Designing crosslinked hyaluronic acid hydrogels with tunable mechanical properties for biomedical applications

This study develops a simple copolymerization/crosslinking technique to control the swelling and mechanical properties of hyaluronic acid‐based hydrogels. Because of the widespread acceptance of poly(ethylene glycol) in biomedical applications, functionalized oligomers of ethylene glycol (EG) were used as comonomers to crosslink methacrylated hyaluronic acid (MHA). The swelling degree, shear and elastic moduli, and fracture properties (stress and strain) of the gels were investigated as a function of the crosslinking oligomer length and reactive group(s). It was hypothesized that acrylated oligomers would increase the crosslink density of the gels through formation of kinetic chains by reducing the steric hindrances that otherwise may limit efficient crosslinking of hyaluronic acid into gels. Specifically, after crosslinking 13 wt % MHA (47% degree of methacrylation) with 0.06 mol % of (EG)_n‐diacrylate, the swelling ratio of the MHA gel decreased from 27 to 15 g/g and the shear modulus increased from 140 to 270 kPa as n increased from 1 to 13 units. The length and functionality (i.e., acrylate vs. methacrylate) of the oligomer controlled the crosslink density of the gels. The significant changes in the gel properties obtained with the addition of low levels of the PEG comonomer show that this method allows precise tuning of the physical properties of hyaluronic acid (HA) gels to achieve desired target values for biomedical applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42009.     

Morphology of crosslinked hyaluronic acid porous hydrogels

Hydrogels, based on hyaluronic acid or hyaluronan (HA), are gaining attention as possible cell‐scaffolding materials for the regeneration of a variety of tissues. This article describes how HA, a naturally occurring polymer, has been crosslinked to reduce its degradation rate and freeze dried to produce porous materials suitable for tissue engineering. The resulting pore architecture has been assessed as a function of freezing temperature and freezing rate, type of crosslinkers, and methods used in the crosslinking process. On comparing the average densities of crosslinked and uncrosslinked scaffolds, it is apparent that the chemical modification increases sponge density and wall thickness of the pores while decreasing the pore size. The mechanical response of the modified materials has been investigated by equilibrium‐swelling measurements and compression tests. These materials have an average pore size ranging from 167 to 215 μm, which suggests that they would be a suitable temporary site for cell proliferation. The materials exhibit moderate mechanical integrity and are expected to be capable of withstanding physiological stresses in vivo. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Preparation and property of starch nanoparticles reinforced aldehyde–hydrazide covalently crosslinked PNIPAM hydrogels

Injectable, de‐crosslinkable, and thermosensitive hydrogels are obtained by hydrazide‐functionalized poly(N‐isopropylacrylamide) and aldehyde‐functionalized dextrin through in situ crosslinked method. Natural based and degradable starch nanoparticles (SNPs) are used as fillers in order to improve mechanical property of hydrogels. Internal morphology, dynamic modulus, thermosensitivity property, de‐crosslinking performance, drug release, and in vitro cytotoxicity of hydrogels are investigated. Results show that SNPs disperse well throughout hydrogel and have no significant influence on gelation time and de‐crosslinking performance. Elasticity property of composite hydrogel prepared from 9.0 wt % precursors with 1.5 wt % fillers is improved significantly by SNPs and maximum storage modulus reaches 399.2 kPa, but 89.6 kPa of unreinforced hydrogels. Hydrogels exhibit good thermosensitive performance at alternating cyclic temperature of 25 and 37 °C. Doxorubicin hydrochloride‐loaded hydrogels can release more than 25 days. No significant cytotoxicity to L929 fibroblast cells is observed through a CCK‐8 assay for hydrogels, precursors, and SNPs. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45761.     

Laboratory scale study on rheological behavior,morphological and structural properties of crosslinked polyacrylamide composite hydrogels embedded with date seed powder

