MESO-SCALE PATTERNED COLLECTING TARGET TO INDUCE LOCAL ANISOTROPY AND CURVILINEAR FIBER ORIENTATION IN ELECTRO-DEPOSITED, MICRO-FIBER BASED MITRAL VALVE SCAFFOLDS

Jun 28, 2022, 2:20 PM
10m
Room: S4 A

Room: S4 A

Speaker

Terranova, Pietro (University of Palermo )

Description

Collagen fiber network architecture in the native heart valve leaflets is characterized by preferential orientation and curvilinear arrangement that allow adequate stress distribution and effective leaflet coaptation. Specifically for the mitral valve, collagen fibers are preferentially aligned towards the circumferential direction with a curvilinear arrangement that runs from the posteromedial to the anterolateral commissure1. Tuning the collecting target tangential velocity is a common strategy shared by several techniques such as melt-electrowriting2, jet-spinning3, and Double-Component-Deposition (DCD)4 to achieve physiologically relevant structural anisotropy and circumferential alignment in the belly region of the valve scaffold. Similarly, conical shape collecting targets have been previously presented to obtain curvilinear arrangement in valve scaffolds5. However, the two methodologies cannot be combined. Tangential velocities can only induce circumferentially aligned straight fibers along the 3D geometry of a scaffold, while using conical mandrels produces curvilinear arrangement, which is strictly limited to 2D, planar scaffolds. In addition, the high tangential velocities requested to achieve physiologically relevant anisotropy are generally associated with deposition artifacts in complex 3D scaffold geometries. While the DCD processing method we previously introduced4, utilizes a collecting target made of an electrically conductive and a non-conductive component, this target design enables to manipulate the electrical field at the macro-scale and allows to recapitulate valve anatomy and to dictate various microarchitectural parameters, including fiber diameter and pore size. Yet, the curvilinear arrangement of the fiber network could not be achieved. In this study, we further advance the notion of DCD by manipulating the electrical field of the collecting target with mesoscopic grooves designed to induce local anisotropy and fiber undulation. A micro-grooved cylindrical copper mandrel was used as collector. To evaluate the effects of the groove geometry on the fiber deposition, three variables were considered: width, depth, and frequency which were set as equal to 50, 100, and 150µm. A cylindrical smooth mandrel was utilized as control. A tangential velocity of 0.26m/s, which normally generate isotropic scaffold on flat surfaces, was used for all the fabrications. The spatial electric field distribution was simulated in COMSOL-Multiphysics®. Morphological and mechanical properties of fabricated PEUU scaffolds were characterized by scanning electron microscopy, and biaxial tensile test. The width resulted in being the most effective parameter in terms of its capacity to induce statistically significant levels of circumferential fiber alignment and mechanical anisotropy. This notion was transferred to a collecting target specifically designed to reproduce the three-dimensional anatomy of the mitral valve, demonstrating control over fiber alignment and posteromedial-anterolateral commissure curvilinear arrangement. The in-silico model simulations allowed to visualize the electrical field distribution produced by the groove pattern and elucidate the likely mechanism of fiber deposition associated with local anisotropy at the tissue scale and the curvilinear fiber network at the organ level scale. This seminal study introduces a novel approach to design collecting targets for electro-deposition to advance biomimetics in HV engineering.

1.Rausch, et al., Biomech&mod. in MB, 12.5:1053-1071(2013).
2.Saidy, et al., Front.BEBT, 8:793(2020).
3.Capulli, et al., Biomaterials, 133:229-241(2017).
4.D'Amore, et al., Biomaterials, 150:25-37(2018).
5.Hobson, et al., JBMMR-Part A, 103.9:3101-3106(2015).

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