Protein adsorption on blood-contacting surfaces: A thermodynamic perspective to guide the design of antithrombogenic polymer coatings.

Blood-contacting medical devices often succumb to thrombosis, limiting their durability and safety in clinical applications. Thrombosis is fundamentally initiated by the nonspecific adsorption of proteins to the material surface, which is strongly governed by thermodynamic factors established by the nature of the interaction between the material surface, surrounding water molecules, and the protein itself. Along these lines, different surface materials (such as polymeric, metallic, ceramic, or composite) induce different entropic and enthalpic changes at the surface-protein interface, with material wettability significantly impacting this behavior. Consequently, protein adsorption on medical devices can be modulated by altering their wettability and surface energy. A plethora of polymeric coating modifications have been utilized for this purpose; hydrophobic modifications may promote or inhibit protein adsorption determined by van der Waals forces, while hydrophilic materials achieve this by mainly relying on hydrogen bonding, or unbalanced/balanced electrostatic interactions. This review offers a cohesive understanding of the thermodynamics governing these phenomena, to specifically aid in the design and selection of hemocompatible polymeric coatings for biomedical applications. STATEMENT OF SIGNIFICANCE: Blood-contacting medical devices often succumb to thrombosis, limiting their durability and safety in clinical applications. A plethora of polymeric coating modifications have been utilized for addressing this issue. This review offers a cohesive understanding of the thermodynamics governing these phenomena, to specifically aid in the design and selection of hemocompatible polymeric coatings for biomedical applications.

Bioinspired polymeric heart valves: A combined in vitro and in silico approach.

Background: Polymeric heart valves (PHVs) may address the limitations of mechanical and tissue valves in the treatment of valvular heart disease. In this study, a bioinspired valve was designed, assessed in silico, and validated by an in vitro model to develop a valve with optimum function for pediatric applications. Methods: A bioinspired heart valve was created computationally with leaflet curvature derived from native valve anatomies. A valve diameter of 18 mm was chosen to approach sizes suitable for younger patients. Valves of different thicknesses were fabricated via dip-coating with siloxane-based polyurethane and tested in a pulse duplicator for their hydrodynamic function. The same valves were tested computationally using an arbitrary Lagrangian-Eulerian plus immersed solid approach, in which the fluid-structure interaction between the valves and fluid passing through them was studied and compared with experimental data. Results: Computational analysis showed that valves of 110 to 200 µm thickness had effective orifice areas (EOAs) of 1.20 to 1.30 cm2, with thinner valves exhibiting larger openings. In vitro tests demonstrated that PHVs of similar thickness had EOAs of 1.05 to 1.35 cm2 and regurgitant fractions (RFs) <7%. Valves with thinner leaflets exhibited optimal systolic performance, whereas thicker valves had lower RFs. Conclusions: Bioinspired PHVs demonstrated good hydrodynamic performance that exceeded ISO 5840-2 standards. Both methods of analysis showed similar correlations between leaflet thickness and valve systolic function. Further development of this PHV may lead to enhanced durability and thus a more reliable heart valve replacement than contemporary options.

From Scan to Simulation-A Novel Workflow for Developing Bioinspired Heart Valves.

Current heart valve replacements lack durability and prolonged performance, especially in pediatric patients. In part, these problems may be attributed to the materials chosen for these constructs, but another important contributing factor is the design of the valve, as this dictates hemodynamic performance and impacts leaflet stresses which may accelerate structural valve deterioration. Most current era bioprosthetic valves adhere to a fundamental design where flat leaflets are supported by commissural posts, secured to a sewing ring. This overall design strategy is effective, but functionality and durability can be improved by incorporating features of the native valve geometry. This paper presents a novel workflow for developing and analyzing bio-inspired valve designs computationally. The leaflet curvature was defined using a mathematical equation whose parameters were derived from the three-dimensional model of a native sheep pulmonary valve obtained via microcomputed tomography. Finite element analysis was used to screen the various valve designs proposed in this study by assessing the effect of leaflet thickness, Young's modulus, and height/curvature on snap-through (where leaflets bend against their original curvature), geometric orifice area (GOA) and the stress in the leaflets. This workflow demonstrated benefits for valve designs with leaflet thicknesses between 0.1 and 0.3 mm, Young's moduli less than 50 MPa, and elongated leaflets with higher curvatures. The proposed workflow brings substantial efficiency gains at the design stage, minimizing manufacturing and animal testing during iterative improvements, and offers a bridge between in vitro and more complex in silico studies in the future.