Primary open angle glaucoma represents an eye disease that usually is associated with an increased intraocular pressure (IOP). Implants for micro-invasive glaucoma surgery (MIGS) are gaining importance as a promising option for IOP lowering. Currently available devices are implanted into the eye ab interno based on a clear corneal incision and drain aqueous humour into the schlemm’s canal, suprachoroidal or subconjunctival space. Fibrosis is known as a major limitation for long term success and often leads to the necessity of an additional medication or a surgical re-intervention. The current work focusses on the development of an antifibrotic drug-eluting coating for a minimally invasive implantable glaucoma microstent. Tubular microstent base bodies manufactured from a polycarbonate based silicone elastomer were spray-coated with a chloroform based mixture of the same polymer and the antifibrotic drug pirfenidone (PFD, P2116, Merck KGaA, Germany) in a polymer/drug ratio of 85/15% (w/w). Coating mass of 89 μg according to a drug loading of 1.96 μg mm-2 was aspired. Coating mass was measured using an ultramicrobalance (XP6U, Mettler-Toledo International, Inc., Switzerland). Glaucoma microstent prototypes with a drugeluting coating mass of (84 ± 19) μg (n = 12) were manufactured. Characterization by means of scanning electron microscopy (Quattro S, Thermo Fisher Scientific, FEI Deutschland GmbH, Germany) yielded a reproducible smooth surface of the coating. High performance liquid chromatography (KNAUER Wissenschaftliche Geräte GmbH, Germany) was used for analysis of drug release behaviour in 0.9% NaCl solution at 37°C. The in vitro PFDrelease is characterized by an initial burst phase of approximately 6 h followed by a more retarded release phase. The entire drug was released within 36 h (n = 3). Sterilization processing has a minor impact on drug release kinetics. Appropriate drug stability after sterilization could be proven. Future studies will focus on the antifibrotic properties of drug-eluting glaucoma microstents in animal studies.

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For the treatment of severe symptomatic aortic valve stenosis, minimally invasive heart valve prostheses are increasingly used, especially for elderly patients. The current generation of devices is based on xenogenic leaflet material, involving limitations with regard to calcification and durability. Artificial polymeric leaflet-structures represent a promising approach for improvement of valve performance. Within the current work, finite-element analysis (FEA) design studies of polymeric leaflet structures were conducted. Design of an unpressurized and axiallysymmetric trileaflet heart valve was developed based on nine parameters. Physiological pressurization in FEA was specified, based on in vitro hydrodynamic testing of a commercially available heart valve prosthesis. Hyperelastic constitutive law for polymeric leaflet material was implemented based on experimental stress strain curves resulting from uniaxial tensile and planar shear testing. As a result of FEA, time dependent leaflet deformation of the leaflet structure was calculated. Obtained leaflet dynamics were comparable to in vitro performance of the analyzed prosthesis. As a major design parameter, the lunula angle has demonstrated crucial influence on the performance of the polymeric leaflet structures. FEA represented a useful tool for design of improved polymeric leaflet structures for minimally invasive implantable heart valve prostheses.

Abstract:Computational fluid dynamics (CFD) is a powerful tool to extent knowledge of biomechanical processes in cardiovascular implants.To provide a standardized method the U.S. Food and Drug Administration (FDA) initialized a CFD round robin study. One of the developed benchmark standard models is a generic nozzle geometry, consisting of a cylindrical throat with a conical collector and sudden expansion on either side. Several fluid mechanical data obtained from international institutes by means of CFD and particle image velocimetry (PIV) measurements under different flow regimes (Re = 500, 2000, 3500, 5000 and 6500) are freely available.This database includes only steady state simulations. In this study we performed pulsatile CFD simulations to consider the physiological environment of the coronary vessels. Furthermore, the nozzle geometry was scaled down to coronary dimension (D inlet = 12 mm to 3 mm) while retaining the average Reynolds number Re = 500 constant. The pulsatile character is described by a Womersley number of Wo = 2.065. Our CFD code was previously validated by using FDA´s data for steady state inflow conditions. It could be shown that time averaged wall shear stress and shear stress values agree well with steady state results. We conclude that steady state simulations are valid for hemodynamic analyses if only time averaged values are needed. This could save computational costs of future hemodynamic investigations.In addition, this study expands FDA´s benchmark case by pulsatile inlet condition for further code validation. This could be necessary for the development of new numerical methods as well as for validation of CFD codes used in the approval process of medical devices.

Glaucoma represents the leading cause of irreversible blindness worldwide. Therapeutic approaches are based on the lowering of intraocular pressure (IOP). Micro-invasive glaucoma surgery (MIGS) offers perspectives for implant based IOP-reduction with reduced complication rates compared to conventional surgical approaches. Nevertheless, available devices suffer from complications like hypotony and fibrotic encapsulation. The current work focuses on the development of a minimally invasive implantable drugeluting microstent for the drainage of aqueous humour into suprachoroidal or subconjunctival space. Technical feasibility of a micro-scale resorbable nonwoven for the prevention of hypotony and of a drug-eluting coating for the prevention of fibrosis is assessed. Microstent base bodies with a length of 10 mm and an inner/outer diameter of 0.20 mm / 0.35 mm were manufactured. For the prevention of hypotony, resorbable nonwovens with an adequate flow resistance of 1.543 mmHg/μl min-1 were manufactured in the inflow area of microstents. A drug-eluting coating in the outflow area of microstents was developed based on the model drug fluorescein diacetate. Micro-invasive ab interno implantation of a microstent prototype into suprachoroidal space of a porcine eye post mortem was successfully performed, using an injector device. Future studies will focus on the development of an antifibrotic drug-eluting coating and further in vitro, ex vivo and in vivo testing of the devices.