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Biomaterial-associated infections represent a significant clinical problem, and treatment of these microbial infections is becoming troublesome due to the increasing number of antibiotic-resistant strains. Here, we report a naturally functionalized bacterial polyhydroxyalkanoate (PHACOS) with antibacterial properties. We demonstrate that PHACOS selectively and efficiently inhibits the growth of methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo. This ability has been ascribed to the functionalized side chains containing thioester groups. Significantly less (3.2-fold) biofilm formation of S. aureus was detected on PHACOS compared to biofilms formed on control poly(3-hydroxyoctanoate-co-hydroxyhexanoate) and poly(ethylene terephthalate), but no differences were observed in bacterial adhesion among these polymers. PHACOS elicited minimal cytotoxic and inflammatory effects on murine macrophages and supported normal fibroblast adhesion. In vivo fluorescence imaging demonstrated minimal inflammation and excellent antibacterial activity for PHACOS compared to controls in an in vivo model of implant-associated infection. Additionally, reductions in neutrophils and macrophages in the vicinity of sterile PHACOS compared to sterile PHO implant were observed by immunohistochemistry. Moreover, a similar percentage of inflammatory cells was found in the tissue surrounding sterile PHACOS and S. aureus pre-colonized PHACOS implants, and these levels were significantly lower than S. aureus pre-colonized control polymers. These findings support a contact active surface mode of antibacterial action for PHACOS and establish this functionalized polyhydroxyalkanoate as an infection-resistant biomaterial., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The activity of new anti-angiogenic polymeric drugs was tested in a 3D endothelial cell culture system applied as a model of angiogenesis. The assay was performed in a highly reproducible fibrin matrix that supported endothelial cell attachment, proliferation, migration, and formation of capillary-like structures. Active growth factors (FGF and/or VEGF) were added to the medium to induce the formation of blood vessel-like structures, and the effect of the active polymers was then tested by a semi-quantitative immunostaining protocol and visualized by laser-scanning confocal microscopy. The synthetic heparin-like macromolecules that were tested for their anti-angiogenic efficacy were previously characterized in terms of their anti-proliferative activity in 2D tissue culture. Two different anti-angiogenic monomers, a methacrylic derivative of 5-amino-2-naphthalenesulfonic acid (MANSA) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS), were copolymerized with a hydrophilic monomer (vinyl pyrrolidone, VP) or a hydrophobic monomer (butyl acrylate, BA), giving rise to different copolymeric systems with controlled microstructure and supramolecular organization. Both copolymeric systems have demonstrated a composition-dependent anti-mitogenic effect in "2D in vitro" cell culture experiments using aFGF as pro-angiogenic growth factor and BALB/c 3T3 fibroblast as cell model, as was shown in a previous publication. These 3D experiments provide evidence for the strong and specific modulation of angiogenesis by these systems. The 3D experiments constitute an improvement over 2D in vitro experiments and in vivo experiments with angiogenic drugs and may help to reduce the number of animal experiments., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Beta-tricalcium phosphate (beta-TCP) has been encapsulated with poly(ethylene glycol) (PEG) to improve the filler/cement interface, and it was later incorporated to a poly(methyl methacrylate) bone cement in order to obtain cements with improved stability in the long term. Size and size distribution of the agglomerates forming the initial powder was drastically changed after its dispersion in a PEG aqueous solution. Whereas the initial beta-TCP particles had a 584 microm average diameter, the treated particles (TCP-PEG) presented more than 60% of the particles in a range of 2-6 microm. The effect of adding the treated particles to an acrylic cement was evaluated in terms of curing parameters, in vitro behaviour and mechanical performance. The presence of the TCP-PEG particles did not affect either peak temperature or setting time, indicating a good homogeneity of polymerising mass in contrast to the effect observed with the plain beta-TCP particles, which gave rise to higher setting times. In vitro behaviour studies revealed hydration degree values of the modified cements comparable to that of PMMA cements. Early stages of water uptake was Fickian in nature for all the experimental formulations indicating that the water absorption followed a diffusion controlled mechanism. After 3 months of storage in SBF the experimental formulations presented values of compressive strength in the range 76-78 MPa, higher than the minimum required by ISO 5833 (70 MPa) and those of tensile strength in the range 42-48 MPa, higher than the minimum reported for commercial formulations (30 MPa), but no significant differences in the strengths and elastic modulus were observed with the treatment of the filler particles. This observation was confirmed by ESEM analysis of the tensile fracture surfaces, which revealed a rather good cohesion between the bioceramic particles with some gaps around them, independently of the type of particles. The themogravimetric analysis of dry and wet specimens showed a higher dissolution rate of the plain beta-TCP particles in comparison to the encapsulated ones, indicating that the PEG adsorbed on the surface of the TCP particles could be a way to control the resorbability of the bioceramic component.

