Volume 52 Issue 8, August 2020

Graphene derivatives (e.g., graphene oxide (GO)) have been incorporated in hydrogels to improve the properties (e.g., mechanical strength) of conventional hydrogels and/or develop new functions (e.g., electrical conductivity and drug loading/delivery) for various biomedical applications.

Hydrogels as biocompatible polymer have been attracted materials researchers for mimicking biological systems. One efficient approach to preparing hydrogels is using host–guest interactions between cyclodextrins (CDs) as host units and suitable guest units. The hydrogels formed by CD and guest unit reversible bonds show several biofunctionalities, such as self-healing ability, stimuli responsiveness, the ability to function as soft actuators for use in artificial muscles, and conductive responsiveness.

Stimulus-responsive hydrogels are highly attractive as the surrogate materials that can simulate dynamic mechanical microenvironments surrounding biological cells in vivo. This review tries to provide with comprehensive overviews on the previous achievements, present pitfalls and challenges, and future perspectives on the recent development on stimulus-responsive hydrogel materials for the dynamic control of cell behaviors.

Hydrogels have been used in vascular engineering owing to their mechanical properties and tissue-like characteristics. Hydrogel-based blood vessels can be constructed from natural or synthetic materials alone, or require a combination of both. The manufacturing methods play an important role in constructing vascular engineering to induce the vascular endothelial cells function driven by shear stress and biomechanical force. The different components and methods of engineered vascular hydrogels described in this review would provide useful information for the desired applications of in vitro tissue models.

Peptides conjugated with hydrophobic moieties are typical examples of supramolecular gelators (low molecular weight gelators, LMWGs), which can be designed or programmed to self-assemble to form nanofibers/nanosheets in response to stimuli or microenvironments. In the last decade, several groups have reported that the self-assembly of small gelator molecules achieved inside living cells or on the surfaces of living cells induced selective cell death. This focused review outlines the self-assembly of small gelator molecules inside or around living cells that control cell fate.

Recent advancements in DNA nanotechnology and nanobioengineering allowed the use of DNA as a generic material. Notably, an enzyme-based fabrication method of physical DNA hydrogels opened up a route to realize a novel class of DNA-based materials. Different forms of DNA materials with new applications were created by utilizing its unique characteristics. This Focus Review provides a brief overview of the enzyme-based fabrication method of physical DNA hydrogels and discusses the latest developments in the field.

Biofunctional hydrogels were formed by horseradish peroxidase (HRP)-catalyzed cross-linking reaction. Poly(ethylene glycol) (PEG) incorporated with phenol or thiol group was used as a base polymer to form irreversible or redox responsive cross-links, respectively. Thiolated PEGs showed slower hydrogelation kinetics than phenolated ones; however, in the presence of phenolic small compounds, the cross-linking reaction was promoted without the aid of exogenous hydrogen peroxide. Moreover, in situ incorporation of bioactive entities, such as proteins, realized biofunctionalization of hydrogels for potential applications for bioengineering and biomedical applications.

We proposed a new method to functionalize supramolecular peptide nanofibers using fiber-binding peptides screened from a phage peptide library. The RGDS-conjugated fiber-binding peptides significantly enhanced the adhesion of 3T3-L1 cells on E1Y9 nanofibers through noncovalent modification of E1Y9 nanofibers. This noncovalent modification using fiber-binding peptides was also effective for functionalization of E1Y9 hydrogels as cell culture materials that promoted the proliferation of 3T3-L1 cells. The functionalization of supramolecular peptide nanofibers using molecular recognition peptides will be a powerful tool for the development of functional materials.

This article describes the self-assembly of Fmoc-dipeptides comprising α-methyl-L-phenylalanine. The position and number of methyl groups introduced onto the α carbons of the Fmoc-dipeptides as α-methyl-L-phenylalanine have a marked influence on the morphology of supramolecular nanostructures and the hydrogel formation ability.