Incorporation of biofillers in polymeric hydrogels has continued to receive great attention in recent times because of their excellent properties. In this study, polyacrylamide (PAM) and polyethyleneimine (PEI) were used to develop novel composite hydrogels filled with date seed powder (DSP) via chemical crosslinking technique. Pristine PAM/PEI hydrogel and PAM/PEI‐DSP hydrogels at various DSP loadings were fabricated and subjected to gelation at 40°C for 24 h. The impact of various DSP loadings on the hydrogel samples developed was investigated using hybrid rheometer, SEM, XRD, and FTIR instruments, respectively. Rheological measurements confirmed the viscoelastic responses of the neat PAM/PEI hydrogel and the PAM/PEI‐DSP hydrogels reinforced with various DSP contents (0.8, 2.4, and 4 wt %). The dynamic strain, dynamic frequency and time sweep tests demonstrated that PAM/PEI‐DSP hydrogels were slightly more elastic than the virgin PAM/PEI hydrogel. The SEM characterization revealed the surface micrographs of the neat PAM/PEI hydrogel and the PAM/PEI‐DSP hydrogels at different DSP loadings to be smooth, homogeneous, and dense. Besides, the SEM micrographs supported the incorporation of DSP in the PAM/PEI‐DSP hydrogel samples. XRD analysis showed that the structures of neat PAM/PEI hydrogel and PAM/PEI‐DSP hydrogels filled with various DSP contents were predominantly amorphous while FTIR results confirmed the functional groups and evidence of crosslinking in the neat PAM/PEI hydrogel and the PAM/PEI‐DSP hydrogels embedded with different DSP contents. It is believed that these new hydrogels have huge development potentials and promising future in wastewater treatment and removal of heavy metal ions in aqueous solutions. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42110.     

Regimes of microstructural evolution as observed from rheology and surface morphology of crosslinked poly(vinyl alcohol) and hyaluronic acid blends during gelation

Hyaluronic acid (HA)‐based materials are being investigated because of their role in biological fluids and tissues. Poly(vinyl alcohol) (PVA) when blended with HA at different compositions leads to superior mechanical properties compared to pure HA. The PVAHA blend hydrogels are potential candidates for pharmaceutical, biomedical, and cosmetic applications. It is essential to understand the structure, gelation time, and morphological properties of these hydrogels. In this work, a blend system of PVA crosslinked with glutaraldehyde in the presence of HA is studied. Semidilute solutions of PVA and HA are blended, followed by gelation due to crosslinking. The crosslinked gels as well as the gel cast membranes were examined. The effect of HA on the gelation process is investigated using rheological characterization. It is shown that kinetics of gelation is influenced by HA content, though storage modulus of the gels is influenced marginally. The structural features of PVAHA gels were also probed with scanning electron microscopy and dynamic light scattering. It is argued that there is a complex interplay between intra‐ and intermolecular crosslinking of PVA and PVA–HA interactions during the gel formation. Based on the insights obtained from various probing techniques for PVAHA gels with different HA content, three broad structural features were identified. It is shown that the hydrogel is semi‐interpenetrating network at lower HA content (<10% HA), cocontinuous morphology at moderate HA content and with domains at high HA content (>20% HA). © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41081.     

Preparation and characterization by radiation of hydrogels of PVA and PVP containing Aloe vera

In these studies, hydrogels for wound dressing were made from a mixture of Aloe vera, poly(vinyl alcohol) (PVA) and poly(N‐vinylpyrrolidone) (PVP) by freeze‐thaw, gamma‐ray irradiation, or a two‐step process of freeze‐thaw and gamma‐ray irradiation. Physical properties, such as gelation, water absorptivity, gel strength and degree of water evaporation were examined to evaluate the applicability of these hydrogels to wound dressing. The PVA:PVP ratio was 6:4, and the dry weight of Aloe vera was in the range of 0.4‐1.2 wt %. The solid concentration of PVA/PVP/Aloe vera solution was 15 wt %. Mixtures of PVA/PVP/Aloe vera were exposed to gamma irradiation doses of 25, 35 and 50 kGy to evaluate the effect of irradiation dose on the physical properties of the hydrogels. Gel content and gel strength increased as the concentration of Aloe vera in PVA/PVP/Aloe vera decreased and as irradiation dose increased and freeze‐thaw was repeated. Swelling degree was inversely proportional to gel content and gel strength. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 1612–1618, 2004     

Dextrin crosslinked with poly(lactic acid): A novel hydrogel for controlled drug release application

A new class of biodegradable crosslinked hydrogel, consisting of hydrophobic polylactic acid (PLA) and hydrophilic dextrin in presence of crosslinker N,N‐methylene bisacrylamide (MBA) has been synthesized by free‐radical polymerization technique using potassium persulfate (KPS) as initiator. By variation of crosslinker concentration, a series of hydrogels have been prepared and the optimized grade has been selected on the basis of higher crosslinking efficiency as well as lower equilibrium swelling characteristics, XRD analysis. The hydrogels have been characterized by FTIR spectra, ¹³C‐NMR spectra, CHN analysis, SEM analysis, swelling characteristics, and toxicity study. In vitro release study of model drugs (ciprofloxacin and ornidazole) from hydrogel matrix has been performed in various buffer solutions at 37°C. The drug release kinetics and mechanism have been studied using zero order, first‐order kinetic models, Korsemeyar–Peppas model, Higuchi model, Hixson–Crowell model, and nonlinear Kopcha model. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40039.     

