Multilayered composite-coated ionically crosslinked food-grade hydrogel beads generated from algal alginate for controlled and sustained release of bioactive compounds

Hydrogels have gained interest as sustained-release matrices partly because of their high biocompatibility and ease of preparation. Their wide application has, however, been limited by their poor mechanical strength and their lack of tunability in the performance of bioactive agent delivery. By using the lake substratum as a gel property modifier, in combination with the use of the surface coating approach and the ionic gelation technique, hydrogel beads are generated from algal alginate for controlled and sustained release of bioactive compounds. Both the acute and chronic toxicity of the beads are found to be negligible in 3T3 fibroblasts. The capacity of the beads in retaining the activity of the loaded agent is verified by the negligible change in the action of the loaded compound on foodborne bacteria (viz., Staphylococcus aureus and Escherichia coli). Along with the high flexibility provided by the adopted method in the choice of coating materials, our beads extend the limitations of conventional ionically crosslinked gel systems, and show high potential for applications in functional food development, nutraceutical delivery, and pharmaceutical formulation.

Multilayered composite-coated hydrogel beads are generated from algal alginate as carriers of bioactive compounds. They show high potential for applications in functional food development, nutraceutical delivery, and pharmaceutical formulation.     

Biocompatible supramolecular pseudorotaxane hydrogels for controllable release of doxorubicin in ovarian cancer SKOV-3 cells

A series of injectable and biocompatible delivery DOX-loaded supramolecular hydrogels were fabricated by using presynthesized DOX-2N-β-CD, Pluronic F-127 and α-CD through host–guest interactions and cooperative multivalent hydrogen bonding interactions. The compositions and morphologies of these hydrogels were confirmed by PXRD and SEM measurements. Moreover, the Rheological measurements of these hydrogels were studied and the studies found that they showed a unique thixotropic behavior, indicting a fast self-healing property after the continuous oscillatory shear stress. Using α-CD as a capping agent, slow and sustained DOX release was observed at different pH values after 72 h. The amount of DOX released at pH 7.4 was determined to be 49.0% for hydrogel 1, whereas the releasing amount of the DOX was increased to 66.3% for hydrogel 1 during the same period at pH 5.5 (P < 0.05), indicating a higher release rate of the drug under more acidic conditions. Taking hydrogel 1 as a representative material, the toxicities of DOX and hydrogel 1 on ovarian cancer cells (SKOV-3) at different exposure durations were examined. The results revealed that hydrogel 1 was less cytotoxic than free DOX to SKOV-3 cells (P < 0.05), suggesting sustained release by these hydrogels in the presence of ovarian cancer cells. It is anticipated that this exploration can provide a new strategy for preparing drug delivery systems.

A series of injectable and biocompatible delivery DOX-loaded supramolecular hydrogels were fabricated by using presynthesized DOX-2N-β-CD, Pluronic F-127 and α-CD through host–guest interactions and cooperative multivalent hydrogen bonding interactions.     

Physiologically stable F127-GO supramolecular hydrogel with sustained drug release characteristic for chemotherapy and photothermal therapy

A synthetic method for preparing a Pluronic F127 (F127)-stabilized graphene (GO) supramolecular hydrogel as a safe nanovehicle for combination treatment has been studied. Doxorubicin (DOX) as a model drug is non-covalently bound on the great surface area of GO due to strong π–π interaction, hydrophobic interaction, and the strongest hydrogen bonding. In vitro drug release experiments revealed that this F127-stabilized GO supramolecular hydrogel has a sustained drug release characteristic. Furthermore, the supramolecular hydrogel showed better in vitro antitumor ability under NIR (near infrared) laser irradiation because of the excellent photothermal effect of GO. Moreover, we evaluated its antitumor ability in vivo and the results show that the hydrogel system can also markedly inhibit the growth of a tumor when administered individually, especially under laser irradiation. All these findings make the supramolecular hydrogel system promising for combination therapy with good bioavailability and minimal side effects.

