Thick Electrodes of a Self-Assembled MXene Hydrogel Composite for High-Rate Energy Storage

Supercapacitors based on two-dimensional MXene(Ti_(3)C_(2)T_(z))have shown extraordinary performance in ultrathin electrodes with low mass loading,but usually there is a significant reduction in high-rate performance as the thickness increases,caused by increasing ion diffusion limitation.Further limitations include restacking of the nanosheets,which makes it challenging to realize the full potential of these electrode materials.Herein,we demonstrate the design of a vertically aligned MXene hydrogel composite,achieved by thermal-assisted self-assembled gelation,for high-rate energy storage.The highly interconnected MXene network in the hydrogel architecture provides very good electron transport properties,and its vertical ion channel structure facilitates rapid ion transport.The resulting hydrogel electrode show excellent performance in both aqueous and organic electrolytes with respect to high capacitance,stability,and high-rate capability for up to 300μm thick electrodes,which represents a significant step toward practical applications.

A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

Recent advances in design and applications of biomimetic self-assembled peptide hydrogels for hard tissue regeneration

The development of natural biomaterials applied for hard tissue repair and regeneration is of great importance,especially in societies with a large elderly population.Self-assembled peptide hydrogels are a new generation of biomaterials that provide excellent biocompatibility,tunable mechanical stability,injectability,trigger capability,lack of immunogenic reactions,and the ability to load cells and active pharmaceutical agents for tissue regeneration.Peptide-based hydrogels are ideal templates for the deposition of hydroxyapatite crystals,which can mimic the extracellular matrix.Thus,peptide-based hydrogels enhance hard tissue repair and regeneration compared to conventional methods.This review presents three major self-assembled peptide hydrogels with potential application for bone and dental tissue regeneration,including ionic self-complementary peptides,amphiphilic(surfactant-like)peptides,and triple-helix(collagen-like)peptides.Special attention is given to the main bioactive peptides,the role and importance of self-assembled peptide hydrogels,and a brief overview on molecular simulation of self-assembled peptide hydrogels applied for bone and dental tissue engineering and regeneration.

Self-assembling peptide nanofibrous hydrogel as a promising strategy in nerve repair after traumatic injury in the nervous system

Following injury in central nervous system（CNS）,there are pathological changes in the injured region,which include neuronal death,axonal damage and demyelination,inflammatory response and activation of glial cells.The proliferation of a large number of astrocytes results in the formation of glial scar.

Microrheology and Release Behaviors of Self-Assembled Steroid Hydrogels

A hydrogel is formed by the self-assembly of sodium deoxycholate (NaDC) in aqueous solution with sodium chloride at pH-7.0. The NaDC hydrogel made of the three-dimensional network of nanofibers shows pH-dependent swelling behaviors. Polystyrene particles with a diameter of 100 nm and doxorubicin hydrochloride (DOX) can be easily loaded into the NaDC hydrogel through swelling. By using the loaded polystyrene particles as a light scattering probe, we study the microrheology of the NaDC hydrogel, showing complex viscoelastic properties. The viscous component dominates at both low and high frequencies, while the elastic component dominates in the intermediate range. The cavity size of the nanofiber network can also be estimated to be ~180 nm. We show that the loaded DOX can be slowly released from the hydrogels into aqueous solution. The release profile of DOX is found to depend on the pH value of the solution.

Cartilage-inspired self-assembly glycopeptide hydrogels for cartilage regeneration via ROS scavenging

Cartilage injury represents a frequent dilemma in clinical practice owing to its inherently limited self-renewal capacity.Biomimetic strategy-based engineered biomaterial,capable of coordinated regulation for cellular and microenvironmental crosstalk,provides an adequate avenue to boost cartilage regeneration.The level of oxidative stress in microenvironments is verified to be vital for tissue regeneration,yet it is often overlooked in engineered biomaterials for cartilage regeneration.Herein,inspired by natural cartilage architecture,a fibril-network glycopeptide hydrogel(Nap-FFGRGD@FU),composed of marine-derived polysaccharide fucoidan(FU)and naphthalenephenylalanine-phenylalanine-glycine-arginine-glycine-aspartic peptide(Nap-FFGRGD),was presented through a simple supramolecular self-assembly approach.The Nap-FFGRGD@FU hydrogels exhibit a native cartilage-like architecture,characterized by interwoven collagen fibers and attached proteoglycans.Beyond structural simulation,fucoidan-exerted robust biological effects and Arg-Gly-Asp(RGD)sequence-provided cell attachment sites realized functional reinforcement,synergistically promoted extracellular matrix(ECM)production and reactive oxygen species(ROS)elimination,thus contributing to chondrocytes-ECM harmony.In vitro co-culture with glycopeptide hydrogels not only facilitated cartilage ECM anabolic metabolism but also scavenged ROS accumulation in chondrocytes.Mechanistically,the chondro-protective effects induced by glycopeptide hydrogels rely on the activation of endogenous antioxidant pathways associated with nuclear factor erythroid 2-related factor 2(NRF2).In vivo implantation of glycopeptide hydrogels successfully improved the de novo cartilage generation by 1.65-fold,concomitant with coordinately restructured subchondral bone structure.Collectively,our ingeniously crafted bionic glycopeptide hydrogels simultaneously rewired chondrocytes’function by augmenting anabolic metabolism and rebuilt ECM microenvironment via preserving redox equilibrium,holding great potential for cartilage tissue engineering.

