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In this study, surface modifications for the biodegradable polymers poly(ε-caprolactone) (PCL) and poly(3-hydroxybutyrate) [P(3HB)] were developed in order to improve their suitability as scaffold material for bioartificial vessel prostheses. The challenge of wet-chemical surface modifications is to avoid bulk adjustments resulting in undesired changes in mechanical properties of these polymers. Nevertheless subsequent immobilization and controlled release of potent angiogenic biomolecules like vascular endothelial growth factor (VEGF) from the polymer surface is required. In order to improve the biocompatibility of PCL and P(3HB), terminal hydroxyl groups on the surface of these polymers were generated via oxygen (O2) and carbon dioxide (CO2) plasma. Then, the immobilization of VEGF was achieved through hydrolysable ester bonds using the crosslinker N,N′-disuccinimidyl carbonate (DSC). Our studies demonstrated that the plasma surface activations have no negative influence on the viability of L929 mouse fibroblasts and hemocompatibility. The immobilization of VEGF on the modified polymers via DSC is improved compared to the untreated reference. For the CO2 plasma-chemical activated surfaces we observed the highest VEGF surface immobilization. Our release studies also reveal the highest cumulative release using CO2 plasma-chemical activated samples. [ABSTRACT FROM AUTHOR]

Background/Aims: A clinical approach to prevent secondary cataract after lens implantation involves the intraocular application of pharmacological agents. The goals of our study were to develop an ex vivo model to test the drug effectiveness for lens epithelial cell ablation from the basal membrane and to verify the data in rabbit intraocular lens implantation experiments. Methods: Human capsular rhexis specimens were incubated with drugs and the residual cells were differentiated by use of the Live-Dead assay and quantified by staining with Hoechst dye. After phakoemulsification of rabbit eyes and before intraocular lens implantation, capsular bags were filled with drug-loaded hyaluronic acid for 5 min. Results: An ex vivo model was established which allows the testing of drugs on lens epithelial cell ablation. Drug treatment reduced the number of viable cells on the specimens drastically, ranging between 0.44 ± 0.53% (6.0 ± 7.3 cells/mm2) for disulfiram, 0.27 ± 0.50% (3.7 ± 6.9 cells/mm2) for methotrexate and 0.07 ± 0.19% (0.1 ± 0.27 cells/mm2) for actinomycin D. Rabbit eyes treated with a mixture of methotrexate/actinomycin D showed no posterior capsule opacification at 4 months and a low opacification 6 months postoperatively. Without drug treatment low opacification starts 6 weeks postoperatively. Conclusions: The drug screening in the described ex vivo model can help to reduce the number of preclinical studies for secondary cataract prevention. The successful ex vivo cell ablation by methotrexate/actinomycin D was confirmed by a delayed in vivo secondary cataract formation. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: A novel in vitro dissolution test for drug-eluting stents (DES) based on the compendial flow-through cell was developed. The model contains an additional compartment simulating the vessel wall enabling the examination of drug release and distribution. The compartment consists of alginate hydrogel containing a central aperture forming the lumen for stent placement and media flow. The method was tested utilizing stents coated with hydrophilic (fluorescein sodium) and hydrophobic (triamterene) fluorescent model substances as well as the cytostatic drug doxorubicin hydrochloride and compared to standard dissolution methods. The results show the suitability of the developed method to observe drug release and distribution. The determination of model substance content in the compartments media, hydrogel and stent yielded differing distribution patterns for the model compounds and enabled the observation of redistribution processes. The dissolution profiles differed from the results of compendial dissolution testing. Besides lower endpoints and slower rises of media concentrations due to distribution into the hydrogel, the release rates from the stent coatings were altered. These findings emphasize the necessity to adapt dissolution testing for DES to the unique conditions influencing delivery to the vessel wall to learn more about local distribution and to anticipate the in vivo performance of DES. [Copyright &y& Elsevier]

The article focuses on the development of biofunctionalized materials for surgical applications. It mentions that the interest is due to the increasing demand from surgeons and patients for smart and effective implants. It notes that biocompatibility is important for the implanted device because it largely determine the performance of the device. It is stated that foreign body reaction to the artificial material can be improved through a surface coating of the supporting matrix with proteins.

