Katrin Sternberg

Suitability of porcine pericardial tissue for heart valve engineering: Biomechanical properties

In this study, biomechanical properties of porcine pericardium and aortic valvular leaflet tissue were comparatively investigated in tensile tests. Fresh porcine pericardium and aortic valves were harvested from domestic pig cadavers. Specimens were prepared from either native or glutaraldehyde-fixed tissue. Uniaxial tensile testing was conducted in physiological saline solution at 37°C. The results show a clear distinction regarding the biomechanical behaviour of native pericardium and aortic valvular leaflet tissue. It could be demonstrated that the implemented fixation process can influence the properties of native pericardium towards the biomechanical behaviour of aortic valvular leaflet tissue.

Infiltration of 3D printed tricalciumphosphate scaffolds with biodegradable polymers and biomolecules for local drug delivery.

D printing is well suited and the most impor- tant technique to produce scaffolds with a reproducible complex internal structure directly from powder materials based on tricalciumphosphates (TCP) for the reconstruc- tion of bone defects. In this study, we could show success- ful infiltration of fabricated TCP scaffolds with biode- gradable polymers and a model biomolecule in order to provide the structure with a sustained drug release func- tion.

Parameters of Endothelial Function are Dependent on Polymeric Surface Material

Although the first generation of drug-eluting stents have revolutionized the treatment of coronary artery disease in terms of reduction of in-stent-restenosis, there is increasing evidence that the applied surface polymer coatings could be responsible for adverse effects like delayed healing, late stent-thrombosis, local hypersensitivity reaction and remaining in-stent restenosis. Biodegradable polymers are hence investigated. However, tissue response to these materials in terms of vessel healing, inflammation and biocompatibility is not described in detail yet. In this context, the present study was designed to investigate endothelial cell function on biodegradable polymers using human endothelial cells applied to an in vitro flow chamber model with laminar shear stress exposure. Our data demonstrate a material dependent endothelial cell function.

Spray-coating process development, manufacture, quality assessment and drug release behavior of peripheral drug-eluting stents

Manufacture of peripheral DES requires development of process technologies to accommodate their geometrical and biomechanical specifics. In this study, a spray-coating process for peripheral DES coatings was developed. Peripheralsize, self-expanding nickel titanium stents (7.0 x 40 mm) were coated with the biodegradable polymer poly(L-lactide) (PLLA) incorporated with the immunosuppressant sirolimus (SIR) in a ratio of 82.5/17.5 % w/w. Coating mass was 3400 μg. A parameter study was conducted to assess optimum coating parameters. The coated DES were evaluated for coating morphology, thickness, and integrity. Drug release behavior was assessed by HPLC. SEM evaluation confirmed a smooth, defect-free PLLA/SIR coating with complete strut coverage. A coating thickness of 5.5 ± 0.4 μm was determined by CLSM. SIR release was traced over up to 430 h, exhibiting an initial burst over 30 h, followed by a steady, retarded drug release. Altogether, the results indicate the technical feasibility of self-expanding, peripheral DES.

In vitro estimation of drug loss during the implantation procedure of drug-eluting stents

Drug-eluting stents are drug/device combinatory products designed to physically re-establish the blood flow in arteriosclerotic blood vessels and deliver anti-proliferative drugs to the stented vessel section to prevent neointimal hyperplasia. Drug that is released during the implantation procedure is washed away with the blood flow. It was our aim to estimate this drug loss using stents coated with fluorescent model substances in an in vitro setup. Stents mounted on balloon catheters were introduced into a polymethacrylate coronary artery model (adapted from ASTM standard F 2394-07 intended for measurement of securement of stents on delivery systems) via a guiding catheter. The system was perfused by phosphate buffered saline pH 7.4 at a flow-rate adapted to the blood flow-rate in coronary arteries. The perfusate was collected in fractions and model substance content was determined fluorimetrically. The hydrophilic model substance fluorescein sodium was released very fast resulting in a loss of approximately 64 % of the drug load within the first minute and up to 82 % after 5 minutes. The hydrophobic model substance triamterene was released much slower from the coating. A total loss of 5 % was detected after 5 minutes. Furthermore, commercially available sirolimus-eluting Cypher Select + stents were tested. Release into the media was not detected. Obviously, the drug-free top coating effectively prevented drug release during the simulated passage to the site of implantation. An in vitro test system to estimate drug loss during the implantation procedure of drug-eluting stents was successfully established. First results using fluorescent model substances indicate that vast losses have to be expected when using fast releasing delivery systems. Therefore, the model may also prove valuable for the in vitro testing of drug-eluting balloons. Further adaptations, such as the inclusion of biorelevant media, may be suitable to further improve the predictability of in vivo performance.

