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Alginate is a natural polymer of marine origin and, due to its exceptional properties, has great importance as an essential component for the preparation of hydrogels and scaffolds for biomedical applications. The design of biologically interactive hydrogels and scaffolds with advanced, expected and required properties are one of the key issues for successful outcomes in the healing of injured tissues. This review paper presents the multifunctional biomedical applications of alginate-based hydrogels and scaffolds in selected areas, highlighting the key effect of alginate and its influence on the essential properties of the selected biomedical applications. The first part covers scientific achievements for alginate in dermal tissue regeneration, drug delivery systems, cancer treatment, and antimicrobials. The second part is dedicated to our scientific results obtained for the research opus of hydrogel materials for scaffolds based on alginate in synergy with different materials (polymers and bioactive agents). Alginate has proved to be an exceptional polymer for combining with other naturally occurring and synthetic polymers, as well as loading bioactive therapeutic agents to achieve dermal, controlled drug delivery, cancer treatment, and antimicrobial purposes. Our research was based on combinations of alginate with gelatin, 2-hydroxyethyl methacrylate, apatite, graphene oxide and iron(III) oxide, as well as curcumin and resveratrol as bioactive agents. Important features of the prepared scaffolds, such as morphology, porosity, absorption capacity, hydrophilicity, mechanical properties, in vitro degradation, and in vitro and in vivo biocompatibility, have shown favorable properties for the aforementioned applications, and alginate has been an important link in achieving these properties. Alginate, as a component of these systems, proved to be an indispensable factor and played an excellent “role” in the optimal adjustment of the tested properties. This study provides valuable data and information for researchers and demonstrates the importance of the role of alginate as a biomaterial in the design of hydrogels and scaffolds that are powerful medical “tools” for biomedical applications.

The design and use of new potent and specific antimicrobial systems are of crucial importance in the medical field. This will help relieve, fight, and eradicate infections and thus improve human health. The use of metals in various forms as antimicrobial therapeutics has been known since ancient times. In this sense, polymeric hydrogel matrices as multifunctional materials and in combination with various metal forms can be a great alternative to conventional treatments for infections. Hydrogels possess high hydrophilicity, specific three-dimensional networks, fine biocompatibility, and cell adhesion and are therefore suitable as materials for the loading of active antimicrobial agents and acting in antimicrobial areas. The biocompatible nature of hydrogels’ matrices makes them a convenient starting platform to develop biocompatible, selective, active controlled-release antimicrobial materials. Hydrogels based on acrylate and itaconic acid were synthesized and loaded with silver (Ag+), copper (Cu2+), and zinc (Zn2+) ions as a controlled release and antimicrobial system to test release properties and antimicrobial activity in contact with microbes. The metal ions/hydrogel systems exhibited favorable biocompatibility, release profiles, and antimicrobial activity against methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Escherichia coli, and Candida albicans microbes, and have shown that they have the capacity to “fight” with the life-threatening infections. Antimicrobial activity depends on types of metal ions, the composition of polymeric matrices, as well as the types of microbes. Designed metal ions/poly(acrylate/itaconic acid) antimicrobial systems have shown to have good potential as antimicrobial therapeutics and suitable biomaterials for medical applications.

The design and evaluation of novel 2-hydroxyethyl methacrylate/gelatin/alginate/graphene oxide hydrogels as innovative scaffolding biomaterials, which concurrently are the suitable drug delivery carrier, was proposed. The hydrogels were prepared by the adapted porogen leaching method; this is also the first time this method has been used to incorporate nanocolloidal graphene oxide through the hydrogel and simultaneously form porous structures. The effects of a material’s composition on its chemical, morphological, mechanical, and swelling properties, as well as on cell viability and in vitro degradation, were assessed using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), measurements of Young’s modulus, gravimetric method and MTT test, respectively. The engineered hydrogels show good swelling capacity, fully hydrophilic surfaces, tunable porosity (from 56 to 76%) and mechanical properties (from 1.69 to 4.78 MPa), curcumin entrapment efficiency above 99% and excellent curcumin release performances. In vitro cytotoxicity on healthy human fibroblast (MRC5 cells) by MTT test reveal that the materials are nontoxic and biocompatible, proposing novel hydrogels for in vivo clinical evaluation to optimize tissue regeneration treatments by coupling the hydrogels with cells and different active agents to create material/biofactor hybrids with new levels of biofunctionality.