The F127-GO-DOX supramolecular hydrogel system with sustained drug release characteristic for chemotherapy and photothermal therapy.     

Synthesis of nanomedicine hydrogel microcapsules by droplet microfluidic process and their pH and temperature dependent release

Chitosan and alginate hydrogels are attractive because they are highly biocompatible and suitable for developing nanomedicine microcapsules. Here we fabricated a polydimethylsiloxane-based droplet microfluidic reactor to synthesize nanomedicine hydrogel microcapsules using Au@CoFeB–Rg3 as a nanomedicine model and a mixture of sodium alginate and PEG-g-chitosan crosslinked by genipin as a hydrogel model. The release kinetics of nanomedicines from the hydrogel were evaluated by simulating the pH and temperature of the digestive tract during drug transport and those of the target pathological cell microenvironment. Their pH and temperature-dependent release kinetics were studied by measuring the mass loss of small pieces of thin films formed by the nanomedicine-encapsulating hydrogels in buffers of pH 1.2, 7.4, and 5.5, which replicate the pH of the stomach, gut and blood, and cancer microenvironment, respectively, at 20 °C and 37 °C, corresponding to the storage temperature of hydrogels before use and normal body temperature. Interestingly, nanomedicine-encapsulating hydrogels can undergo rapid decomposition at pH 5.5 and are relatively stable at pH 7.4 at 37 °C, which are desirable qualities for drug delivery, controlled release, and residue elimination after achieving target effects. These results indicate that the designed nanomedicine hydrogel microcapsule system is suitable for oral administration.

A kind of pH and temperature dependent interpenetrating hydrogel was designed and synthesized via crosslinking of alginate and polyethylene-glycol grafting chitosan by genipin for encapsulated nanomedicine with controlled release.     

A sodium alginate-based sustained-release IPN hydrogel and its applications

Interpenetrating polymer network (IPN) hydrogels are crosslinked by two or more polymer networks, providing free volume space in the three-dimensional network structure, and providing conditions for the sustained and controlled release of drugs. The IPN hydrogels based on the natural polymer sodium alginate can form a stable porous network structure. Due to its excellent biocompatibility, the loaded drug can be sustained to the maximum extent without affecting its pharmacological effect. Sodium alginate-based IPN hydrogels have broad application prospects in the field of sustained and controlled drug release. This paper begins with an overview of the formation of alginate-based IPN hydrogels; summarizes the types of alginate-based IPN hydrogels; and discusses the pharmaceutical applications of alginate-based IPN hydrogels. We aim to give an overview of the research on IPN hydrogels based on sodium alginate in sustained and controlled drug release systems.

Interpenetrating polymer network (IPN) hydrogels are crosslinked by two or more polymer networks, providing free volume space in the three-dimensional network structure, and providing conditions for the sustained and controlled release of drugs.     

Design and performance of a poly(vinyl alcohol)/silk fibroin enzymatically crosslinked semi-interpenetrating hydrogel for a potential hydrophobic drug delivery

In this study, in order to obtain hydrogels with good properties for sustained release of hydrophobic drugs or for tissue engineering, poly(vinyl alcohol) (PVA)/silk fibroin (SF) semi-interpenetrating (semi-IPN) hydrogels with varied ratios of PVA/SF were enzymatically cross-linked using horseradish peroxidase. A vial inversion test determined approximate gelation times of PVA/SF hydrogels ranging from 5 to 10 min. The hydrogels with varied ratios showed differences in pore size and morphology. Mass loss rate of hydrogels increased from 15% to 58% with increasing PVA concentration. Stable hydrogels with PVA/SF at 0.5 : 1 w/w showed the best swelling ratio values in distilled water (7.36). FTIR analysis revealed that silk fibroin in these hydrogels exhibited the coexistence of amorphous and silk I crystalline structures and the SF and PVA molecules interacted with each other well. The mechanical properties of the composite hydrogels were controlled by the SF content. From the cell viability results, it was found that the hydrogels exerted very low cytotoxicity. Paeonol was chosen as the hydrophobic drug model for release studies from the hydrogels. Paeonol can be uniformly loaded into the composite hydrogels using the emulsifying property of PVA and paeonol release from the hydrogels was dependent on the PVA/SF ratio. This study applied a novel type of enzymatically crosslinked semi-IPN hydrogel that may have potential applications in drug delivery.

