Magnetic hydrogels with supracolloidal structures prepared by suspension polymerization stabilized by Fe2O3 nanoparticles

Magnetic hydrogels with supracolloidal structures were fabricated by suspension polymerization of N-isopropylacrylamide (NIPAm) and/or acrylamide (Am) stabilized by Fe₂O₃ nanoparticles. Fe₂O₃ nanoparticles can self-assemble at liquid–liquid interfaces to form stable water in oil Pickering emulsion droplets. Monomers dissolved in suspended aqueous droplets were subsequently polymerized at 60 °C. When NIPAm was homopolymerized the PNIPAm produced deposited from the interior water phase onto the interface to form Fe₂O₃/PNIPAm nanocomposite shells because of its hydrophobicity at the reaction temperature. Magnetic and thermosensitive hollow microcapsules were obtained. When Am was homopolymerized magnetic core–shell microcapsules with PAm hydrogel cores and Fe₂O₃ nanoparticle shells were obtained. When NIPAm and Am were co-polymerized, magnetic hydrogel microcapsules with two kinds of supracolloidal structures were obtained varying with the NIPAm/Am ratio. These microcapsule beads may find applications as delivery vehicles for biomolecules, drugs, cosmetics, food supplements and living cells. Suspension polymerization based on Pickering emulsion droplets opens up a new route to synthesize a variety of hybrid hydrogels with supracolloidal structures.     

Oxidized Pectin Cross-Linked Carboxymethyl Chitosan: A New Class of Hydrogels

Abstract

Oxidation of pectin was performed with sodium periodate to prepare pectin dialdehyde (PD). In this study we used the cross-linking reaction of the active aldehyde of PD and the amino of carboxymethyl chitosan (CMC) to prepare the hydrogels. By controlling the proportion of pectin dialdehyde and CMC we made different kinds of hydrogels. We systematically studied the characters of the hydrogels using Fourier transform infrared spectroscopy analysis of the pectin dialdehyde, CMC and the hydrogels, and also X-ray diffractometry and scanning electron microscopy analysis of the instrument of the hydrogels. Equilibrium swelling showed that the gels retained about 88–93% water. The water vapor transmission rate (WVTR) and the evaporation of water from gels showed that such hydrogels were optimal for maintaining a moist environment conducive for wound healing. Examination of the hemolytic potential showed that the hydrogels were nonhemolytic in nature. The hydrogels were non-toxic and blood-compatible. This hydrogel prepared from oxidized pectin and CMC without employing any extraneous cross-linking agents is expected to have potential as wound-dressing material.     

Synthesis,Characteristics and Potential Application of Poly(β-Amino Ester Urethane)-Based Multiblock Co-Polymers as an Injectable,Biodegradable and pH/Temperature-Sensitive Hydrogel System

Physical polymeric hydrogels have significant potential for use as injectable depot drug/protein-delivery systems. In this study, a series of novel injectable, biodegradable and pH/temperature-sensitive multiblock co-polymer physical hydrogels composed of poly(ethylene glycol) (PEG) and poly(β-amino ester urethane) (PEU) was synthesized by the polyaddition between the isocyanate groups of 1,6-diisocyanato hexamethylene and the hydroxyl groups of PEG and a synthesized monomer BTB (or ETE) in chloroform in the presence of dibutyltin dilaurate as a catalyst. The synthesized co-polymers were characterized by nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy and gel-permeation chromatography. Aqueous solutions of the co-polymers showed a sol-to-gel phase transition with increasing pH and a gel-to-sol phase transition with increasing temperature. The gel regions covered the physiological conditions (37°C, pH 7.4) and could be controlled by changing the molecular weight of PEG, PEG/PEU ratio and co-polymer solution concentration. A gel formed rapidly in situ after injecting the co-polymer solution subcutaneously into SD rats and remained for more than 2 weeks in the body. The cytotoxicity tests confirmed the non-cytotoxicity of this co-polymer hydrogel. The controlled in vitro release of the model anticancer drug, doxorubicin, from this hydrogel occurred over a 7-day period. This hydrogel is a potential candidate for biomedical applications and drug/protein-delivery systems.     