Background: The aim of the study was to evaluate the antibacterial effect of a drug releasing poly (3-hydroxybutyrate) (P(3HB)) implant coating in comparison to pure titanium on Aggregatibacter actinomycetemcomitans as a model periodontopathogen to prevent biofilm formation on implant surfaces. Methods: Titanium discs were coated with P(3HB) containing 5% (w) and 10% (w) of metronidazole, either with and without a P(3HB) topcoat. The biofilm formation was evaluated after 1, 4 and 9 days in a dynamic flow chamber system. Microbial adherence was quantified by determination of bacterial surface coverage. Results: The evaluated formulations of P(3HB)/metronidazole showed an antibacterial effect especially in the first 24 h. Prolonged incubation for 9 days showed reduced bacterial adhesion only on polymer coatings loaded with 10% (w) of metronidazole both with and without topcoat. Conclusions: The evaluated coating formulations can provide protection from an Aggregatibacter actinomycetemcomitans in vitro biofilm formation for the time period which was evaluated. [ABSTRACT FROM AUTHOR]

In this study, the production of poly(ethylene glycol) diacrylate (PEGDA) scaffolds by micro-stereolithography based on diode laser curing (DLC) is demonstrated. Sample scaffolds are also loaded with acetylsalicylic acid (ASS) as model drug. The samples are immersed in physiological NaCl solution and the drug release characteristics are tested. We show that DLC is a useful technique to prepare drug-loaded PEGDA scaffolds. The compressive strength of the enriched and DLC-cured PEGDA is between 7 and 10 MPa, dependent on ASS concentration. ASS free samples reach 14 MPa. The release experiments show an initial burst release phase and the ASS is released within the first 3 hours. [ABSTRACT FROM AUTHOR]

In vitro drug release testing is an appropriate approach to identify critical parameters helping to predict drug release from drug-eluting stents (DES) prior to studying drug release behavior under in vivo conditions. Drug release and distribution from DES coated with a fluorescent model substance were studied in vitro using the vessel-simulating flow-through cell equipped with different long-term stable hydrogel compartments composed of agarose, polyacrylamide or poly(vinyl alcohol). The obtained experimental results were compared with the results of finite-element modeling obtained using experimentally determined diffusion coefficients and partition coefficients. In spite of differences regarding these parameters, experimental and mathematical data yielded only minor differences between the different gels regarding the release and distribution behavior and reasonable agreement between the modeling and the experiment was obtained. In an attempt to further elucidate the dosage form behavior, the diffusion coefficients in the gel as well as in the stent coating were systematically varied in the finite-element model. Changes in the diffusivity in the stent coating mainly impacted on the initial concentrations. Slower diffusion inside the hydrogel yielded a retarded elution from the stent coating and a higher model substance accumulation in the gel compartment at late time points. [ABSTRACT FROM AUTHOR]

Purpose: For developing injectable lenses the retention properties of the capsular bag are important. Therefore the apparent permeability coefficients of sodium fluorescein and fluorescent dextrans of different sizes were determined for the human anterior lens capsule to calculate a molecular weight cutoff from these data. In addition, permeability coefficients of drugs helpful for the suppression of secondary cataract were determined. Materials and Methods: Capsulorhexis specimens were fixed in a specially designed two compartment diffusion chamber to investigate the permeation of sodium fluorescein and fluorescent dextrans of different sizes (10, 40, 70 and 150 kDa) for 24 h ( n ≥ 3) and of the antiproliferative drugs actinomycin D and methotrexate for 0.5, 24, 48 and 72 h ( n ≥ 3). Results: The molecular weight cutoff of the anterior lens capsule was found to be 166 ± 82 kDa. After 0.5 h, no passage of actinomycin D and methotrexate was detectable through the lens capsule. The apparent permeability coefficients for actinomycin D and methotrexate were calculated to 0.71 ± 0.02 µm/s and to 0.80 ± 0.13 µm/s, respectively. Conclusions: The capsular bag retains fluorescent dextrans with a molecular weight of >166 kDa. Hence, prepolymers are required to polymerize rapidly to be retained inside of the capsular bag. In addition, low-molecular substances intended as antiproliferative drugs for secondary cataract prevention should be applied within a time frame of five minutes in such a way that cells adjacent to the capsular bag will not be damaged. [ABSTRACT FROM AUTHOR]