Enzymatically cross-linked PVA/SF semi-IPN hydrogels with tunable pore structure have potential applications in sustained release of hydrophobic drug.     

Dual release kinetics in a single dosage from core–shell hydrogel scaffolds

The development of drug delivery systems with microencapsulated therapeutic agents is a promising approach to the sustained and controlled delivery of various drug molecules. The incorporation of dual release kinetics to such delivery devices further adds to their applicability. Herein, novel core–shell scaffolds composed of sodium deoxycholate and trishydroxymethylaminomethane (NaDC–Tris) have been developed with the aim of delivering two different drugs with variable release rates using the same delivery vehicle. Data obtained from XRD studies, sol–gel transition temperature measurement, rheology and fluorescence studies of the core–shell systems indicate a significant alteration in the core and the shell microstructural properties in a given system as compared to the pure hydrogels of identical compositions. The release of the model drugs Fluorescein (FL) and Rhodamine B (RhB) from the shell and the core, respectively, of the two core–shell designs studied exhibited distinctly different release kinetics. In the 25@250 core–shell system, 100% release of FL from the shell and 19% release of RhB from the core was observed within the first 5 hours, while 24.5 hours was required for the complete release of RhB from the core. For the 100@250 system, similar behaviour was observed with varied release rates and a sigmoidal increase in the core release rate upon disappearance from the shell. Cell viability studies suggested the minimal toxicity of the developed delivery vehicles towards NMuMG and WI-38 cells in the concentration range investigated. The reported core–shell systems composed of a single low molecular weight gelator with dual release kinetics may be designed as per the desired application for the consecutive release of therapeutic agents as required, as well as combination therapy commonly used to treat diseases such as diabetes and cancer.

A single LMW gelator based core–shell hydrogel with dual release kinetics.     

Preparing 3D-printable silk fibroin hydrogels with robustness by a two-step crosslinking method

Regenerated silk fibroin (RSF) features excellent biocompatibility and high-strength mechanical properties. However, traditional RSF-based materials can hardly be applied in 3D printing, which has shown great potential in producing artificial implants. In this work, we report a 3D printable RSF hydrogel formed by a weak, chemically crosslinked network. After the 3D printing process, the mechanical properties of the above hydrogel can be remarkably improved by a ripening process. The maximum compressive modulus of this RSF hydrogel is 2.5 MPa, reaching the same order of magnitude as natural elastomers such as cartilage. The mechanical properties of this hydrogel are superior to most RSF-based 3D printed hydrogels. The investigation of gelation mechanism reveals that the chemically crosslinked network can constrain the growth of β-sheet structures of RSF to form a dense and uniform physical network. Such a physically crosslinked network endows the high strength and good resilience of RSF hydrogels. With both good biocompatibility and mechanical properties, this double-network hydrogel has potential in producing 3D printed scaffolds for tissue engineering.

Schematic showing the fabrication process of the 3D-printed robust double-network RSF hydrogels.     

The biofunctionalization of titanium nanotube with chitosan/genipin heparin hydrogel and the controlled release of IL-4 for anti-coagulation and anti-thrombus through accelerating endothelialization