The rheological and thermal characteristics of freeze-thawed hydrogels containing hydrogen peroxide for potential wound healing applications

The current study involves the development of a hydrogel carrier for a H₂O₂ delivery system. In this work poly (vinyl alcohol) (PVA) and poly (acrylic acid) (PAA) based hydrogels were prepared, and their mechanical and physical properties examined. The novel aspect of this research is the differing functionality created by varying the concentration of H₂O₂. The mechanical and thermal properties were determined by parallel plate rheometry and modulated differential scanning calorimetry (MDSC) respectively. The results indicated that the hydrogels containing H₂O₂ are significantly weaker than those synthesised using water alone at test temperatures of 30 and 45 ^°C. MDSC analysis suggested that thermal transitions occur at temperatures that may make these hydrogels useful as temperature sensitive drug delivery systems. The chemical structure of the hydrogels was confirmed by means of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), while swelling experiments in distilled water indicate that the swelling of the gels is temperature dependent.     

Hyaluronic acid-modified hydrothermally synthesized iron oxide nanoparticles for targeted tumor MR imaging

We report a polyethyleneimine (PEI)-mediated approach to synthesizing hyaluronic acid (HA)-targeted magnetic iron oxide nanoparticles (Fe₃O₄ NPs) for in vivo targeted tumor magnetic resonance (MR) imaging applications. In this work, Fe₃O₄ NPs stabilized by PEI were first synthesized via a one-pot hydrothermal method. The formed PEI-stabilized Fe₃O₄ NPs were then modified with fluorescein isothiocyanate (FI) and HA with two different molecular weights to obtain two different Fe₃O₄ NPs (Fe₃O₄–PEI–FI–HA_6K and Fe₃O₄–PEI–FI–HA_31K NPs) with a size of 15–16 nm. The formed HA-modified multifunctional Fe₃O₄ NPs were characterized via different techniques. We show that the multifunctional Fe₃O₄ NPs are water-dispersible and colloidal stable in different aqueous media. In vitro cell viability and hemolysis studies reveal that the particles are quite cytocompatible and hemocompatible in the given concentration range. Furthermore, confocal microscopy and flow cytometry data demonstrate that HA-targeted Fe₃O₄ NPs are able to be uptaken specifically by cancer cells overexpressing CD44 receptors, and be used as efficient probes for targeted MR imaging of cancer cells in vitro and xenografted tumor models in vivo. With the tunable amine-based conjugation chemistry, the PEI-stabilized Fe₃O₄ NPs may be functionalized with other biological ligands or drugs for diagnosis and therapy of different biological systems.     

Tetronic-grafted chitosan hydrogel as an injectable and biocompatible scaffold for biomedical applications

In recent years, injectable chitosan-based hydrogels have been widely studied towards biomedical applications because of their potential performance in drug/cell delivery and tissue regeneration. In this study, we introduce a simple and organic solvent-free method to prepare tyramine–tetronic–grafted chitosan (TTeC) via activation of four terminal hydroxyl groups of tetronic, partial tyramine conjugate into the activated product and grafting the remaining activated moiety of tetronic-tyramine onto chitosan. The grafted copolymer was well characterized by UV–Visible, ¹H NMR, and Thermogravimetric analysis. The aqueous TTeC copolymer solution rapidly formed hydrogel in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H₂O₂) at physiological conditions. The gelation time of the hydrogel was performed within a time period of 4–60?s, when the concentrations of HRP, H₂O₂, and polymers varied. The hydrogel exhibited highly porous structure which could be controlled by using H₂O₂. In vitro cytotoxicity study with Human Foreskin Fibroblast cell using live/dead assay indicated that the hydrogel had high cytocompatibility and could play a role as a scaffold for cell adhesion. The injectable hydrogels did not cause any inflammation after two weeks and one day of the in vivo injection. The obtained results demonstrated a great potential of the TTeC hydrogel in biomedical applications.     

