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Since the management of infections becomes prior global healthcare issue, the "post antibiotic era" requires innovative and interdisciplinary approach. As an alternative to widespread and, nowdays mostly uneffective, antibiotic treatment of infections, the series of hydrogels were developed and further investigated as novel antibacterial biomaterials. The hydrogels based on 2-hydroxyethyl acrylate and itaconic acid were synthesized and used for silver(I) ions incorporation. The structural, thermal and swelling characteristics were examined by Fourier transform infrared spectroscopy, differential scanning calorimetry, and swelling study conducted in wide range of pHs at 37 degrees C. Results confirmed the expected structure, while the glass transition temperatures (T-g) of the hydrogels were detected in range of 10-37 degrees C. The in vitro release study revealed suitability of these pH sensitive hydrogels as the systems for topical delivery of silver(I) ions. Performed MTT test and Comet assay proved biocompatibility of the hydrogels, as well as the absence of acute genotoxic effect on human fibroblast cells (MRC-5). The hydrogels exhibited satisfying antibacterial activity against methicillin sensitive Staphylococcus aureus (MSSA) and methicillin resistant Staphylococcus aureus (MRSA), indicating the capacity to treat the life-threatening infections.

Hydrogel scaffolding biomaterials are one of the most attractive polymeric biomaterials for regenerative engineering and can be engineered into tissue mimetic scaffolds to support cell growth due to their similarity to the native extracellular matrix. The novel, versatile hydrogel scaffolds based on alginate, gelatin, 2-hydroxyethyl methacrylate, and inorganic agent hydroxyapatite were prepared by modified cryogelation. The chemical composition, morphology, porosity, mechanical properties, effects on cell viability, in vitro degradation, in vitro and in vivo biocompatibility were tested to correlate the material’s composition with the corresponding properties. Scaffolds showed an interconnected porous microstructure, satisfactory mechanical strength, favorable hydrophilicity, degradation, and suitable in vitro and in vivo biocompatible behavior. Materials showed good biocompatibility with healthy human fibroblast in cell culture, as well as in vivo with zebrafish assay, suggesting newly synthesized hydrogel scaffolds as a potential new generation of hydrogel scaffolding biomaterials with tunable properties for versatile biomedical applications and tissue regeneration.

We have studied the effect of compositions and methods of preparation on the physico-chemical and biocompatible behavior of the hydrogel matrices. Hydrogel matrices are synthesized by free radical polymerization of 2-hydroxyethyl methacrylate net and with gelatin. Highly porous hydrogel structures were obtained by porogenation, and by cryogenic treatment followed by freeze-drying. All samples were characterized for structural, morphological, absorption, degradation and in vitro (healthy human fibroblast cell line) and in vivo (zebrafish Danio rerio) biocompatible properties. The obtained results show that cryo samples, especially with gelatin show better, favorable absorption, morphological and biocompatible properties in comparison with PHEMA samples, which makes these materials highly attractive for biomedical uses.

The discovery of novel biodegradable biomaterials able to support and control cellular activity as well as development of an enhanced and efficient method for their fabrication, are of paramount importance in the field of tissue engineering. This study highlights the design of novel degradable hydrogels based on gelatin and hydroxyethyl (meth)acrylates using the innovative combined two-step sequential microwave-assisted and UV photo-polymerization technique. Chemical composition, morphology, swelling capacity and degradation rate of the synthesized hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), swelling and weight loss measurements. As an initial step for evaluation of performance of the hydrogels in the biological environment, the in vitro biocompatibility of these hydrogels, was evaluated using L929 mouse fibroblasts. Obtained results demonstrated that the hydrogels possess a porous morphology with interconnected pores, 50% in vitro degradation after 7 months, and satisfied biocompatibility on L929 fibroblast cells. These unique performances of the hydrogels make them promising candidates for in vivo evaluation in clinical studies aiming at tissue regeneration.