The valve replacement is the main treatment of heart valve disease. However, thrombus formation following valve replacement has always been a major clinical drawback. Accelerating the endothelialization of cardiac valve prosthesis is the main approach to reduce thrombus. In the current study, a titanium nanotube was biofunctionalized with a chitosan/genipin heparin hydrogel and the controlled release of interleukin-4 (IL-4), and its regulation of macrophages was investigated to see if it could influence endothelial cells to eventually accelerate endothelialization. TNT60 (titanium dioxide nanotubes, 60 V) with nanoarray was obtained by anodic oxidation of 60 V, and IL-4 was loaded into the nanotube by vacuum drying. The hydrogel (chitosan : genipin = 4 : 1) was applied to the surface of the nanotubes following drying, and the heparin drops were placed on the hydrogel surface with chitosan as the polycation and heparin as the polyanion. A TNT/IL-4/G (G = gel, chitosan/genipin heparin) delivery system was prepared. Our results demonstrated that the biofunctionalization of titanium nanotube with chitosan/genipin heparin hydrogel and the controlled release of IL-4 had a significant regulatory effect on macrophage M2 polarization, reducing the inflammatory factor release and higher secretion of VEGF (vascular endothelial growth factor), which can accelerate the endothelialization of the implant.

The valve replacement is the main treatment of heart valve disease.     

Cellulose-based self-healing hydrogel through boronic ester bonds with excellent biocompatibility and conductivity

Self-healing hydrogels based on degradable resources have developed rapidly in the past decade due to their extensive bioapplications with biosecurity. In this research, a new kind of cellulose-based self-healing hydrogel with bio-degradability is constructed through boronic ester linkage. The carboxyethyl cellulose-graft-phenylboronic acid (CMC–B(OH)₂) was synthesized through condensation reaction conveniently and then hydrogels were prepared with dynamic boronic ester cross-linking. The chemical structures, microscopic morphologies, mechanical and self-healing properties of the hydrogels were investigated intensively through Fourier transform infrared (FT-IR) spectroscopy, rheological, SEM and tensile testing. The hydrogels formed instantly without any additional catalyst and exhibit excellent self-healing ability with good mechanical properties. Moreover, the hydrogels were applied for controlled release of doxorubicin (DOX·HCl) and showed a successive slow release profile. Importantly, the hydrogel exhibited excellent biocompatibility and show potential applications in controlled drug delivery, 3D cell culture and tissue engineering.

Self-healing hydrogel with excellent biocompatibility and conductivity fabricated from cellulose through boronic ester bond.     

Encapsulation of BSA in hybrid PEG hydrogels: stability and controlled release

Hybrid hydrogels based on silylated polyethylene glycol, Si-PEG, were evaluated as hybrid matrices able to trap, stabilize and release bovine serum albumin (BSA) in a controlled manner. Parameters of the inorganic condensation reaction leading to a siloxane (Si–O–Si) three dimensional network were carefully investigated, in particular the temperature, the surrounding hygrometry and the Si-PEG concentration. The resulting hydrogel structural features affected the stability, swelling, and mechanical properties of the network, leading to different protein release profiles. Elongated polymer assemblies were observed, the length of which ranged from 150 nm to over 5 μm. The length could be correlated to the Si–O–Si condensation rate from 60% (hydrogels obtained at 24 °C) to about 90% (xerogels obtained at 24 °C), respectively. Consequently, the controlled release of BSA could be achieved from hours to several weeks, with respect to the fibers'' length and the condensation rate. The protein stability was evaluated by means of a thermal study. The main results gave insight into the biomolecule structure preservation during polymerisation, with ΔG < 0 for encapsulated BSA in any conditions, below the melting temperature (65 °C).

Silylated hybrid hydrogels of polyethylene glycol were designed to trap, stabilize and release a model protein (bovine serum albumin). Fine-tuning sol–gel reactions lead to sustained release of BSA over weeks, with good insight of protein stability.     

Photocurable ABA triblock copolymer-based ion gels utilizing photodimerization of coumarin

Herein, we develop a photocurable ABA triblock copolymer-based ion gel, which can be converted from a thermally processable, physically crosslinked ion gel to a thermally and mechanically stable, chemically crosslinked ion gel via photoinduced dimerization. The A block consists of a random copolymer of N-isopropylacrylamide and a coumarin-containing acrylate monomer, while the B block consists of an ionic liquid-philic poly(ethylene oxide). Due to the upper critical solution temperature-type phase behavior of the A block, the ABA triblock copolymer undergoes gel-to-sol transitions in a hydrophobic ionic liquid as the temperature is increased. Furthermore, under ultraviolet (UV) light irradiation, the physical crosslinks formed by association of the A blocks in the gel at low temperatures become chemically crosslinked as a result of photodimerization of the coumarin moieties in the A block; this results in conversion from a thermo-reversible, physically crosslinked ion gel to a thermo-irreversible, chemically crosslinked ion gel. The rheological changes of the ion gel upon UV irradiation have been investigated in detail. In addition, photopatterning of the ion gel has been realized by exploiting the photocurable behavior of the ABA triblock copolymer in the ionic liquid.