Background: To assess technical feasibility and biocompatibility of a new Sirolimus (SIR)-eluting biodegradable poly-l-lactide (PLLA) stent for peripheral vascular application. Material and methods: In 15 pigs, both common carotid arteries (CCA) were surgically exposed and clamped in the proximal segment. After transverse incision, 12 316L stents, 12 unloaded and 6 SIR-loaded PLLA stents mounted on 6.0 × 40-mm balloon catheters were randomly implanted into the CCA and inflated to 8 bar. Angiographic equipment was not available. Stented CCA were explanted after 1 week (6 pigs; 316L versus PLLA) and 6 weeks (9 pigs; 316L versus PLLA versus SIR-PLLA), and processed for quantitative histomorphometry and estimation of vascular inflammation and injury scores. Results: No animals were lost during follow-up. All stents were patent on histological analysis without any signs of excessive recoiling or collapse. Unloaded PLLA stents showed decreased residual lumen area and increased neointimal area after 1 week (13.16 ± 0.34, 1.94 ± 0.26) and 6 weeks (11.57 ± 0.30, 2.85 ± 0.24) as compared with 316L stents (15.26 ± 0.13, 1.27 ± 0.41 and 13.99 ± 0.51, 1.54 ± 0.59). SIR-eluting stents demonstrated comparable neointimal area (1.75 ± 0.38) and 50% lower intimal thickness as compared with 316L stents after 6 weeks, but a slightly decreased residual lumen (13.06 ± 0.32) in the consequence of differences in strut thickness (PLLA, 270 μm; 316L, 155 μm). The vascular inflammation score against PLLA-stents could be reduced by Sirolimus. The vascular injury scores were low and similar in all groups. Conclusions: PLLA stents showed sufficient mechanical stability after porcine CCA stenting. By incorporation of Sirolimus, a significant reduction of the inflammatory and neointimal response to the PLLA stent was seen without systemic toxicity or thrombotic complications. These findings need to be assessed with longer follow-up to confirm maintenance of efficacy. The greater strut height of PLLA stents is a major limitation and requires modification. [Copyright &y& Elsevier]

Background: The development of endoluminal stents from polymeric materials requires an understanding of the basic mechanical properties of the polymer and the effects of manufacturing and sterilization on those properties. Methods: Pure poly(L-lactide) (PLLA ) and PLLA containing varying amounts of triethylcitrate (TEC) as a plasticizer (5-10-15%) were studied. The specimens were solution-cast and CO2 laser-cut. Specimen dimensions were adapted to the strut size of polymeric vascular stents. The properties of the PLLA micro-specimens were assessed before and after sterilization (EtO cold gas, H2O2-plasma, beta- and gamma-irradiation). Tensile tests, and creep and recovery tests were carried out at 37°C. Additionally the thermal and thermo-mechanical characteristics were investigated using dynamic-mechanical analysis (DMA) and differential scanning calorimetry (DSC). Results: The results showed the dramatic influence of the plasticizer content and sterilization procedure on the mechanical properties of the material. Laser cutting had a lesser effect. Hence the effects of processing and sterilization must not be overlooked in the material selection and design phases of the development process leading to clinical use. Altogether, the results of these studies provide a clearer understanding of the complex interaction between the laser machining process and terminal sterilization on the primary mechanical properties of PLLA and PLLA plasticized with TEC. [ABSTRACT FROM AUTHOR]

Drug-eluting stents (DES) have reduced in-stent-restenosis drastically. Yet, the stent surface material directly interacts with cascades of biological processes leading to an activation of cellular defense mechanisms. To prevent adverse clinical implications, to date almost every patient with a coronary artery disease is treated with statins. Besides their clinical benefit, statins exert a number of pleiotropic effects on endothelial cells (ECs). Since maintenance of EC function and reduction of uncontrolled smooth muscle cell (SMC) proliferation represents a challenge for new generation DES, we investigated the effect of atorvastatin (ATOR) on human coronary artery cells grown on biodegradable polymers. Our results show a cell type-dependent effect of ATOR on ECs and SMCs. We observed polymer-dependent changes in IC50 values and an altered ATOR-uptake leading to an attenuation of statin-mediated effects on SMC growth. We conclude that the selected biodegradable polymers negatively influence the anti-proliferative effect of ATOR on SMCs. Hence, the process of developing new polymers for DES coating should involve the characterization of material-related changes in mechanisms of drug actions. [ABSTRACT FROM AUTHOR]

