Co-assembled Hydrogels Research Articles

De Novo Design of Functional Coassembling Organic-Inorganic Hydrogels for Hierarchical Mineralization and Neovascularization.

Synthetic nanostructured materials incorporating both organic and inorganic components offer a unique, powerful, and versatile class of materials for widespread applications due to the distinct, yet complementary, nature of the intrinsic properties of the different constituents. We report a supramolecular system based on synthetic nanoclay (Laponite, Lap) and peptide amphiphiles (PAs, PAH3) rationally designed to coassemble into nanostructured hydrogels with high structural integrity and a spectrum of bioactivities. Spectroscopic and scattering techniques and molecular dynamic simulation approaches were harnessed to confirm that PAH3 nanofibers electrostatically adsorbed and conformed to the surface of Lap nanodisks. Electron and atomic force microscopies also confirmed an increase in diameter and surface area of PAH3 nanofibers after coassembly with Lap. Dynamic oscillatory rheology revealed that the coassembled PAH3-Lap hydrogels displayed high stiffness and robust self-healing behavior while gas adsorption analysis confirmed a hierarchical and heterogeneous porosity. Furthermore, this distinctive structure within the three-dimensional (3D) matrix provided spatial confinement for the nucleation and hierarchical organization of high-aspect ratio hydroxyapatite nanorods into well-defined spherical clusters within the 3D matrix. Applicability of the organic–inorganic PAH3-Lap hydrogels was assessed in vitro using human bone marrow-derived stromal cells (hBMSCs) and ex vivo using a chick chorioallantoic membrane (CAM) assay. The results demonstrated that the organic–inorganic PAH3-Lap hydrogels promote human skeletal cell proliferation and, upon mineralization, integrate with the CAM, are infiltrated by blood vessels, stimulate extracellular matrix production, and facilitate extensive mineral deposition relative to the controls.

Sequential drug release of co-assembled supramolecular hydrogel as synergistic therapy against Staphylococcus aureus endophthalmitis

Although endophthalmitis is a serious sight-threatening disorder, combining anti-inflammatory agents and antibiotics has provided new methods for effectively controlling it. This paper reports that the co-assembly of a sparingly soluble antibiotic (levofloxacin; Lev) and dexamethasone-peptide amphiphile (Dex-SA-RGD) instantly generates a macroscopically supramolecular hydrogel (Lev/Dex-SA-RGD) without any external stimulus under physiological conditions, which could be used in synergistic therapy to cure endophthalmitis induced by Staphylococcus aureus (i.e., S. aureus). The resulting co-assembled supramolecular hydrogel was thoroughly characterized using rheology, circular dichroism, and transmission electron microscopy. An in vitro drug release study showed that Lev was rapidly released from the supramolecular hydrogel within 6 h, while Dex-SA-RGD escaped from the supramolecular hydrogel as a result of matrix erosion, and then acted as a prodrug to provide the sequentially slow release of active dexamethasone via the hydrolytic route. The Lev/Dex-SA-RGD supramolecular hydrogel showed high antibacterial activities against both gram-negative and gram-positive strains. Moreover, a rabbit endophthalmitis model induced by S. aureus showed that the intravitreal injection of the Lev/Dex-SA-RGD supramolecular hydrogel resulted in excellent therapeutic efficacy with no apparent damage or destruction of the retina, and dramatically suppressed inflammatory responses (e.g., leukocyte and lymphocyte infiltration, microglial activation, cytokine production, and retinal cell death). As a rational approach to investigate and apply the co-assembled hydrogel, this work presents the potential of synergistic intervention to prevent retinal tissue damage and vision impairment, and ultimately shows the clinical benefits of using supramolecular hydrogels for ocular drug delivery.