This work reports the development of new partially biodegradable acrylic bone cements based on corn starch/cellulose acetate blends (SCA), prepared by the free radical polymerization of methyl methacrylate and acrylic acid at low temperature. Amounts of biocompatible, osteoconductive and osteophilic mineral component such as hydroxylapatite (sintered and non-sintered), were incorporated in different percentages to confer a bone-bonding character to the bone cements in this type of applications. All cement formulations were characterized by 1H NMR spectroscopy. Curing parameters and mechanical properties were determined finding formulations which complete the ASTM legislation. Hydration degree, degradation studies, as well as bioactivity tests were performed in all prepared formulations. The developed systems show a range of properties that might allow for their application as self-curing bone cements, exhibiting several advantages with respect to other commercially available bone cements.

A method has been developed in which a layer of p-aminosalicylic acid (4-amino-2-hydroxybenzoic acid) (PAS), a water soluble pharmaceutical compound of the nonsteroidal anti-inflammatory drug (NSAID) class with antiaggregant platelet activity, is covalently immobilized onto a segmented polyurethane, Biospan (SPU) surface. Thus, SPU surfaces were modified by grafting of hexamethylenediisocyanate. and the free isocyanate remaining on the SPU surface were then coupled through a condensation reaction to amine groups of p-aminosalicylic acid. The bonding of PAS from aqueous solution onto SPU surface was studied by ATR-FTIR. UV and fluorescence spectroscopy. Plateau levels of coupled PAS were reached within 1.2 microg/cm2 using PAS solution concentrations of 1mg/ ml. The surface wettability of the polymeric films measured by contact angle indicate that the introduction of the PAS turns the surface more hydrophilic (theta(water) = 43.1 +/- 2.1) relatively to the original SPU films (theta(water) = 70.3 +/- 1.9). The in vitro albumin (BSA) adsorption shows that the PAS-SPU films adsorb more BSA (250/microgmm2) than the original SPU (112 microg mm2). Thrombogenicity was assessed by measuring the thrombus formation and platelet adhesion of the SPU containing PAS relatively to nonmodified SPU surfaces. The polymeric surfaces with immobilized PAS had better nonthrombogenic characteristics as indicated by the low platelet adhesion, high adsorption of albumin relatively to fibrinogen and low thrombus formation, making them potentially good candidates for biomedical applications.

Soluble, uncrosslinked and high molecular weight copolymers of vinylpyrrolidone, VP, with 2-hydroxyethyl methacrylate, HEMA, prepared by free radical copolymerization, are proposed as supports for the modulated release of drugs, taking cyclosporine as a model system. The copolymerization parameters described as reactivity ratios, rVP = 0.08 and rHEMA = 7.97, indicate that the copolymer systems prepared at high conversion have two main components with a microstructural arrangement which depends on the average composition, i.e., an initial HEMA-rich copolymer and a final PVP homopolymer or VP-rich copolymer. This microstructural distribution controls the resorption rate of the polymeric support and therefore the release process of cyclosporine which is demonstrated experimentally by the application of a modern technique known as micellar electrokinetic capillary chromatography (MEKC).

Chitosan/polyacrylic acid I PN's were prepared by radical polymerization of acrylic acid, AA, activated at low temperature, in an aqueous/alcoholic chitosan dispersion. AA monomer to polymer conversion and membrane compositions were determined by elemental analysis and FTIR. Evidences of interpolyelectrolite complex formation were found from the FTIR spectra as well. The gravimetric measurements and the elemental analysis after some exhaustive PAA extraction support the existence of some PAA grafting on the reactive amine group of the chitosan. Swelling degree of the membranes is highly dependent on pH and composition, showing a higher swelling in membranes richer in AA and increased pH due to the breaking of interpolyelectrolite salt bonds.