Purpose: Drug-eluting stents (DES) based on permanent polymeric coating matrices have been introduced to overcome the in stent restenosis associated with bare metal stents (BMS). A further step was the development of DES with biodegradable polymeric coatings to address the risk of thrombosis associated with first-generation DES. In this study we evaluate the biocompatibility of biodegradable polymer materials for their potential use as coating matrices for DES or as materials for fully bioabsorbable vascular stents. Materials and Methods: Five different polymers, poly(L-lactide) PLLA, poly(D,L-lactide) PDLLA, poly(L-lactide-co-glycolide) P(LLA-co-GA), poly(D,L-lactide-co-glycolide) P(DLLA-co-GA) and poly(L-lactide-co-ε-caprolactone), P(LLA-co-CL) were examined in vitro without and with surface modification. The surface modification of polymers was performed by means of wet-chemical (NaOH and ethylenediamine (EDA)) and plasma-chemical (O2 and NH3) processes. The biocompatibility studies were performed on three different cell types: immortalized mouse fibroblasts (cell line L929), human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC). The biocompatibility was examined quantitatively using in vitro cytotoxicity assay. Cells were investigated immunocytochemically for expression of specific markers, and morphology was visualized using confocal laser scanning (CLSM) and scanning electron (SEM) microscopy. Additionally, polymer surfaces were examined for their thrombogenicity using an established hemocompatibility test. Results: Both endothelial cell types exhibited poor viability and adhesion on all five unmodified polymer surfaces. The biocompatibility of the polymers could be influenced positively by surface modifications. In particular, a reproducible effect was observed for NH3-plasma treatment, which enhanced the cell viability, adhesion and morphology on all five polymeric surfaces. Conclusion: Surface modification of polymers can provide a useful approach to enhance their biocompatibility. For clinical application, attempts should be made to stabilize the plasma modification and use it for coupling of biomolecules to accelerate the re-endothelialization of stent surfaces in vivo. [ABSTRACT FROM AUTHOR]

In this study we present the development of an injectable polymeric drug delivery system for subconjunctival treatment of primary open angle glaucoma. The system consists of hyaluronic acid sodium salt (HA), which is commonly used in ophthalmology in anterior segment surgery, and an isocyanate-functionalized 1,2-ethylene glycol bis(dilactic acid) (ELA-NCO). The polymer mixtures with different ratios of HA to ELA-NCO (1/1, 1/4, and 1/10 (v/v)) were investigated for biocompatibility, degradation behavior and applicability as a sustained release system. For the latter, the lipophilic latanoprost ester pro-drug (LA) was incorporated into the HA/ELA-NCO system. In vitro , a sustained LA release over a period of about 60 days was achieved. In cell culture experiments, the HA/ELA-NCO (1/1, (v/v)) system was proven to be biocompatible for human and rabbit Tenon's fibroblasts. Examination of in vitro degradation behavior revealed a total mass loss of more than 60% during the observation period of 26 weeks. In vivo , LA was continuously released for 152 days into rabbit aqueous humor and serum. Histological investigations revealed a marked leuko-lymphocytic infiltration soon after subconjunctival injection. Thereafter, the initial tissue reaction declined concomitantly with a continuous degradation of the polymer, which was completed after 10 months. Our study demonstrates the suitability of the polymer resulting from the reaction of HA with ELA-NCO as an injectable local drug delivery system for glaucoma therapy, combining biocompatibility and biodegradability with prolonged drug release. [ABSTRACT FROM AUTHOR]

Drug-coated balloons (DCB), which have emerged as a therapeutic alternative to drug-eluting stents in percutaneous cardiovascular intervention, are well described with regard to clinical efficacy and safety within a number of clinical studies. In vitro studies elucidating the correlation between coating additive and DCB performance are however rare but considered important for the understanding of DCB requirements and the improvement of established DCB. In this regard, we examined three different DCB-systems, which were developed in former studies based on the ionic liquid cetylpyridinium salicylate, the body-own hydrogel hyaluronic acid and the pharmaceutically well-established hydrogel polyvinylpyrrolidone, considering coating morphology, coating thickness, drug-loss, drug-transfer to the vessel wall, residual drug-concentration on the balloon surface and entire drug-load during simulated use in an in vitro vessel model. Moreover, we investigated particle release of the different DCB during simulated use and determined the influence of the three coatings on the mechanical behavior of the balloon catheter. We could show that coating characteristics can be indeed correlated with the performance of DCB. For instance, paclitaxel incorporation in the matrix can reduce the drug wash-off and benefit a high drug transfer. Additionally, a thin coating with a smooth surface and high but delayed solubility can reduce drug wash-off and decrease particle burden. As a result, we suggest that it is very important to characterize DCB in terms of mentioned properties in vitro in addition to their clinical efficacy in order to better understand their function and provide more data for the clinicians to improve the tool of DCB in coronary angioplasty. [ABSTRACT FROM AUTHOR]