Supramolecular co-assembly of self-adjuvanting nanofibrious peptide hydrogel enhances cancer vaccination by activating MyD88-dependent NF-κB signaling pathway without inflammation

Peptide vaccine targeting tumor-specific antigens is a promising cancer treatment regimen. However, peptide vaccines are commonly low-immunogenic, leading to suboptimal antitumor T-cell responses. Current peptide vaccination approaches are challenged by the variability of peptide physicochemical characters and vaccine formulations, flexibility, and the broad feasibility. Here, the supramolecular co-assembly of antigen epitope-conjugated peptides (ECPs) targeting CD8 or CD4 T-cell receptors was used to engineer a nanofibrious hydrogel vaccine platform. This approach provided precise and tunable loading of peptide antigens in nanofibers, which notably increased the antigen uptake, cross-presentation, and activation of dendritic cells (DCs). Immunization in mice indicated that the co-assembled peptide hydrogel did not induce local inflammation responses and elicited significantly promoted T-cell immunity by activating the MyD88-dependent NF-κB signaling pathway in DCs. Vaccination of mice using co-assembled peptide vaccine stimulated both enhanced CD8 and CD4 T cells against EG.7-OVA tumors without additional immunoadjuvants or delivery systems, and resulted in a more remarkable cancer immunotherapy efficacy, compared with free peptide vaccine or aluminum-adjuvanted peptide formulation. Altogether, peptide co-assembly demonstrated by three independent pairs of ECPs is a facile, customizable, and chemically defined approach for co-delivering peptide antigens in self-adjuvanting hydrogel vaccines that could induce stronger anticancer T-cell responses.

Co-assembled Supramolecular Nanofibers With Tunable Surface Properties for Efficient Vaccine Delivery.

The utilization of nanotechnology to deliver vaccines and modulate immunity has shown great potential in cancer therapy. Peptide-based supramolecular hydrogels as novel vaccine adjuvants have been found to effectively improve the immune response and tumor curative effect. In this study, we designed a set of reduction-responsive self-assembled peptide precursors (Fbp-GDFDFDYD(E, S, or K)-ss-ERGD), which can be reduced by glutathione (GSH) into Fbp-GDFDFDYD(E, S or K)-SH for forming of hydrogel with different surface properties (E-gel, S-gel, and K-gel, respectively). Using the same method, co-assembled hydrogel vaccines (E-vac, S-vac, and K-vac, respectively) can also be prepared by mixing different precursors with antigens before GSH reduction. Through TEM observation of the nanostructure, we found that all the co-assembled hydrogels, especially K-vac, possessed much denser and more unified nanofiber networks as compared with antigen-free hydrogels, which were very suitable for antigen storage and vaccine delivery. Although the three peptides adopted similar β-sheet secondary structures, the mechanical properties of their resulted co-assembled hydrogel vaccines were obviously different. Compared to E-vac, S-vac had a much weaker mechanical property, while K-vac had a much higher. In vivo experiments, co-assembled hydrogel vaccines, especially K-vac, also promoted antibody production and anti-tumor immune responses more significantly than the other two vaccines. Our results demonstrated that co-assembled hydrogels formed by peptides and antigens co-assembly could act as effective vaccine delivery systems for boosting antibody production, and different immune effects can be acquired by tuning the surface properties of the involved self-assembling peptides.

Evaluation of a Peptide-Based Coassembled Nanofibrous and Thixotropic Hydrogel for Dermal Wound Healing.

The development of a peptide-based coassembled thixotropic hydrogel is a promising biomaterial, which could be used for dermal wound healing application. Cyclodextrins are widely used as biocompatible cyclic oligosaccharides that have hydrophilic exterior and hydrophobic interior for the formation of functional biomaterials. The current work presents a paradigm of a coassembled hydrogel with suitable mechanical strength that exhibits in vivo wound healing efficacy. In this report, we have designed and synthesized an Amoc (9-anthracenemethoxycarbonyl)-capped dipeptide, which self-assembles into a tough and robust hydrogel owing to participation of various noncovalent interactions. The mechanical strength of the self-assembling peptide-based hydrogel is tuned by incorporation of equimolar β-cyclodextrin (CD), which leads to the formation of a coassembled hydrogel suitable for wound healing application. The coassembled hydrogel exhibits simple syringe injectability and is thixotropic in nature. The nanostructural morphology of the coassembled hydrogel reveals a highly cross-linked and entangled nanofibrillar network. Several spectroscopic data elucidate the presence of noncovalent interactions between CD and peptide, which could be the driving force for the formation of ordered nanostructures. The coassembled hydrogel shows potent antibacterial activity against Gram-positive pathogenic bacteria. In vitro biocompatibility of the coassembled hydrogel has been investigated with the human embryonic kidney (HEK293) and MCF-7 cell lines. Additionally, confocal laser scanning microscopic data show cellular uptake of the coassembled hydrogel with blue fluorescence. Moreover, the in vivo wound healing activity of the coassembled hydrogel has been investigated by the histopathology study. The biochemical parameters such as nitric oxide and collagen contents have been evaluated by Griess and hydroxy proline assays. All the results corroborate the wound healing efficacy of a nanofibrillar antibacterial coassembled hydrogel.