Nanostructured hybrid hydrogels prepared by a combination of atom transfer radical polymerization and free radical polymerization

A new method to prepare nanostructured hybrid hydrogels by incorporating well-defined poly(oligo (ethylene oxide) monomethyl ether methacrylate) (POEO₃₀₀MA) nanogels of sizes 110–120 nm into a larger three-dimensional (3D) matrix was developed for drug delivery scaffolds for tissue engineering applications. Rhodamine B isothiocyanate-labeled dextran (RITC-Dx) or fluorescein isothiocyanate-labeled dextran (FITC-Dx)-loaded POEO₃₀₀MA nanogels with pendant hydroxyl groups were prepared by activators generated electron transfer atom transfer radical polymerization (AGET ATRP) in cyclohexane inverse miniemulsion. Hydroxyl-containing nanogels were functionalized with methacrylated groups to generate photoreactive nanospheres.¹H NMR spectroscopy confirmed that polymerizable nanogels were successfully incorporated covalently into 3D hyaluronic acid-glycidyl methacrylate (HAGM) hydrogels after free radical photopolymerization (FRP). The introduction of disulfide moieties into the polymerizable groups resulted in a controlled release of nanogels from cross-linked HAGM hydrogels under a reducing environment. The effect of gel hybridization on the macroscopic properties (swelling and mechanics) was studied. It is shown that swelling and nanogel content are independent of scaffold mechanics. In-vitro assays showed the nanostructured hybrid hydrogels were cytocompatible and the GRGDS (Gly–Arg–Gly–Asp–Ser) contained in the nanogel structure promoted cell–substrate interactions within 4 days of incubation. These nanostructured hydrogels have potential as an artificial extracellular matrix (ECM) impermeable to low molecular weight biomolecules and with controlled pharmaceutical release capability. Moreover, the nanogels can control drug or biomolecule delivery, while hyaluronic acid based-hydrogels can act as a macroscopic scaffold for tissue regeneration and regulator for nanogel release.     

Arginine-glycine-aspartic acid modified rosette nanotube–hydrogel composites for bone tissue engineering

An RGDSK (Arg-Gly-Asp-Ser-Lys) modified rosette nanotube (RNT) hydrogel composite with unique surface chemistry and favorable cytocompatibility properties for bone repair was developed and investigated. The RNTs are biologically inspired nanomaterials obtained through the self-assembly of a DNA base analog (G∧C base) with tailorable chemical functionality and physical properties. In this study, a cell-adhesive RGDSK peptide was covalently attached to the G∧C base, assembled into RNTs, and structurally characterized by ¹H/¹³C NMR spectroscopy, mass spectrometry, and electron microscopy. Importantly, results showed that the RGDSK modified RNT hydrogels caused around a 200% increase in osteoblast (bone-forming cell) adhesion relative to hydrogel controls. In addition, osteoblast proliferation was enhanced on RNT hydrogels compared to hydrogel controls after 3 days, which further confirmed the promising cytocompatibility properties of this scaffold. When analyzing the mechanism of increased osteoblast density on RNT hydrogels, it was found that more fibronectin (a protein which promotes osteoblast adhesion) adsorption occurred on RNT coated hydrogels than uncoated hydrogels. As osteoblast adhesion was greatly enhanced on RNT coated hydrogels compared to poly l-lysine and collagen coated hydrogels, this study indicated that not only the surface chemistry was important in improving osteoblast density (via lysine or RGD groups functionalized on RNTs), but also the biomimetic nanoscale properties of RNTs provided a cell-favorable environment. These results warrant further studies on RNTs in hydrogels for better bone tissue regeneration.     

Rétention prolongée de TGFβ1 par des hydrogels à base de dextrane fonctionnalisé : synthèse, caractérisation et évaluations biologiques

Due to a short half-life, growth factors, which could be used as therapeutic agents, usually require carriers able to protect their biological activity and to sustain protein delivery in situ. It was shown that water-soluble functionalized dextrans (DMCB) present some heparin-like properties, especially the capacity to interact with Heparin-Binding Growth Factors such as TGFβ₁. In this study, dextran-based hydrogels were synthesized by cross-linking a DMCB with native dextrans to develop a TGFβ₁ release carrier. In vivo, these hydrogels were demonstrated to be biocompatible and to allow good cell invasion. In vitro, functionalized hydrogels retained 50 to 60% of initially loaded growth factor contrary to unfunctionalized hydrogels. The degree of hydrogel functionalization did not influence the amount of entrapped growth factor. Nevertheless, it modulated the prominent type of interactions between TGFβ₁ and hydrogels.     