An easy and efficient route to synthesize gel materials based on polymeric ionic liquids (PILs) is presented. The radical polymerization of imidazolium (Im)-based ionic liquids (ILs) bearing a vinyl group ([VEIm][Br], [VEIm][Ac], [VBIm][Br], [VBIm][Cl]) with crosslinker (CL) N,N′-methylenebisacrylamide (Bis) in water results in polyionic liquid hydrogels. Thermal and mechanical properties (tensile and compression tests) are investigated and compared with two different types of hydrogels. One is a polyacrylamide (PAAm) hydrogel having covalent-type crosslinking. The other is an alginate-based hydrogel having ionic-type crosslinking. Prepared IL-hydrogel materials provide favorable flexibility, adjustable by varying the CL ratio and water content. The higher the CL ratio is, the higher the fragility of the gel matrix. The gelation time of the hydrogels depends on the alkyl chain length, as well as the size of the anion. [ABSTRACT FROM AUTHOR]

Abstract: Commercial non-degradable glaucoma implants are often associated with undesired hypotony, fibrosis, long term failure, and damage of adjacent tissues, which may be overcome by a multifunctional polymeric microstent for suprachoroidal drainage. This study reports the design and fabrication of such devices with tailorable internal diameters (50–300μm) by solvent-free, continuous hot melt extrusion from blends of poly[(ε-caprolactone)-co-glycolide] and poly(ε-caprolactone) [PCL]. A spatially directed release was supported by bilayered microstents with an internal drug-free PCL layer, and a quantitative description of release kinetics with diclofenac sodium as model drug was provided. Furthermore, the slow degradation pattern (>1year) was analyzed and potential effects of 1–5wt.% drug loading on material properties were excluded. Translational aspects including sterilization by γ-irradiation on dry ice, in vitro biocompatibility, and in vivo implantation were addressed. The promising results support further functional analysis of long-term in vivo performance and suppression of disadvantageous capsule formation. [Copyright &y& Elsevier]

Drug-coated balloons are medical devices designed to locally deliver drug to diseased segments of the vessel wall. For these dosage forms, drug transfer to the vessel wall needs to be examined in detail, since drug released into the blood is cleared from the site. In order to examine drug transfer, a new in vitro setup was developed combining the estimation of drug loss during advancement to the site of application in a model coronary artery pathway with a hydrogel compartment representing, as a very simplified model, the vessel wall. The transfer of fluorescent model substances as well as the drug paclitaxel from coated balloons to the simulated vessel wall was evaluated using this method. The model was suitable to quantify the fractions transferred to the hydrogel and also to qualitatively assess distribution patterns in the hydrogel film. In the case of fluorescein sodium, rhodamin b and paclitaxel, vast amounts of the coated substance were lost during the simulated passage and only very small fractions of about 1% of the total load were transferred to the gel. This must be attributed to good water solubility of the fluorescent substances and the mechanical instability of the paclitaxel coating. Transfer of the hydrophobic model substance triamterene was however nearly unaffected by the preliminary tracking procedure with transferred fractions ranging from 8% to 14%. Analysis of model substance distribution yielded inhomogeneous distributions indicating that the coating was not evenly distributed on the balloon surface and that a great fraction of the coating liquid did not penetrate the folds of the balloon. This finding is contradictory to the generally accepted assumption of a drug depot inside the folds and emphasizes the necessity to thoroughly characterize in vitro performance of drug-coated balloons to support the very promising clinical data. [ABSTRACT FROM AUTHOR]

Novel biodegradablematerials with tunable hydrolytic degradationrate are prepared by grafting of phosphonoethylated polyglycidolswith polyesters. First, the hydrolytically degradable polyester graftsare attached to polyglycidols partially grafted with phosphonoethylateddiethyl esters through chemical-catalyzed grafting using tin(II) octanoate,then the diethyl ester groups are chemoselectively converted to thecorresponding monoester (mixed phosphonate/phosphonic acid) usingalkali metal halides. The products are characterized by means of 1H, 13C, and 31P NMR spectroscopy, aswell as size-exclusion chromatography and differential scanning calorimetry.The in vitro degradation of the copolymers is studied in phosphatebuffered solution at 55 °C. The copolymers are of the same architecture,molecular weight, and crystallinity, only differing in the pendantphosphonate and mixed phosphonate/phosphonic acid groups, respectively.On the basis of mass loss, decrease of the molecular weight, and morphologicalanalysis of the copolymers, the strong impact of mixed phosphonate/phosphonicacid groups on the hydrolytic degradation rate is demonstrated. [ABSTRACT FROM AUTHOR]

