Surface engineering in artificial heart valves

Valvular heart disease refers to any cardiovascular condition that affects one or more of the heart’s four valves: the aortic and mitral valves on the left side of the heart, and the pulmonic and tricuspid valves on the right side. While these conditions primarily develop as a result of aging, they can also be caused by congenital abnormalities, specific diseases, or physiological processes such as rheumatic heart disease and pregnancy. Surgical replacement of the faulty valve with prosthetic valves remains the preferred and most effective treatment for all types of VHD. In 2020, over 180,000 heart valve replacements were performed in the US alone [1]. Charles Hufnagel is considered the pioneer in the design of prosthetic heart valves. The first Hufnagel heart valve was implanted in 1952 using a Lucite tube and methacrylate ball in the descending aorta. Over the past century, significant advancements have been made in the development of prosthetic heart valves, and continuing research is dedicated to engineering optimal designs. [2] (Figure 1). The prosthetic heart valve comprises three components: the valve ring, the valve leaf, and the sewing ring (Figure 2). The valve ring and leaf are typically made of titanium, 316L stainless steel (SS) or cobaltchromium (Co-Cr) alloys, low-temperature isotropic pyrolytic carbon, or expanded polytetrafluoroethylene (ePTFE) or polyethylene terephthalate (PET) [3]. While progressive designs of prosthetic heart valves have improved haemodynamic properties, the introduction of a foreign object into the human body comes with its own set of complications [5]. The common problems include thrombosis, haemorrhage related to anticoagulant use, infections, valve failure, tissue hyperplasia, and overgrowth. Thrombogenicity or clot formation on the surfaces of the internal prosthesis is triggered by the adhesion and activation of platelets on them. This in turn is guided by the protein layer, especially human plasma fibrinogen (HPF). Inflammatory reactions such as restenosis and calcification are also caused by the release of toxic ions from the metals or alloys and the degradation of polymeric components of the artificial valves. A promising strategy to limit thrombogenicity is to modulate HPF behaviour at the blood-material interface by altering the physicochemical properties of the valve’s (or any prosthetic device’s) surface. Surface modifications aim to optimize various aspects of blood-material interactions, including protein adsorption, thrombin generation and blood coagulation, platelet adhesion, aggregation and activation, and cellular behaviour at the prosthesis surface [6]. A recent study showed the relationship between surface crystallographic structure and platelet adhesion. Valve rings are often made of titanium or pyrolytic carbon, the surface of which is often engineered to have a layer of titanium oxide [7]. The rutile crystallographic structure typically has three lowindex (110), (100), and (101) facets. HPF has been reported to unfold into a trinodular form on the hydrophobic (110) facet and has a globular conformation in the more hydrophilic (001) facet [8]. Such conformational changes result in altered platelet adhesion in the two phases. As seen in Figure 3, the hydrophilic (001) phase has a higher distribution of platelets, and therefore presents a higher risk of thrombogenicity [9]. Two approaches have been reported for the surface modification of heart valves – the application of surface coatings, and the patterning of the valve surface. Early approaches to surface modification involved applying a bioinert coating that acts as a physical barrier between the valve and the biomedium (blood). Various carbon coatings, including diamond-like carbon, have been utilized to enhance the biocompatibility and hemocompatibility of implants [10]. Studies have shown that hydrogen-free DLC (diamond-like carbon) coatings with a higher bonding ratio of sp/sp2 exhibit improved blood compatibility [11]. The use of ultrananocrystalline diamond (UNCD) coatings avoids graphitization and film delamination in pyrolytic carbon-based mechanical heart valves. UNCD also results in minimum thrombin formation, in comparison to pyrolytic carbon alone, boron-doped UNCD, microcrystalline diamond, and silicon carbide films, represented as Pyc, BD-UNCD, MCD, and SiC, respectively, in Figure 4. Ceramic coatings such as TiO2 and TiN have also been studied because of their biocompatibility and