Recent Advances in the Modification and Improvement of Bioprosthetic Heart Valves.

Valvular heart disease (VHD) has become a burden and a growing public health problem in humans, causing significant morbidity and mortality worldwide. An increasing number of patients with severe VHD need to undergo heart valve replacement surgery, and artificial heart valves are in high demand. However, allogeneic valves from donors are lacking and cannot meet clinical practice needs. A mechanical heart valve can activate the coagulation pathway after contact with blood after implantation in the cardiovascular system, leading to thrombosis. Therefore, bioprosthetic heart valves (BHVs) are still a promising way to solve this problem. However, there are still challenges in the use of BHVs. For example, their longevity is still unsatisfactory due to the defects, such as thrombosis, structural valve degeneration, calcification, insufficient re-endothelialization, and the inflammatory response. Therefore, strategies and methods are needed to effectively improve the biocompatibility and longevity of BHVs. This review describes the recent research advances in BHVs and strategies to improve their biocompatibility and longevity.

Biomimetic-modified bioprosthetic heart valves with Cysteine-Alanine-Glycine peptide for anti-thrombotic, endothelialization and anti-calcification.

In recent years, bioprosthetic heart valves (BHVs) prepared by cross-linking porcine or bovine pericardium with glutaraldehyde (Glut) have received widespread attention due to their excellent hemocompatibility and hydrodynamic properties. However, the failure of BHVs induced by thrombosis and difficulty in endothelialization still exists in clinical practice. Improving the biocompatibility and endothelialization potential of BHVs is conducive to promoting their anti-thrombosis properties and prolonging their service life. Herein, Cysteine-Alanine-Glycine (CAG) peptide was introduced into the biomimetic BHV materials modified by 2-methacryloyloxyethyl phosphorylcholine (MPC) to improve their anti-thrombosis and promoting-endothelialization performances. MPC can improve the anti-adsorption performance of BHV materials, as well as, CAG contributes to the adhesion and proliferation of endothelial cells on the surface of BHV materials. The results of experiments showed that the biomimetic modification strategy with MPC and CAG reduce the thrombosis of BHV materials and improve their endothelialization in vitro. More importantly, the calcification of BHV significantly reduced by inhibiting the expression of M1 macrophage-related factors (IL-6, iNOS) and promoting the expression of M2 macrophage-related factors (IL-10, CD206). We believe that the valve-modified strategy is expected to provide effective solutions to clinical valve problems.

Arginine-grafted porcine pericardium by copolymerization to improve the cytocompatibility, hemocompatibility and anti-calcification properties of bioprosthetic heart valve materials.

Bioprosthetic heart valves (BHVs) have been used widely due to the development of transcatheter heart valve replacement technology. However, glutaraldehyde crosslinked pericardium (GA), which is widely used as a leaflet material for BHVs, still has disadvantages, including cytotoxicity, thrombosis, and calcification, which lead to the dysfunction and degeneration of BHVs. Herein, we prepared a methacrylated arginine-grafted BHV through the copolymerization of methacrylated arginine and methacrylated porcine pericardium (PP). Briefly, PP was crosslinked by glutaraldehyde and methacrylated polylysine (pLy-MA) to obtain methacrylated PP (pLy-GA), and the pLy-GA was then copolymerized with methacrylated arginine to prepare methacrylated arginine-grafted PP (pLy-GA-Arg). The introduction of Arg-MA improved the ability of PP to resist platelet adhesion, and compared with GA, platelet adhesion decreased by 78% which exhibited improved antithrombotic properties. pLy-GA-Arg exhibited improved cytocompatibility and the relative proliferation rate of HUVECs increased by 2 times compared with GA. After 60 days of subcutaneous implantation, the calcification degree of pLy-GA-Arg was significantly lower than that of GA (4.37 ± 0.33 µg mg-1versus 157.46 ± 41.74 µg mg-1). The introduction of arginine improved the hemocompatibility and cytocompatibility of PP and reduced its calcification, offering a potential option for BHV fabrication in the future.

Biomechanical properties and healing effects of chitin patch in a rat full-thickness abdominal wall defect model.

Hernia repair is usually accompanied with the implantation of a synthetic mesh, which frequently results in a foreign body response and serious complications. In the present study, a novel biodegradable chitin-based hernia patch was prepared and characterized. Biomechanical properties and biodegradability of the chitin patch were quantified in vitro and in vivo. In repair of the rat abdominal wall full-thickness defect model, the chitin patch induced more abundant new blood vessels with milder tissue inflammation and fibrosis compared with polypropylene mesh. Chitin patch effectively inhibited excessive secretion of inflammation-associated cytokines (IL-6 and TNF-α) (p < 0.01) and significantly increased the secretion of healing-related cytokines (FGF1 and TGF-ß1) (p < 0.01). Accompanied by biodegradation of the chitin patch, intra-abdominal adhesions caused by the chitin patch decreased significantly, and the tensile strength of the repaired site could meet the biomechanical requirements of human abdominal wall. After the one-year observation period, the defected abdominal wall returned to the appropriate thickness with no obvious complication or hernia occurrence. In a conclusion, the newly designed chitin patch showed good biomechanical properties and satisfactory healing effects on the full-thickness defect of abdominal wall, which makes it promising candidate for clinical hernia treatment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1349-1357, 2018.