Hemodynamic evaluation of biomaterial-based surgery for Tetralogy of Fallot using a biorobotic heart, in silico, and ovine models.

Tetralogy of Fallot is a congenital heart disease affecting newborns and involves stenosis of the right ventricular outflow tract (RVOT). Surgical correction often widens the RVOT with a transannular enlargement patch, but this causes issues including pulmonary valve insufficiency and progressive right ventricle failure. A monocusp valve can prevent pulmonary regurgitation; however, valve failure resulting from factors including leaflet design, morphology, and immune response can occur, ultimately resulting in pulmonary insufficiency. A multimodal platform to quantitatively evaluate the effect of shape, size, and material on clinical outcomes could optimize monocusp design. This study introduces a benchtop soft biorobotic heart model, a computational fluid model of the RVOT, and a monocusp valve made from an entirely biological cell-assembled extracellular matrix (CAM) to tackle the multifaceted issue of monocusp failure. The hydrodynamic and mechanical performance of RVOT repair strategies was assessed in biorobotic and computational platforms. The monocusp valve design was validated in vivo in ovine models through echocardiography, cardiac magnetic resonance, and catheterization. These models supported assessment of surgical feasibility, handling, suturability, and hemodynamic and mechanical monocusp capabilities. The CAM-based monocusp offered a competent pulmonary valve with regurgitation of 4.6 ± 0.9% and a transvalvular pressure gradient of 4.3 ± 1.4 millimeters of mercury after 7 days of implantation in sheep. The biorobotic heart model, in silico analysis, and in vivo RVOT modeling allowed iteration in monocusp design not now feasible in a clinical environment and will support future surgical testing of biomaterials for complex congenital heart malformations.

Development and characterization of biological sutures made of cell-assembled extracellular matrix.

Most vascular surgical repair procedures, such as vessel anastomoses, requires using suture materials that are mechanically efficient and accepted by the patient's body. These materials are essentially composed of synthetic polymers, such as polypropylene (ProleneTM) or polyglactin (VicrylTM). However, once implanted in patients, they are recognized as foreign bodies, and the patient's immune system will degrade, encapsulate, or even expel them. In this study, we developed innovative biological sutures for cardiovascular surgical repairs using Cell-Assembled extracellular Matrix (CAM)-based ribbons. After a mechanical characterization of the CAM-based ribbons, sutures were made with hydrated or twisted/dried ribbons with an initial width of 2 or 3 mm. These biological sutures were mechanically characterized and used to anastomoseex vivoanimal aortas. Data showed that our biological sutures display lower permeability and higher burst resistance than standard ProleneTMsuture material.In vivocarotid anastomoses realized in sheep demonstrated that our biological sutures are compatible with standard vascular surgery techniques. Echography confirmed the absence of thrombus and perfect homeostasis with no blood leakage was obtained within the first 10 min after closing the anastomosis. Finally, our findings confirmed the effectiveness and clinical relevance of these innovative biological sutures.