The aim of this work was to synthesize a series of semi-interpenetrating polymer networks (semi-IPNs) of 2-hydroxyethyl acrylate and itaconic acid, in the presence of poly(N-vinylpyrrolidone). Samples were synthesized by free radical copolymerization with constant PVP and variable IA content and characterized for structural, morphological, thermal, swelling, drug release, antibacterial and cytotoxic properties. The chemical structure of samples was confirmed by Fourier-transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) was used to examine morphology of samples and glass transition temperatures were determined by differential scanning calorimetry (DCS). The pH and temperature sensitivity was confirmed by measuring the dependence of the degree of swelling on pH and temperature. All samples show volume phase transition temperature (VPTT) around 47 °C. Drug release profiles were investigated using vitamin B3 as a model drug. The vitamin B3 transport mechanism was studied by fitting experimental data to five different model equations and calculating the corresponding parameters. It was also observed that IA content has a marked influence on the release profiles of vitamin B3, so the rate of drug release can be designed by changing the HEA/IA ratio. Cell viability, performed using MTT test, was high for all samples and all concentration of extract used. The antibacterial activity of hydrogels was determined against Pseudomonas aeruginosa. It turns out that IA content and time of exposure have an influence on the antibacterial potential. All samples showed satisfied cell viability. Due to these characteristics, P(HEA/IA)/PVP semi-IPNs represent interesting biomaterials for biomedical applications.

In this study, three series of semi-interpenetrating networks were synthesized based on 2-hydroxyethyl methacrylate (HEMA), 2-hydroxyethyl acrylate (HEA), itaconic acid (IA), and poly(vinyl pyrrolidone) (PVP) as interpenetrating polymer. Syntheses were performed by free radical cross-linking/polymerization reaction. The first series represented hydrogels based on 2-hydroxyethyl methacrylate, poly(vinyl pyrrolidone), and itaconic acid, varying of poly(vinyl pyrrolidone) content. The second series of samples were hydrogels based on 2-hydroxyethyl acrylate, poly(vinyl pyrrolidone), and itaconic acid, varying of itaconic acid content. The third series of synthesized samples were based on 2-hydroxyethyl acrylate, poly(vinyl pyrrolidone), and itaconic acid, varying of poly(vinyl pyrrolidone) content. The content of component was varied in order to examine the influence on the structure, pH- and temperature-sensitive swelling-“intelligent” behavior, mechanical properties of hydrogels, as well as antimicrobial and biocompatible potential of hydrogels. Poly(vinyl pyrrolidone) is a linear polymer, which shows satisfactory biocompatibility and hydrophilicity. Itaconic acid gives pH-sensitive-“intelligent” behavior and better hydrophilicity. Hydrogels based on HEMA and HEA show excellent biocompatibility and satisfactory hydrophilicity. All three series of samples showed satisfactory cytocompatibility, as well as the antimicrobial potential tested against most common microbes. The results obtained and presented in this research can contribute to the development of new efficient polymeric biomaterials for biomedical applications.

The strategy of combining polymers of natural and synthetic origin with inorganic components to use their unique synergistic effect for the development of the novel, sophisticated, and efficient 3D polymeric biomaterials, whose structure and properties mimic the extracellular matrix and simultaneously represent the suitable hydrogel platform for controlled drug release, is presented. The novel versatile 2-hydroxyethyl methacrylate/gelatin/alginate/iron(III) oxide based hydrogels are prepared by a simple but effective method-modified porogenation. Chemical composition, morphology, swelling capacity, porosity, mechanical properties, effects on cell viability, and in vitro degradation are tested to correlate the material's composition with the corresponding properties. The hydrogels show an interconnected porous microstructure, satisfactory mechanical strength, pH-sensitivity, and favorable curcumin release performances. The materials show good compatibility with healthy human fibroblast in cell culture judged by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, suggesting newly synthesized hydrogels as potentially a new generation of 3D biomaterials with tunable properties for versatile biomedical and pharmaceutical applications.

In this study, three series of hydrogels based on 2-hydroxyethyl acrylate and itaconic acid, unloaded, with incorporated copper(II) ions and reduced copper, were successfully prepared, characterized and evaluated as novel wound healing materials. Fourier transform infrared spectroscopy (FTIR) confirmed the expected structure of obtained hydrogels. Scanning electron microscopy (SEM) revealed porous morphology of unloaded hydrogels, and the morphological modifications in case of loaded hydrogels. Thermal characteristics were examined by differential scanning calorimetry (DSC) and the glass transition temperatures were observed in range of 12-50 degrees C. Swelling study was conducted in wide range of pHs at 37 degrees C, confirming pH sensitive behaviour for all three series of hydrogels. The in vitro copper release was investigated and the experimental data were analysed using several models in order to elucidate the transport mechanism. The antimicrobial assay revealed excellent antimicrobial activity, over 99% against Escherichia coli, Staphylococcus aureus and Candida albicans, as well as good correlation with the copper release experiments. In accordance with potential application, water vapour transmission rate, oxygen penetration, dispersion characteristics, fluid retention were observed and the suitability of the hydrogels for wound healing application was discussed.

