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Biocompatible and biodegradable polymer nanofibers displaying superparamagnetic properties.

Superparamagnetic polymer nanofibers intended for drug delivery and therapy are considered here. Magnetite (Fe3O4) nanoparticles in the diameter range of 5-10 nm were synthesized in aqueous solution. Polymer nanofibers containing magnetite nanoparticles were prepared from commercially available poly(hydroxyethyl methacrylate), PHEMA, and poly-L-lactide (PLLA) by the electrospinning technique. Nanofibers with diameters ranging from 50 to 300 nm were obtained. Nanofibers containing up to 35 wt % magnetite nanoparticles displayed superparamagnetism at room temperature. The blocking temperature was about 50 K for an applied field of 500 Oe, and the saturation magnetization was 3.5 emu g(-1) and 1.1 emu g(-1) for Fe3O4/PHEMA and Fe3O4/PLLA nanofibers, respectively, and depended on the amount of Fe3O4 nanoparticles in the nanocomposites. To test such magnetic nano-objects for applications as drug carriers and drug-release systems we incorporated a fluorescent albumin with dog fluorescein isothiocyanate (ADFI).

Biocompatible Materials↗

2-methacryloyloxyethyl N-butylcarbamate: a new co-monomer for synthesis of polyurethane hydrogels with improved mechanical properties for biomedical applications.

Hydrogels with tunable hydrophilic and mechanical properties were synthesized by the free radical polymerization of 2-hydroxyethyl methacrylate (HEMA) and 2-methacryloyloxyethyl N-butylcarbamate. The resulting hydrogels were investigated for their equilibrium water content, sessile drop water contact angles, gel fraction, mechanical properties and protein adsorption. Results indicated that co-polymer hydrogels have good hydrophilicity and that, with the incorporation of the 2-methacryloyloxyethyl N-butylcarbamate, mechanical properties could be improved significantly. without affecting other important properties. Lysozyme and albumin adsorption experiments demonstrated that, similar to most hydrogel materials, the co-polymer hydrogels adsorb more lysozyme than albumin and that the adsorption was dependent on hydrophilicity. The control poly(HEMA) hydrogels were found to adsorb more protein than the co-polymer hydrogels; this is thought to be primarily a consequence of protein absorption rather than protein adsorption.

Calorimetry, Differential Scanning↗

Hydrogels in endovascular embolization. III. Radiopaque spherical particles, their preparation and properties.

The synthesis and properties of spherical radiopaque hydrogel particles designed for endovascular occlusion are reported. These particles were prepared by the hydroxyl acylation of low crosslinked poly (2-hydroxyethyl methacrylate) beads with a nontoxic radiopaque compound based on triiodobenzoic acid, without affecting their properties which are advantages in medical practice. The effect of the iodine content on the size of dry and swollen particles is discussed. It has been found that an iodine content of about 25-30 wt% is desirable in order to obtain an easily recognizable X-ray image. These particles make the immediate control of embolus application easy and enable periodical inspection of the polymer to check the successful blockage of the vessel. They also open up the method of endovascular occlusion to further improvement.

Contrast Media↗

In-situ injectable physically and chemically gelling NIPAAm-based copolymer system for embolization.

The goal of this work is to make an injectable physically and chemically cross-linking NIPAAm-based copolymer system for endovascular embolization. A copolymer with N-isopropylacrylamide (NIPAAm) and hydroxyethyl methacrylate (HEMA) was synthesized and converted to poly(NIPAAm-co-HEMA-acrylate) functionalized with olefins. When poly(NIPAAm-co-HEMA-acrylate) was mixed with pentaerythritol tetrakis 3-mercaptopropionate (QT) stoichiometrically in a 0.1 N PBS solution of pH 7.4, it formed a temperature-sensitive hydrogel with low swelling through the Michael-type addition reaction and showed improved elastic properties at low frequency compared to physical gelation. This material could be useful for applications requiring water-soluble injection but lower swelling and lower creep properties than available with other soluble in-situ-gelling materials.

Acrylamides↗

Traumatic cranial defects reconstructed with the HTR-PMI cranioplastic implant.