Photoinduced dimerization of coumarin was utilized to develop a photocurable ABA triblock copolymer-based ion gel.     

Efficient adsorption and full spectrum photocatalytic degradation of low concentration PPCPs promoted by graphene/TiO2 nanowires hybrid structure in 3D hydrogel networks

The removal of low concentration PPCPs from water is a challenging issue. A graphene hydrogel with 3D networks shows great potential for accelerating eddy diffusion of low concentration PPCPs. Herein, to further promote its molecular diffusion, a graphene/TiO₂ nanowires (GNW) hybrid structure was implanted into graphene hydrogel. The as-prepared rGO/GNW hydrogel exhibited significantly enhanced adsorption–photocatalytic performance and excellent stability for low concentration ethenzamide, a typical pharmaceutical pollutant in water, under vacuum ultraviolet (VUV), ultraviolet (UV), visible and near-infrared light irradiation. When the initial ethenzamide concentration was 500 ppb and catalyst dosage was 10 mg/150 mL, ethenzamide was completely removed in 3 min and the corresponding photocatalytic apparent rate constant was 2.20 times that by GNW, 4.09 times that by rGO/P25 and 4.31 times that by rGO/NW under VUV irradiation, respectively, and its removal rate attained 99.0% in 120 min and the corresponding photocatalytic apparent rate constant was 2.06 times that by GNW, 3.34 times that by rGO/P25 and 17.42 times that by rGO/NW under UV irradiation, respectively. The GNW hybrid structure in the hydrogel played a vital role in overcoming the mass transfer resistance of low concentration PPCPs. The as-prepared rGO/GNW hydrogel exhibits significant potential for the removal of low concentration PPCPs from water.

A 3D rGO/GNW hydrogel exhibits efficient adsorption, full spectrum photocatalytic performance and significant potential for low concentration PPCP removal from water.     

A pH-sensitive,stimuli-responsive,superabsorbent, smart hydrogel from psyllium (Plantago ovata) for intelligent drug delivery

Herein, we report a polysaccharide-based hydrogel isolated from psyllium husk (a well-known dietary fiber) and evaluated for its swelling properties in deionized water (DW) at different physiological pH values, i.e., 1.2, 6.8 and 7.4. Swelling of psyllium hydrogel (PSH) in DW under the influence of temperature and at different concentrations of NaCl and KCl solutions was also examined. A pH-dependent swelling pattern of PSH was observed following the order DW > pH 7.4 > pH 6.8 > pH 1.2. Stimuli-responsive swelling and deswelling (on–off switching) behavior of PSH was observed in DW and ethanol, DW and normal saline, at pH 7.4 and pH 1.2 environments, respectively. Similar swelling behavior and on–off switching attribute of PSH-containing tablets indicated the unaltered nature of PSH even after compression. Scanning electron micrographs of swollen and then freeze-dried PSH via transverse and longitudinal cross-sections revealed hollow channels with an average pore size of 6 ± 2 μm. Furthermore, PSH concentration-dependent sustained release of theophylline from tablet formulation was witnessed for >15 h following the non-Fickian diffusion mechanism. Subacute toxicity studies revealed the non-toxic nature of PSH. Therefore, dietary fiber-based material, i.e., PSH could be a valuable pharmaceutical excipient for intelligent and targeted drug delivery.

Herein, we report the dynamic swelling, stimuli responsive swelling-deswelling properties, sub-acute toxicity studies and sustained drug release potential of a polysaccharide-based hydrogel isolated from psyllium husk (a well-known dietary fiber).     