Two-dimensional Effects of Hydrogel Self-organized from IKVAV-containing Peptides on Growth and Differentiation of NSCs

The neural stem cells （NSCs） were seeded in the surface layer of hydrogels made of IKVAV-containing peptide amphiphile. Two-dimensional effects of hydrogel on growth and differentiation of NSCs were investigated. Peptide was synthesized in solid way. Cells were harvested from the cerebral cortex of neonatal mice, identified by immunohistochemical methods. Cells were incubated in the surface layer of self-assembled peptide hydrogel and coverslips for seven days respectively,detected immunocytochemically for NF and GFAP. The molecular weight （Mw） of Peptide was 1438 and purity was 95.22%. Cells were identified as Nestin-positive NSCs. TEM showed that hydrogel was composed of interactive nanofibers. NSCs extended processes, and were able to be dif- ferentiated into NF-positive neurons with red fluorescence and GFAP-positive astrocytes with green one in the surface of hydrogel. However, NSCs only formed undifferentiated neurospheres in the surface layer of coverslips. Results indicate that the self-assembled hydrogel from peptide amphiphile has good cyto-compatibility to NSCs and induced their differentiation.

Polyamine-Polymeric Micelle Hybrid Hydrogel: Microscopic Properties of Crosslinkers Affecting Macroscopic Rheological Properties of Hydrogel

We have developed a hybrid hydrogel that is formed from a crosslinkable polymeric micelle and a polyamine. Under optimal conditions, the hydrogel rapidly formed in one second after a crosslinkable polymeric micelle solution was mixed with a polyamine solution. We could change the hydrogel’s gelation properties, such as the storage modulus and gelation time by tuning the molecular weights of block copolymers and by tuning the pH of the dissolving-solvent of the hydrogel’s constituent components. Furthermore, we have clarified here that the structural difference among the micelles acting as crosslinkers can affect the gelation properties of the hydrogel. According to our findings, the hydrogel that was formed from the polymeric micelles possessing a highly packed (i.e., well-entangled or crosslinked) inner core exhibited a higher storage modulus than the hydrogel that was formed from the polymeric micelles possessing a lowly packed structure. Our results demonstrate that a microscopic structural difference among crosslinkers can induce a macroscopic change in the properties of the resulting hydrogels. For medical applications, the hydrogel proposed in the present paper can encapsulate the hydrophobic compounds in crosslinkers (polymeric micelles) so that the hydrogel can be available as the biomaterial for their sustained release.

Collagen fibril-like injectable hydrogels from self-assembled nanoparticles for promoting wound healing

Soft hydrogels are excellent candidate materials for repairing various tissue defects,yet the mechanical strength,anti-swelling properties,and biocompatibility of many soft hydrogels need to be improved.Herein,inspired by the nanostructure of collagen fibrils,we developed a strategy toward achieving a soft but tough,anti-swelling nanofibrillar hydrogel by combining the self-assembly and chemical crosslinking of nanoparticles.Specifically,the collagen fibril-like injectable hydrogel was subtly designed and fabricated by self-assembling methylacrylyl hydroxypropyl chitosan(HM)with laponite(LAP)to form nanoparticles,followed by the inter-nanoparticle bonding through photo-crosslinking.The assembly mechanism of nanoparticles was elucidated by both experimental and simulation techniques.Due to the unique structure of the crosslinked nanoparticles,the nanocomposite hydrogels exhibited low stiffness(G’<2 kPa),high compressive strength(709 kPa),and anti-swelling(swelling ratio of 1.07 in PBS)properties.Additionally,by harnessing the photo-crosslinking ability of the nanoparticles,the nanocomposite hydrogels were processed as microgels,which can be three-dimensionally(3D)printed into complex shapes.Furthermore,we demonstrated that these nanocomposite hydrogels are highly biocompatible,biodegradability,and can effectively promote fibroblast migration and accelerate blood vessel formation during wound healing.This work presents a promising approach to develop biomimetic,nanofibrillar soft hydrogels for regenerative medicine applications.

