Fumio Yoshii

Hydrogels and their medical applications

Abstract Biomaterials play a key role in most approaches for engineering tissues as substitutes for functional replacement, for components of devices related to therapy and diagnosis, for drug delivery systems and supportive scaffolds for guided tissue growth. Modern biomaterials could be composed of various components, e.g. metals, ceramics, natural tissues, polymers. In this last group, the hydrogels, hydrophilic polymeric gels with requested biocompatibility and designed interaction with living surrounding seem to be one of the most promising group of biomaterials. Especially, if they are formed by means of ionizing radiation. In early 1950s, the pioneers of the radiation chemistry of polymers began some experiments with radiation crosslinking of hydrophilic polymers. However, hydrogels were analyzed mainly from the point of view of the phenomenon associated with radiation synthesis, with topology of network and relation between radiation parameters of the processes. Fundamental monographs on radiation polymer physics and chemistry written by A. Charlesby (Atomic Radition and polymers, Pergamon Press, Oxford, 1960) and A. Chapiro (Radiation Chemistry of Polymeric Systems, Interscience, New York, 1962) proceed from this time. The noticeable interest in the application of radiation techniques to obtain hydrogels for biomedical purposes began in the late sixties as a result of the papers and patents invented by Japanese and American scientists, headed by Kaetsu in Japan and Hoffman in USA. Immobilization of biologically active species in hydrogel matrices, their use as drug delivery systems and enzyme traps as well as the modification of material surfaces to improve biocompatibility and their ability to bond antigens and antibodies had been the main subjects of these investigations. In this article a brief summary of investigations on mechanism and kinetics of radiation formation of hydrogels as well as some examples of commercialized hydrogel biomaterials have been presented.

Radiation formation of hydrogels for biomedical purposes. Some remarks and comments

Abstract Formation of hydrogels by means of radiation technique is described and some differences connected with irradiation in solid state and solution are pointed out. Structures of primary macroeradicals of some hydrophillic polymers are given. Examples of applications of hydrogels as drug delivery systems, implants, injectable systems, stimuli-responsive systems, hybrid-type organs as well as general requirements for such systems are reviewed. Hydrogel wound dressings produced by radiation technology and marketed in the Central Europe are described.

Radiation-induced degradation of sodium alginate

Abstract Alginates were irradiated as solids or in aqueous solution with Co 60 gamma rays in the dose range of 20 to 500 kGy to investigate the effect of radiation on alginates. Degradation was observed both in the solid state and solution. The degradation in solution was remarkably greater than that in the solid. For example, the molecular weight of alginate in 1% (w/v) solution decreased from 6×10 −5 for 0 kGy to 8×10 −3 for 20 kGy irradiation while the equivalent degradation by solid irradiation required 500 kGy. Degradation G-values were 1.9 for solid and 55 for solution, respectively. The free radicals from irradiated water must be responsible for the degradation in solution. The degradation was also accompanied by a color change to deep brown for highly degraded alginate. Little color change was observed on irradiation in the presence of oxygen. UV spectra showed a distinct absorption peak at 265 nm for colored alginates, increasing with dose. The fact that discoloration of colored alginate was caused on exposure to ozone suggests a formation of double bond in the pyranose-ring.

Hydrogel of biodegradable cellulose derivatives. I. Radiation-induced crosslinking of CMC

Radiation crosslinking of carboxymethylcellulose (CMC) with a degree of substitution (DS) from 0.7 to 2.2 was the subject of the current investigation. CMC was irradiated in solid-state and aqueous solutions at various irradiation doses. The DS and the concentration of the aqueous solution had a remarkable affect on the crosslinking of CMC. Irradiation of CMC, even with a high DS, 2.2 in solid state, and a low DS, 0.7 in 10% aqueous solution, resulted in degradation. However, it was found that irradiation of CMC with a relatively high DS, 1.32, led to crosslinking in a 5% aqueous solution, and 20% CMC gave the highest gel fraction. CMC with a DS of 2.2 induced higher crosslinking than that with a DS of 1.32 at lower doses with the same concentration. Hence, it was apparent that a high DS and a high concentration in an aqueous solution were favorable for high crosslinking of CMC. It is assumed that; high radiation crosslinking of CMC was induced by the increased mobility of its molecules in water and by the formation of CMC radicals from the abstraction of H atoms from macromolecules in the intermediate products of water radiolysis. A preliminary biodegradation study confirmed that crosslinked CMC hydrogel can be digested by a cellulase enzyme

Syntheses of PVA/starch grafted hydrogels by irradiation

A series of excellent polyvinyl alcohol (PVA)/starch blend hydrogels were prepared by gamma and electron beam radiation at room temperature. The influence of dose, the content of starch in blend systems on the properties of the prepared hydrogels was investigated. The gel strength was improved obviously after adding starch into PVA hydrogels, but the swelling properties decreased slightly due to poor hydrophilicity of starch. In order to elucidate the effect of component of starch on the properties of PVA/starch hydrogels as well as the formation mechanism of PVA/starch blend hydrogels under irradiation, the two components of starch, amylose and amylopectin, were chosen to blend with PVA to prepare the hydrogels, respectively. The results indicated that the amylose of starch was a key component that influenced the properties of PVA/starch blend hydrogels. The further analyses of FTIR, DSC and TGA spectra of the prepared gels after extracting sol manifested that there was a grafting reaction between PVA and starch molecules besides the crosslinking of PVA molecules under irradiation, and the amylose of starch was a key reactive component.