Controlling Fibroblast Proliferation with Dimensionality-Specific Response by Stiffness of Injectable Gelatin Hydrogels

Abstract

We report an injectable hydrogel system with tunable stiffness for controlling the proliferation rate of human fibroblasts (HFF-1) in both two-dimensional (2D) and three-dimensional (3D) culture environments for potential use as a wound dressing material. The hydrogel composed of gelatin–hydroxyphenylpropionic acid (Gtn–HPA) conjugate was formed by the oxidative coupling of HPA moieties catalyzed by hydrogen peroxide (H₂O₂) and horseradish peroxidase (HRP). The stiffness of the hydrogels was controlled well by varying the H₂O₂ concentration. The effects of hydrogel stiffness on the proliferation rate of HFF-1 in both 2D and 3D were investigated. We found that the proliferation rate of HFF-1 using Gtn–HPA hydrogels was strongly dependent on the hydrogel stiffness, with a dimensionality-specific response. In the 2D studies, the HFF-1 exhibited a higher proliferation rate when the stiffness of the hydrogel was increased. In contrast, the HFF-1 cultured inside the hydrogel remained non-proliferative for 12 days before a stiffness-dependent proliferation profile was shown. The proliferation rate decreased with an increase in stiffness of the hydrogel in a 3D culture environment, unlike in a 2D environment.     

Polyethyleneimine-mediated synthesis of folic acid-targeted iron oxide nanoparticles for in vivo tumor MR imaging

We report a facile polyethyleneimine (PEI)-mediated approach to synthesizing folic acid (FA)-targeted magnetic iron oxide nanoparticles (Fe₃O₄ NPs) for in vivo magnetic resonance (MR) imaging of tumors. In this study, stable PEI-coated Fe₃O₄ NPs were prepared by a one-pot hydrothermal route. The aminated Fe₃O₄ NPs with PEI coating enabled covalent conjugation of fluorescein isothiocyanate (FI) and folate-conjugated polyethylene glycol (PEG) with one end of carboxyl groups (FA-PEG-COOH). Followed by final acetylation, FA-targeted PEGylated Fe₃O₄ NPs (Fe₃O₄-PEI-Ac-FI-PEG-FA NPs) were formed. The formed multifunctional Fe₃O₄ NPs were characterized via different techniques. We show that the PEI-mediated approach along with the PEGylation conjugation enables the generation of water-dispersible and stable multifunctional Fe₃O₄ NPs, and the particles are quite cytocompatible and hemocompatible in the given concentration range as confirmed by in vitro cytotoxicity assay, cell morphology observation, and hemolysis assay. In addition, flow cytometry and confocal microscopy data show that the multifunctional Fe₃O₄ NPs are able to target a model cancer cell line (KB cells) overexpressing FA receptors in vitro. Importantly, the FA-targeted Fe₃O₄ NPs are able to be used as an efficient nanoprobe for MR imaging of cancer cells in vitro and a xenografted tumor model in vivo via an active FA targeting pathway. With the facile PEI-mediated formation strategy and PEGylation conjugation chemistry, the Fe₃O₄ NPs may be multifunctionalized with other biological ligands for MR imaging of different biological systems.     

Thiol-ene crosslinking polyamidoamine dendrimer-hyaluronic acid hydrogel system for biomedical applications

A series of alkene functionalized polyamidoamine (PAMAM) dendrimers were synthesized to prepare in situ forming hydrogels with varied gelation time and mechanical properties through crosslinking with thiolated hyaluronic acid (HS-HA). By varying the alkenyl groups on the dendrimers, the gelation time displayed a large range from 8 seconds to 18 hours, and the modulus of the hydrogels ranged from 36 to 183 Pa under experimental conditions. Investigation by ¹H-NMR spectroscopy revealed that the gelation time and the stiffness of the hydrogels were governed by the degree of electron deficiency of alkenyl groups on the dendrimers. This research provided a systematic study on the relationship between chemical structures versus gelation time and mechanical properties of hydrogels, which could guide the way to synthesize in situ forming hydrogels with designated gelation time and stiffness for biomedical applications. Further, a RGD peptide was attached to the PAMAM dendrimers to enhance cell attachment and proliferation. Viability assays of Human Umbilical Vein Endothelial Cells (HUVEC) in the synthesized hydrogels demonstrated the biocompatibility of the hydrogels after 48 hours of culturing, and the RGD peptide improved the viability of HUVEC cells in hydrogels. We believe the PAMAM/HA hydrogel system is a tuneable and biocompatible system for diverse biomedical applications.     

