Fabrication and characterization of artificial heart valves composed of poly(ethylene glycol) and natural protein fibers

Abstract

Event Abstract Back to Event Fabrication and characterization of artificial heart valves composed of poly(ethylene glycol) and natural protein fibers Qian Li1, Yun Bai1, Hemin Nie2, Rui Yang1 and Xing Zhang1 1 Institute of Metal Research, Chinese Academy of Sciences, China 2 Hunan University, College of Biology, China Introduction: The number of patients requiring heart valve replacement increasing from approximately 290,000 in 2003 to over 850,000 in 2050[1]. Current devices for valve replacement have significant limitations. For example, mechanical valves require anticoagulation in the lifetime of the patients[2]. Bioprosthetic heart valves (BHVs) have relatively poor durability due to leaflet mineralization and mechanical fatigue[3],[4]. Herein, poly(ethylene glycol) (PEG) and natural protein fiber composites with mechanical property similar to native valves were fabricated as artificial heart valve leaflets, which likely provide advanced solutions to the limitations of current treatments. Materials and Methods: The eggshell membranes (ESMs) were separated and soaked in 8M acetic acid to dissolve the existing calcium carbonate granules. The cleaned ESMs soaked with a poly(ethylene glycol) diacrylate (PEGDA) pre-polymer solution were aligned in a PDMS mold and sealed between glass slides, which was then crosslinked by white light to form the PEG hydrogel. The resulting PEG-ESM composite was further crosslinked by a 0.5 wt.% glutaraldehyde (GA) solution. The ESM and PEG-ESM samples were soaked in a type I collagenase solution and a pronase solution, respectively, to evaluate the enzyme degradation at different time periods. Uniaxial tension tests were performed to calculate the elastic moduli and elongation percentage of these samples. Subcutaneous implantation on the back area of Sprague Dawley (SD) rats for 2 weeks was used to evaluate the biocompatibility of the PEG-ESM samples. Results and Discussion: ESMs were mainly composed of natural protein fibers (e.g. collagens I, V, X) with an average thickness ~2.0 μm. The ESMs had an average elastic modulus ~4.4 MPa, which substantially increased to ~6.9 MPa by GA crosslinking, close to that of aortic heart valve leaflets (1-15 MPa). For the PEG-ESM composites, the elastic modulus increased with the increase of ESM volume percentage. For example, the elastic modulus was ~3.4 MPa for the composite (~600μm thick) with six layers of ESMs, which was significantly larger than that with two layers of ESMs (~1.1 MPa). Our results showed that there was a significant decrease of elastic modulus of ESMs by enzyme treatment (6.9 MPa before treatment and 4.7 MPa after treatment), but no significant decrease for the PEG-ESM samples, indicating that incorporation of PEG can prevent the enzyme degradation of ESM proteins (Fig. 1). Fig. 1. Elastic moduli of different samples: ESM samples with GA crosslinking before collagenase I treatment (A) and after treatment (B) for 2 weeks, and PEG-ESM samples before collagenase I treatment (C) and after treatment (D). Hematoxylin and eosin (H&E) staining of sections of host tissues adjacent to the PEG-ESM implants showed no sign of macrophage cells, suggesting that there was no immune rejection of the implants in vivo (Fig. 2). Fig. 2. H&E staining of host tissues showed good integrity of tissue structures and no sign of macrophage cells: (A) 4x, (B) 10x magnification. Conclusions: Advanced PEG-ESM composites were fabricated by photo crosslinking of PEGDA with ESMs, which was further crosslinked by glutaraldehyde. The novel PEG-ESM composites have an average elastic modulus comparable to those from native aortic valve leaflets, which also show good resistance of enzyme degradation and no immune rejection in vivo, thus, are suitable as artificial valve leaflets. This work was supported by National Natural Science Foundation of China (NSFC #31300788) and Chinese Academy of Sciences (CAS Hundred-Talent Program).