Synthesis of antibacterial PVA/CM-chitosan blend hydrogels with electron beam irradiation

A series of excellent hydrogels were prepared from poly(vinyl alcohol) (PVA) and carboxymethylated chitosan (CM-chitosan) with electron beam irradiation (EB) at room temperature. Electron spectroscopy analysis of the blend hydrogels revealed that good miscibility was sustained between CM-chitosan and PVA. The properties of the prepared hydrogels, such as the mechanical properties, gel fraction and swelling behavior were investigated. The mechanical properties and equilibrium degree of swelling improved obviously after adding CM-chitosan into PVA hydrogels. The gel fraction determined gravimetrically showed that a part of CM-chitosan was immobilized onto PVA hydrogel. The further analyses of FTIR and DSC spectra of the prepared gels after extracting sol manifested that there was a grafting interaction between PVA and CM-chitosan molecules under irradiation. The antibacterial activity of the hydrogels against Escherichia coli was also measured via optical density method. The blend hydrogels exhibited satisfying antibacterial activity against E. coli, even when the CM-chitosan concentration was only 3 wt%.

Electron beam crosslinked PEO and PEO/PVA hydrogels for wound dressing

Abstract In order to prepare polyethylene oxide (PEO) hydrogel for wound dressing, different molecular weight PEO and PEO/poly(vinyl alcohol), PVA blend hydrogels were obtained with electron beam irradiation. Gel formation of PEO in aqueous solution was saturated at 40 kGy and the achieved gel fraction was 60–70%. The PEO hydrogel obtained was very fragile, hence PVA was added at 10–30% to give toughness to the PEO hydrogel. The PEO/PVA hydrogel blend showed satisfactory properties for wound dressing. To evaluate the healing effect of PEO/PVA hydrogel blend for dressing, the hydrogel covered a wound formed on the back of marmots. Healing under the wet environment of the hydrogel dressing had some advantages compared with that of gauze dressing which gives a dry environment: (1) the healing rate is faster, (2) easier to change the dressing, i.e. the hydrogel can be peeled off without any damage to the regenerated surface, and (3) no dressing material remains on the wound.

High-melt-strength polypropylene with electron beam irradiation in the presence of polyfunctional monomers

High-melt-strength polypropylene (PP) was achieved with irradiation by an electron beam generated from an accelerator in the presence of polyfunctional monomers (PFM). Among 16 PFMs, the relatively shorter molecular chain bifunctional monomers such as 1,4-butanediol diacrylate (BDDA) and 1,6-hexanediol diacrylate (HDDA) were the most effective for enhancing the melt strength of PP. The concentration and dose of the HDDA to obtain the high melt strength PP in irradiation under nitrogen gas atmosphere were 1.5 mmol/100 g PP and 1 kGy, respectively. DSC measurement and dynamic mechanical analysis showed that the thermal behavior of the high-melt-strength PP was different from that of the original PP. Crystallinity and crystallization temperature during cooling after heating were lower and higher in high melt strength PP than original PP, respectively. Elongational viscosity at 180°C of the high-melt-strength PP showed a remarkable increase at a certain elongational time with constant strain rate, demonstrating the typical property of high-melt-strength samples. This implies that a few higher molecular chains of PP, formed by intermolecular combination of its chain by HDDA in irradiation, give higher melt strength to induce entanglement of molecular chains.

Degradation of poly(l-lactic acid) by γ-irradiation

Abstract Poly( l -lactic acid) (PLA), was irradiated with γ-rays in air and in vacuum at 25°C. Melting point T m , glass transition temperature T g and number-average molecular weight M n decreased with increasing irradiation dose. At low doses, T m , T g and M n decreased sharply and then the rate became slower. Up to 200 kGy, PLA was predominantly degraded by random chain-scission. Above 200 kGy, recombination reactions or partial crosslinking may occur in addition to chain-scission. The degree of chain-scission G s of irradiated PLA was calculated to be 1.97 in air and 0.83 in vacuum. The decrease in M n , T m and T g of the sample in air was faster than in vacuum because of oxidative chain-scission. Biodegradation of PLA was retarded with increasing dose due to the introduction of crosslinking during irradiation. ESR spectroscopy showed five kinds of radicals assigned to three kinds of ESR spectra.

Radiation modification of starch-based plastic sheets

Transparent starch-based plastic sheets were prepared by irradiation of compression-molded starch-based mixture in physical gel state with electron beam (EB) at room temperature. The influence of radiation, plasticizers, water and poly vinyl alcohol (PVA) on the properties of the sheets was investigated. After irradiation, the ductility and tensile strength of the sheets was improved due to the chemical reactions, which was demonstrated by determination of gel fraction and DSC profiles, between starch macromolecules under the action of ionizing radiation. Glycerol, ethylene glycol (EG), poly ethylene glycol (PEG, 600, 1000) was selected as plasticizer to add into starch sheets. The results showed that glycerol was an excellent plasticizer of starch so that the ductility of starch sheets was improved obviously (elongation at break increased). The presence of water was necessary for the preparation of the sheets in this work. With the increasing of the content of starch in starch-based mixture, the tensile strength of the sheets decreased due to the decrease of the degree of the crosslinking of starch. Furthermore, PVA, a biodegradable and flexible-chain polymer, was incorporated into starch-based sheets, the properties of the sheets such as the flexibility (elongation at break) and wet strength was improved obviously.