Antimicrobial Activity with Enhanced Mechanical Properties in Phenylalanine-Based Chiral Coassembled Hydrogels: The Influence of Pyridine Hydrazide Derivatives.

Hydrazide derivatives are known to display a wide range of biological properties including antimicrobial activities, hence making them desirable candidates for soft biomaterials. Herein, we report chiral supramolecular coassembled hydrogels obtained from two phenylalanine gelators (L/DPF and B2L/D) and two dicarbohydrazide molecules (pyridine-2,6-dicarbohydrazide (PDH) and (2,2'-bipyridine)-5,5'-dicarbohydrazide (BDH)) that exhibited enhanced mechanical properties, chirality modulation, and antimicrobial activity. Four lines of coassembled hydrogels were obtained (i.e., L/DPF-PDH, L/DPF-BDH, B2L/D-PDH, and B2L/D-BDH) through hydrogen bonding and π-π stacking with some level of an interpenetrating network, as revealed by the structural characterization analysis. Mechanical properties were significantly improved, especially in the case of hybrid gels involving BDH, with improved average elastic modulus (G') values of 3430 and 3167 Pa for DPF-BDH and B2D-BDH (1:3, molar concentration) over 140 and 1680 Pa for DPF and B2D gelators, respectively. This was attributed to the improved π-π stacking and interpenetrating network due to the bipyridine group and its ease to form fibrous precipitates in the process of heating and cooling to room temperature. PDH, on the other hand, was able to modulate chirality in the L/DPF gelator due to its more planar and less bulky nature and showed antimicrobial activity against Pseudomonas aeruginosa (Gram-negative). Interestingly, when PDH was coassembled with the B2L/D gelator, the hybrid gels exhibited antimicrobial activity against Staphylococcus aureus (Gram-positive) and P. aeruginosa (Gram-negative) by virtue of a synergistic effect of the gelator and the azomethine group of PHD. Hence, by moving from bipyridine (BDH) to pyridine (PDH) as a core structure in the hydrazide molecules, the resulting hybrid hydrogels exhibited desirable properties of antimicrobial activity and improved mechanical attributes.

Effects of fluoro substitutions and electrostatic interactions on the self-assembled structures and hydrogelation of tripeptides: tuning the mechanical properties of co-assembled hydrogels.

A series of FFK tripeptides capped with phenylacetic acid of various fluoro-substitutions at the N-terminus has been synthesized and examined for self-assembly under aqueous conditions. The material properties of the FFK tripeptides dramatically changed from precipitate to hydrogel phase upon increasing the number of fluorine atoms. Peptides linked with benzyl (B-FFK) or monofluoro-benzyl (MFB-FFK) groups rapidly form solid precipitates under physiological pH conditions. The trifluoro-decorated compound (TFB-FFK) self-assembled into a metastable hydrogel which slowly transformed into a solid precipitate upon standing. A stable hydrogel formation was noticed in the case of the pentafluorobenzyl-diphenylalanyllysine (PFB-FFK) compound. TEM analysis indicates that the PFB-FFK peptide assembled into twisted nanofibril structures, which are predominantly stabilized by strong quadrupole π-stacking interactions and electrostatic interactions of amino acid side chains. Furthermore, the combination of PFB-FFK and PFB-FFD peptides was also investigated for hydrogelation and the self-assembly of such systems resulted in the formation of untwisted 1D nanofibril structures. Supramolecular coassembled hydrogels of variable stiffness have also been achieved by modulating the concentration of the peptide components, which was evident from the rheological analysis. Such low molecular weight (LMW) peptide materials with tuneable mechanical properties might be a potential material for a wide range of applications in nanotechnology and biotechnology.

Tuning the Supramolecular Structure and Function of Collagen Mimetic Ionic Complementary Peptides via Electrostatic Interactions.