The adsorption of Ni2+ ions from water solutions by using hydrogels based on 2-hydroxyethyl acrylate (HEA) and itaconic acid (IA) was studied. Hydrogel synthesis was optimized with response surface methodology (RSM). The hydrogel with the best adsorption capacity towards Ni2+ ions was chosen for further experiments. The hydrogel was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis before and after the adsorption of Ni2+ ions. Batch equilibrium experiments were conducted to investigate the influence of solution pH, hydrogel weight, ionic strength, adsorption time, temperature and initial concentration of nickel ions on the adsorption. Time-dependent adsorption fitted the best to the pseudo-second-order kinetic model. A thermodynamic study revealed that the adsorption was an exothermic and non-spontaneous process. Five isotherm models were studied, and the best fit was obtained with the Redlich–Peterson model. Consecutive adsorption/desorption studies indicated that the HEA/IA hydrogel can be efficiently used as a sorbent for the removal of Ni2+ ions from the water solution. This study develops a potential adsorbent for the effective removal of trace nickel ions.

Antibacterial hydrogels, as an advanced approach, can create optimal conditions for wound healing, even in the fight against stubborn and difficult‐to‐treat wound infections. Interestingly, pH is an often neglected clinical parameter, although it has a significant impact on the wound healing process. At different stages of wound healing, the pH in the wound bed changes from slightly alkaline to neutral to acidic. To develop novel pH‐sensitive antibacterial hydrogel dressings, Zn2+‐loaded poly(2‐hydroxyethyl acrylate/itaconic acid) hydrogels are synthesized. The hydrogels exhibit pH‐sensitive swelling in the physiologically relevant pH range, with a pronounced swelling ability at neutral pH. The controlled release of Zn2+ occurs in a buffer of pH 7.40 at 37 °C. The liquid transport mechanism and release kinetics are evaluated using the specific kinetic models of Ritger‐Peppas and Peppas‐Sahlin. The effect of Zn2+ on structural, thermal, swelling, cytocompatibility, and antibacterial properties is evaluated by Fourier transform infrared spectroscopy, differential scanning calorimetry, swelling studies, MTT, and antibacterial tests. The hydrogels show excellent antibacterial activity against Escherichia coli. The research opens new perspectives for efficient wound healing management, and the extension of the study will be orchestrated by optimising the hydrogel composition to achieve improved performance. [ABSTRACT FROM AUTHOR]

A series of poly(2-hydroxyethyl acrylate-co-itaconic acid), P(HEA/IA), hydrogels with different HEA/IA ratio, were synthesized using free radical crosslinking/copolymerization and investigated as sorbents for Pb2+ ions from aqueous solutions. Hydrogels were characterized using DMA, FTIR, DSC, SEM and AFM. The adsorption was found to be highly dependent on hydrogel composition, solution pH, sorbent weight, ionic strength and contact time. Five isotherm models, Langmuir, Freundlich, Redlich-Peterson, Temkin and Dubinin-Radushkevich, were applied to the sorption data. The best fit was obtained with Redlich-Peterson isotherm. The separation factor, RL, value indicated favorable sorption for Pb2+ ions. The maximum sorption capacities were 392.2 and 409.8 mg/g for P(HEA/2IA) and P(HEA/10IA), respectively. Kinetic data showed best fit with pseudo-second-order model. Thermodynamic studies revealed that the reaction was exothermic and proceeds with a decrease in entropy. Moreover, P(HEA/IA) hydrogel showed the most pronounced sorption toward Pb2+ ions from environment containing Cu2+, Zn2+, Cd2+, Ni2+ and Co2+ ions. Sorption/desorption experiments, showed that the P(HEA/IA) hydrogels could be reused without significant loss of the initial properties even after three adsorption-desorption cycles. [Projekat Ministarstva nauke Republike Srbije, br. 172015 i br. 172062]