The synthesis and characteristics of sodium alginate/graphene oxide composite films crosslinked with multivalent cations

Association of a method of the incorporation of graphene oxide (GO) into sodium alginate (Na‐alg) polymer matrix with a method of the use multivalent cations crosslinker was put forward to synthesize novel Na‐alg/GO nanocomposite films. The structures, morphologies, and the properties of Na‐alg/GO films were characterized by Fourier transform infrared (FTIR) spectroscopy, X‐ray diffraction (XRD), field‐emission scanning electron microscopy (FE‐SEM), thermogravimetric analysis (TGA), and tensile tests. The results revealed that the interlayer distance of GO sheets increased from 0.83 nm to 1.08 nm after assembling with Na‐alg, and Na‐alg inserted into GO layers crosslinking with multivalent cations increased the interlayer distance further. Ionic crosslinking significantly enhanced thermal and mechanical properties of Na‐alg/GO nanocomposite films. In particular, Fe³⁺ led to Na‐alg/GO nanocomposite films of significantly higher tensile strength and modulus than Ca²⁺ and Ba²⁺. The excellent thermal and mechanical properties of these novel Na‐alg/GO nanocomposite films may open up applications for Na‐alg films. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43616.     

Preparation and characterization of alginate hydrogel membranes crosslinked using a water‐soluble carbodiimide

The preparation of alginate hydrogel membranes by the film immersion method was optimized for maximum crosslinking using swelling measurements as an indicator of the degree of crosslinking. The variables investigated were the concentration of the nonsolvent (ethanol) for sodium alginate, water‐soluble carbodiimide (WSC) concentration, and pH of the crosslinking medium. Optimum conditions resulted when the crosslinking medium contained 60 vol % ethanol and 100 mM WSC at pH 4. Membranes prepared using different ethanol concentrations (100 mM WSC, pH 4) and different WSC concentrations (60 vol % ethanol, pH 4) were investigated using infrared spectroscopy. The spectra showed the characteristic ester linkage (crosslinking) band at 1698 cm^?1 in cases where swelling measurements indicated that crosslinking had occurred. Differential scanning calorimetry of noncrosslinked and crosslinked membranes indicated that crosslinking increased the crystallinity of the membrane. Durability trials showed that membranes crosslinked using the optimum conditions determined in this work retained all weight when immersed in water for 32 days. Membranes prepared using these conditions possessed the characteristics required for use in the pervaporation separation of ethanol–water mixtures. These membranes also have potential as protective coatings for hydrophobic, microporous membranes in the membrane distillation and osmotic distillation concentration of feeds containing surface active components. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 747–753, 2003     

Controlled release of insecticide carbaryl from sodium alginate,sodium alginate/gelatin,and sodium alginate/sodium carboxymethyl cellulose blend beads crosslinked with glutaraldehyde

Interpenetrating network polymeric beads of sodium alginate (NaAlg) and its blend with gelatin (gels) or sodium carboxymethyl cellulose (NaCMC) have been prepared by crosslinking with a common crosslinking agent, glutaraldehyde (GA), for the release of insecticide carbaryl (Carb). The prepared beads were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. Scanning electron microscopy confirmed the spherical nature and surface morphology of the particles. Bead characteristics, such as carbaryl entrapment efficiency, particle size, equilibrium swelling degree, and carbaryl release kinetics, were determined. The effects of the preparation conditions, such as Carb/NaAlg ratio, time of exposure to GA, blend ratio, and temperature of release medium on the carbaryl release, were investigated for 25 days at 25°C. It was observed that the carbaryl release decreased with increase in crosslinking of network, while it increased with increase in Carb/NaAlg ratio and temperature. The release of carbaryl also increased with increase in Gel or NaCMC content in the blend beads. The highest carbaryl release was found to be 100%, for the beads that were prepared with 1 : 1 NaAlg/Gel at 16 days. The diffusion coefficients have been calculated for the transport of insecticide through the polymeric beads, using initial time approximation method. These values were also consistent with the carbaryl release data. The carbaryl release from most of the bead formulations followed the Fickian trend. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 1310–1319, 2006     

Incorporation of norbixin in biodegradable alginate films crosslinked with Ca2+: Pro-oxidant action

Alginate is a biopolymer with film-forming properties that can be used as food packaging material. Norbixin is a carotenoid with antioxidant properties, commonly used as a natural food coloring. The research objective was to create calcium-crosslinked alginate films and incorporated with norbixin concentrations (N%) of 0.05%, 0.10%, and 0.50% (g norbixin/g alginate). The polymer matrix helped to retard the thermal degradation of norbixin during the drying process and decreased leaching losses during the crosslinking process. The addition of norbixin influenced film opacity in ultraviolet light (all N%) and visible light (higher N%), causing an increase in red-yellow coloration. Only the higher N% influenced the water vapor permeability of film. Norbixin thus improved the overall barrier properties of the crosslinked sodium alginate film, with a 0.50 N% showing the most promising results. When used as sunflower oil packaging, films with a N% above 0.10 provided pro-oxidant activity during storage.     