Robust microfluidic construction of hybrid microfibers based on konjac glucomannan and their drug release performance

The exploration of methods to produce a novel wound dressing with sustained drug release properties in ultrasmall scales is of great scientific and technological interest. Herein, we propose konjac glucomannan/polyvinylidene fluoride (KGM/PVDF) hybrid microfibers having hydrophilic and hydrophobic segments based on microfluidic-oriented core–sheath composite microfibers, where the KGM/PVDF hybrid microfibers are wrapped in situ in CH₃OH. The morphology of KGM/PVDF microfibers is uniform, smooth, and crack-free. Enrofloxacin (Enro) is loaded onto the microfibers as a representative cargo to test their release performance. The KGM/PVDF/Enro microfibers show sustained drug release performance (13 days), excellent heat resistance, antibacterial activity and promotion of wound healing. This study is an avenue toward the microfluidic design of hydrophilic/hydrophobic hybrid microfibers as wound dressings, and it will guide the development of next-generation wound dressing.

The exploration of methods to produce a novel wound dressing with sustained drug release properties in ultrasmall scales is of great scientific and technological interest.     

Strategy to design a smart photocleavable and pH sensitive chitosan based hydrogel through a novel crosslinker: a potential vehicle for controlled drug delivery

We report herein the synthesis of a novel photocleavable crosslinker, 4-formylphenyl 4-((4-formylphenoxy)methyl)-3-nitrobenzoate (CHO–ONB–CHO) and its joining with amine-based polysaccharides, viz. chitosan, resulting in the formation of a dual stimuli-responsive (ONB–chitosan) hydrogel having UV- and pH-responsive sites. The detailed mechanism for the formation of CHO–ONB–CHO and ONB–chitosan hydrogel is proposed. The (CHO–ONB–CHO) crosslinker was characterized using ¹H-NMR, LCMS and UV-visible spectroscopy. The dual responsive hydrogel is characterized by FTIR, SEM, XRD, DSC and TGA. The crosslinked hydrogel displayed mechanical robustness with a storage modulus of about 1741 pa. The pH-responsiveness of the hydrogel was studied via equilibrium swelling studies in various pH media at 37 °C. The photocleavable behavior of the crosslinker was observed in the UV-absorption range of 310–340 nm and the hydrogel exhibited maximum swelling at pH 5.7. The higher swelling of the hydrogel in acidic conditions and its photo-responsiveness can be exploited for the controlled, temporal and spatial release of therapeutic drugs at any inflammatory areas with acidic environments. It was observed that the hydrogel exhibited higher drug release at pH 5.7 than at pH 7.4.

We report the synthesis of a novel photocleavable crosslinker and its joining with amine-based polysachharides, viz. chitosan, resulting in the formation of a dual stimuli-responsive hydrogel having UV- and pH-responsive sites.     

Photo-triggered cargo release from liposome chlorin e6-bearing pullulan hybrid nanoparticles via membrane permeabilization

A liposome chlorin e6-bearing pullulan nanogel hybrid was prepared as a light-triggered payload release platform. The current system enabled manipulation of the release profile of model drugs encapsulated by liposomes. Gelatin hydrogels that comprised hybrid nanoparticles could successfully control the delivery of cargo molecules to human mesenchymal stem cells with light stimuli without injury to the cells.

A liposome chlorin e6-bearing pullulan nanogel hybrid was prepared as a light-triggered payload release platform.     