Collagen, the most abundant component of natural ECM, has attracted interest of scientific communities to replicate its multihierarchical self-assembling structure. Recent developments in collagen mimetic peptides were inclined toward the production of self-assembling short peptides capable of mimicking complex higher order structures with tunable mechanical properties. Here, we report for the first time, the crucial molecular design of oppositely charged collagen mimetic shortest bioactive pentapeptide sequences, as a minimalistic building block for development of next-generation biomaterials. Our rational design involves synthesis of two pentapeptides, where the fundamental molecular motif of collagen, that is, Gly-X-Y has been mutated at the central position with positively charged, lysine, and negatively charged, aspartate, residues. Depending on their overall surface charge, these peptides showed high propensity to form self-supporting hydrogel either at acidic or basic pH, which limits their biomedical applications. Interestingly, simple mixing of the two peptides was found to induce the coassembly of these designed peptides, which drives the formation of self-supporting hydrogel at physiological pH and thus enhanced the potential of exploring these peptides for biomedical purposes. This coassembly of ionic peptides was accompanied by the enhancement in the mechanical stiffness of the gels and reduction in overall zeta potential of the combined hydrogel, which provides the evidence for additional electrostatic interactions. Furthermore, the thixotropic nature of these gels offers an additional advantage of exploration of designer biomaterials as injectable gels. The nanofibers of coassembled hydrogel were found to be highly biocompatible to the fibroblast cells compared to the individual peptides, which was evident from their cytotoxicity studies. We anticipate that our rational design of ECM protein mimics in the form of short bioactive peptides will contribute significantly to the development of novel biomaterials and play a crucial role in the field of tissue engineering and regenerative medicines.

Tuning the Handedness: Role of Chiral Component in Peptide-Appended Bolaamphiphile-Based Coassembled Hydrogels.

Chirality is the intrinsic property of a molecule that can be tuned by the change in chirality of a molecule or by the addition of a chiral component as an external stimulus. An l-leucine-based dipeptide-appended succinic acid-based bolaamphiphile coassembled with d-tartaric acid to form supramolecular right-handed nanostructured hydrogel, whereas l-tartaric acid coassembled to form supramolecular left-handed nanostructured hydrogel. Scanning electron microscopy and transmission electron microscopy experiments revealed the right- and left-handed helical nanofibers that are responsible for the formation of supramolecular nanostructured hydrogels. The synergistic chiral effect of l-leucine in peptide bolaamphiphile and d/l-tartaric acid plays a significant role in bicomponent gelation with helical nanofibers. The first two amino acids attached to both sides of succinic acid moiety act as a tuning button for supramolecular chirality of amino acids/peptides attached with succinic acid-based bolaamphiphiles. The second amino acid plays the role of modulating supramolecular chirality if the first two amino acids act neutrally to the chirality of bolaamphiphiles, which was confirmed by circular dichroism spectroscopy.

Co-assembled supramolecular hydrogels of cell adhesive peptide and alginate for rapid hemostasis and efficacious wound healing.

Injectable hydrogels are promising materials for applications in non-compressive wound management. Yet difficulties remain for the fabrication of mechanically stable hydrogel materials with inherent functionalities in both hemostatic control and wound healing without additional supplements of growth factors. Herein, we reported the co-assembly of a cell adhesive peptide conjugate (Pept-1) and alginate (ALG), to confer supramolecular hydrogels with excellent mechanical properties and high efficacy in both hemostatic control and wound healing requiring no additional growth factors. The co-assembling process of Pept-1 and ALG, which was mediated by electrostatic interactions and metal chelation, afforded a composite hydrogel with denser nanofibrillar structures and better mechanical strength when comparing to the Pept-1 gel alone. As-prepared Pept-1/ALG hydrogels exhibited excellent injectability and thixotropic properties, making them ideal materials for wound dressing. The composite hydrogel induced fast hemostasis when spiked with whole blood in vitro, and reduced the amount of bleeding to ∼18% of the untreated control in a liver puncture mouse model. Meanwhile, it promoted adhesion and migration of fibroblast NIH3T3 cells in vitro, and accelerated the rate of wound healing in a full-thickness skin defect model of mice. In addition, the Pept-1/ALG hydrogel showed excellent biocompatibility with no obvious hemolytic activity. In future, the strategy of utilizing co-assembled nanostructures composed of biofunctional peptides and polysaccharides could be further exploited to construct a broad range of nanocomposite materials for a variety of biomedical applications.

Co-assembled supramolecular hydrogels of doxorubicin and indomethacin-derived peptide conjugates for synergistic inhibition of cancer cell growth.