Preparation of crosslinked composite nanoparticles

Crosslinked composite nanoparticles were prepared by adding a trifunctional monomer (trimethyol propane trimethacrylate) or a difunctional monomer (divinyl benzene) as a crosslinker into the emulsion polymerization system of styrene in the presence of inorganic nanosilica. A coupling agent, 3‐methacryloxypropyltrimethoxysilane (MPS), was added along with the monomer, crosslinker, and silica to improve the interfacial interaction between silica and polymer and thus to obtain high binding efficiency. The role of MPS was examined. The effects of crosslinkers on the kinetics of emulsion polymerization, monomer conversion, and yield were investigated. The morphology of the composite particles was observed by TEM. The particle size and size distribution of composite latex particles were measured by the dynamic light scattering method. The binding efficiency and swelling ratio were determined by reluxing the sample in xylene using a Soxhlet extraction apparatus. FTIR spectra and TGA verified the participation of crosslinker and silica. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 1538–1544, 2005     

Thin film composite sodium alginate membranes for dehydration of acetic acid and isobutanol

Dehydration of widely used organic solvents such as acetic acid (AA) and isobutanol (IB) is challenging tasks, which form close boiling mixtures with water. Sodium alginate (SA) thin film composite membranes were prepared and crosslinked with 2,4‐toluene diisocyanate (TDI) and glutaraldehyde for dehydration of IB and AA/water mixtures through pervaporation (PV). The crosslinked and uncrosslinked SA composite membranes were characterized by Fourier transform infrared spectroscopy (FTIR), X‐ray diffraction, thermogravimetric analysis, scanning electron microscopy, and universal testing machine for intermolecular interactions, crystalline nature, thermal stability, surface morphology, and tensile strength, respectively. At a feed composition of 98 wt % IB and 95 wt % AA aqueous solutions, the TDI crosslinked SA composite membrane exhibited separation factors of 3229 and 708 with reasonable fluxes of 0.021 and 0.012 kg m^?2 h^?1, respectively. The results obtained in the study for IB and AA systems were compared with other SA membranes reported in the literature. The membranes appeared to have potential for commercial PV ability to dehydrate the solvents up to desirable purity levels (>99%) and feasibility of preparing them in a composite form which would enable scale‐up into modular configurations. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014 , 131, 40018.     

Synthetic polymeric absorbent for dye based on chemically crosslinked acrylamide/mesaconic acid hydrogels

Adsorption properties of copolymers of acrylamide and mesaconic acid (CAME) in aqueous Basic Blue 12 (Nile blue chloride) solution have been investigated. Chemically crosslinked CAME hydrogels with various compositions were prepared from ternary mixtures of acrylamide (A), mesaconic(ME) acid, and water by free radical polymerization in aqueous solution, using a multifunctional crosslinker such as ethylene glycol dimethacrylate (EGDMA). Dynamic swelling tests in water was applied to the hydrogels. Weight swelling ratio (S) values have been calculated. Sorption of Basic Blue 12 (BB 12) onto CAME hydrogels was studied by batch sorption technique at 25°C. In the experiments of the sorption, L type sorption in the Giles classification system was found. Some binding parameters such as initial binding constant (K_i), equilibrium constant (K), monolayer coverage (n), site‐size (u), and maximum fractional occupancy (Ô) for CAME hydrogels‐BB 12 binding system were calculated by using Klotz, Scatchard, and Langmuir linearization methods. Finally, the amount of sorbed BB 12 per gram of dry hydrogel (q) was calculated to be 2.28 × 10^?6–7.91× 10^?6 mol BB 12 per gram for hydrogels. Sorption % was changed range 16.09–58.86%. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 405–413, 2006     

Enzymatic and ionic crosslinked gelatin/K‐carrageenan IPN hydrogels as potential biomaterials