Hydrothermal Self-assembly Synthesis of Mn3O4Reduced Graphene Oxide Hydrogel and Its High Electrochemical Performance for Supercapacitors

In the present work Mn3O4/reduced graphene oxide hydrogel （Mn3O4-rGOH） with three dimensional （3D） networks was fabricated by a hydrothermal self-assembly route. The morphology, composition, and microstructure of the as-obtained samples were characterized using powder X-ray diffraction （XRD）, X-ray photoelectron spectroscopy （XPS）, thermogravimetry analysis （TG）, atomic absorption spectrometry （AAS）, field emission scanning electron microscopy （FESEM） and transmission electron microscope （TEM）. Moreover, the electrochemical behaviors were evaluated by cyclic voltammogram （CV）, galvanostatic charge-discharge and electrochemical impedance spectroscopy （EIS）. The test results indicated that the hydrogel with 6.9% Mn3O4 achieved specific capacitance of 148 F.g^-1 at a specific current of 1 A.g^-1, and showed excellent cycling stabilily with no decay after 1200 cycles. In addition, its specific capacitance could retain 70% even at 20 A.g^- 1 in comparison with that at 1 A.g ^-1 and the operating window was up to 1.8 V in a neutral electrolyte.

Enzyme-instructed self-assembly of peptides containing phosphoserine to form supramolecular hydrogels as potential soft biomaterials

Enzyme-instructed self-assembly （EISA） offers a facile approach to explore the supramolecular assemblies of small molecules in cellular milieu for a variety of biomedical applications. One of the commonly used enzymes is phosphatase, but the study of the substrates of phosphatases mainly focuses on the phos- photyrosine containing peptides. In this work, we examine the EISA of phosphoserine containing small peptides for the first time by designing and synthesizing a series of precursors containing only phosphoserine or both phos- phoserine and phosphotyrosine. Conjugating a phospho- serine to the C-terminal of a well-established self- assembling peptide backbone, （naphthalene-2-1y）-acetyl- diphenylalanine （NapFF）, affords a novel hydrogelation precursor for EISA. The incorporation ofphosphotyrosine, another substrate of phosphatase, into the resulting precursor, provides one more enzymatic trigger on a single molecule, and meanwhile increases the precursors＇ propensity to aggregate after being fully dephosphorylated. Exchanging the positions of phosphorylated serine and tyrosine in the peptide backbone provides insights on how the specific molecular structures influence self-assembling behaviors of small peptides and the subsequent cellular responses. Moreover, the utilization of D-amino acids largely enhances the biostability of the peptides, thus providing a unique soft material for potential biomedical applications.

Bioinspired supramolecular nanofiber hydrogel through self-assembly of biphenyl-tripeptide for tissue engineering

Supramolecular nanofiber peptide assemblies had been used to construct functional hydrogel biomaterials and achieved great progress.Here,a new class of biphenyl-tripeptides with different C-terminal amino acids sequences transposition were developed,which could self-assemble to form robust supramolecular nanofiber hydrogels from 0.7 to 13.8 kPa at ultra-low weight percent(about 0.27 wt%).Using molecular dynamics simulations to interrogate the physicochemical properties of designed biphenyl-tripeptide sequences in atomic detail,reasonable hydrogen bond interactions and“FF”brick(phenylalanine-phenylalanine)promoted the formation of supramolecular fibrous hydrogels.The biomechanical properties and intermolecular interactions were also analyzed by rheology and spectroscopy analysis to optimize amino acid sequence.Enhanced L929 cells adhesion and proliferation demonstrated good biocompatibility of the hydrogels.The storage modulus of BPAA-AFF with 10 nm nanofibers self-assembling was around 13.8 kPa,and the morphology was similar to natural extracellular matrix.These supramolecular nanofiber hydrogels could effectively support chondrocytes spreading and proliferation,and specifically enhance chondrogenic related genes expression and chondrogenic matrix secretion.Such biomimetic supramolecular short peptide biomaterials hold great potential in regenerative medicine as promising innovative matrices because of their simple and regular molecular structure and excellent biological performance.

