Profiling of time-dependent human plasma protein adsorption on non-coated and heparin-coated oxygenator membranes.

Patients with severe lung diseases are highly dependent on lung support systems. Despite many improvements, long-term use is not possible, mainly because of the strong body defence reactions (e.g.

Development of a novel low-background noise blood loop model for testing blood-contacting biomaterials and medical devices in fresh human blood.

A novel low volume blood loop model (Ension Triad System [ETS]) incorporating pulsatile flow and a proprietary low-activation blood-contacting surface (Ension bioactive surface [EBS]) enabling high signal-to-noise performance is described. The ETS system incorporates a test chamber that allows direct comparison of material samples or finished medical devices such as catheters with varying compositions and/or surface treatments. ETS performance is presented from two independent organizations (Medtronic and MLM Labs) and includes results for hemolysis (pfHgb), platelet count, platelet activation (βTG), coagulation (TAT), inflammation (PMN Elastase, PMN CD112b, and monocyte CD112b) and immune response (SC5b-9) were made on: (1) the EBS-treated system itself without a test material (No Material, NM); (2) the EBS-treated system with an idealized untreated catheter (UC); and (3) the EBS-treated system with the prototype catheter treated with the EBS surface treatment (CC).

Development and in vitro evaluation of infection resistant materials: A novel surface modification process for silicone and Dacron.

Silicone and Dacron are used in a wide spectrum of implantable and indwelling medical products. They elicit a foreign body response, which results in a chronic inflammatory environment and collagenous encapsulation of the medical device that compromises the immune system's ability to effectively fight infections at the biomaterial surface. The objective of this work is to evaluate a novel process to modify silicone and Dacron with a bioactive collagen surface coupled to a gentamicin impregnated hydrogel graft and assess the surface's cytocompatibility and infection resistance properties.

Effects of surface-bound and intravenously administered heparin on cell-surface interactions: inflammation and coagulation.

Intravenous administration of heparin and heparin-bonded extracorporeal circuits are frequently used to mitigate the deleterious effects of blood contact with synthetic materials. The work described here utilized human blood in a micro-perfusion circuit to experimentally examine the effects of intravenous and surface-bound heparin on cellular activation. Activation markers of coagulation and of the inflammatory response were examined using flow cytometry; specifically, markers of platelet, monocyte, polymorphonuclear leukocyte (PMN), and lymphocyte activation were quantified.

In vitro assessment of blood compatibility: residual and dynamic markers of cellular activation.

The blood compatibility of materials and surfaces used for medical device fabrication is a crucial factor in their function and effectiveness. Expansion of device use into more sensitive and longer term applications warrants increasingly detailed evaluations of blood compatibility that reach beyond the customary measures mandated by regulatory requirements. A panel of tests that assess both deposition on the surface and activation of circulating blood in contact with the surface has been developed.

Direct left ventricle-to-coronary artery stent restores perfusion to chronic ischemic swine myocardium.

Background: Direct left ventricle (LV)-to-coronary artery shunts (VSTENT) have been proposed as an alternative means of myocardial revascularization. The goal of this study was to examine quantitative changes in myocardial perfusion and possible mechanisms of revascularization with an LV-to-coronary shunt.

Methods: Ameroid occluders were implanted on the proximal left anterior descending coronary artery (LAD) of 6 pigs to create chronic ischemia.

Direct left ventricle to great cardiac vein retroperfusion: a novel alternative to myocardial revascularization.

Background: As the number of patients with diffuse coronary artery disease continues to grow, there is renewed interest in alternative methods of perfusing the ischemic myocardium. We tested the feasibility of myocardial retroperfusion via a direct left ventricle-to-great cardiac vein (LV-GCV) conduit to support regional contractility in this setting.

Methods: LV-GCV flow was established using an extracorporeal circuit in 5 dogs.

Intramyocardial left ventricle-to-coronary artery stent: a novel approach for the treatment of coronary artery disease.

Background: The direct intramyocardial left ventricle-to-coronary artery stent may provide an optional minimally invasive technique for coronary artery bypass graft surgery. We seek to test whether blood flow and regional myocardial function improve with this stent in totally ischemic myocardium.

