Photocrosslinkable chitosan hydrogels and their biomedical applications

Chitosan is a bioactive macromolecule with a wide variety of applications due to its excellent biological properties such as biodegradability, biocompatibility, and antibacterial activity, and so forth. This highlight focuses on the preparation of photoactive chitosans, the formation of photocrosslinkable chitosan hydrogels, and the related photopolymerization mechanisms. Moreover, the great potential applications of photocrosslinkable chitosan hydrogels for human tissues are also discussed. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1862–1871     

Synthesis and characterization of thermoresponsive hydrogels cross-linked with chitosan

Hydrogels composed of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) were prepared by redox polymerization with degradable chitosan cross-linkers. Chitosan degradable cross-linkers were synthesized by the acrylation of the amine groups of glucosamine units within chitosan and characterized with ¹H NMR. With the chitosan cross-linkers, loosely cross-linked poly(N-isopropylacryamideco-acrylic acid) [P(NIPAAm-co-AAc)] hydrogels were prepared, and their phase transition behavior, lower critical solution temperature (LCST), water content and degradation properties were investigated. The chitosan cross-linked P(NIPAAm-co-AAc) hydrogels were pliable and transparent at room temperature. The LCST could be adjusted at 32∼39°C by alternating the feed ratio. Swelling was influenced by NIPAAm/AAc monomer ratio, cross-linking density, swelling media, and temperature. All hydrogels with different feeding ratios contained more than 95% water at 25°C in the ultra pure water and phosphate-buffered saline (PBS, pH = 7.4 ± 0.1), and had a prospective swelling in the simulated gastric fluids (SGF, pH = 1.2) > 72.54%. In degradation studies, breakdown of the chitosan cross-linked P(NIPAAm-co-AAc) hydrogels was dependent on the cross-linking density. The chitosan cross-linked P(NIPAAm-co-AAc) hydrogels which can be tailored to create environmentally-responsive artificial extracellular materials have great potential for future use.      

Swelling behavior of chitosan hydrogels in ionic liquid-water binary systems

The swelling behavior of chitosan hydrogels in ionic liquid-water binary systems was studied using hydrophilic room-temperature ionic liquids (RTILs) to elucidate the swelling mechanism of chitosan hydrogels. No penetration of RTIL into a dry chitosan material was observed. Swelling was achieved by soaking in water-RTIL binary mixtures, with larger swelling observed at higher water contents. In one instance, the binary mixture was acidic and produced larger than expected swelling due to the dissociation of the amine groups in the chitosan. The equilibrium binary system content behavior of the chitosan hydrogels depended upon the amount of free water, which is a measure of the number of water molecules that do not interact with the ionic liquid. After evaporation of water, remnant RTIL remained in the chitosan network and hardness testing indicated a plasticization effect, suggesting that the RTIL molecularly mixed with the chitosan. Chitosan hydrogels containing only RTIL were prepared by dropping pure RTIL onto a fully preswollen hydrogel followed by water evaporation. This method may be a useful means for preparing air-stable swollen chitosan gels.     

In situ forming physical hydrogels for three-dimensional tissue morphogenesis

In situ forming physical hydrogels are formed through a biologically benign reaction between two multi-arm macromers, one containing terminal thiol and the other containing terminal vinyl sulfone groups. One macromer is self-assembled through a coiled-coil domain; and the physical junction of this macromer confers the physical nature to the whole network. Unlike covalently cross-linked hydrogels in which material degradation is a prerequisite for three-dimensional cell movement, these physical hydrogels have junctions that undergo reversible dissociation and re-association, constitutively opening paths for cell movement. Epithelial cells encapsulated in these hydrogels can form hollow spherical cysts without the need for material degradation.     

Mechanically tough and recoverable hydrogels via dual physical crosslinkings

Development of functional tough hydrogels with new network structures and energy dissipation mechanisms has great promise for many applications. Here, a new type of physical hydrogel crosslinked by hydrophobic association and hydrogen bonds was synthesized by a facile micellar copolymerization of hydrophobic methyl acrylate (MA) monomers and hydrophilic N-hydroxyethyl acrylamide (HEAA) monomers in the presence of Tween80 micelles. Strong hydrophobic association between inner MA and Tween80 and hydrogen bonds between external polyHEAA and Tween80 provide two distinct crosslinkers to construct mechanically tough and recoverable network. Mechanical properties of polyHEAA-MA@Tween80 hydrogels strongly depended on network components (HEAA, MA; Tween80 concentrations). At optimal conditions, the hydrogels can achieve fracture stress of 700 kPa, fracture strain of 1687 mm/mm, elastic modulus of 195 kPa, and tearing energy of 1598 J/m². Due to the reversible nature of physical interactions, polyHEAA-MA@Tween80 hydrogels can achieve fast stiffness/toughness recovery of 60%/33% without any external stimuli and resting time at room temperature. This work demonstrates a new design strategy to fabricate a new a single-network hydrogel with high mechanical and self-recovery properties by incorporating both hydrophobic association and hydrogen bonds in the network, which may provide alternative viewpoint for the design of multifunctional tough hydrogels. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 1294–1305     

