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.

Despite their overall success, different blood-contacting medical devices such as heart valves, stents, and so forth, are still plagued with hemocompatibility issues which often result in the need for subsequent replacement and/or life-long anticoagulation therapy. Consequently, there is a significant interest in developing biomaterials that can address these issues. Polymeric-based materials have been proposed for use in many applications due to their ability to be finely tuned through manufacturing and surface modification to enhance hemocompatibility. In this study, we have developed a novel, hydrophilic biomaterial comprised of an interpenetrating polymer network (IPN) of hyaluronan (HA) and linear low density polyethylene (LLDPE). HA is a highly lubricous, anionic polysaccharide ubiquitously found in the human body. It is currently being investigated for a vast array of biomedical applications including cardiovascular therapies such as hydrogel-based regenerative cell therapies for myocardial infarction, HA-coated stents, and surface modifications of polyurethane and metals for use in blood-contacting implants. The aim of this study was to assess the in vitro thrombogenic response of the hydrophilic polymer surface, HA-LLDPE for future potential use as flexible heart valve leaflets. The results indicate that HA-LLDPE is non-toxic and reduces thromobogenicity as compared to LLDPE surfaces, asserting its feasibility for use as a blood-contacting biomaterial. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1964-1975, 2018.

Male cockroaches Gromphadorhina portentosa were made to run at 0.03, 0.07, and 0.12 kilometer per hour on a miniature treadmill within a small respirometer. Oxygen consumption was directly related to running velocity. The half-time necessary for oxygen consumption to reach a steady state during exercise was about 1 minute and the half-time for recovery was 4 to 6 minutes. The energetic cost of transport was comparable to that for bipedal and quadrupedal vertebrates.

Heart disease continues to be the leading cause of death in the United States. The demand for cardiovascular bypass procedures increases annually. Expanded polytetrafluoroethylene is a popular material for replacement implants, but it does have drawbacks such as high thrombogenicity and low patency, particularly in small diameter grafts. Hyaluronan, a naturally occurring polysaccharide in the human body, is known for its wound healing and anticoagulant properties. In this work, we demonstrate that treating the luminal surface of expanded polytetrafluoroethylene grafts with hyaluronan improves hemocompatibility without notably changing its mechanical properties and without significant cytotoxic effects. Surface characterization such as ATR-FTIR and contact angle goniometry demonstrates that hyaluronan treatment successfully changes the surface chemistry and increases hydrophilicity. Tensile properties such as elastic modulus, tensile strength, yield stress and ultimate strain are unchanged by hyaluronan enhancement. Durability data from flow loop studies demonstrate that hyaluronan is durable on the expanded polytetrafluoroethylene inner lumen. Hemocompatibility tests reveal that hyaluronan-treated expanded polytetrafluoroethylene reduces blood clotting and platelet activation. Together our results indicate that hyaluronan-enhanced expanded polytetrafluoroethylene is a promising candidate material for cardiovascular grafts.

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Flexible heart valve leaflets made from hyaluronan-enhanced linear low-density polyethylene interpenetrating polymeric network (HA-LLDPE IPN) films have been shown to provide good hemodynamics, but the resulting surfaces were not consistent; therefore, the present work tries to mitigate this problem by developing a vapor cross-linked HA-LLDPE IPN. Herein, the HA-LLDPE fabrication process is studied, and its parameters are varied to assess their effects on the IPN formation. Thermal analysis and gas chromatography-mass spectrometry were used to quantify the effects of different treatment conditions on material properties. Water contact angle goniometry, infrared spectroscopy, and toluidine blue O (TBO) staining were used to characterize the surface of the HA-LLDPE IPN. The results show that a hydrophilic surface is formed on HA-LLDPE, which is indicative of HA. HA surface density data from TBO staining show consistent HA distribution on the surface. The IPN fabrication process does not affect the tensile properties that make LLDPE an attractive material for use in flexible heart valve leaflets. The 28 day in vitro biological assays show HA-LLDPE to be noncytotoxic and resistant to enzymatic degradation. The HA-LLDPE showed less platelet adhesion and caused less platelet activation than the plain LLDPE or tissue culture polystyrene. All of the results indicate that vapor cross-linked HA-LLDPE IPN is a promising material for use as flexible leaflets for heart valve replacements.

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