The objective of our study was to develop new antimicrobial hydrogels silver/poly(2-hydroxyethyl methacrylate/ itaconic acid) (Ag/P(HEMA/IA)). The P(HEMA/IA) samples, with different HEMA/IA ratio, were prepared by free radical crosslinking copolymerization. Ag ion were introduced in hydrogels by immersing dried P(HEMA/IA) disks in silver(I) salt solution, which was confirmed by FTIR spectroscopy. The in vitro controlled release of silver(I) ion from (Ag/P(HEMA/IA)) gels, and antimicrobial activity during the release period were also studied. The release profiles have shown a two-phase exponential profile, with fast initial phase, followed by a much slower release rate. Kinetic parameters determined, have indicated Fickian transport of Ag(I) ion in the initial phase. It is perceived that the antimicrobial activity of the Ag/P(HEMA/IA) depends on IA content. Excellent antimicrobial potential was maintained during the entire release time.

The aim of this paper is to propose equations for the diffusion of drugs for investigated drug/hydrogel systems using the parameters affecting the transport of drug through poly(2-hydroxyethyl methacrylate/itaconic acid) (P(HEMA/IA)), poly(2-hydroxyethyl acrylate/itaconic acid) (P(HEA/IA)), and poly(2-hydroxyethyl methacrylate/poly(alkylene glycol) (meth)acrylates) (P(HEMA/BIS)) copolymeric hydrogels. Different monomer types, as well as the variable content of some components in hydrogel composition (the amount of ionizable comonomer (IA) and different type of nonionic poly(alkylene glycol) (meth)acrylates), ultimately defined the pore size available for drug diffusion. The hydrogels synthesized ranged from nonporous to microporous, based on the classification in accordance to the pore size, and could be classified as hydrogels that contain ionic groups and hydrogels without ionic groups. The drugs selected for this study are bronchodilators-theophylline (TPH), fenethylline hydrochloride (FE), and antibiotic-cephalexin (CEX). Results of in vitro drug release tests defined the release systems based on the drug type, as well as the type of hydrogel used. The diffusion coefficient of drugs and the restriction coefficient, , defined as the ratio of solute to ‘pore’ radius (rs/rζ ) that describes the ease of drug release from the gels, were used as factors that govern the release process.

In this study novel series of hydrogels, based on 2-hydroxyethyl methacrylate (HEMA), itaconic acid (IA) and poly(ethylene glycol) dimethacrylates (PEGDMA) (of varying molecular weight and concentration) were prepared by free radical crosslinking copolymerization. Preliminary hemocompatibility characterization of hydrogels obtained by hemolytic activity assay indicated good compatibility with blood. Preliminary biocompatibility characterization of P(HEMA/IA/PEGDMA) hydrogels, done by the cytotoxicity assays using the HeLa cell line revails that the cell viability of all samples was the range of 97−100%, with no significant decrease in cell viability with the change of PEGDMA molecular weight and concentration. Swelling studies were conducted for all P(HEMA/IA/PEGDMA) samples in a physiological pH and temperature range and network parameters were determined. Swelling studies showed pH sensitive behaviour, typical for anionic hydrogels, and temperature dependent swelling. The effects of concentration of PEGDMA component on hydrogel swelling properties depend on the PEGDMA molecular weight. The samples with 550PEGDMA show different swelling capacities when 550PEGDMA content is changed, whereas for P(HEMA/IA/875PEGDMA) samples there was practically no difference in equilibrium degree of swelling, qe ,with varying 875PEGDMA content, which trend is the same as in the case of qe versus pH dependences. It was concluded that P(HEMA/IA/PEGDMA) hydrogels show good potential to be used as biomedical materials.

