In this work, bioinspired anisotropic polymeric heart valves were fabricated using composite materials from polyurethane (PU) and natural cellulose fiber bundles. Cellulose fibers with good alignment were obtained from balsa wood by a top-down process, which were then distributed in polyurethane to prepare cellulose fiber bundles reinforced polyurethane (CPU) by hot pressing. The storage modulus of the CPU along the direction parallel to the fiber alignment was 16.70 ± 0.80 MPa, whereas that along the direction perpendicular to the fiber alignment was 8.41 ± 0.94 MPa by dynamic mechanical analysis (DMA) tests at 1 Hz, comparable to aortic valve leaflets. Moreover, 2-methacryloyloxyethyl phosphorylcholine (MPC) was grafted onto the CPU surface (CPU-MPC) to improve hemocompatibility. With MPC modification, the water contact angle decreased significantly from 54.58° ± 2.98° to 26.42° ± 3.50°, and the platelet adhesion was reduced by 92%, compared to the original CPU. In vitro cell culture proved that both CPU and CPU-MPC samples did not show any cytotoxicity. Furthermore, the CPU composites were used to fabricate polymeric heart valves, which showed excellent hydrodynamic performance with a large orifice area (1.70 cm 2 ) and low regurgitation fraction (0.7%), meeting the requirements of ISO 5840–2 standard.
With the advancement of minimally invasive interventional therapy, biological heart valves (BHVs) have been extensively used in clinics. However, BHVs are generally prone to degeneration within 10–15 years after implantation due to defects including cytotoxicity, immune response, calcification and thrombosis, which are closely related to glutaraldehyde-crosslinking. In this work, we prepared a functionalized BHV through the in situ polymerization of methacrylated porcine pericardium and 2-hydroxyethyl methacrylate to avoid and overcome the defects of glutaraldehyde-crosslinked BHVs. The functionalized BHV was proven to be stable against enzymatic degradation and compatible towards HUVECs. After implantation in rats subcutaneously, a significantly mitigated immune response and reduced calcification were observed in the functionalized BHV. With the grafting of hydrophilic 2-hydroxyethyl methacrylate polymers, the antithrombogenicity of BHV was markedly enhanced by resisting the unfavorable adhesion of blood components. Moreover, the hydrodynamics of the functionalized BHV totally conformed to ISO 5840-3 under a wide range of simulated physiological conditions. These results indicate that the functionalized BHV with enhanced biocompatibility, anticalcification property and antithrombogenicity exhibited a low risk of degeneration and should be explored for further application.
Currently, the only treatment for moderate and severe aortic valve calcification disease is valve replacement. The clinical use of bioprosthetic heart valves (BHVs) is limited because of device failure caused by structural degeneration, such as the calcification of BHV leaflets. In the present study, poly(ethylene glycol) diacrylate (PEGDA) was incorporated with zwitterion (2-[methacryloyloxy]ethyl)dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA) forming a balanced charged network, which was further used to modify decellularized heart valves (DHV) and improve anticalcification properties. Valvular prostheses were designed and manufactured to comply with the requirements of ISO-5840 for valve fluid dynamics (i.e., effective orifice area = 1.9 cm2, regurgitant fraction = 1.5% for Φ25 mm surgical valve at heart stroke of 80 mL). Weight loss of artificial heart valves (PEGDA-SBMA-DHV) was less than 5.5% after enzymatic hydrolysis for 12 h. No obvious calcification was observed in artificial heart valves that were modified with PEGDA-SBMA, whereas calcification was found in decellularized heart valves and the PEGDA-modified group. Furthermore, histological staining results indicated that artificial heart valves (PEGDA-SBMA-DHV) with a balanced charged network elicited negligible inflammation. Thus, balanced charged networks of PEGDA-SBMA with cationic and anionic groups can prevent the transportation of Ca2+ ions and enzyme molecules, conferring efficient anticalcification properties to artificial heart valves.
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