapping elements in developing the materials, while addressing the variabilities, diversity, and complementarities in the constitution and applications of the systems. The introduction of new triggers for dissolving hydrogels is often dictated by their sequestered applications and is a continuous materials science challenge. Grinstaff and Konieczynska present in their Account the synthesis of biocompatible dendritic hydrogels that include in their network thiol− thioester exchange reactive groups as functional units for aqueous dissolution of the hydrogels. The use of the hydrogels © 2017 American Chemical Society
Published: April 18, 2017 657
DOI: 10.1021/acs.accounts.7b00142 Acc. Chem. Res. 2017, 50, 657−658
Accounts of Chemical Research
Editorial
proteins and the generation of protein gradients in the hydrogel network, specific interactions with cells could be evaluated. This is demonstrated by studying the interactions between hydrogelbound VEGF-165 and endothelial cells or retinal stem cells. Hamachi and Shigemitsu describe in their Account the synthesis of supramolecular hydrogels that respond to physical triggers, such as heat or light, and chemical stimuli, such as pH or metal ions. The incorporation of enzymes, peptides, fluorescent chemosensors, or inorganic nanomaterials into the hydrogel matrix is claimed to mimic cell functionalities and to provide functional materials for sense-and-treat medical applications. I thank all the authors who participated in the formulation of this special issue on stimuli-responsive hydrogels. The collection of Accounts has summarized recent advances and highlights in the area. This series of papers will, certainly, provide essential information for newcomers to the field and will inspire further studies in the area.
signaling molecules, such as ATP, or DNA restriction enzymes, is described by Liu and co-workers. The incorporation of living cells in the hydrogels allows the printing of the cell-modified hydrogels on surfaces and the probing of the dynamics of cells proliferation through the permeability of nutrients across the hydrogel network. A related report by Liu, Luo, and their coworkers introduces the synthesis of all DNA hydrogels by the enzymatic ligation of X-shaped DNA and linear plasmids. Incorporation of enzymes into the hydrogels allowed the synthesis of proteins without the involvement of living cells, and the cross-linked DNA matrices revealed metamaterial properties controlled by the water-uptake of the composite. The synthesis of stimuli-responsive nucleic acid-cross-linked acrylamide hydrogels is described by Willner and co-workers. Metal ions, pH, G-quadruplexes, and temperature are used to trigger the reversible hydrogel-to-solution or hydrogel-to-solid transitions. By incorporation of two cross-linking elements into the hydrogel, and the selective unlocking one of the crosslinking elements, hydrogels of controlled switchable stiffness and porosities are generated. The hydrogel, stabilized cooperatively by two cross-linking motifs, are used to develop “shape-memory” hydrogels. The assembly of stimuli-responsive DNA-acrylamide hydrogels on surfaces and the control of interfacial electron transfer reactions at electrode surfaces are demonstrated. In addition, a generic method to synthesize stimuli-responsive DNA-based microcapsules for controlled drug release is introduced. The concept of “shape-memory” hydrogels and their applications are introduced in a series of several Accounts. The “shape-memory” effect is defined as an elastic deformation (programming) of a sample into a temporary shape stabilized by reversible covalent or physical cross-links. Subjecting the temporary shaped material to appropriate triggers affects the cross-linking units to the extent that the original shape of the material is recovered. The development of hydrophobic “shapememory” hydrogels is discussed by Lendlein and co-workers. By the tethering of hydrophobic crystallizable side chains into a hydrophilic polymer network and further incorporation of an additional functional side-chain, triple shape-memory stimuliresponsive hydrogels were realized. Light, pH, or ions were used as shape-triggering functions. Suggested applications of shape memory hydrogels as soft actuators and cell manipulations are discussed. The design of shape morphing materials by the inclusion of stiff elements in soft stimuli-responsive hydrogels is presented by Jeon, Hauser, and Hayward. The stiff inclusion patterns program the bending and swelling of the composites, thereby providing access to a wide array of complex 3D structures. By the incorporation of photothermally active nanoparticles into the hydrogels, programmable and reprogrammable light-responsive shape-morphing systems are demonstrated. Finally, Salvekar, Huang, Xiao, and their colleagues describe the water-responsive shape recovery of a cross-linked poly(ethylene glycol) biodegradable hydrogel. By elucidation of the mechanism and kinetics of the waterresponsive shape recovery of the polymer, the possible application of the polymer for vascular occlusion is discussed. Several Accounts address the use of stimuli-responsive hydrogels as functional matrices mimicking the cellular microenvironments for cell growth. Shoichet and colleagues describe the development of photosensitive agarose and hyaluronic acid hydrogels that enable single- or two-photon patterned immobilization of biomolecules within the 3D hydrogel network. By control of the spatial location of the
Itamar Willner, Guest Editor
■
The Hebrew University of Jerusalem
AUTHOR INFORMATION
ORCID
Itamar Willner: 0000-0001-9710-9077 Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS.
658
DOI: 10.1021/acs.accounts.7b00142 Acc. Chem. Res. 2017, 50, 657−658