Series of novel dual-sensitive poly(2-hydroxypropyl acrylate/itaconic acid) hydrogels were designed as multifunctional drug delivery system which can provide several advantages including drug protection, self-regulated oscillatory release and targeted delivery to a single entity. The hydrogels were synthesized by the free-radical crosslinking copolymerization and evaluated as carriers for hydrophobic drug, Oxaprozin, with specific controlled release properties. Structural, morphological, thermal, surface charge, swelling and antimicrobial properties of the hydrogels were investigated for unloaded and Oxaprozin-loaded samples. Swelling studies demonstrated pH- and temperature-sensitivity of drug-free and drug-loaded P(HPA/IA) hydrogels. The results of swelling and oscillatory swelling, and swelling behavior of drug-free, and drug-loaded hydrogels in simulated gastrointestinal conditions, and in vitro Oxaprozin release studies confirmed these hydrogels as a highly effective colon-specific drug delivery system with excellent performance of long-term controlled release. These unique properties make the P(HPA/IA) hydrogels highly attractive materials for developing multifunctional drug delivery systems.

Gelatin hydrogels have great potential in regenerative medicine but their weak mechanical properties are a major drawback for the load-bearing applications, such as scaffolds for tissue engineering. To overcome this deficiency, novel biodegradable hydrogels with improved mechanical properties were prepared by combining gelatine with 2-hydroxyethyl methacrylate (HEMA), using a double network synthetic procedure. The first, superporous and mechanically strong network, was obtained by free radical polymerization of HEMA at cryogenic temperature, in the presence of gelatin. Degradable poly (beta-amino ester) (PBAE) macromers of different chemical composition or molecular weight were used as crosslinkers to introduce hydrolytically labile bonds in PHEMA. The second gelatin network was formed by crosslinking gelatin with glutaraldehyde. For comparison, a set of biodegradable PHEMA networks was obtained by polymerization of HEMA at cryogenic temperature. All samples were characterized revealing that mechanical strength, swelling behavior and degradation rate as well as high biocompatibility of new IPNs are in accordance with values required for scaffolds in tissue engineering applications and that tuning of these properties is accomplished by simply using different PBAE macromers. This is peer-reviewed version of the article: Filipović, V., Nedeljkovic, B. D. B., Vukomanovic, M.,& Tomić, S. Lj. (2018). Biocompatible and degradable scaffolds based on 2-hydroxyethyl methacrylate, gelatin and poly(beta amino ester) crosslinkers. Polymer TestingElsevier Sci Ltd, Oxford., 68, 270-278. [https://doi.org/10.1016/j.polymertesting.2018.04.024] The published version: [https://cer.ihtm.bg.ac.rs/handle/123456789/2440]

Novel hydrogels based on 2-hydroxyethyl methacrylate (HEMA), itaconic acid (IA) and different poly (alkylene glycol) (meth)acrylates (PAGM) (P(HEMA/IA/PAGM)) were synthesized. We investigated the influence of different PAGM components, with acrylic or methacrylic acid residues in the main chain and ethylene glycol (EG) and/or propylene glycol (PG) units in pendant chains of varying length, on the nature and inherent properties of P(HEMA/IA/PAGM) copolymeric hydrogels. Swelling studies revealed pH sensitive behavior of P(HEMA/IA/PAGM) samples. Hydrogel structure and morphology were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM), which confirmed their chemical structure and differences in pore size. The shear modulus values for P(HEMA/IA/PAGM) hydrogels were close to that of PHEMA, but slightly lower than the value for P(HEMA/IA). Cephalexin (CEX) drug release profiles from P(HEMA/IA/PAGM) samples showed a marked dependence on the PAGM component. The presence of IA also influenced the release rate of CEX, leading to a faster release when IA was combined with the more hydrophilic PAGM component. An in vitro assay of P(HEMA/IA/PAGM) cytotoxicity showed good cell viability. The results obtained indicate that P(HEMA/IA/PAGM) hydrogel properties were significantly dependent on the PAGM component, meaning that the type of side chains can be used to tune the characteristics of such biomaterials. These properties make P(HEMA/IA/PAGM) copolymeric hydrogels applicable in biomedical and biotechnological fields and controlled drug delivery.