Titanium mesh, polymethyl methacrylate application, and autogenous bone grafting have been used to reconstruct traumatic cranial defects, with varying success. A more recent technique utilizing hard tissue replacement-patient matched implants (HTR-PMIs) involves the production of a cranioplastic implant using three-dimensional computed tomography imaging. It has proven less time-consuming and provides an excellent cosmetic result for the patient. The authors present two case reports using this technique to correct traumatic cranial defects. Both patients exhibited satisfactory results and no postoperative complications. The authors believe this relatively new technique represents an advance in the management of large cranial defects.

Adult↗

PHEMA hydrogels obtained by a novel low-heat curing procedure with a potential for in situ preparation.

In this work, we report on poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels obtained by a low heat curing reaction. These materials are suitable for in situ preparation and therefore endowed with a potential for several biomedical applications. The novel procedure adopted involves as the first step the synthesis of a soluble oligomeric PHEMA precursor containing polymerizable functions as side substituents. As the second step, the precursor is dissolved in equal amounts of 2-hydroxyethyl methacrylate (HEMA) and water, to form a viscous but still injectable syrup. A low temperature water soluble initiator is then added. The curing reaction starts promptly and is completed within few minutes. During the entire process the internal temperature never rises above 40 degrees C. Preliminary mechanical characterizations performed on the hydrogels in their water-swollen state and diffusion tests in absorption/desorption experiments clearly indicated that on all respects the novel hydrogels are comparable with conventional PHEMA hydrogels obtained according to literature from HEMA in the presence of divinyl crosslinkers. However, the much shorter curing time combined with the far lower curing temperature endow the new hydrogels with a higher potential in view of specific surgical requirements, and particularly for in situ preparation.

Absorption↗

A clinical study of antimicrobial agents delivered to burn wounds from a drug-loaded synthetic dressing.

This report is of an investigation of the release of antimicrobial agents from a solid barrier dressing when applied to second- and third-degree burn wounds. The synthetic dressings were formed by a mixture of polyethylene glycol-400 (PEG), poly-2-hydroxethyl methacrylate (PHEMA) and one of the test drugs: silver sulfadiazine (AgSD), gentamicin, silver nitrate, or nitrofurazone. The dressings were formed directly on the burn wounds of 33 patients from a paste prepared from a mixture of PEG-PHEMA and drug. These dressings remained in place for 3 days, covering 12 to 64 square inches of the wound. In six patients, the entire burn wounds were covered with the dressings in which the treated areas were each about 200 square inches. The use of drug-loaded synthetic dressings extended to cover major portions of the burn wounds reduced the work required for nursing care and lessened patient discomfort.

Adolescent↗

Apatite formation on poly(2-hydroxyethyl methacrylate)-silica hybrids prepared by sol-gel process.

Hybrids of poly(2-hydroxyethyl methacrylate) (PHEMA), a polymer that has been employed in a wide variety of biomedical applications, and silica-gel, which exhibits a well-known bioactivity, were produced. The obtained hybrids were characterized and their in vitro ability to induce the formation of a calcium phosphate layer on the surface was evaluated. The surface area of hybrids decreased with increasing amounts of PHEMA so that hybrids with more than approximately 40% PHEMA are virtually non-porous. All hybrids induced the formation of a calcium phosphate layer on their surfaces when soaked into simulated body fluid. The induction time and the morphology of the apatite layer varied according to the polymer content.

Apatites↗

Clinical results of implantation of the Chirila keratoprosthesis in rabbits.

AIMS/BACKGROUND: An ideal keratoprosthesis (KPro) would closely resemble a donor corneal button in terms of its surgical handling, optics, and capacity to heal with host tissue in order to avoid many of the complications associated with the KPros which are currently in clinical use. This study was carried out to assess the long term clinical outcomes on implantation of the core and skirt poly(2-hydroxyethyl methacrylate) KPro in animals. METHODS: 20 KPros were made and implanted as full thickness corneal replacements into rabbits and followed for up to 21 months to date. RESULTS: 80% of the prostheses have been retained, with a low incidence of complications such as cataract, glaucoma, and retroprosthetic membrane formation which are frequently associated with KPro surgery. CONCLUSIONS: KPros of this type may offer promise in the treatment of patients for whom penetrating keratoplasty with donor material carries a poor prognosis. Refinement of the KPro and further animal trials, including implantation into abnormal corneas, are however mandatory before human implantation could be planned.

