This book covers the following topics: recent developments in three dimensional and unsteady turbulence boundary-layer computations; flows far from equilibrium via molecular dynamics; physics of convention-solidification interaction; the continental shelf bottom boundary layer; gravity currents in rotating systems; strange attractors in fluids: another view; eddies, waves, circulation, and mixing: statistical geofluid mechanics; regular and mach reflection of shock waves; ship propellers; coherent structures; the critical layer and stability; general circulation of the oceans; characteristic-based schemes for the euler equations; vortex flows in aerodynamics; steady and unsteady boundary-layer separation; and wind wave prediction.

Annual Review of Fluid Mechanics

This invention relates to the design and function of a compressible valve replacement prosthesis, collared or uncollared, which can be deployed into a beating heart without extracorporeal circulation using a transcatheter delivery system. The design as discussed focuses on the deployment of a device via a minimally invasive fashion and by way of example considers a minimally invasive surgical procedure preferably utilizing the intercostal or subxyphoid space for valve introduction. In order to accomplish this, the valve is formed in such a manner that it can be compressed to fit within a delivery system and secondarily ejected from the delivery system into the annulus of a target valve such as a mitral valve or tricuspid valve.

Prosthetic valves and related inventions

As an Extracellular Matrix (ECM) component, Hyaluronic acid (HA) plays a multi-faceted role in cell migration, proliferation and differentiation at micro level and system level events such as tissue water homeostasis. Among its biological functions, it is known to interact with cytokines and contribute to their retention in ECM microenvironment. In addition to its biological functions, it has advantageous physical properties which result in the industrial endeavors in the synthesis and extraction of HA for variety of applications ranging from medical to cosmetic. Recently, HA and its derivatives have been the focus of active research for applications in biomedical device coatings, drug delivery systems and in the form of scaffolds or cell-laden hydrogels for tissue engineering. A specific reason for the increase in use of HA based structures is their immunomodulatory and regeneration inducing capacities. In this context, this article reviews recent literature on modulation of the implantable biomaterial microenvironment by systems based on HA and its derivatives, particularly hydrogels and microscale coatings that are able to deliver cytokines in order to reduce the adverse immune reactions and promote tissue healing.

Hyaluronic Acid and Its Derivatives in Coating and Delivery Systems: Applications in Tissue Engineering, Regenerative Medicine and Immunomodulation

http://smooz.4your.net/masterson/images/file/PHV%20Review%20Biomaterials.pdf

Polymeric heart valves for surgical implantation, catheter-based technologies and heart assist devices.

This invention relates to the design and function of a device which allows for retrieval of a previously implanted valve prosthesis from a beating heart without extracorporeal circulation using a transcatheter retrieval system, including a guide component to facilitate the compression of the valve and retraction into a retrieval catheter, as well as an improved prosthetic transcatheter heart valve having one or more of: a series of radially extending tines having a loop terminus to improve sealing a deployed prosthetic mitral valve against hemodynamic leaking, a pre-compressible stent-in-stent design, or an articulating cuff attached to a covered stent-valve and a commissural sealing skirt structure attached to the underside of the articulating cuff.

Multi-component designs for heart valve retrieval device, sealing structures and stent assembly

Shear stress on blood cells and platelets transported in a turbulent flow dictates the fate and biological activity of these cells. We present a theoretical link between energy dissipation in turbulent flows to the shear stress that cells experience and show that for the case of physiological turbulent blood flow: (a) the Newtonian assumption is valid, (b) turbulent eddies are universal for the most complex of blood flow problems, and (c) shear stress distribution on turbulent blood flows is possibly universal. Further we resolve a long standing inconsistency in hemolysis between laminar and turbulent flow using the theoretical framework. This work demonstrates that energy dissipation as opposed to bulk shear stress in laminar or turbulent blood flow dictates local mechanical environment of blood cells and platelets universally.

/pdf/theory-to-predict-shear-stress-on-cells-in-turbulent-blood-1xhrj5tba5.pdf

Theory to predict shear stress on cells in turbulent blood flow

Polymeric heart valves (PHVs) hold the promise to be more durable than bioprosthetic heart valves and less thrombogenic than mechanical heart valves. We introduce a new framework to manufacture hemocompatible polymeric leaflets for HV (PHV) applications using a novel material comprised of interpenetrating networks (IPNs) of hyaluronan (HA) and linear low density polyethylene (LLDPE). We establish and characterize the feasibility of the material as a substitute leaflet material through basic hemodynamic measurements in a trileaflet configuration, in addition to demonstrating superior platelet response and clotting characteristics. Plain LLDPE sheets were swollen in a solution of silylated-HA, the silylated-HA was then crosslinked to itself before it was reverted back to native HA via hydrolysis. Leaflets were characterized with respect to (1) bending stiffness, (2) hydrophilicity, (3) whole blood clotting, and (4) cell (platelet and leukocyte) adhesion under static conditions using fresh human blood. In vitro hemodynamic testing of prototype HA/LLDPE IPN PHVs was used to assess feasibility as functional HVs. Bending stiffness was not significantly different from natural fresh leaflets. HA/LLDPE IPNs were more hydrophilic than LLDPE controls. HA/LLDPE IPNs caused less whole blood clotting and reduced cell adhesion compared to the plain LLDPE control. Prototype PHVs made with HA/LLDPE IPNs demonstrated an acceptable regurgitation fraction of 4.77 ± 0.42%, and effective orifice area in the range 2.34 ± 0.5 cm2. These results demonstrate strong potential for IPNs between HA and polymers as future hemocompatible HV leaflets. Further studies are necessary to assess durability and calcification resistance.