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.

In this study we prepared hydrogels based on 2-hydroxyethyl methacrylate (HEMA): PHEMA homopolymer and two terpolymers of HEMA, itaconic acid (IA) and two poly(alkylene glycol) (meth) acrylates (PAGM): poly(ethylene glycol)(6) acrylate (P(HEMA/IA/PAGM1)) and poly(propylene glycol)(5) methacrylate (P(HEMA/IA/PAGM2)). Hydrogels were synthesized by gamma-irradiated radical polymerization and subjected to swelling measurements and genotoxicity evaluation. Swelling studies confirmed that these hydrogels deserve consideration as biomaterials due to their ability to swell in phosphate buffer but maintaining physical integrity for a prolonged contact time after equilibrium state has been reached. Comet assay showed certain genotoxic effect following cell exposure to extracts of hydrogels, which was dependent on the concentration of extracts, chemical composition of hydrogels and the degree of crosslinking. The influence of concentration on genotoxicity was the most pronounced. The synthesis of these novel HEMA-based hydrogels should be optimized so as to reduce their toxicity and enable the use in clinical practice.

New semi-interpenetrating networks (semi-IPNHs) (P(HEMA/IA)/PVP) were prepared by free radical crosslinking copolymerization of 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA, 5 mol%), in the presence of poly(vinyl pyrrolidone) (PVP, 2, 5, and 10 mol%), as an interpenetrating agent. The structure of the semi-IPNHs was confirmed by Fourier transform infrared spectroscopy, and morphology study was performed by scanning electron microscopy, which revealed the characteristic porous morphology. The results obtained by dynamic mechanical analysis showed the improvement of mechanical properties with increasing PVP content in semi-IPNs. The maximum swelling was observed for all studied systems at a slightly acidic media (around pH 6), so it can be said that the content of PVP has no influence on the swelling behavior, in the PVP range investigated. Along with the pH sensitivity, which was expected due to the presence of IA, semi-IPNHs showed temperature-sensitive swelling properties, with the lower critical solution temperature value around 41 degrees C, which is in the physiologically interesting interval. The antimicrobial activity of the samples was tested using E. coli, S. aureus, and C. albicans pathogens. It was noticed that the antimicrobial potential depends on type of microbes, time of exposure, and PVP content in the samples. Due to their good antimicrobial and mechanical properties these stimuli-sensitive semi-IPNHs have potential to be used as biomaterials for the applications in medicine and pharmacy.

This work describes radiolytic synthesis of silver nanoparticles (Ag NPs) within the poly(N-vinyl-2-pyrrolidone) (PVP) hydrogel. The hydrogel matrix was obtained by gamma irradiation-induced cross-linking, while the in situ reduction of Ag(+) ions was performed using strong reducing species formed under water radiolysis. Absorption spectrum of the Ag/PVP nanocomposite confirmed the formation of Ag NPs, showing the surface plasmon band maxima at 405 nm. Ag/PVP nanocomposites were characterized by XRD and TEM analysis, accompanied with investigations of swelling and diffusion properties in the simulated body fluid at 37 degrees C, and mechanical properties in bioreactor conditions. It was shown that Ag/PVP nanocomposite exhibited higher values of equilibrium swelling degree, Youngs modulus, and molar mass between crosslinks, while lower values of the diffusion coefficient and effective crosslink density were obtained, as compared to the pure PVP. (C) 2011 Elsevier Ltd. All rights reserved.