Arginine-based polyester amide/polysaccharide hydrogels and their biological response

An advanced family of biodegradable cationic hybrid hydrogels was designed and fabricated from two precursors via a UV photocrosslinking in an aqueous medium: unsaturated arginine (Arg)-based functional poly(ester amide) (Arg-UPEA) and glycidyl methacrylate chitosan (GMA-chitosan). These Arg-UPEA/GMA-chitosan hybrid hydrogels were characterized in terms of their chemical structure, equilibrium swelling ratio (Q_eq), compressive modulus, interior morphology and biodegradation properties. Lysozyme effectively accelerated the biodegradation of the hybrid hydrogels. The mixture of both precursors in an aqueous solution showed near non-cytotoxicity toward porcine aortic valve smooth muscle cells at total concentrations up to 6 mg ml⁻¹. The live/dead assay data showed that 3T3 fibroblasts were able to attach and grow on the hybrid hydrogel and pure GMA-chitosan hydrogel well. Arg-UPEA/GMA-chitosan hybrid hydrogels activated both TNF-α and NO production by RAW 264.7 macrophages, and the arginase activity was also elevated. The integration of the biodegradable Arg-UPEA into the GMA-chitosan can provide advantages in terms of elevated and balanced NO production and arginase activity that free Arg supplement could not achieve. The hybrid hydrogels may have potential application as a wound healing accelerator.     

Development of an arginine-based cationic hydrogel platform: Synthesis,characterization and biomedical applications

A series of biodegradable and biocompatible cationic hybrid hydrogels was developed from water-soluble arginine-based unsaturated polymer (Arg-AG) and poly(ethylene glycol) diacrylate (PEG-DA) by a photocrosslinking method. The physicochemical, mechanical and biological properties of these hydrogels were intensively examined. The hydrogels were characterized in terms of equilibrium swelling ratio (Q_eq), compression modulus and interior morphology. The effects of the chemical structure of the two Arg-AG precursors and the feed ratio of these precursors on the properties of resulting hybrid hydrogels were investigated. The crosslinking density and mechanical strength of the hybrid hydrogels increased with an increase in allylglycine (AG) content in the Arg-AG precursor, as the gelation efficiency (G_f) increased from 80% to 90%, but the swelling and pore size of the hybrid hydrogels decreased as the equilibrium swelling weight (Q_eq) decreased from 1890% to 1330% and the pore size from 28 to 22 μm. The short-term in vitro biodegradation properties of hydrogels were investigated as a function of Arg-AG chemical structures and enzymes. Hybrid hydrogels showed faster biodegradation in an enzyme solution than in a phosphate-buffered saline solution. Bovine serum albumin and insulin release profiles indicated that this cationic hydrogel system could significantly improve the sustained release of the negatively charged proteins. The cellular response of the hybrid hydrogels was preliminarily evaluated by cell attachment, encapsulation and proliferation tests using live–dead and MTT assay. The results showed that the hybrid hydrogels supported cell attachment well and were nontoxic to the cells.     