Abstract: Drug-coated balloons (DCB), which have emerged as therapeutic alternative to drug-eluting stents in percutaneous cardiovascular intervention, are well described with regard to clinical efficiency and safety within a number of clinical studies. In vitro studies elucidating the correlation of coating method and composition with DCB performance are however rare but considered important for the understanding of DCB requirements and the improvement of established DCB. In this context, we evaluated the applicability of a pipetting, dip-coating, and spray-coating process for the establishment of DCB based on paclitaxel (PTX) and the ionic liquid cetylpyridinium salicylate (Cetpyrsal) as novel innovative additive in three different compositions. Among tested methods and compositions, the pipetting process with 50wt.% PTX resulted in most promising coatings as drug load was less controllable by the other processes and higher PTX contents led to considerable drug crystallization, as visualized by electron microscopy, accelerating PTX loss during short-term elution. Applying these conditions, homogeneous coatings could be applied on balloon catheter, whose simulated use in an in vitro vessel model revealed percental drug losses of 36 and 28% during transit and percental drug transfers of 12 and 40% under expansion for coatings applied in expanded and folded balloon condition, respectively. In comparison to literature values, these results support the high potential of Cetpyrsal as novel DCB matrix regarding low drug loss and efficient drug transfer. [Copyright &y& Elsevier]

Due to improved tissue regeneration and the enabling of post-operative minimally invasive interventions in the same vessel segment, biodegradable polymeric scaffolds represent a competitive approach to permanent metallic stents in vascular applications. Despite these advantages some challenges, such as the improvement of the scaffold mechanics and enhancement of scaffold visibility during the implantation procedure, are persisting. Therefore, the scope of our studies was to investigate the potential of gold, silver and magnetite nanoparticles incorporated in a polymeric blend of poly(L-lactide)/poly(4-hydroxybutyrate) for image enhancement in X-ray, magnetic resonance or near-infrared imaging. Their impact on mechanical properties of such modified scaffold materials was also evaluated. [ABSTRACT FROM AUTHOR]

The development of drug-eluting coatings based on hyaluronic acid (HA) is especially promising for implant-associated local drug delivery (LDD) systems, whose implantation provokes high insertion forces, as, for instance, cochlear implants or drug-coated balloons (DCB). The lubricious character of HA can then reduce the coefficient of friction and serve as drug reservoir simultaneously. In this context, we investigated several plasma- and wet-chemical methods for the deposition of HA-based coatings with LDD function on polyamide 12 as a model implant surface, conventionally used for DCB. In contrast to aminosilane, epoxy silane surface layers allowed the covalent attachment of a smooth and uniform HA base layer, which provided good adherence of further HA layers deposited by manual dip coating at a subsequent processing stage. The applied HA-crosslinking procedure during dip coating influences the transfer and release of paclitaxel, which could be reproducibly incorporated via infiltration. While crosslinking with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride provided HA coatings on DCB, which allowed for an efficient paclitaxel transfer upon expansion in a vessel model, crosslinking with glutardialdehyde resulted in a slower drug release being more appropriate for implants with longer residence time in the body. The developed HA coating is hence well suited for spontaneous and sustained LDD. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study is the characterization of fibroblasts mainly responsible for fibrosis processes associated with trabeculectomy or microstent implantation for glaucoma therapy. Therefore we isolated human primary fibroblasts from choroidea, sclera, Tenon capsule, and orbital fat tissues. These fibroblast subpopulations were analysed in vitro for expression of the extracellular matrix components which are responsible for postoperative scarring in glaucoma therapy. For scarring the proteins of the collagen family are predominant and so we focused on the expression of collagen I, collagen III and collagen VI in every fibroblast subpopulation. Also, the extracellular matrix protein fibronectin which crosslinks collagen fibres or other extracellular matrix components and cell surfaces, was analyzed. Collagen I, III and VI were prominent in every fibroblast subpopulation. The highest amounts of collagen III were found in hCF and hOF, whereas the signal in hSF and hTF was negligible. Additionally, there is a link between scarring processes and proliferating potential of fibroblasts, in case of microstent implantation triggered through the infiltration of inflammatory cells. Thus we analyzed fibroblast subpopulations for the presence of TGF-β1 which is one of the most important cytokines involved in proliferation processes. TGF-β1 was prominent in all fibroblast subpopulations with lowest expression in hCF cultures. To prevent postoperative fibroblast proliferation we analyzed in vitro the proliferation-inhibitors paclitaxel and mitomycin C which are potential candidates in drug eluting drainage systems on ocular fibroblast subpopulations. These inhibitors arrest fibroblast proliferation and viability, being, however, not very specific and have a cytotoxic potential also on healthy tissues surrounding the microstent outflow area. Significant differences in protein synthesis of fibroblasts subpopulations which could be specific targets for inhibition may help to find out fibroblast specific inhibitors to prevent postoperative scarring and could prevent patients from secondary surgery after microstent implantation. [Copyright &y& Elsevier]