In this study a 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 cross-linking 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 revealed that the cell viability of all samples was in 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. U radu je izvedena sinteza dva nova tipa kopolimernih hidrogelova na bazi 2- -hidroksietil (met)akrilata, itakonske kiseline i poli(etilen glikol) dimetakrilata, s ciljem primene ovih polimernih sistema u biomedicinske svrhe. Testirana je biokompatibilnost preko probe hemokompatibilnosti. Hemolitička aktivnost svih hidrogelova je bila u dozvoljenim granicama, prihvatljivim za biomedicinsku primenu. Studije bubrenja hidrogelova, izvedene u opsegu fizioloških pH i temperaturnih vrednosti, pokazale su da bubrenje zavisi od pH i temperature. Sintetisani hidrogelovi su pokazali sličan trend zavisnosti stepena bubrenja od pH i temperature. Sadržaj 550PEGDMA u hidrogelu utiče na stepen bubrenja, dok koncentracija 875PEGDMA komponente vrlo malo utiče na stepen bubrenja. Hidrogel sa 15 mol% 550PEGDMA manje bubri od uzoraka sa manjim sadržajem ove komponente (5 i 10 mol%), što ukazuje da pri toj koncentraciji preovladava umrežavajuće dejstvo ove komponente. Duži PEG lanci u 875PEGDMA su fleksibilniji, pa je efekat umrežavanja uravnotežen sa efektom fleksibilnosti lanca, što ima za posledicu slično bubrenje za sve uzorke u opsegu koncentracija koje su korišćene u ovom radu.

In this study, superporous hydrogels were synthesized by free radical polymerization of 2-hydroxyethyl methacrylate without and in the presence of gelatin. Highly porous hydrogel structures were obtained by two different techniques: using a gas blowing agent, sodium bicarbonate, and a cryogenic treatment followed by freeze-drying. After the gel synthesis, gelatin molecules were covalently immobilised onto PHEMA via glytaraldehyde activation. All samples were characterized for morphological, mechanical, swelling and antibacterial properties. The results obtained show that samples with gelatin show better properties in comparison with PHEMA samples, which make these materials highly attractive for developing hydrogel scaffolds for tissue regeneration.

A series of dual-sensitive poly(2-hydroxypropyl acrylate/itaconic acid) (P(HPA/IA)) hydrogels were synthesized and evaluated as potential highly effective antiproliferative drug delivery system. Investigated hydrophobic antiproliferative agent, Ni(II) complex with Oxaprozin, was successfully synthesized and efficiently loaded into the’”intelligent” P(HPA/IA) hydrogels. Swelling studies showed that loaded agent did not annul pH- and temperature-sensitivity of the investigated hydrogels. In vitro antiproliferative activity of investigated complex against human cervical (HeLa) and melanoma cancer (FemX) cell lines was tested. The results of in vitro release study at different pH values confirmed synthesized hydrogels loaded with investigated complex as a highly effective pH-triggered drug delivery system for the advanced anticancer therapy as well as for the targeted treatment of intestine/colon cancers.

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]

In order to evaluate biological response and potential toxicity prior to clinical use as wound dressing materials, three series of hydrogels, based on 2-hydroxyethyl acrylate (HEA) and itaconic acid (IA), unloaded, with incorporated copper(II) ions and reduced copper, were subjected to cytotoxicity testing on L929 cell line (mouse fibroblasts). MTT test revealed proper fibroblast growth in the presence of tested hydrogels, with an absence of any acute toxic effects. Mechanical properties of all three hydrogel series were studied by dynamic mechanical analysis (DMA) and obtained results indicated dominant elastic over viscous behaviour, which supports their application in wound management. The temperature sensitive behaviour of the hydrogels was detected in swelling study conducted in wide range of temperature values 25–50 °C, in buffer pH 7.40. The hydrogels exhibited excellent microbial barrier characteristics against Pseudomonas aeruginosa, reducing the risk of bacterial infection in wound bed.

The copolymeric hydrogels based on 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) were synthesized by gamma radiation induced radical polymerization. Swelling and thermodynamic properties of PHEMA and copolymeric P(HEMA/IA) hydrogels with different IA contents (2, 3.5 and 5 mol%) were studied in a wide pH and temperature range. Initial studies of so-prepared hydrogels show interesting pH and temperature sensitivity in swelling and drug release behavior. Special attention was devoted to temperature investigations around physiological temperature (37 degrees C), where small changes in temperature significantly influence swelling and drug release of these hydrogels. Due to maximum swelling of hydrogels around 40 degrees C, the P(HEMA/IA) hydrogel containing 5mol% of IA without and with drug-antibiotic (gentamicin) were investigated at pH 7.40 and in the temperature range 25-42 degrees C, in order to evaluate their potential for medical applications. (c) 2007 Elsevier Ltd. All rights reserved. 11th Tihany Symposium on Radiation Chemistry, Aug 26-31, 2006, Eger, Hungary

The effects of gamma irradiation on the structure and properties of hydroxyapatite/poly L-lactide (HAp/PLLA) biomaterial have been investigated. Effects of radiation on microstructure, degradation of polymer part and thermal stability of composite were determined by scanning electronic microscopy (SEM), gel permeation chromatography (GPC) and thermogravimetric analysis (TGA), respectively. Mechanical properties were obtained through mechanical strength and elasticity modulus. Presented results show that properties of HAp/PLLA decay with irradiation dose, but for doses required for sterilization, changes and damaging effects are acceptable. (C) 2006 Elsevier Ltd. All rights reserved.