Precursor-involved and Conversion Rate-controlled Self-assembly of a ＇Super Gelator＇ in Thixotropic Hydrogels for Drug Delivery

Enzymatic hydrogelation is a totally different process to the heating-cooling gelation process, in which the pre- cursors of the gelators can be involved during the formation of self-assembled structures. Using thixotropic hy- drogels formed by a super gelator as our studied system, we demonstrated that the enzyme concentration/conversion rate of enzymatic reaction had a strong influence on the morphology of resulting self-assembled nanostructures and the property of resulting hydrogels. The principle demonstrated in this study not only helps to understand and elucidate the phenomenon of self-assembly triggered by enzymes in biological systems, but also offers a unique methodology to control the morphology of self-assembled structures for specific applications such as controlled drug re- lease.

The Physical Chemistry for the Self-assembly of Peptide Hydrogels

Peptide hydrogels have been widely used for diverse biomedical applications. However, our current understanding of the physical principles underlying the self-assembly process is still limited. In this review, we summarize our current understanding on the physical chemistry principles from the basic interactions that drive the self-assembly process to the energy landscapes that dictate the thermodynamics and kinetics of the process. We discuss the effect of different factors that affect the kinetics of the self-assembly of peptide fibrils and how this is related to the macroscopic gelation process. We provide our understanding on the molecular origin of the complex and rugged energy landscape for the self-assembly of peptide hydrogels. The hierarchical self-assembled structures and the diverse self-assembling mechanism make it difficult and challenging to rationally design the physical and chemical properties of peptide hydrogels at the molecular revel. We also give our personal perspective to the potential future directions in this field.

Hierarchical Self-assembly of G-Quadruplexes Based Hydrogel Consisting of Guanine and Peptide Epitope

Guanosine-based hydrogels have attracted considerable attention because of their simplicity and easy preparation.However,the sugar moiety limits its further applications because of the necessity of sugar in the hydrogel formation.This work reports a G-quadruplexes-based hydrogel consisting of guanine and peptide epitope to form a supramolecular hydrogel in the presence of metal cations.Using the metal ion-responsive peptide epitope from the ion channel to replace sugar motif at N9 position of guanosine results in a novel nucleopeptide.The results show that the gelation time,the diameter of nanofibers,the anisotropic property,and the mechanical property of the hydrogel can be simply controlled using metal cations.The magnesium and calcium ions direct the alignment of nanofibers to form anisotropic nano-bundles.The mechanistic studies indicate the formation of G-quadruplexes in the hydrogel.Compared to the storage modulus of nucleopeptide without the metal cation,adding zinc ions results in an over three-order increase in mechanical properties.Cytotoxicity experiment indicates the good biocompatibility of our hydrogel.Moreover,we demonstrate that the guanine-capped peptide could release STING agonist in a controlled manner.This work illustrates a simple way to modulate the property of the nucleopeptide hydrogel to develop soft materials.

Bioinspired self-assembly supramolecular hydrogel for ocular drug delivery

Based on a recent report concerning endogenous agents(i.e., pyridoxal phosphate, adenosine triphosphate, adenosine monophosphate, folinic acid) that modulate the oligomerization of apoptosis-associated speck-like protein(ASC) via the peptide epitope of KKFKLKL, we rationally designed and synthesized a nonapeptide(Nap FFKKFKLKL), which can co-assemble with dexamethasone sodium phosphate(Dexp) to generate a Nap FFKKFKLKL/Dexp supramolecular hydrogel for ocular drug delivery.The Nap FFKKFKLKL/Dexp hydrogel formed instantly after the complexation of Nap FFKKFKLKL with Dexp in aqueous solution. The formed supramolecular hydrogels were thoroughly characterized by transmission electron microscopy(TEM), fluorescent spectrum, circular dichroism(CD) spectra and rheology. The peptide concentration significantly affected the in vitro release behavior of Dexp from the supramolecular hydrogel, and the higher peptide concentration resulted in the slower drug release.Following a single intravitreal injection, the proposed Nap FFKKFKLKL/Dexp hydrogel displayed good intraocular biocompatibility without having an adverse impact on the retinal architecture and eyesight functions during one month of follow-up. Using an experimental autoimmune uveitis(EAU) rat model,we demonstrated that the resulting Nap FFKKFKLKL/Dexp hydrogel had potent capacity to alleviate the intraocular inflammation and retain the morphology of retinal architecture. Overall, the resulting Nap FFKKFKLKL/Dexp hydrogel may be a promising drug carrier system to treat various posterior disorders(i.e., uveitis).

