Three-Dimensional Elastomeric Scaffolds Designed with Cardiac-Mimetic Structural and Mechanical Features

Abstract

Tissue-engineered constructs, at the interface of material science, biology, engineering, and medicine, have the capacity to improve outcomes for cardiac patients by providing living cells and degradable biomaterials that can regenerate the native myocardium. With an ultimate goal of both delivering cells and providing mechanical support to the healing heart, we designed three-dimensional (3D) elastomeric scaffolds with (1) stiffnesses and anisotropy mimicking explanted myocardial specimens as predicted by finite-element (FE) modeling, (2) systematically varied combinations of rectangular pore pattern, pore aspect ratio, and strut width, and (3) structural features approaching tissue scale. Based on predicted mechanical properties, three scaffold designs were selected from eight candidates for fabrication from poly(glycerol sebacate) by micromolding from silicon wafers. Large 20×20 mm scaffolds with high aspect ratio features (5:1 strut height:strut width) were reproducibly cast, cured, and demolded at a relatively high throughput. Empirically measured mechanical properties demonstrated that scaffolds were cardiac mimetic and validated FE model predictions. Two-layered scaffolds providing fully interconnected pore networks were fabricated by layer-by-layer assembly. C2C12 myoblasts cultured on one-layered scaffolds exhibited specific patterns of cell elongation and interconnectivity that appeared to be guided by the scaffold pore pattern. Neonatal rat heart cells cultured on two-layered scaffolds for 1 week were contractile, both spontaneously and in response to electrical stimulation, and expressed sarcomeric α-actinin, a cardiac biomarker. This work not only demonstrated several scaffold designs that promoted functional assembly of rat heart cells, but also provided the foundation for further computational and empirical investigations of 3D elastomeric scaffolds for cardiac tissue engineering.

Influence of crosslinking on the mechanical behavior of 3D printed alginate scaffolds: Experimental and numerical approaches

“…In some tissue engineering applications, such as nerve and skin regeneration, the linear, low-strain region of the stress-strain curve was used to calculate the elastic modulus of samples and considered to represent physiological behavior in the human vasculature (Amensag and McFetridge, 2014). In a similar study, isotropic linear elastic behavior was reported and 10% strain used to calculate the elastic modulus of scaffolds fabricated as cardiac-mimetic structures; furthermore, 10 to 25% strain was reported as the cardiac-relevant strain range in physiological conditions (Neal et al, 2012). Finally, a finite element study assigned linear elastic elements to a model to predict the mechanical properties of tissue-engineered cartilage constructs (Sengers et al, 2004).…”

Building New Hearts: A Review of Trends in Cardiac Tissue Engineering

“…Other aspects being investigated include the modulation of material architecture (37) and the incorporation of conductive materials, such as nanotubes (18), to improve myocyte morphology and function. In addition, investigators are trying to determine which cell types should be delivered to the injured area to achieve the greatest improvement in cardiac function (i.e.…”

Bioprinting in cardiovascular tissue engineering: a review

“…In this approach, cells are seeded onto the scaffolds before going through tissue maturation. In scaffold fabrication, several methods, such as solvent casting [28][29][30] , molding [31] and electrospinning [32][33][34][35][36][37][38] , have been used. Features on the fabricated scaffolds can affect cell responses directly.…”