Heart valve tissue engineering (HVTE) is one of the most advanced and newest approaches for the treatment of valvular heart diseases. Therefore, the main goal in the present study is to construct and characterize a three-dimensional antibacterial heart valve scaffold based on tissue engineering to solve the current limitations of valvular disease treatment methods. For this purpose, three polyglycerol sebacate polymers, polycaprolactone and gelatin ratios (PGS50:PCL40:GLT10) were combined by a multi-step melting method and the primary scaffold was produced using the melt molding method in a designed three-dimensional mold. During construction; the drug ciprofloxacin (CPFX) was also loaded into the scaffold as an antibacterial agent. The surface of the scaffold was covered with a coating layer of PGS-GLT using immersion technique and with the help of EDC-NHS material as a cross-linking agent. The surface topography test and morphological eva‎luations of the scaffold showed that adding a bonding coating layer to the surface of the scaffold; It can significantly increase the integrity and smoothness of the surface. Also, the contact angle in the sample without the coating layer containing the drug was measured as 21.18 degrees, while it reached 28.73 degrees after creating the coating layer and hydrophilic cross-links. The tensile strength of the optimal scaffold had a coating of 3.42 MPa, tensile modulus of 7.13 MPa, elasticity coefficient of 33%, and bending strength of 5.18 MPa and a bending modulus of 12.3 MPa, which is a significant improvement compared to the scaffold without a coating layer were significant (P<0.05). Also, the scaffold's resistance to suturing in the scaffold with a cover layer was equal to 6.98 newtons, which prevents the structure from collapsing during implantation in the body. The results of eva‎luating the calcification rate on the three-dimensional scaffold; showed a lower amount of calcium deposition (6.12 ± 0.35 µg/mg-1) on the surface of the scaffold with cross-linked coating layer compared to the scaffold without coating layer (1.27 ± 2.14 µg/mg-1). In the eva‎luation of compatible blood, the scaffolds with a cross-linked covering layer showed non-clotting behavior, favorable platelet adhesion and no lysis of red blood cells, which are considered compatible blood. In the eva‎luation of antibacterial activity, the scaffold with a coating layer containing drug (optimal) showed an effective antibacterial activity against both Gram-negative and Gram-positive bacteria. Also, the drug release results showed that this optimal scaffold can release ciprofloxacin gradually and continuously for more than 120 hours, which is very useful in reducing the risk of infection in the period after heart valve replacement and repair surgery. eva‎luation of cellular response and biocompatibility of scaffolds was performed with two types of HUVEC cells and human cardiac fibroblast isolated from human cardiac tissue. The results of cell nucleus and cell membrane staining by Hoechst and Calcein-AM methods, as well as eva‎luation of cytotoxicity by Alamarblue and MTT methods; It showed that scaffolds with coating layer, in addition to reducing cytotoxicity, have better cell growth and adhesion conditions. According to the obtained results, the present study of the idea of creating a 3D antibacterial and biocompatible biomimetic heart valve scaffold, and the important role of the elastomeric coating layer in improving physical-mechanical properties; Calcification and blood compatibility support it and show bright horizons in the field of heart valve tissue engineering and heart valve replacement surgery in a minimally invasive way.

شيدا لباف , شقايق حق جوي جوانمرد

محمد رفيعي نيا , انوشه زرگر خرازي , منصور جنتي