Biofunctionalization of Polymer Implant Surfaces: From Drug Delivery to Stable Surface Functionality.

Biofunctionalization strategies can be adapted to allow short-term and long-term biomolecule immobilization. By using different protocols for the modification of poly(L-lactide), we evidenced the possibility of drug release control as well as the provision of stable surface functionality at the example of vascular endothelial growth factors and anti-CD34 antibodies, respectively.

Implications for the biofunctionalization of drug-eluting devices at the example of a site-selective antibody modification for drug eluting stents

Abstract Functionality of implant surfaces is considerably determined by the conformations of immobilized biomolecules adjustable by the applied surface modification approach. Moreover, surface modification of drug eluting systems often needs to be thoroughly optimized with regard to possible drug losses associated with a loss of functionality. Here, we thoroughly investigate biomolecule surface loading, functionality, morphology and stability in dependence of modification conditions at the example of a site-selective immobilization of anti-CD34 antibodies (CD34-Ab) to drug-eluting stents with the aim of providing general information on the biofunctionalization of drug eluting systems. In this context, we demonstrate that the reaction time of biomolecule immobilization defines achievable surface loads but also drug loss. We could moreover show that the used site-selective immobilization procedure elevated the surface functionality considerably in comparison to surfaces modified by random physisorption. Furthermore investigated bionfunctional stability gives important indications for storage conditions of biofunctionalized implants.

Investigation of in Vitro Drug Release Behaviour of Drug-Eluting Stents Using a Perfusion Culture System

The use of coronary drug-eluting stents (DES) for the treatment of coronary heart disease is well established. Since the success of the DES is dependent on the drug, the type of the polymeric carrier, the stent coating design and in this context on the drug release profile, the exact in vitro determination of the drug release characteristics under flow conditions is very important. Hence, a perfusion culture system was used in order to analyse the release behaviour of DES, dilated in arteries, close to in vivo

Coating Thickness Determination on Drug-Eluting Stents - Comparison of Methods

Different methods for the characterization of drug-eluting stent coatings relevant in process development and quality assurance are scrutinized. The results obtained by optical nondestructive methods as confocal laser scanning microscopy and spectral reflectometry are compared with results obtained by direct microscopic investigation of longitudinal cross sections. Comparison shows close agreement for all three techniques. The methods might thus be relevant for the characterization of other drug-coated medical devices with spectral reflectometry as the most effective.

Feasibility of Polymer/Drug Coating on Absorbable and Permanent Stent Platforms - Technological Challenges

Coating of drug-eluting stents demands different technologies depending on the nature of the stent platform, the intended coating design, and the coating materials. In this study, the complementary potentials of a spray-coating technology and a fluidized bed coating technology were assessed. Absorbable polymer stents and permanent metallic stents were coated with polymer/drug matrices based on poly(L-lactide) incorporated with the immunosuppressant sirolimus and the model substances fluorescein sodium, curcumin, and quinine. Process parameters were adjusted to yield optimal coating morphology. While spray-coating could be used to deposit even conversely asymmetric abluminal/luminal coating sandwiches, fluidized bed coating has shown tremendous throughput at a significant coating quality.