/pdf/hemocompatibility-and-hemodynamics-of-novel-hyaluronan-25llzbas5c.pdf

Hemocompatibility and Hemodynamics of Novel Hyaluronan–Polyethylene Materials for Flexible Heart Valve Leaflets

Provided herein is a composite, comprising: a polymer host selected from the group consisting of low-density polyethylene (LDPE), linear low-density polyethylene (LLDPE), polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), and polypropylene (PP), polyurethane, polycaprolactone (PCL), polydimethylsiloxane (PDMS), polymethylmethacrylate (PMMA), and polyoxymethylene (POM); and a guest molecule comprising hyaluronic acid; wherein the guest molecule is disposed within the polymer host, and wherein the guest molecule is covalently bonded to at least one other guest molecule. Also provided herein are methods for forming the composite, and blood-contracting devices made from the composite, such as heart valves and vascular grafts.

Glycosaminoglycan and synthetic polymer materials for blood-contacting applications

We hypothesize that the formation of the closing vortex and subsequent b-datum regurgitation jet in bileaflet mechanical heart valves is governed by the magnitude of the driving mean aortic pressure (MAP), and that this sensitivity does impact the blood damage index (BDI) corresponding to platelet activation and lysis. High spatial resolution time resolved (1 kHz) as well as phase locked particle image velocimetry techniques captured the dynamic leaflet closure and regurgitation jet of a model 25 mm St. Jude Medical BMHV. Cell trajectories were estimated using Lagrangian particle tracking analysis while the leaflet kinematics was quantified by tracking the leaflet tip-position throughout closure. The non-principal as well as principal shear stress loading histories along each cell trajectory revealed BDI for platelet activation and lysis as a function of cell initial position, release time-point, and blood pressure. Results show that the leaflet closing time reduces by roughly 10 ms, in response to an increase in MAP by 40 mmHg. We report that higher MAP leads to a stronger b-datum vortex and jet formation. Platelet activation BDI lowers with a higher MAP due to reduction in exposure times despite an increase in principal shear stress experienced. Platelet lysis BDI however increases with higher MAP. Maximum BDI may occur for cells initially in the b-datum zone during the onset of leaflet closure. Our results provide a better understanding of BDI of the regurgitant b-datum jet and sheds light on the potential importance of blood damage testing under hypertensive conditions.

Effect of Hypertension on the Closing Dynamics and Lagrangian Blood Damage Index Measure of the B-Datum Regurgitant Jet in a Bileaflet Mechanical Heart Valve

The most widely implanted prosthetic heart valves are either mechanical or bioprosthetic. While the former suffers from thrombotic risks, the latter suffers from a lack of durability. Textile valves, alternatively, can be designed with durability and to exhibit hemodynamics similar to the native valve, lowering the risk for thrombosis. Deviations from native valve hemodynamics can result in an increased Reynolds Shear Stress (RSS), which has the potential to instigate hemolysis or shear-induced thrombosis. This study is aimed at characterizing flow in multiple textile valve designs with an aim of developing a low profile valve. Valves were created using a shaping process based on heating a textile membrane and placed within a left heart simulator. Turbulence and bulk hemodynamics were assessed through particle imaging velocimetry, along with flow and pressure measurements. Overall, RSS was reduced for low profile valves relative to high profile valves, but was otherwise similar among low profile valves involving different fabric designs. However, leakage was found in 3 of the 4 low profile valve designs driving the fabric design for low profile valves. Through textile design, low profile valves can be created with favorable hemodynamics.

Marcio Forleo

Papers

Theory to predict shear stress on cells in turbulent blood flow

Hemocompatibility and Hemodynamics of Novel Hyaluronan–Polyethylene Materials for Flexible Heart Valve Leaflets

Glycosaminoglycan and synthetic polymer materials for blood-contacting applications

Effect of Hypertension on the Closing Dynamics and Lagrangian Blood Damage Index Measure of the B-Datum Regurgitant Jet in a Bileaflet Mechanical Heart Valve

Reynolds shear stress for textile prosthetic heart valves in relation to fabric design.