Bi-functional silica nanoparticles for simultaneous enhancement of mechanical strength and swelling capacity of hydrogels

A combination of strong load-bearing capacity and high swelling degree is desired in hydrogels for many applications including drug delivery, tissue engineering, and biomedical engineering. However, a compromising relationship exists between these two most important characteristics of hydrogels. Improving both of these important properties simultaneously in a single hydrogel material is still beyond the satisfactory limit. Herein, we report a novel approach to address this problem by introducing a silica-based bi-functional 3D crosslinker. Our bi-functional silica nanoparticles (BF-Si NPs) possess amine groups that are able to offer pseudo-crosslinking effects induced by inter-cohesive bonding, and acrylate groups that can form conventional covalent crosslinking in the same hydrogel. We fabricated polyacrylic acid (PAc-Si) and polyacrylamide (PAm-Si) hydrogels using our BF-Si NPs via free radical polymerization to demonstrate this concept. Incorporation of the BF-Si crosslinkers into the hydrogels has resulted in a large enhancement in the mechanical properties compared to conventional hydrogel crosslinked with N,N′-methylene bisacrylamide (MBA). For instance, tensile strength and the toughness increased by more than 6 times and 10 times, respectively, upon replacing MBA with BF-Si in polyacrylamide hydrogel. Moreover, the hydrogels crosslinked with BF-Si exhibited a remarkably elevated level of swelling capacity in the aqueous medium. Our facile yet smart strategy of employing the 3D bi-functional crosslinker for combining high swelling degree and strong mechanical properties in the same hydrogels can be extended to the fabrication of many similar acrylate or vinyl polymer hydrogels.

Bi-functional silica crosslinkers simultaneously enhance the mechanical strength and swelling capacity of the polyacrylic acid and polyacrylamide hydrogels.     

Dual-enzymatically crosslinked and injectable hyaluronic acid hydrogels for potential application in tissue engineering

Recently, in situ formed injectable hydrogels have shown great potential in biomedical applications as therapeutic implants or carriers in tissue repair and regeneration. They can seal or fill the damaged tissue to function as cell/drug delivery vehicle perfectly through a minimally invasive surgical procedure. In this study, hyaluronic acid (HA) is functionalized with tyramine to produce an injectable hydrogel dual-enzymatically crosslinked by horseradish peroxidase (HRP) and galactose oxidase (GalOX). This new tyramine-modified HA (HT) hydrogel exhibited good injectability, favorable cytocompatibility to mice bone marrow mesenchymal stem cells (BMSCs), and low inflammatory response verified by cytotoxicity assay in vitro and an in situ subcutaneous injection study in vivo. In addition, the gelation time, swelling behavior, and degradation rate of the HT hydrogel could be adjusted through varying the concentrations of HT and GalOX in a certain range. These encouraging results suggest that such biocompatible HT hydrogels might have potential application in three-dimensional stem cell culture and tissue engineering.

A new hyaluronic acid hydrogel dual-enzymatically cross-linked by HRP and GalOX and application for three-dimensional stem cell culture and tissue engineering.     

A conductive sodium alginate and carboxymethyl chitosan hydrogel doped with polypyrrole for peripheral nerve regeneration

Polymer materials with electrically conductive properties have good applications in their respective fields because of their special properties. However, they usually exhibited poor mechanical properties and biocompatibility. In this work, we present a simple approach to prepare conductive sodium alginate (SA) and carboxymethyl chitosan (CMCS) polymer hydrogels (SA/CMCS/PPy) that can provide sufficient help for peripheral nerve regeneration. SA/CMCS hydrogel was cross-linked by calcium ions provided by the sustained release system consisting of d-glucono-δ-lactone (GDL) and superfine calcium carbonate (CaCO₃), and the conductivity of the hydrogel was provided by doped with polypyrrole (PPy). Gelation time, swelling ratio, porosity and Young''s modulus of the conductive SA/CMCS/PPy hydrogel were adjusted by polypyrrole content, and the conductivity of it was within 2.41 × 10⁻⁵ to 8.03 × 10⁻³ S cm⁻¹. The advantages of conductive hydrogels in cell growth were verified by controlling electrical stimulation of cell experiments, and the hydrogels were also used as a filling material for the nerve conduit in animal experiments. The SA/CMCS/PPy conductive hydrogel showed good biocompatibility and repair features as a bioactive biomaterial, we expect this conductive hydrogel will have a good potential in the neural tissue engineering.

Polymer materials with electrically conductive properties have good applications in their respective fields because of their special properties.