In this work new hybrid hydrogels were prepared by radical copolymerization of 2-hydroxyethyl methacrylate, itaconic acid, poly(vinylpyrrolidone) and silver particles. FTIR spectroscopy has confirmed binding of silver particels in hydrogels. Swelling studies performed in in vitro conditions showed dependence on PVP content and temperature. It can be seen that the antimicrobial activity of the Ag/P(HEMA/IA)PVP hybrid hydrogels depends on the PVP moiety and with the increase of PVP content the microbial contamination is more efficiently reduced. The best sensitivity was obtained for the polymers tested for antimicrobial activity against the yeast C. albicans, one of the most commonly encountered human pathogens, causing a wide variety of infections ranging from mucosal infections in generally healthy persons to life-threatening systemic infections in individuals with impaired immunity. A slightly less susceptible to antimicrobial effect of hydrogels was obtained for the Gram-positive bacteria S. aureus, where the reduction of cells was about 70 % after two hours of exposure, for the sample with the highest PVP content. The least susceptible to the antimicrobial activity of hydrogels examined was the Gram-negative bacteria E. coli, where the percent of cell reduction was below 20 %. Bearing in mind the influence of the time of exposure of microbes to the Ag/P(HEMA/IA)/PVP hybrid hydrogels, it was observed that the reduction of the number of cells depends on time, microbial culture and type of hybrid hydrogel sample. Due to their swelling and antimicrobial properties, silver/poly(2-hydroxyethyl methacrylate/itaconic acid)/poly(vinylpyrrolidone) hybrid hydrogles show potential to use in the field of biomedicine, especially for treatment of skin and burns in dermocosmetics.

Silver(I) itaconic acid-based hydrogel complexes were synthesized and characterized in order to examine the potential use of these systems; FTIR, AFM, in vitro fluid-uptake, metal sorption and antibacterial activity assay measurements were used for the characterization. Metal (silver(I)) ion uptaken by IA-based hydrogels was determined by inductively coupled plasma mass spectrometry. The coordination sites for metal ions were identified and the stability in in vitro condition was determined. Incorporation of silver(I) ions into hydrogels and the influence of these ions on the diffusion properties of hydrogels were analyzed and discussed, too; it was found that the itaconic acid moiety in hydrogels is the determining factor which influences metal ion binding and therefore fluid uptake inside the polymeric network. Furthermore, silver(I) itaconic acid-based hydrogel showed a satisfactory antibacterial activity. The most advanced feature of these materials is that the silver ions embedded throughout the networks leaches out via controlled manner with time in aqueous media. Therefore, the ions escape from the swollen networks with time and interact with the bacteria. Because of a good dispersion of silver ions in Ag(I)-P(HEMA/2IA) hydrogel complex, we have evaluated the antibacterial activity for this sample. As expected, the number of colonies grown surrounding the Ag(I)- -P(HEMA/2IA) hydrogel complex was found to be almost nil, whereas the pure P(HEMA/2IA) hydrogel did not show any effect on Escherichia coli. Therefore, we conclude that the Ag(I)-P(HEMA/IA) hydrogel complexes are excellent antibacterial materials. Due to these facts, the silver ion IA- -based hydrogel complexes reported here might be used as smart materials in the range of biomedical applications, including drug-delivery devices, biosensors, wound healing dressings, tissue reconstruction and organ repair.

pH and temperature sensitive hydrogels, based on 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) copolymers, were prepared by gamma irradiation and characterized in order to examine their potential use in biomedical applications. The influence of comonomer ratio in these smart copolymers on their morphology, mechanical properties, biocompatibility and microbe penetration capability was investigated. The mechanical properties of copolymers were investigated using the dynamic mechanical analysis (DMA), while their morphology was examined by scanning electron microscopy (SEM). The morphology and mechanical properties of these hydrogels were found to be suitable for most requirements of biomedical applications. The in vitro study of P(HEMA/IA) biocompatibility showed no evidence of cell toxicity nor any considerable hemolytic activity. Furthermore, the microbe penetration test showed that neither Staphylococcus aureus nor Escherichia coli passed through the hydogel dressing; thus the P(HEMA/IA) dressing could be considered a good barrier against microbes. All results indicate that stimuli-responsive P(HEMA/IA) hydrogels have great potential for biomedical applications, especially for skin treatment and wound dressings.