Injectable in situ forming biodegradable chitosan–hyaluronic acid based hydrogels for cartilage tissue engineering

Injectable, biodegradable scaffolds are important biomaterials for tissue engineering and drug delivery. Hydrogels derived from natural polysaccharides are ideal scaffolds as they resemble the extracellular matrices of tissues comprised of various glycosaminoglycans (GAGs). Here, we report a new class of biocompatible and biodegradable composite hydrogels derived from water-soluble chitosan and oxidized hyaluronic acid upon mixing, without the addition of a chemical crosslinking agent. The gelation is attributed to the Schiff base reaction between amino and aldehyde groups of polysaccharide derivatives. In the current work, N-succinyl-chitosan (S-CS) and aldehyde hyaluronic acid (A-HA) were synthesized for preparation of the composite hydrogels. The polysaccharide derivatives and composite hydrogels were characterized by FTIR spectroscopy. The effect of the ratio of S-CS and A-HA on the gelation time, microstructure, surface morphology, equilibrium swelling, compressive modulus, and in vitro degradation of composite hydrogels was examined. The potential of the composite hydrogel as an injectable scaffold was demonstrated by the encapsulation of bovine articular chondrocytes within the composite hydrogel matrix in vitro. The results demonstrated that the composite hydrogel supported cell survival and the cells retained chondrocytic morphology. These characteristics provide a potential opportunity to use the injectable, composite hydrogels in tissue engineering applications.     

Mechanical and structural response of a hybrid hydrogel based on chitosan and poly(vinyl alcohol) cross-linked with epichlorohydrin for potential use in tissue engineering

The development and characterization of a hybrid hydrogel based on chitosan (CS) and poly(vinyl alcohol) (PVA) chemically cross-linked with epichlorohydrin (ECH) is presented. The mechanical response of these hydrogels was evaluated by uniaxial tensile tests; in addition, their structural properties such as average molecular weight between cross-link points (M_crl), mesh size (D_N), and volume fraction (v_s) were determined. This was done using the equivalent polymer network theory in combination with the obtained results from tensile and swelling tests. The films showed Young’s modulus values of 11?±?2?MPa and 9?±?1?MPa for none irradiated and ultraviolet (UV) irradiated hydrogels, respectively. The cell viability was assessed using Calcein AM and Ethidium homodimer-1 assay and environmental scanning electron microscopy. The 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan thiazolyl blue formazan (MTT Formazan assay) results did not show cytotoxic effects; this was in good agreement with nuclear magnetic resonance and fourier transform infrared spectroscopies; their results did not show traces of ECH. This indicated that after the crosslinking process, there was no free ECH; furthermore, any possibility of ECH release in the construct during cell culture was discarded. The CS-PVA-ECH hybrid hydrogel allowed cell growth and extracellular matrix formation and showed adequate mechanical, structural, and biological properties for potential use in tissue engineering applications.     

A magnetic chitosan hydrogel for sustained and prolonged delivery of Bacillus Calmette–Guérin in the treatment of bladder cancer

The aim of this study was to develop a magnetic thermosensitive hydrogel as intravesical Bacillus Calmette–Guérin (BCG) delivery system, which was formulated with chitosan (CS), β-glycerophosphate (GP) and Fe₃O₄ magnetic nanoparticle (Fe₃O₄-MNP). The gelation time and magnetic response of the gel system were investigated. The morphology of the gel was displayed by scanning electron microscope. Frozen section examination was creatively employed for exhibiting the structure of the gel and determining its intravesical residence time. The antitumor effect and local immune activity of BCG loaded magnetic gel were evaluated. The flowing solution of CS/GP under room temperature could gelate rapidly at body temperature both in vitro and in vivo. The magnetic injectable hydrogels significantly prolonged intravesical BCG residence time under an applied magnetic field. In comparison to traditional BCG therapy for superficial bladder tumor, BCG delivered by the gel system induced a stronger Th1 immune response and revealed higher antitumor efficacy.     

Modulation of chondrocyte functions and stiffness-dependent cartilage repair using an injectable enzymatically crosslinked hydrogel with tunable mechanical properties