Conjugation of indomethacin with a self-assembling peptide moiety affords co-assembled supramolecular nanostructures of doxorubicin and peptide derivatives for tunable release of two drugs and synergistic effects against cancer cells, which illustrates a simple and effective approach to utilize co-assembled nanostructures for co-delivery of self-complementary drug pairs.

Achiral isomers controlled circularly polarized luminescence in supramolecular hydrogels.

Although chiral functional materials showing circularly polarized luminescence (CPL) are being widely reported, it remains a challenge to provide convenient and universal strategies for constructing controllable CPL-active materials with a high luminescence dissymmetry factor (glum). Herein, the supramolecular chirality as well as the CPL handedness of phenylalanine-based hydrogels can be effectively regulated by commercial achiral naphthylamine isomers through non-covalent interactions. Typically, the co-assembled hydrogels exhibit considerably high |glum| values in the range of 5.62 × 10-3-8.74 × 10-3. The CPL inversion is mainly facilitated by intermolecular hydrogen bonds and π-π stacking between the achiral and chiral molecules, which might be induced by the reorientations of the assembled molecules. This work may provide an alternative method to construct tunable CPL-active materials.

Scaffolds Formed via the Non-Equilibrium Supramolecular Assembly of the Synergistic ECM Peptides RGD and PHSRN Demonstrate Improved Cell Attachment in 3D.

Self-assembling peptides (SAPs) are a relatively new class of low molecular weight gelators which immobilize their solvent through the spontaneous formation of (fibrillar) nanoarchitectures. As peptides are derived from proteins, these hydrogels are ideal for use as biocompatible scaffolds for regenerative medicine. Importantly, due to the propensity of peptide sequences to act as signals in nature, they are easily functionalized to be cell instructive via the inclusion of bioactive epitopes. In nature, the fibronectin peptide sequence, arginine-glycine-aspartic acid (RGD) synergistically promotes the integrin α5β1 mediated cell adhesion with another epitope, proline-histidine-serine-arginine-asparagine (PHSRN); however most functionalization strategies focus on RGD alone. Here, for the first time, we discuss the biomimetic inclusion of both these sequences within a self-assembled minimalistic peptide hydrogel. Here, based on our work with Fmoc-FRGDF (N-flourenylmethyloxycarbonyl phenylalanine-arginine-glycine-aspartic acid-phenylalanine), we show it is possible to present two epitopes simultaneously via the assembly of the epitopes by the coassembly of two SAPs, and compare this to the effectiveness of the signals in a single peptide; Fmoc-FRGDF: Fmoc-PHSRN (N-flourenylmethyloxycarbonyl-proline-histidine-serine-arginine-asparagine) and Fmoc-FRGDFPHSRN (N-flourenylmethyloxycarbonyl-phenylalanine-arginine-glycine-asparticacid-phenylalanine-proline-histidine-serine-arginine-asparagine). We show both produced self-supporting hydrogel underpinned by entangled nanofibrils, however, the stiffness of coassembled hydrogel was over two orders of magnitude higher than either Fmoc-FRGDF or Fmoc-FRGDFPHSRN alone. In-vitro three-dimensional cell culture of human mammary fibroblasts on the hydrogel mixed peptide showed dramatically improved adhesion, spreading and proliferation over Fmoc-FRGDF. However, the long peptide did not provide effective cell attachment. The results demonstrated the selective synergy effect of PHSRN with RGD is an effective way to augment the robustness and functionality of self-assembled bioscaffolds.

Transfer and Dynamic Inversion of Coassembled Supramolecular Chirality through 2D-Sheet to Rolled-Up Tubular Structure.

Transfer and inversion of supramolecular chirality from chiral calix[4]arene analogs (3D and 3L) with an alanine moiety to an achiral bipyridine derivative (1) with glycine moieties in a coassembled hydrogel are demonstrated. Molecular chirality of 3D and 3L could transfer supramolecular chirality to an achiral bipyridine derivative 1. Moreover, addition of 0.6 equiv of 3D or 3L to 1 induced supramolecular chirality inversion of 1. More interestingly, the 2D-sheet structure of the coassembled hydrogels formed with 0.2 equiv of 3D or 3L changed to a rolled-up tubular structure in the presence of 0.6 equiv of 3D or 3L. The chirality inversion and morphology change are mainly mediated by intermolecular hydrogen-bonding interactions between the achiral and chiral molecules, which might be induced by reorientations of the assembled molecules, confirmed by density functional theory calculations.