Animals↗

Micro- and nanoscale modification of poly(2-hydroxyethyl methacrylate) hydrogels by AFM lithography and nanoparticle incorporation.

Poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels are widely used as biomaterials. Due to their unique combination of biocompatibility and good mechanical properties, they have potential as scaffolds for tissue engineering applications. To this purpose, topographic and chemical patterning at the nano- to the mesoscale is crucial in order to favor and to characterize cell adhesion and proliferation. Here we report the characterization of as-prepared and patterned PHEMA hydrogels, produced by conventional radical polymerization in water and dimethylformamide. We have obtained chemical and morphological micro- and nanoscale patterning by atomic force microscopy based lithography. We also demonstrate that it is possible to incorporate carbon nanoparticles in the hydrogel matrix by supersonic cluster beam deposition.

Biocompatible Materials↗

Irritation effects of residual products derived from p(HEMA) gels. II. Compounds extracted from hydrogels.

Samples of poly(2-hydroxyethyl methacrylate) p(HEMA) hydrogels were prepared using three different polymerization initiators. The gels were washed in water under standard conditions. The extracts were then examined for intradermal irritation in rats using a radioactive indicator (113mIn). The irritation effects were dependent on the concentrations of the irritating substances and also on the gel type. Solid discs made of the gels, washed to varying degrees of purity, were also implanted into rats. Tissue irritation, as well as some other biological responses, were followed in situ using the radioindicator and common histological techniques. The irritation effects were very mild (even with the unextracted gel material). A possible explanation for the events taking place at the site of implantation is presented.

Animals↗

Activation of complement in human serum by some synthetic polymers used for intraocular lenses.

Determination of the potential to activate complement can be used as one criterion in testing the biocompatibility of various synthetic polymers that are utilized in the medical field. Intraocular lenses (IOLs) made of poly(methyl methacrylate) (PMMA) with PMMA loops, poly(hydroxyethyl methacrylate) (PHEMA) lenses, silicone lenses, and PMMA lenses with polypropylene loops were examined in this study. The concentrations of the activation peptides C3a, C4a and C5a were measured by radioimmunoassay (r.i.a.) in human serum after incubation with and without IOLs for up to 12 h. The presence of silicone lenses caused an increase in C3a levels. In the presence of polypropylene loops, the concentrations of both C3a and C5a were significantly higher than in serum incubated alone. There was no statistically significant increase in the concentration of C4a caused by any of the materials tested. The results suggest that IOLs made from silicone or lenses with polypropylene loops activate the complement system via the alternative pathway.

Biocompatible Materials↗

Stability and activity of immobilized hydrolytic enzymes in two-liquid-phase systems: acid phosphatase, beta-glucosidase, and beta-fructofuranosidase entrapped in poly(2-hydroxyethyl methacrylate) matrices.

Enzyme storage stability and hydrolysis yield were measured in experiments carried out with three model hydrolytic enzymes: acid phosphatase (EC 3.1.3.2), beta-glucosidase (EC 3.2.1.4), and beta-fructofuranosidase (EC 3.2.1.26) entrapped in hydrogels of poly(2-hydroxyethyl methacrylate). Runs were performed at 30 degrees C, under intensive stirring (500 rev min-1), in 50% v/v biphasic media prepared with buffer and organic solvents, whose log P value varied from 0.68 to 8.8. Storage stability was also monitored in the pure solvents. The small average particle size (125-210 microns) and the intensive stirring eliminate hindrances of intra- and interphase mass transfer resistances. The hydrophilic matrix protects the enzymes against thermal and chemical deactivation, thus allowing good production per unit weight of biocatalyst. In biphasic media, storage stability, with the exception of acid phosphatase, was not dependent on solvent polarity. On the contrary, a significant trend was observed when the enzymes were stored in neat organic solvents.

Acid Phosphatase↗

Swelling/deswelling of anionic copolymer gels.