Lactose-coupled amphiphilic ureas are worked as low-molecular-weight hydrogelators (LMWHGs). Their gelation abilities are sensitive to the length of the hydrophobic alkyl chain. Gradual gel-to-sol phase transition of the supramolecular hydrogel was occurred by adding β-galactosidase (β-Gal) as a result of enzymatic hydrolysis of the lactose moiety. Supramolecular hydrogels could stably entrap cationic organic dyes even in water. The entrapped dye could be gradually released in the presence of β-Gal, along with the gel-to-sol phase transition.

A bola-type π-conjugated amphiphile containing Phe-Lys dipeptide showed a pH- and guest-induced phase transition from the granular aggregate to the fibrous architecture and formed a supramolecular hydrogel. Using this stimuli-responsiveness, the hydrogel system was successfully applied to the selective discrimination of glycosaminoglycans composed of a sulfated sugar unit.

Multicomponent hydrogel systems were formed using combinations of three self-assembled peptide based gelators with motifs inspired by fibronectin, collagen, and laminin, respectively. After a systematic study on the how the properties of hydrogels correlate with cell growth and proliferation, it was found that cell growth was significantly impacted by the hydrogels’ resistance to strain which was defined by their crossover point. This indicates that the ability of the gel to efficiently store the work of deformation during cell division is the most important factor for cellular proliferation.

Chitinous nanofibers (NFs) exhibit a specific physiological activity not observed in the powdered form. Herein, we aimed to develop a cell-adhesive chitinous NF-based flexible hydrogel. The desired cell-adhesive flexible hydrogel was obtained by introducing cationic groups and vinyl polymerizable functional groups on the surface deacetylated chitin NFs as well as copolymerizing it with N-isopropylacrylamide monomer in an aqueous system. Cells adhered to the gel could be detached by cooling to 4 °C. The composite hydrogel fabricated here may be useful as a cell culture scaffold material in regenerative medicine.

Stabilization of microtubules occurs by paclitaxel bound to the taxoid site and cevipabulin (and its derivative) bound to the taxoid site and/or vinca alkaloid domain of the β-tubulin in tubulin heterodimer.

Preoperative marking or tattooing is performed in clinical situations using an India ink to identify gastrointestinal lesions. However, diffusion of the carbon particles from the ink results in unclear marking. We observed that subcutaneously injected sodium alginate solutions formed a gel and prevented the diffusion of carbon particles into the tissues of mice. Similar results were observed in resected porcine large intestines. The tattooed area was well correlated with the molecular weight and viscosity of sodium alginate, indicating that an adequately viscous sodium alginate hydrogel is useful for clear marking.

A fluidic substrate behaving as a hydrophobic viscoelastic liquid was designed as a tool to investigate the role of matrix viscosity on the alteration of breast cancer cellular fate. The fluidity level of fluidic substrate was tuned by modulating the molecular weight of poly(ε-caprolactone-co-D,L-lactide). MCF-7 cells responded to the change in fluidity level of fluidic substrates by forming weak attachment. On high-fluidity substrate, MCF-7 cells formed 3D aggregates, while coalesced on low-fluidity substrate. More importantly, the fluidic substrate mechanically promoted senescence of MCF-7 cells regardless the fluidity level of substrate.

The functionalization of laminarin with boronic acid groups was described. This biopolymer readily established boronate ester-crosslinked gels with poly(vinyl alcohol) within seconds under physiological conditions. The resultant hydrogels exhibited interesting self-healing properties, reactive oxygen species responsiveness and cytocompatibility.

In this report, we evaluated the interplay between molecular weight and mass ratio of polymer during development of viscoelastic properties in HA/FmocFF hybrid supramolecular hydrogels. Rheology was the main tool to assess this complex relationship and the kinetics of network formation during self-assembly were correlated with inherent material properties. Formation of long-rang elastic interactions, ductility and plastic flow were strongly dependent on both size and concentration of polymer, providing a convenient application window to tune the flow properties of the hybrid hydrogels according to the intended application.