Modified chitosan 4. Superabsorbent hydrogels from poly(acrylic acid-co-acrylamide) grafted chitosan with salt- and pH-responsiveness properties

Graft copolymerization of mixtures of acrylic acid (AA) and acrylamide (AAm) onto chitosan was carried out by using potassium persulfate (KPS) as a free radical initiator in the presence of methylenebisacrylamide (MBA) as a crosslinker. The effect of reaction variables, such as MBA concentration and AA/AAm ratio on the water absorbency capacity have been investigated. The polymer structures were confirmed by FTIR spectroscopy. Water absorbencies were compared for the hydrogels before and after alkaline hydrolysis. In the non-hydrolyzed hydrogel, enhanced water absorbency was obtained with increasing AA in monomer feed. However, after saponification, the sample with high AAm ratio exhibited more water absorbency. These behaviors were discussed according to structural parameters. The swelling kinetics of the superabsorbing hydrogels was studied as well. The hydrogels exhibited ampholytic and reversible pH-responsiveness characteristics. The swelling variations were explained according to swelling theory based on the hydrogel chemical structure. The hydrogels exhibited salt-sensitivity and cation exchange properties. The pH-reversibility and on-off switching properties of the hydrogels make the intelligent polymers as good candidates for considering as potential carriers for bioactive agents, e.g. drugs.     

Thermodynamic properties of chitosan-based hydrogels in the range 0–350 K

The heat capacity, the temperature, and the enthalpy of physical transformations of hydrogels based on the copolymer of acrylamide and chitosan with N,N-methylene-bis(acrylamide) as a crosslinking agent, hydrogels based on the mixture of poly(vinylpyrrolidone) and chitosan with glutaric aldehyde as the crosslinking agent, and dehydrated hydrogels has been studied in the range 85–350 K with the use of adiabatic vacuum calorimetry. The temperatures and enthalpies of melting of free water in hydrogels have been determined. From the experimental data obtained, the thermodynamic functions C° _p (T), H° (T) ? H°(0), S° (T) ? S°(0), and G° (T) ? H°(0) have been calculated for the temperature range 0–350 K. The ratio of free and bound water in the hydrogels under study has been determined by calorimetry.     

Synthesis and characterization of novel carboxymethyl chitosan grafted polylactide hydrogels for controlled drug delivery

Novel carboxymethyl chitosan‐polylactide (CMCS‐g‐PLA) hydrogels were prepared by using 1‐(3‐dimethylaminopropyl)‐3‐ethylcarbodiimide hydrochloride/N‐hydroxysuccinimide (EDC/NHS) as crosslinking agent and catalyst at room temperature. Solid‐state ¹³C‐NMR, SEM, and FT‐IR measurements showed that PLA blocks are successfully grafted onto the CMCS main chains. DSC measurements confirmed the effective crosslinking of carboxymethyl chitosan. With increasing the amount of EDC/NHS, the crosslink destiny of CMCS‐g‐PLA copolymers is improved. The swelling ratio of CMCS‐g‐PLA hydrogels is pH dependent, showing a minimum in the pH range of 3 to 5. Rheological studies confirmed the formation of hydrogels. The higher the crosslinking density, the higher the storage modulus of hydrogels. CMCS‐g‐PLA hydrogels only slightly degrade in PBS for 10 days. In the presence of lysozyme, however, hydrogels with low crosslink density are totally degraded in 10 days. Drug release studies show that after 96 h, 95% of thymopentin is released under in vitro conditions. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis and characterization of antibacterial semi-interpenetrating carboxymethyl chitosan/poly (acrylonitrile) hydrogels

Blend hydrogels composed of carboxymethyl chitosan (CMCh) and poly (acrylonitrile) (PAN) were synthesized via crosslinking method. Several analyses were made to investigate both physical and thermal properties of CMCh/PAN hydrogels like; FTIR, scanning electron microscope, XRD and thermogravimetric analysis (TGA). TGA results showed that CMCh/PAN hydrogels are thermally more stable than CMCh and their thermal stability increases as PAN content increases in the hydrogel. Moreover, the swelling behavior of CMCh/PAN hydrogels was studied in different buffer solutions. It was found that CMCh/PAN hydrogels swell much more than PAN especially at pH 9. The hydrogels sorption for different dyestuff and various metal ions like; Cu²⁺, Cd²⁺ and Co²⁺ were also studied. In this work, antibacterial characteristic of hydrogels was mainly investigated towards Escherichia coli (E. coli) as a serious disease-leading bacterium. All tested hydrogels have clearly presented good antibacterial activity as CMCh content increases in the hydrogels.     