The administration of drugs using biodegradable polymer nanoparticles as carriers has generated immense interest due to their excellent biocompatibility and the prolonged drug release. The scope of this work was to determine the applicability of sirolimus-loaded biodegradable poly(D,L-lactide) (PDLLA) nanoparticles as drug carriers to prevent restenotic processes after stent implantation. The average 250 nm sized 20%(w/w) sirolimus-loaded nanoparticles were extensively characterized with regard to in vitro degradation, biocompatibility and in vitro drug release. The particles show biphasic release kinetics consisting of a short burst release of 50%(w/w) sirolimus payload, followed by a longer, slower release phase, which are desirable for the application as a drug delivery carrier. All presented results exhibit the potential of sirolimus-loaded PDLLA nanoparticles as promising local and sustained drug delivery systems administered intraluminally to reduce in-stent restenosis after stent implantation. [ABSTRACT FROM AUTHOR]

Abstract: The recently introduced vessel-simulating flow-through cell offers new possibilities to examine the release from drug-eluting stents in vitro. In comparison with standard dissolution methods, the additional compartment allows for the examination of distribution processes and creates dissolution conditions which simulate the physiological situation at the site of implantation. It was shown previously that these conditions have a distinct influence on the release rate from the stent coating. In this work, different preparation techniques were developed to examine the spatial distribution within the compartment simulating the vessel wall. These methods allowed for the examination of diffusion depth and the distribution resulting in the innermost layer of the compartment simulating the vessel wall. Furthermore, the in vitro release and distribution examined experimentally were modelled mathematically using finite element (FE) methods to gain further insight into the release and distribution behaviour. The FE modelling employing the experimentally determined diffusion coefficients yielded a good general description of the experimental data. The results of the modelling also provided important indications that inhomogeneous coating layer thicknesses around the strut may result from the coating process which influence release and distribution behaviour. Taken together, the vessel-simulating flow-through cell in combination with FE modelling represents a unique method to analyse drug release and distribution from drug-eluting stents in vitro with particular opportunities regarding the examination of spatial distributions within the vessel-simulating compartment. [Copyright &y& Elsevier]

Purpose: To evaluate the utility of high-resolution magnetic resonance imaging (MRI) in assessing the normal and refilled lens geometry in rabbits after lens-refilling surgery. Setting: University of Rostock, Rostock, Germany. Design: Experimental study. Methods: High-resolution ocular MRIs were acquired (7.1 T ClinScan) using a 2-channel coil with 4 coil elements and T2-weighted turbo spin-echo sequences (slice thickness 700 μm, field of view 40 mm × 40 mm) in rabbits after lens refilling surgery combined with intraoperative treatment to prevent lens epithelial cell proliferation. Single slices were used to assess the refilled lenses 3 years postoperatively. Results: The entire geometry (cross-sectional area, radius of curvature, axial and equatorial diameters) of the crystalline and refilled lenses was visualized by in vivo 7.1T MRI 3 years postoperatively (in-plane resolution: 125 μm × 125 μm). In refilled eyes, the capsule and the homogenous silicone polymer remained in close contact with no visible interface. The dimensions of the refilled lens were significantly smaller than those of the crystalline lens of the contralateral eye. Conclusions: High-resolution MRI allows in vivo visualization and analysis of the spatial arrangement of the lens in rabbit eyes after lens refilling surgery and overcomes a number of major limitations in the quantitative evaluation of the lens shape. Further efforts are required to optimize the amount of polymer injected during lens refilling to achieve a predictable refractive outcome after lens refilling surgery. Financial Disclosure: Drs. Stachs, Langner, Sternberg, Martin, Schmitz, Hosten and Guthoff have no financial or proprietary interest in any material or method mentioned. Additional financial disclosure is found in the footnotes. [ABSTRACT FROM AUTHOR]