We developed an injectable hydrogel system to evaluate the effect of hydrogel stiffness on chondrocyte cellular functions in a three-dimensional (3D) environment and its subsequent influence on ectopic cartilage formation and early-stage osteochondral defect repair in a rabbit model. The hydrogels, composed of gelatin-hydroxyphenylpropionic acid (Gtn-HPA) conjugate, were formed using oxidative coupling of HPA moieties catalyzed by hydrogen peroxide (H₂O₂) and horseradish peroxidase (HRP). The storage modulus (G′) of the hydrogels, which was tunable by changing the H₂O₂ and Gtn-HPA concentrations, ranged from 570 Pa to 2750 Pa. It was found that the cellular functions of chondrocytes encapsulated in hydrogels, including cell proliferation, biosynthesis of collagen and sulfated glycosaminoglycans (sGAG), as well as gene expression of type I (Col-I) and type II collagen (Col-II), were strongly affected by the stiffness of the hydrogels. Of note, chondrocytes cultured within the Gtn-HPA hydrogel of medium stiffness (G′ = 1000 Pa) produced highest level of sGAG production, as well as highest ratio of Col-II to Col-I gene expression among the Gtn-HPA hydrogels of different stiffness. Consistent with the results from in vitro and in vivo ectopic cartilage formation, osteochondral defect repair in a rabbit model showed stiffness-dependent tissue repair, with defects implanted with chondrocytes in hydrogels of medium stiffness having markedly more hyaline cartilage formation, smoother surface and better integration with adjacent cartilage, compared to defects treated with hydrogels of low or high stiffness. These results suggest that the tunable stiffness of Gtn-HPA hydrogels modulates chondrocyte cellular functions, and has a dramatic impact on cartilage tissue histogenesis and repair.     

Injectable in situ cross-linking hyaluronic acid/carboxymethyl cellulose based hydrogels for drug release

A series of injectable in situ cross-linking hyaluronic acid/carboxymethyl cellulose based hydrogels (HA/CMC) was prepared via disulfide bonds by the oxidation of dissolved oxygen. The results showed that HA/CMC hydrogels exhibited tunable gelling time, appropriate rheology properties, high swelling ratio, good stability, and sustained drug release ability. The gelling time of HA/CMC hydrogels ranged from 1.4 to 7.0 min, and the values of the storage modulus, complex shear modulus, dynamic viscosity, and yield stress of HA3/CMC3 hydrogel were about 5869 Pa, 5870 Pa, 587 Pa·s, and 1969 Pa, respectively. The degradation percentage of HA1/CMC1, HA2/CMC2, and HA3/CMC3 hydrogels were about 60, 49, and 41% after incubating 42 days, and the in vitro cumulative release percentage of BSA from HA1/CMC1, HA2/CMC2, and HA3/CMC3 drug-loaded hydrogels were about 99, 91, and 82% after 30 days. The series of injectable in situ cross-linking HA/CMC hydrogels exhibited good comprehensive performance, signifying that these hydrogels could be potentially used in the fields of short- and medium-term controlled drug release, cell encapsulation, regenerative medicine, and tissue engineering.     

Modified carrageenan. 2. Hydrolyzed crosslinked κ-carrageenan-g-PAAm as a novel smart superabsorbent hydrogel with low salt sensitivity

A novel pH-responsive superabsorbing hydrogel based on κ-carrageenan (κC) was prepared through polyacrylamide crosslinking grafting followed by alkaline hydrolysis. The hydrogel structure was confirmed using FT-IR spectroscopy. The hydrolysis conditions were systematically optimized to obtain a hydrogel with maximum swelling capacity. Thus, the reaction variables, including the hydrolysis time and temperature, concentration of sodium hydroxide, amount of hydrogel hydrolyzed and post-neutralization pH, were optimized. The swelling measurements of the hydrogels were conducted in 0.15 M aqueous solutions of LiCl, NaCl, KCl, CaCl₂ and AlCl₃. As observed for the hydrolyzed hydrogel (H-carragPAM), it was found that a 'charge screening' action of small cations and carboxylate anions affected the swelling in univalent salt solutions. In the case of the non-hydrolyzed hydrogel (carragPAM), however, a converse trend was observed. As a result, carragPAM and H-carragPAM superabsorbent hydrogels showed a maximum swelling of 45 and 135 g/g in LiCl and KCl solutions, respectively. Due to the high swelling capacity in salt solutions, the hydrogels may be referred to as anti-salt superabsrbents. The swelling of superabsorbing hydrogels was examined in buffer solutions with pH values ranging between 1 and 13. The H-carragPAM hydrogel exhibited a pH-responsie character so that a swelling-deswelling pulsatile behavior was recorded at pH 4 and 9. The swelling kinetics of H-carragPAM were preliminary investigated.