Characterisation and morphology of biodegradable chitosan / synthetic polymer blends

Chitosan has been used to form miscible, biodegradable blends with hydrophilic synthetic polymers as PVA and PEO. Characterisation of the blends by DSC, IR and microscopy analysis was made giving much attention to possible interactions of molecular polar group in the polymer chains. PVA/chitosan are found to be amorphous in the whole range of composition having one glass transition temperature. Molecular interactions in the pair of polymers are connected with amide group of chitosan and hydroxyl groups of PVA. PEO/chitosan blends stay amorphous up to 0.2 weight fraction of PEO. For a higher amount of PEO that polymer crystallises forming a spherulite crystalline structure. We correlate the overall kinetics of crystallisation and melting behaviour of solid, semicrystalline blends PEO/chitosan in the form of thin films for a set of PEO species of different blend composition with a morphological structure of the blends. Negative values of the Flory-Huggins interaction parameter due to specific interactions by hydrogen bonding through ether group of PEO and hydroxyl group of chitosan were evaluated. Amide groups do not participate in the molecular interaction between PEO and chitosan molecules. Avrami equation was applied to describe kinetics of crystallisation of pure PEO and PEO/chitosan blends of various compositions.     

Metal adsorption of carboxymethyl cellulose/carboxymethyl chitosan blend hydrogels prepared by Gamma irradiation

Blend hydrogels based on the carboxymethyl cellulose (CMC) and carboxymethyl chitosan (CMCts) were prepared by γ-irradiation of a high concentrated CMC/CMCts aqueous solution. Properties of the hydrogels, such as gel fraction, swelling ratio, gel strength, and metal adsorption for Pb and Au were investigated. The gel fraction increased with increasing dose, while the swelling ratio decreased with increasing it. The obtained blend hydrogels had high adsorption performance which was controlled by adjusting the composition of CMC/CMCts.     

Swelling kinetics and release characteristic of crosslinked chitosan: Polyether polymer network (semi-IPN) hydrogels

The aqueous swelling kinetics of a series of crosslinked chitosan (cr-CS) with glutaraldehyde (GA) interpenetrating polyether hydrogels have been studied as functions of pH, the N-deacetylation degree of chitosan, the amount of crosslinking agent, the electrolyte composition in solution, temperature, and gel composition. Based on these results, the swelling mechanism of the hydrogels was discussed. The release profiles of chlorhexidini acetas from the semi-IPN were also investigated. © 1994 John Wiley & Sons, Inc.     

Effect of sol–gel synthesis conditions on the physical properties of silica hydrogels

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Influence of chitosan and epoxy cross-linking on physical properties of binary blends

In this study, blends of chitosan (Cs) and bisphenol-F-diglycidyl ether (3.80 × 10^?3 to 3.80 × 10^?2 mol) were cast by the solution route. FT-IR results suggested that chitosan was cross-linked at terminal amino groups through diepoxide linkage. The chitosan films became less flexible and stiffer upon reaction with epoxy. Blending improved percentage elongation (31%) and toughness (10 MPa), whereas Young’s modulus (145 MPa) and tensile strength (45 MPa) were decreased. Extent of weight loss in Cs/BPFDGE was lower (15%) than that of original precursors (chitosan 33%). Moreover, blending of chitosan with BPFDGE increased water absorption properties due to generation of hydrophilic ?OH groups.     

Preparation and properties of novel hydrogels from oxidized konjac glucomannan cross-linked chitosan for in vitro drug delivery

In this paper, a novel composite hydrogel was prepared by the use of dialdehyde konjac glucomannan (DAK) as macromolecular cross-linking agent for chitosan (CS). This biocompatible material cross-links and gels in minutes. The structure and morphology were characterized by various analyses. The results indicate that the hydrogels formed through the Schiff-base reaction between the amino groups of CS chains and the aldehyde groups of DAK. The cross-link density (rho(x)) increases with the enhancement of DAK content in hydrogels, while equilibrium swelling ratio (SR) and the average molecular weight between cross-links (Mc) value decrease. Drug release was evaluated by varying the pH of the release medium, reversed dependence of release rate on the equilibrium SR of hydrogel indicated that drug release may be impeded by the association of drug with the polymer. Importantly, this process offers an entirely new window of materials preparation when compared with the traditional preparation of CS-based hydrogels with small molecules cross-linking agent.     

Rational design of biocompatible IPNs hydrogels containing carboxymethyl starch and trimethyl chitosan chloride with high antibacterial activity

Cellulose - Antimicrobial hydrogels have enticed a major concern for repairing soft tissues, particularly prohibiting bacterial infections that are frequently accompanied by impaired wound healing....