Mechanical modeling of the maturation process for tissue-engineered implants: application to biohybrid heart valves

The development of tissue-engineered cardiovascular implants can improve the lives of large segments of our society who suffer from cardiovascular diseases. Regenerative tissues are fabricated using a process called tissue maturation. Furthermore, it is highly challenging to produce cardiovascular regenerative implants with sufficient mechanical strength to withstand the loading conditions within the human body. Therefore, biohybrid implants for which the regenerative tissue is reinforced by standard reinforcement material (e.g. textile or 3d printed scaffold) can be an interesting solution. In silico models can significantly contribute to characterizing, designing, and optimizing biohybrid implants. The first step towards this goal is to develop a computational model for the maturation process of tissue-engineered implants. This paper focuses on the mechanical modeling of textile-reinforced tissue-engineered cardiovascular implants. First, we propose an energy-based approach to compute the collagen evolution during the maturation process. Then, we apply the concept of structural tensors to model the anisotropic behavior of the extracellular matrix and the textile scaffold. Next, the newly developed material model is embedded into a special solid-shell finite element formulation with reduced integration. Finally, we use our framework to compute two structural problems: a pressurized shell construct and a tubular-shaped heart valve. The results show the ability of the model to predict collagen growth in response to the boundary conditions applied during the maturation process. Consequently, we can predict the implant's mechanical response, such as the deformation and stresses of the implant.Comment: Preprint submitted to Elsevie

Bio-Inspired Fiber Reinforcement for Aortic Valves:Scaffold Production Process and Characterization

The application of tissue-engineered heart valves in the high-pressure circulatory system is still challenging. One possible solution is the development of biohybrid scaffolds with textile reinforcement to achieve improved mechanical properties. In this article, we present a manufacturing process of bio-inspired fiber reinforcement for an aortic valve scaffold. The reinforcement structure consists of polyvinylidene difluoride monofilament fibers that are biomimetically arranged by a novel winding process. The fibers were embedded and fixated into electrospun polycarbonate urethane on a cylindrical collector. The scaffold was characterized by biaxial tensile strength, bending stiffness, burst pressure and hemodynamically in a mock circulation system. The produced fiber-reinforced scaffold showed adequate acute mechanical and hemodynamic properties. The transvalvular pressure gradient was 3.02 & PLUSMN; 0.26 mmHg with an effective orifice area of 2.12 & PLUSMN; 0.22 cm2. The valves sustained aortic conditions, fulfilling the ISO-5840 standards. The fiber-reinforced scaffold failed in a circumferential direction at a stress of 461.64 & PLUSMN; 58.87 N/m and a strain of 49.43 & PLUSMN; 7.53%. These values were above the levels of tested native heart valve tissue. Overall, we demonstrated a novel manufacturing approach to develop a fiber-reinforced biomimetic scaffold for aortic heart valve tissue engineering. The characterization showed that this approach is promising for an in situ valve replacement