Studies of dynamic and equilibrium swelling of ionic gels are important in understanding the diffusion of physiologically important fluids in materials for site-specific controlled drug delivery applications. The dynamic and equilibrium swelling properties of dry glassy poly(2-hydroxyethyl methacrylate-co-methacrylic acid) and poly(2-hydroxyethyl methacrylate-co-acrylic acid) polymeric networks were studied as a function of pH, ionic strength, nature of the counterion and buffer composition. The mechanism of water diffusion in these gels became more anomalous as the pH of the swelling medium increased and as the ionic strength decreased at a constant pH > or = pKa,gel. The mechanism of water diffusion was Fickian in all unbuffered swelling media at pH 4.0, which is lower than the pKa,gel. The pKa,gel of these gels was between 5.5 and 6. At pH 4.0, the diffusion mechanism was independent of ionic strength. This swelling behaviour is explained in terms of the concept of ion osmotic swelling pressure and ion exchange kinetics.

Biocompatible Materials↗

Poly(2-hydroxyethyl methacrylate) film as a drug delivery system for pilocarpine.

This work investigates pilocarpine trapped in a matrix diffusion-controlled drug delivery system using hydrophilic inserts of Poly(2-hydroxyethyl methacrylate) (pHEMA) to ensure an increased bioavailability of pilocarpine and prolong the length of time in which the medication remains in the eyes of the test subjects. The physical and chemical properties of pilocarpine were investigated to elucidate the mechanism of drug-polymer interaction and the effect on drug release behavior of controlled release polymeric devices. In vitro release studies indicated that pilocarpine continued to be released from the inserts for a 24 h period. The results of intraocular pressure tests performed on albino rabbits were consistent with the observed in vitro behavior. The pressure decrease was significant for a period longer than 48 h. It confirms that the inserts, as sustainable releasing devices, are promising carriers for ophthalmic drug delivery systems.

Animals↗

Development of a poly(2-hydroxyethyl methacrylate) orbital implant allowing direct muscle attachment and tissue ingrowth.

PURPOSE: To develop a poly(2-hydroxyethyl methacrylate) orbital implant that allows tissue ingrowth and direct muscle attachment to minimize the risk of extrusion and to enhance cosmesis. METHODS: Assessment of clinical outcomes and histologic findings after implantation of 18 prototype prostheses into rabbits. The implants were not wrapped with other tissues or materials. RESULTS: One case of infection was observed but there were no extrusions, with up to 21 months follow-up. Biocolonization was confirmed histologically. Good movement was observed when a cosmetic shell was fitted. CONCLUSIONS: The prototype prosthesis appears promising, with particular advantages being the direct attachment of extraocular muscles, good cosmesis and movement, and a low complication rate in this pilot study.

Animals↗

Haemostatic activity of ethamsylate and aminocaproic acid adsorbed poly(2-hydroxyethyl methacrylate) particles.

A haemostatic material suitable for embolization was prepared by the adsorption of haemostatics--ethamsylate and aminocaproic acid in the spherical particles of porous poly(2-hydroxyethyl methacrylate) (p(HEMA)). The degree of purification of ethamsylate-treated particles was tested by an analysis of donor blood in contact with the material. An evaluation of the haemostatic properties of these materials was obtained by the determination of the indicators of blood clotting: activated partial thromboplastin time, thrombin time, and prothrombin time. Ethamsylate or aminocaproic acid-containing p(HEMA) has a distinct haemostatic effect on pathological blood of patients suffering from focal alterations of the liver. These haemostatic emboli materials show promise for the immediate control of various haemorrhages; when introduced into a zone with increased haemorrhage, they may help to correct disturbed haemostasis.

Adsorption↗

Poly(2-hydroxyethyl methacrylate) beads for the preoperative endovascular occlusion of branches of the hepatic artery in focal alterations of the liver.

Spherical particles of porous poly(2-hydroxyethyl methacrylate) have been used in the treatment of patients suffering from focal alterations of the liver, namely haemangioma and hypervascular tumour. The treatment consisted of the preoperative endovascular occlusion of branches of the hepatic artery using these spherical particles, and was followed by an operation. The main merit of the preoperative occlusion of blood vessels is that it substantially reduces blood loss during surgery. In order to determine the optimal time for the operation on the liver, indicators of the coagulation system were examined in successive terms of the postemboilization period. Reaction of the organism to endovascular occlusion is reflected in hypercoagulation changes in the coagulation system.

Blood Loss, Surgical↗