Regulating Mechanical Properties of Polymer-Supramolecular Double-Network Hydrogel by Supramolecular Self-assembling Structures

Main observation and conclusion Polymer-supramolecular double-network hydrogels(PS-DN hydrogels)often show much improved recovery rates than conventional double-network hydrogels because of the fast self-assembling properties,making them attractive candidates for tissue engineering and flexible electronics.However,as the supramolecular network is dynamic and susceptible to break under low strains,the overall mechanical properties of PS-DN hydrogels are still limited.Here,we report the mechanical properties for PS-DN hydrogels can be significantly improved by tuning the supramolecular network structures.A single amino acid change of the self-assembling peptide can tune the assembled structures from nanofiber to nanoribbon.Such a microscopic structural change can greatly increase the Young's modulus(107.4 kPa),fracture stress(0.48 MPa),and toughness(0.38 MJ·m^(–3))of the PS-DN hydrogels.Moreover,the structural change also leads to slightly faster recovery rates(<1 s).We propose that such dramatically different mechanical properties can be understood by the impact of individual peptide rupture events on the overall network connectivity in the two scenarios.Our study may provide new inspirations for combining high mechanical strength and fast recovery in double network hydrogels by tuning the supramolecular network structures.

Functional self-assembling peptide nanofiber hydrogel for peripheral nerve regeneration

Peripheral nerves are fragile and easily damaged,usually resulting in nervous tissue loss,motor and sensory function loss.Advances in neuroscience and engineering have been significantly contributing to bridge the damage nerve and create permissive environment for axonal regrowth across lesions.We have successfully designed two self-assembling peptides by modifying RADA 16-I with two functional motifs IKVAV and RGD.Nanofiber hydrogel formed when combing the two neutral solutions together,defined as RADA 16-Mix that overcomes the main drawback of RADA16-I associated with low pH.In the present study,we transplanted the RADA 16-Mix hydrogel into the transected rat sciatic nerve gap and effect on axonal regeneration was examined and compared with the traditional RADA16-I hydrogel.The regenerated nerves were found to grow along the walls of the large cavities formed in the graft of RADA16-I hydrogel,while the nerves grew into the RADA 16-Mix hydrogel toward distal position.RADA 16-Mix hydrogel induced more axons regeneration and Schwann cells immigration than RADA16-I hydrogel,resulting in better functional recovery as determined by the gait-stance duration percentage and the formation of new neuromuscular junction structures.Therefore,our results indicated that the functional SAP RADA16-Mix nanofibrous hydrogel provided a better environment for peripheral nerve regeneration than RADA16-I hydrogel and could be potentially used in peripheral nerve injury repair.

A neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel enhances rat sciatic nerve regeneration

Nerve guidance conduit （NGC） is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment using physical and/or chemical guidance cues. In this study, a neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel that could promote PC12 cell adhesion, proliferation, and neuronal differentiation in vitro was prefilled in the lumen of a hollow chitosan tube （hCST） to accelerate axonal regeneration in a rat sciatic nerve defect model. The functionalized self-assembling peptide was developed by introducing a neurotrophic peptide （RGI, RGIDKRHWNSQ） derived from brain-derived neurotrophic factor （BDNF） to the C-terminus of the self-assembling peptide RADA16-I （Ac-（RADA）4-CONH2）. Morphological, histological, electrophysiological, and functional analyses demonstrated that the RGI-functionalized, self-assembling, peptide nanofiber hydrogel RAD/RGI could produce a neurotrophic microenvironment that markedly improved axonal regeneration with enhanced re-myelination and motor functional recovery.

Self-assembled structures of a semi-rigid polyanion in aqueous solutions and hydrogels

Poly(2,2'-disulfonyl-4,4'-benzidine terephthalamide) (PBDT), a kind of liquid-crystalline (LC) molecule, has high molecular weight, negative charge and a semi-rigid structure. The aqueous solution of PBDT shows nematic liquid crystalline state above a critical PBDT concentration, CLC*, of 2 wt%-3wt%. Different from the flexible polyelectrolyte, PBDT shows a variety of self-assembling structures in aqueous solution with and without salt due to the semi-rigid nature and highly charged property. In addition, the hydrogels with ordered structure are developed by polymerizing a cationic monomer N-[3-(N,N-dimethylamino) propyl] acrylamide methyl chloride quarternary (DMAPAA-Q) in the presence of a small amount of PBDT below the CLC*. During the polymerization of cationic monomer, the polycations form a complex with semi-rigid PBDT through electrostatic interaction; these complexes self-assemble into ordered structures that are frozen in the hydrogel. Several different structures, including the anisotropic, dual network-like structure, and cylindrically symmetric structure, with various length scales from micrometer to millimeter, are observed. The hydrogels with ordered liquid crystalline assemblies and particular optical properties should promise applications in many fields, such as in bionics, tissue engineering, and mechano-optical sensors.