Methods: The stent device was implanted in 8 anesthetized dogs using an open chest approach, arteriotomy of the proximal left anterior descending coronary artery, and connection of the vessel to the left ventricular chamber.

A DNA Motif Lexicon: cataloguing and annotating sequences.

The rapid proliferation of genomic DNA sequences has created a significant need for software that can both focus on relatively small areas (such as within genes or promoters) and provide wide-zoom views of patterns across entire genomes. We present our DNA Motif Lexicon that enables users to perform genome-wide searches for motifs of interest and create customizable results pages, where results differ in the degree and extent of annotation. Searching for a particular motif is akin to a word search in a natural language; our motif lexicon speaks to this new time when we will increasingly rely upon DNA dictionaries that offer rich types of annotation.

Surface engineering of titanium by collagen immobilization. Surface characterization and in vitro and in vivo studies.

Collagen was covalently linked to the surface of Titanium (Ti) by a surface modification process involving deposition of a thin film from hydrocarbon plasma followed by acrylic acid grafting. The composition and properties of surface-modified Ti were investigated by a number of surface sensitive techniques: XPS, ATR-IR, atomic force microscopy and AFM force-separation curves. In vitro tests were performed to check samples cytotoxicity and the behavior of osteoblast-like SaOS-2 cells.

Thrombogenicity of polysaccharide-coated surfaces.

Heparinization of artificial surfaces has been proven to reduce the intrinsic thrombogenicity of such surfaces. The mechanism by which immobilized heparin reduces thrombogenicity is not completely understood. In the present study heparin-, alginic acid- and chondroitin-6-sulphate-coated surfaces were examined for protein adsorption, platelet adhesion and thrombin generation.

(Electron) microscopic observations on tissue integration of collagen-immobilized polyurethane.

The foreign body reactions to collagen-immobilized polyurethane (PU-CI) films during subcutaneous implantation in rats were characterized. The underlying concept is that collagen-immobilization will improve the tissue integration. Since the method of collagen-immobilization involves the covalent coupling of collagen to an acrylic acid (AA) based surface graft, both non-modified PU and PU-AA were used as controls.

Animal study on surface-modified defibrillator systems: Indications for enhanced infection resistance.

One of the most important problems with ICD systems is infection. The aim of this study was an in vivo evaluation of the efficacy of defibrillator systems in terms of infection resistance. The polyurethane leads were coupled with heparin and loaded with the antibiotic gentamicin, while the PGs were modified to release gentamicin.

Tissue reactions to epoxy-crosslinked porcine heart valves post-treated with detergents or a dicarboxylic acid.

Calcification limits the long-term durability of xenograft glutaraldehyde (GA)-crosslinked heart valves. Previously, a study in rats showed that epoxy-crosslinked heart valves reduced lymphocyte reactions to the same extent as the GA-crosslinked control and induced a similar foreign-body response and calcification reaction. The present study was aimed at reducing the occurrence of calcification of epoxy-crosslinked tissue.

The kinetics of 1,4-butanediol diglycidyl ether crosslinking of dermal sheep collagen.

Dermal sheep collagen was crosslinked with 1,4-butanediol diglycidyl ether (BDDGE) or modified with glycidyl isopropyl ether (PGE). The reduction in amine groups as a function of time was followed to study the overall reaction kinetics of collagen with either BDDGE or PGE. Linearization of the experimental data resulted in a reaction order of 2 with respect to the amine groups in the PGE masking reaction, whereas a reaction order of 2.

In vivo behavior of epoxy-crosslinked porcine heart valve cusps and walls.

Calcification limits the long-term durability of xenograft glutaraldehyde-crosslinked heart valves. In this study, epoxy-crosslinked porcine aortic valve tissue was evaluated after subcutaneous implantation in weanling rats. Non-crosslinked valves and valves crosslinked with glutaraldehyde or carbodiimide functioned as control.

Characterization and biocompatibility of epoxy-crosslinked dermal sheep collagens.