Conclusion: We conclude that PHB patch material may fulfil the specific requirements that are necessary for a dural substitute, including defect closure, stability and biocompatibility. Our results support the assumed positive influence of PHB on bone regeneration. Objectives: Although many experimental and clinical studies have been performed to identify a suitable material to repair defects of the dura mater, no ideal dural substitute is currently available. PHB is a biodegradable and biocompatible polymer that might serve as dural substitute and osteosynthesis material in cranial bone defects. Materials and methods: Different standardized PHB patches were used in six minipigs for covering defined bone defects in the anterior skull base including a dura mater lesion as well as in the frontal sinus front wall. After a defined time of implantation of 3, 6, and 9 months PHB patches were explanted and examined for clinical findings, biodegradation, presence of microorganisms, histological findings, and electron microscopy. Results: The examinations revealed an increasing closure of bone defect corresponding with time. The anterior skull base bone defect was completely closed after 9 months. The histological findings revealed a connective tissue and callus formation around the PHB patches with fibroblasts and foreign body/giant cell reaction growing through PHB membrane pores. There were no reactions or adhesions between brain and PHB or dura mater and PHB, respectively. Investigations of biodegradation and electron microscopy revealed a continuous breakdown of PHB in the course of time with variations due to different PHB structures. Microbiological investigations could not detect any florid intracranial infection. [ABSTRACT FROM AUTHOR]

For the development of a resorbable gastrointestinal patch, the in vitro degradation of solution-cast films of poly(3-hydroxybutyrate) (PHB), modifications of PHB expected to influence its degradation time, as well a poly(l-lactide) (PLLA) was examined. The molecular weight of pure PHB decreased by one-half after 1 year in buffer solution (pH 7.4, 37°C). Acceleration in molecular weight decrease was observed by blending with atactic PHB, whereas no influence was found with low-molecular weight PHB. Leaching of a water-soluble additive led to a slight acceleration of PHB degradability. In contrast, a deceleration in degradation rate was observed with the addition of a hydrophobic plasticizer. In vitro tests indicated an accelerating effect of pancreatin on PHB degradation, whereas PLLA degradation remained essentially uninfluenced. In comparison to simple hydrolysis, the degradation rate of PHB was accelerated about threefold.From the in vitro results, a PHB/atactic PHB blend was selected for repair of a bowel defect in Wistar rats. A patch film was fabricated by a dipping/leaching method. Twenty-six weeks post-implantation, material remnants were found in only one of four animals. The bowel defects were closed in all cases. It could be assessed that the patch material resists the intestinal secretions for a sufficiently long time but that it finally degrades completely. [Copyright &y& Elsevier]

To utilize the Icare tonometer TAO1 for intraocular pressure (IOP) determination in experimental animals. To calculate true IOP calibration functions for rabbit and porcine eyes. Enucleated eyes of 3-year-old healthy experimental rabbits (New Zealand white), and healthy 1 year old experimental pigs (Deutsche Landrasse) were used for the determination of IOP. Manometric (Geuder GmbH, Heidelberg/Germany) and rebound tonometry (Icare tonometer TAO1, Icare, Helsinki/Finland) were used to record IOP in enucleated animal eyes (rabbit n = 2, pig n = 3). The Icare tonometer TAO1 measurements underestimated true IOP by 37-60% in rabbit eyes and 17-63% in porcine eyes. IOP values obtained by both rebound and manometric tonometry for rabbit and porcine eyes followed a linear regression curve. Linear functions were calculated to correct the Icare tonometer TAO1 measurements to true IOP for both rabbit ( p = 1.4244 p + 4.2421) and porcine eyes ( p = 1.0799 p + 5.8557). The Icare tonometer TAO1 can be utilized for IOP determination in rabbit and porcine eyes when measured values are corrected with the appropriate linear function. [ABSTRACT FROM AUTHOR]

Due to increasing rates of periprosthetic joint infections (PJI), new approaches are needed to minimize the infection risk. The first goal of this study was to modify a well-established infection model to test surface-active antimicrobial systems. The second goal was to evaluate the antimicrobial activity of a silver multilayer (SML) coating. In vitro tests with SML items showed a >4 Log reduction in a proliferation assay and a 2.2 Log reduction in an agar immersion test (7 d). In the in vivo model blank and SML coated K-wires were seeded with ~2 × 104 CFU of a methicillin-sensitive Staphylococcus epidermidis (MSSE) and inserted into the intramedullary tibial canal of rabbits. After 7 days, the animals were sacrificed and a clinical, microbiological and histological analysis was performed. Microbiology showed a 1.6 Log pathogen reduction on the surface of SML items (p = 0.022) and in loosely attached tissue (p = 0.012). In the SML group 7 of 12 SML items were completely free of pathogens (cure rate = 58%, p = 0.002), while only 1 of 12 blank items were free of pathogens (cure rate = 8%, p = 0.110). No silver was detected in the blood or urine of the SML treated animals and only scarcely in the liver or adjacent lymph nodes. In summary, an in vivo infection model to test implants with bacterial pre-incubation was established and the antimicrobial activity of the SML coating was successfully proven. [ABSTRACT FROM AUTHOR]