Self-assembly of single amino acid/pyrene conjugates with unique structure-morphology relationship.

This article describes the self-assembly of π-conjugated building blocks composed of single amino acid and pyrene (Py) moieties. In aqueous conditions, the Py-capped amino acids undergo self-assembly through various non-covalent interactions such as hydrogen-bonding, π-π stacking as well as electrostatic interactions to form supramolecular nanostructures in acidic and basic conditions. Interestingly, we found that the blend of different Py-gelators with oppositely charged amino acids (Py-Glu and Py-Lys) displays unique nano-structural morphologies and gelation properties of the resulting hydrogels at physiological pH when compared with single Py conjugates, which was attributed to additional electrostatic interactions. Overall, this report illustrates the importance of two-component supramolecular co-assembled hydrogels and their structure-morphology relationship, improved mechanical properties, and biocompatibility and thus provides a new insight into the design of self-assembled nanomaterials.

Two-Component Fluorescent-Semiconducting Hydrogel from Naphthalene Diimide-Appended Peptide with Long-Chain Amines: Variation in Thermal and Mechanical Strengths of Gels.

Two-component fluorescent hydrogels have been discovered, containing the mixtures of naphthalene diimide (NDI)-conjugated peptide-functionalized bola-amphiphile and primary amines with long alkyl chains at physiological pH 7.46. The aggregation-induced enhanced emission associated with an NDI-appended peptide in aqueous medium is rare, as water is known to be a good quencher of fluorescence. In this study, an NDI-containing gelator peptide forms a highly fluorescent aggregate in aqueous medium. Absorption and emission spectroscopic techniques reveal the formation of J-aggregates among the chromophoric moieties in their aggregated state in aqueous medium. However, this NDI-containing peptide does not form any gel in aqueous medium. In the presence of the primary amines with long alkyl chains in the buffer solution, it forms two-component fluorescent hydrogels exhibiting bright yellow fluorescence under a UV lamp (365 nm). Probably, the acid-amine interaction between the amines and the bola-amphiphile triggers the gel formation, as evident from Fourier transform infrared data, indicating the presence of a carboxylate group (-COO-) and an ammonium species (NH3+) in the coassembled two-component gel system. Low- and wide-angle powder X-ray diffraction and small-angle X-ray scattering further support the fact that the coassembled state in the gel form is produced by the supramolecular interaction between the NDI-based bola-amphiphile and the long-chain amines. Field-emission scanning electron microscopy and high-resolution transmission electron microscopy images reveal that the π-conjugated coassembled hydrogels exhibit nanofibrillar network morphologies. Interestingly, the coassembled hydrogels exhibit an enhanced fluorescence emission, excited-state lifetime, and quantum yield when compared with those of the NDI-containing amphiphile alone in its self-assembled state in aqueous medium. Moreover, the thermal stability and mechanical strength of these gels have been successfully tuned by varying the alkyl chain length of the corresponding amine. Moreover, these NDI-peptide-conjugated soft materials exhibit semiconducting behavior in their respective coassembled states. This holds future promise to use these peptide-appended NDI-based coassembled soft materials for applications in optoelectronic and other devices.

Installing Logic Gates to Multiresponsive Supramolecular Hydrogel Co-assembled from Phenylalanine Amphiphile and Bis(pyridinyl) Derivative.

Recently, logic gates based on multiresponsive hydrogel systems are attractive because of their potential biological applications. A quite simple supramolecular hydrogel co-assembled from phenylalanine-based amphiphile (LPF2) and bis(pyridinyl) derivative (AP) is constructed. The co-assembled hydrogel exhibited a macroscopic gel-sol transition in response to four distinct input stimuli: temperature, acid, base, and light. A set of techniques including microscopic, spectroscopic, and rheological measurements demonstrate this performance and confirm that the hydrogel is formed through intermolecular hydrogen bonds between amide/pyridine moieties and carbonyl groups. On the basis of its mutiple-stimulus responsiveness, installing gel-based supramolecular logic gates (OR and XOR) is achieved. It may promote the possibility to develop smart soft materials, such as gels, that can be used as tools releasing a drug quantitatively by rational design and fine control of the external stimuli.