New types of hydrogels were prepared by the radical copolymerization of 2-hydroxyethyl methacrylate, itaconic acid and four different poly(alkylene glycol) (meth)acrylate components (Bisomers) in a water/ethanol mixture as solvent. The polymers swell in water at 25°C to yield homogeneous transparent hydrogels. All the hydrogels displayed pH sensitive behavior in buffers of the pH range from 2.20 to 7.40, under conditions similar to those of biological fluids. The presence of these two comonomers, which were added to HEMA, increased the swelling degree of the hydrogels and gave gels with better elasticity. The hydrogels were thermally stable in the vicinity of the physiological temperature (37°C). The copolymer containing pure poly(ethylene glycol) acrylate units generally had the best properties. The tests performed on the hydrogels confirmed that they were neither hemolytic nor cytotoxic. The copolymer samples showed better cell viability and less hemolytic activity than the PHEMA sample, confirming the assumption that poly(alkylene glycols) improve the biocompatibility of hydrogels. Due to their swelling and mechanical characteristics, as well as the very good biocompatibility and bioadhesive properties, poly(Bisomer/HEMA/IA) hydrogels are promising for utilization in the field of biomedicals, especially for the controlled release of drugs. Radikalnom kopolimerizacijom 2-hidroksietil metakrilata (HEMA), itakonske kiseline (IK) i četiri tipa poli(alkilen glikol) (met)akrilata (Bisomera-BIS) dobijeni su novi poli(BIS/HEMA/IK) hidrogelovi, u smeši voda/etanol kao rastvaraču. Ispitan je uticaj tipa Bisomera na bubrenje u puferima pH 2,20-7,40, u uslovima sličnim biološkim fluidima. Takođe, praćenje i uticaj na mehanička svojstva, morfologiju i termičko ponašanje dobijenih gelova. Testiranje biokompatibilnosti in vitro napoli (BIS/HEMA/IK) hidrogelovima pokazuje da nema ćelijske toksičnosti, niti hemolitičke aktivnosti. Gelovi poseduju zadovoljavajuću bioadhezivnost.

Interpolymer complexes of poly(itaconic acid) and poly(ethylene glycol) (PIA/PEG) were prepared by two different procedures: simple mixing of preformed PIA and PEG and by polymerization of itaconic acid on poly(ethylene glycol) as a template. Complex formation was attributed to hydrogen bond formation between the carboxyl group of PIA and the ether group of PEG. The two types of complexes were characterized by viscometric measurements, thermogravimetric analysis (TGA), Fourier-transform infrared (FTIR) spectroscopy and adhesive force measurements. The results indicate that complexes prepared by template polymerization have a stronger hydrogen bonding and hence more ordered structure and better mucoadhesive properties.

Two series of novel hydrogels, based on 2-hydroxyethyl acrylate (HEA), itaconic acid (IA), and two poly(ethylene glycol) dimethacrylates (PEGDMA), of different ethylene glycol chain lengths, were prepared by free radical crosslinking copolymerization. The influence of different ethylene glycol chain lengths and concentration in P(HEA/IA/PEGDMA) hydrogels on biocompatibility, swelling and thermal properties was investigated. All samples in contact with blood showed a mean hemolysis value lt 1.0 % in the direct contact assay, and even lt 0.5 % in the indirect contact assay, for in vitro testing conditions. Swelling studies, conducted in a physiological pH and temperature range, showed pH sensitivity and relatively small changes of equilibrium swelling with temperature, which varied with PEGDMA molecular weight. The glass transition temperatures (T (g)) of P(HEA/IA/PEGDMA) networks were in the range 28.1-36.9 A degrees C, respectively, and also dependent on copolymer composition. Due to good biocompatibility, favorable swelling, and thermal properties these hydrogels show good potential for biomedical uses.