Dermal sheep collagen (DSC), which was crosslinked with 1, 4-butanediol diglycidyl ether (BD) by using four different conditions, was characterized and its biocompatibility was evaluated after subcutaneous implantation in rats. Crosslinking at pH 9.0 (BD90) or with successive epoxy and carbodiimide steps (BD45EN) resulted in a large increase in the shrinkage temperature (T(s)) in combination with a clear reduction in amines.

Crosslinking and modification of dermal sheep collagen using 1, 4-butanediol diglycidyl ether.

Crosslinking of dermal sheep collagen (DSC) was accomplished using 1, 4-butanediol diglycidyl ether (BDDGE). At pH values > 8.0, epoxide groups of BDDGE will react with amine groups of collagen.

Successive epoxy and carbodiimide cross-linking of dermal sheep collagen.

Cross-linking of dermal sheep collagen (N-DSC, T(S) = 46 degrees C, number of amine groups = 31 (n/1000)) with 1,4-butanediol diglycidyl ether (BDDGE) at pH 9.0 resulted in a material (BD90) with a high T(S)(69 degrees C), a decreased number of amine groups of 15 (n/1000) and a high resistance towards collagenase and pronase degradation. Reaction of DSC with BDDGE at pH 4.

Heparin coating of tantalum coronary stents reduces surface thrombin generation but not factor IXa generation.

In the present study we used an in-vitro technique to examine initiation and propagation of blood coagulation at the surface of tantalum coronary stents exposed to flowing platelet-rich and platelet-free plasma. The time course of factor IXa production at the surface of the stent was not influenced by platelets. In spite of a significant factor IXa production, no thrombin activity was detected when the tantalum stent was exposed to platelet-free plasma; only when the stent was exposed to platelet-rich plasma was extensive thrombin production observed.

Ex vivo testing of heparin-coated extracorporeal circuits: bovine experiments.

In this study the intrinsic thrombogenicity of the extracorporeal circuits and the benefit of heparin-bonded circuits in an extracorporeal life support system without full systemic heparinization and with minimal interference of the so called material-independent factors was tested in four calves. In two circuits (group A) all blood-contacting surfaces were coated with end-point-attached heparin and the other two were non-coated (group B). Under standardized conditions the calves were perfused at a blood flow rate of 2 L/min.

Tissue reactions to bacteria-challenged implantable leads with enhanced infection resistance.

Tissue reactions to implantable pacemaker leads were investigated in an early infection model in rabbits. Both standard leads and surface-modified leads were used. The surface modification technique was applied to achieve controlled release of the antibiotic gentamicin.

Initiation and propagation of blood coagulation at artificial surfaces studied in a capillary flow reactor.

We have made use of a novel flow reactor to study the initiation and propagation of the ex vivo blood coagulation processes at artificial surfaces. The flow reactor consisted of a primary glass or polymer capillary that is connected to a secondary glass capillary, which inner wall was coated with a phospholipid bilayer of 25 mol% dioleoylphosphatidylserine/75 mol% dioleoylphosphatidylcholine (DOPS/DOPC). Citrated platelet free plasma and a CaCl2 solution were delivered by syringe pumps and mixed just before the entrance of the flow reactor.

Tissue reactions to bacteria-inoculated rat lead samples. II. Effect of local gentamicin release through surface-modified polyurethane tubing.

A surface modification technique was developed to achieve controlled release of gentamicin from implanted polyurethane (PU) rat lead samples. PU tubing first was provided with an acrylic acid/acrylamide copolymer surface graft and then loaded with gentamicin. This surface modification technique resulted in release of gentamicin base (GB) and was applied either to the inner luminal surface only (PU-GB-1x) or to both the inner and outer surfaces (PU-GB-2x).

Tissue reactions to bacteria-inoculated rat lead samples. I. Effect of local gentamicin release through vicinal sponge or solution-dipping.

The effect of local gentamicin release through a vicinal collagen sponge or through preoperative solution-dipping of rat lead samples was investigated in an early-infection model. The efficacy of these methods and their effect on tissue response were determined. It was demonstrated that both methods of local gentamicin release suppress lead-related infectious complications as compared to the control lead, which showed a high presence of inflamed/infected tissues and bacterial growth at each explantation time point.