Conducting hydrogel of a naphthalenetetracarboxylic dianhydride derivative and polyaniline: different electronic properties in gel and xerogel states

An aminoisophthalic acid derivative of naphthalenetetracarboxylic dianhydride (NDI) is synthesized to produce a hydrogel via acid–base treatment. NDI is used to make co-assembled hydrogels with polyaniline (PANI) by in situ polymerization of aniline, and these are named NP0.5, NP1.0 and NP1.5 according to the amount (ml) of anilinium chloride solution. The NDI gel exhibits a fibrillar network morphology, and in the NDI-PANI gels a change in fiber texture occurs. The FTIR and NMR spectra indicate the presence of supramolecular interactions in the NDI-PANI gels and the PANI produced in the gel is in the emeraldine salt (ES) form which is also supported by UV-vis spectroscopy results. X-ray diffraction indicates the NDI gel has a lamellar structure and the lamellar distance increases significantly in the NDI-PANI gels. A schematic model of the supramolecularly organized structure with alternating NDI and PANI chains is proposed for fiber formation. Rheological study indicates storage (G′) and loss (G′′) moduli to be invariant with frequency and a 213- and 112-time increase in G′ and G′′ is observed for the NP1.5 gel. Also, it's elasticity increases by 22 463%, yield stress by 905% and stiffness by 88%, as compared to those of the NDI gel. The NP1 xerogel exhibits the highest dc conductivity (5.2 × 10−3 S cm−1) and the current (I)–voltage (V) curves of the xerogels are different from those of the gels; the former exhibits the characteristics of a semiconductor–metal junction and the latter exhibits negative differential resistance with rectification properties, simultaneously. The Nyquist plots of the impedance values also indicate a difference between the xerogel and gel state; in the former only semicircles are observed, but in the latter a semicircle and a sloping line are noticed. The difference in the I–V properties in the xerogel and gel state is attributed to the diffusion controlled movement of the charge carriers through the water molecules in the gels and it is supported by the sloping line in the Nyquist plot of the gels.

Gram-positive antimicrobial activity of amino acid-based hydrogels.

Antimicrobial hydrogels are prepared based on the co-assembly of commercial Fmoc-phenylalanine and Fmoc-leucine, which act as the hydrogelator and antimicrobial building block, respectively. This co-assembled antimicrobial hydrogel is demonstrated to exhibit selective bactericidal activity for gram-positive bacteria while being biocompatible with normal mammalian cells, showing great potential as an antimicrobial coating for clinical anti-infective applications.

Co-assembled conductive hydrogel of N-fluorenylmethoxycarbonyl phenylalanine with polyaniline.

A metastable coassembled hydrogel of N-Fluorenylmethoxycarbonyl (Fmoc) phenylalanine (FP) with aniline (FP-ANI), upon polymerization, produces a stable green-colored coassembled FP-polyaniline (FP-PANI) hydrogel. The coassembly is produced by supramolecular interactions between FP and ANI/PANI. WAXS spectra suggest that structures of FP powder, FP-ANI, and FP-PANI xerogels are different from each other. The FP-ANI gel exhibits a mixture of doughnut and fiber morphology, but the FP-PANI gel exhibits a nanotubular morphology. UV-vis spectroscopy suggests that the doped state of PANI and the fluorescence property of FP completely vanish in the FP-PANI gel. The storage and loss modulii (G' and G″) of the FP-PANI gel are higher than those of the FP-ANI gel. The FP-ANI gel breaks at a lower oscillator stress (57 Pa) than the FP-PANI gel (93 Pa), which exhibits a good strain recovery demonstrating excellent viscoelastic properties. The FP-PANI gel also exhibits a dc conductivity (1.2 × 10(-2) S·cm(-1)) that is seven orders higher than that of the FP-ANI gel because of the doped nature of PANI. The current-voltage (I-V) characteristic curve of FP-PANI xerogel resembles the behavior of a semiconductor-metal junction, and upon white light irradiation, it exhibits a reversible on-off cycle with a constant photocurrent value of 0.1 mA. The Nyquist plot obtained from impedance measurements of the FP-PANI xerogel is different from that obtained for the FP-ANI xerogel, and it exhibits almost a semicircle, indicating the existence of both resistive and capacitive features connected in parallel mode.