Hydrogels based on 2-hydroxyethyl methacrylate (HEMA), different poly(ethylene glycol) dimethacrylates (PEGDMA) and itaconic acid (IA) were prepared by free radical crosslinking copolymerization. The influence of different PEGDMA content and type, with PEG chain length of 550 and 875, on the structure, morphology, biocompatibility, swelling and release properties of P(HEMA/IA/550PEGDMA) and P(HEMA/IA/875PEGDMA) copolymeric hydrogels have been investigated. Preliminary biocompatibility characterization of P(HEMA/IA/PEGDMA) hydrogels, done by the cytotoxicity assays using the HeLa cell line, indicated satisfactory cytocompatibility. Swelling studies were conducted for all samples in a physiological pH and temperature range, showing a noticeable pH sensitivity and temperature dependent equilibrium swelling. The characterization by Fourier transform infrared (FTIR) spectroscopy confirmed the presence of all monomers used in the gel structure, and morphology study, performed by scanning electron microscopy (SEM), revealed no significant differences between the samples with respect to pore size. In order to elucidate the release mechanism, drug release study was carried out in vitro using two forms of vitamin B3: nicotinamide (NAm) and nicotinic acid (NAc). The dissolution profiles were fitted to various mathematical models and the best fit was obtained for first order kinetics. The favorable swelling and drug release properties of P(HEMA/IA/PEGDMA) hydrogels make them good candidates to be used as biomaterials.

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 and thermal properties, biocompatibility and microbe penetration capability was investigated. The mechanical properties of copolymers were investigated using the dynamic mechanical analysis (DMA), while their thermal properties and morphology were examined by thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The morphology, mechanical and thermal 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. (C) 2009 Elsevier Ltd. All rights reserved.

Metal nanoparticles embedded in crosslinking polymer matrices i.e. hydrogels are novel class of materials which have attracted great attention due to applications in catalysis, photonics, optic, pharmaceutics and biomedicine. This work describes novel, simple and facile radiolytic synthesis of silver nanoparticles (AgNPs) within the poly(N-vinyl-2-pyrrolidone) (PVP) hydrogel. The hydrogel matrix was previously obtained by gamma irradiation induced crosslinking, while the in situ reduction of \(\mathrm{Ag}^{+}\) ions was performed using strongly reducing species formed under the radiolysis of water. Absorption spectrum of Ag/PVP hydrogel shows the presence of surface plasmon band with maxima at 400 nm, which confirms formation of AgNPs (diameter less than 10 nm). Swelling properties of synthesized hydrogels, neat PVP and Ag/PVP nanocomposite, were investigated in the SBF (simulated body fluid) solution at \(37^{\circ}\mathrm{C}\). Obtained results show that Ag/PVP hydrogel nanocomposite has higher equilibrium swelling compared with neat PVP hydrogel. Moreover, kinetics parameters were calculated from the swelling curves. The fluid transport mechanism is non-Fickian for both PVP and Ag/PVP hydrogels, meaning that both diffusion and polymer relaxation control the fluid transport.

In this work, novel hydrogels based on 2-hydroxyethyl methacrylate (HEMA) and different poly(alkylene glycol)(meth)acrylates (BIS) were prepared by radiation-induced copolymerization. The influence of different BIS types with variation in chain length, based on ethylene glycol (EG) and/or propylene glycol (PG) pendant units, on the nature and inherent properties of P(HEMA/BIS) copolymeric hydrogels was the main idea of this paper. Swelling studies were conducted for all types of P(HEMA/BIS) copolymeric hydrogels in a wide pH and temperature range. Additional characterization of structure, morphology and thermal behaviour of the obtained hydrogels was conducted by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and thermogravimetric (TG) analysis. The modelling of drug release and diffusion characteristics was tested using cephalexin (CEX). The results indicate that P(HEMA/BIS) hydrogels properties are significantly dependent on the type of BIS. The hydrogels with ethylene glycol (EG) pendant chains show a noticeable pH and/or temperature sensitivity and can be considered smart hydrogels. The introduction of propylene glycol (PG) units, pure and mixed with ethylene glycol (EG) pendant chains, can additionally tune the characteristics of such gels. Furthermore, drug release studies indicate that these types of P(HEMA/BIS) copolymeric hydrogels are suitable candidates for controlled drug release systems. (C) 2010 Elsevier B.V. All rights reserved.