Hydrogels of a natural origin have attracted considerable attention in the field of tissue engineering due to their resemblance to ECM, defined degradability and compatibility with biological systems. In this study, we introduced carrageenan into a gelatin network, creating IPN hydrogels through biological methods of enzymatic and ionic crosslinking. Their gelation processes were monitored and confirmed by rheology analysis. The combination of biochemical and physical crosslinking processes enables the formation of biohydrogels with tunable mechanical properties, swelling ratios and degradation behaviors while maintaining the biocompatibilities of natural materials. The mechanical strength increased with an increase in carrageenan content while swelling ratio and degradability decreased correspondingly. In addition, the IPN hydrogels were shown to support adhesion and proliferation of L929 cell line. All the results highlighted the use of biological crosslinked gelatin‐carrageenan IPN hydrogels in the context of tissue engineering. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 10.1002/app.40975.     

Swelling kinetic study and characterization of crosslinked hydrogels containing silver nanoparticles

The ammonium persulfate induced polymerization of acrylamide in the presence of silver nitrate (AgNO₃) and N,N′‐methylenebisacrylamide as a crosslinking agent were used to prepare crosslinked hydrogels containing silver ions. Subjecting this hydrogel to reduction with sodium hydroxide brought to focus the nanosilver hydrogel composites. Characterization of the latter, including proof of existence of silver nanoparticles in the hydrogel, was made. The number of silver nanoparticles embedded in the hydrogel matrix was higher at higher concentration of AgNO₃ used in the preparation of the nanosilver hydrogel composite. The characterization was performed by the use of ultraviolet–visible spectroscopy and transmission electron microscopy. The swellability of the hydrogel containing nanosilver particles was also studied, and the dependence of the swellability on the abundance of silver nanoparticles in the hydrogel composite was verified. It was further disclosed that the kinetic model matched the experimental data; meanwhile, the diffusion of water into the hydrogel was non‐Fickian type. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Platinum and palladium ions adsorption at the trace amounts by radiation crosslinked carboxymethylchitin and carboxymethylchitosan hydrogels

Adsorption of palladium and platinum ions at the trace amounts onto radiation crosslinked carboxymethylchitin (CMCht) and carboxymethylchitosan (CMChts) has been investigated. Maximum adsorption capacities for palladium were 2.679 and 1.053 mg/g dry gel, whereas for platinum they were 2.513 and 1.155 mg/dry gel for CMCht and CMChts, respectively. Retention capacity values for palladium were 0.45 and 0.06; for platinum 0.25 and 0.11 mEquiv./g for CMCht and CMChts, correspondingly. It has been shown that adsorption of Pd and Pt ions onto both hydrogels were dependent on the chloric and nitric ions concentration. Desorption experiments in HCl and HNO₃ solutions proved that adsorption is governed by chelating mechanism rather than ion‐exchange one. SEM‐EDX spectroscopy showed that palladium and platinum ions were homogeneously distributed in all sections of hydrogel matrix. DSC experiments demonstrated decreasing in the decomposition temperature of polymers after inclusion of palladium and platinum ions, suggesting that metals are causing lowering of stability in polymer structural integrity. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 4015–4023, 2007     

Characterization of sodium alginate membrane crosslinked with glutaraldehyde in pervaporation separation

Dense sodium alginate (SA) membranes crosslinked with glutaraldehyde (GA) have been prepared by the solution method, wherein a nonsolvent of SA (acetone) was used in a reaction solution instead of an aqueous salt solution. Through infrared radation, X-ray diffractometry, and the swelling measurement, the crosslinking reaction between the hydroxyl groups of SA and the aldehyde groups of GA was characterized. To investigate the selective sorption behavior of the crosslinked SA membranes, swelling measurements of the membranes in ethanol-water mixtures of 70–90 wt % ethanol contents were conducted by equipment that was able to measure precisely the concentration and amount of the liquid absorbed in the membranes. It was observed that the crosslinking could reduce both the solubility of water in the resulting membrane and the permselectivity of the membrane toward water at the expense of membrane stability against water. The pervaporation separation of a ethanol-water mixture was conducted with the membranes prepared at different GA contents in the reaction solution. When the membrane was prepared at a higher GA content, both flux and separation factor to water were found to be reduced, thus resulting from the more crosslinking structure in it. The pervaporation separations of ethanol-water mixtures were also performed at different feed compositions and temperatures ranging from 40 to 80°C. A decline in the pervaporative performance was observed due to the relaxation of polymeric chains taking place during pervaporation, depending on operating temperature and feed composition. The relaxational phenomena were also elucidated through an analysis on experimental data of the membrane performance measured by repeating the operation in the given temperature range. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 67: 209–219, 1998