The comparative reactivity of new tertiary amine activators with the basic chemical structure of N,N-dimethyl-4-toluidine, but reduced toxicity, is analysed. The leaching of the amine compounds from cured cements was studied by analysis of the concentration of the corresponding amine in a physiological saline solution after 3 months of immersion, giving lower values for the new amine compounds as compared to N,N-dimethyl-4-toluidine. The acute toxicity was determined by intravenous injection of saline solutions of the corresponding chlorhydrates in mice and the cytotoxicity by the evolution of specific culture media. The results obtained demonstrate a lower acute toxicity and cytotoxicity of the new activators, even with a noticeable antiseptic action, which makes these materials very interesting from a practical point of view as activators of the curing process of acrylic bone cements for orthopaedic surgery and dentistry.

The permeability to oxygen of hydrogels prepared from copolymers of 2-hydroxymethyl methacrylate and p-methacryloxyl-oxyacetanilide have been studied by using an oxygen electrode in combination with a permeometer. The transmissibility Dk/L and the permeability Dk (where D, k and L are, respectively, the diffusion coefficient, the Henry constant and the thickness of the hydrogel) are measured by a combination of steady state and transitory state measurements. Both transport coefficients increase with the water content, which in turn depends on the copolymer composition. The values of these quantities tend toward a limiting value for water-saturated hydrogels. The ratio of the characteristic volume for diffusion of the oxygen molecule to the free volume of water per mole water is found to be in the vicinity of 0.10, and this value increases slightly as the fraction of the hydrophilic comonomer in the hydrogel increases. A detailed comparison of the biogels studied with six commercial contact lenses has also been performed.

The effect of the size and the size distribution of poly(methyl methacrylate) (PMMA) beads on the classical kinetic parameters, peak temperature and setting time, for acrylic bone cement formulations prepared with PMMA particles in the range 10-60 microns of average diameter and a relatively wide size distribution is analysed. In addition, the combined effects of the concentration of the free radical initiator benzoyl peroxide and the activator N, N-dimethyl-4-toluidine for the different particle sizes are studied and compared with those commercially available formulations like CMW or Rostal. The results obtained indicated that the use of PMMA particles with average diameter of 50-60 microns, and a relatively wide size distribution (10-140 microns diameter), significantly changes the curing parameters (peak temperature and setting time) of the cement formulations in comparison with the classical behaviour of the commercial systems of CMW and Rostal, without any noticeable loss in the mechanical properties, such as tensile strength, elastic moduli, and compressive strength and plastic strain.

A study has been made of the behaviour of knitted and woven Dacron mesh used in the preparation of vascular grafts when coated with either a layer of poly(2-hydroxyethyl methacrylate) or co-polymers of 2-hydroxyethyl methacrylate with 5, 10 or 20 wt% of an acrylic derivative of salicylic acid, 2-methacryloyloxybenzoic acid. In vitro studies were carried out to quantify the loss of polymer under flow conditions, and ex vivo studies were done in dogs to quantify the deposition of 111In-oxine-labelled platelets. The treated materials showed a lesser deposition of platelet thrombi when compared with the control group.

Biocompatible copolymers of N-vinylpyrrolidone (P) and furfuryl methacrylate (F) were prepared by free radical polymerization in N,N-dimethylformamide solution at 50 degrees C, using 2,2'-azobisisobutyronitrile as initiator, at low and high conversion. The microstructure of copolymers prepared at low conversion was determined from the composition data by the application of statistical relationships, considering the terminal copolymerization model of Mayo-Lewis, whereas for high conversion copolymers the noticeable difference between the reactivity of F and P was taken into consideration. The swelling behaviour of films prepared from solutions of copolymers with different composition was followed gravimetrically and the diffusion of water was analysed on the basis of the stress relaxation model of copolymer chains. The results obtained are in good agreement with second-order diffusion kinetics, showing that the hydrophilic character of the films is controlled mainly by the content of P in the copolymer systems and the distribution of comonomeric units along the copolymer systems.

New partially resorbable composite formulations based on components used in surgery were synthesized in rod form (length 15-20 mm, diameter 4 mm). The biostable components were poly(methyl methacrylate) in hydrophobic implants and poly(2-hydroxy ethyl methacrylate) in hydrophilic ones. The biodegradable components were commercially available suture yarn made from poly (alpha-hydroxy esters): polyglycolide, a polyester derived from glycolic acid; and a copolyester of glycolic and lactic acids, polyglactin 910. Biodegradation in phosphate-buffered solution at pH 7.0 and 37 +/- 0.5 degrees C was analysed gravimetrically. There was no measurable loss of mass after treatment for 20-25 d. Composite microstructure was examined by phase-contrast, cross-polarized light microscopy.