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. Sintetisani su kompleksi srebra(I) sa kopolimernim hidrogelovima 2-hidroksietil metakrilata (HEMA) i itakonske kiseline (IK) (Ag(I)-P(HEMA/IK)) u cilju ispitivanja primene ovih sistema kao biomaterijala. Uzorci su karakterisani sledećim metodama: FTIR, AFM, analiza bubrenja u in vitro uslovima, apsorpcija metala i analiza antibakterijske aktivnosti. Apsorpcija srebra(I) u hidrogelove na bazi IK je određena metodom indukovano spregnutne plazma-masene spektrometrije (ICP-MS). Analiziran je uticaj ugrađenih jona Ag na difuziona svojstva komplesiranih hidrogelova. Udeo IK u hidrogelu je preovlađujući faktor koji utiče na vezivanje Ag jona, pa otuda i na apsorpciju fluida u polimernoj mreži. Testovi antibakterijske aktivnosti su pokazali zadovoljavajuća antibakterijska svojstva biomaterijala u odnosu na soj bakterija Escherichia coli.

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. pH i temperaturno osetljivi hidrogelovi na bazi kopolimera 2-hidroksietilmetakrilata (HEMA) i itakonske kiseline (IK) sintetisani su upotrebom gama zračenja i karakterisani s ciljem ispitivanja njihove potencijalne primene kao biomaterijala. Ispitivan je uticaj odnosa komonomera u ovim inteligentnim polimernim biomaterijalima na morfologiju, mehanička svojstva, biokompatibilnost i penetraciju mikroba. Mehanička svojstva kopolimera su ispitivana dinamičko-mehaničkom analizom (DMA), dok je morfologija karakterisana skenirajućom elektronskom mikroskopijom (SEM). Pokazalo se da su morfologija i mehanička svojstva ovih hidrogelova odgovarajući za većinu biomedicinskih primena. In vitro analizom biokompatibilnosti P(HEMA/IK) hidrogelova potvrđeno je da nisu toksični za ćelije niti izazivaju značajnu hemolitičku aktivnost. Takođe, test mikrobne penetracije pokazao je da ni Staphylococcus aureus ni Escherichia coli ne prolaze kroz hidrogelne obloge; stoga se P(HEMA/IK) obloge mogu smatrati dobrom barijerom protiv mikroba, a radi održavanja sterilnosti okolne sredine. Svi rezultati pokazuju da P(HEMA/IK) hidrogelovi imaju veliku mogućnost primene u biomedicini, posebno kod tretmana kože i kao obloge za opekotine.

Ag-poy(BIS-co-HEMA-co-IA) nanocomposites are prepared via in situ reduction of silver salt embedded in swollen polymer gels by employing gamma irradiation. Hydrogels based on 2-hydroxyethyl methacrylate, itaconic acid and four types of poly(alkylene glycol) acrylate or methacrylate (Bisomers) were previously prepared using gamma irradiation. The nanocomposites are characterized by using UV-vis, swelling measurements and thermal analysis. Evolution of plasmon absorption detected by UV-vis spectro photometry indicated generation of Ag nanoparticles in polymer hydrogels. Altering the structure of the hydrogels did not lead to alternation of the position of the absorption maximum. The bulk property of equilibrium swelling is dependent on the presence of the Ag nanostructures. The initial thermal stability of the polymer is slightly increased due to presence of silver as nanofiller. (c) 2007 Elsevier Ltd. All rights reserved. 11th Tihany Symposium on Radiation Chemistry, Aug 26-31, 2006, Eger, Hungary

Calcium hydroxyapatite (HAp) and poly- L -lactide (PLLA) were synthesized chemically. The obtained HAp was of high purity and, after special thermal treatment, of high crystallinity as well. Synthesis of PLLA was performed using L -lactide as a monomer and nontoxic initiator. In this way a polymer of large molar weight (about 400 000) was obtained. The HAp and PLLA obtained were used as constituents of the HAp/PLLA composite biomaterial, a potential material for implants. The composite was obtained by mixing completely dissolved PLLA with granules of HAp. The composite was compacted by cold and hot pressing at pressures of 49.0–490.5 MPa and temperatures of 20–184°C. The material obtained at optimum process parameters had a density of 99.6% and compressive strength of 93.2 MPa.