Electrospun Scaffolds for Heart Valve Tissue Engineering

INTRODUCTION Heart valve replacements are required for a number of heart diseases and replacements, as well as for both pediatric and adult populations. It is estimated that 2.5% of the population has valvular heart disease [1], and annually, over 250,000 people worldwide receive heart valve replacements [1]. Tissue engineering (TE) strategies hold the most promise for permanently restoring the damaged heart valve or nearby tissue. The premise of tissue engineering is to replace or facilitate the regrowth of damaged tissues by creating biodegradable, biocompatible, and mechanically analogous tissue substitutes – such bioresorbable scaffolds. The general method of growing TE analogs involves seeding cells on a fibrous, porous, biomimetic scaffold. As the cells infiltrate the scaffold structure, they grow, divide, and eventually degrade the scaffold matrix and replace it with natural extracellular matrix (ECM). During this process, the scaffold mimics the cells’ ECM via its fibrous structure, and it provides structural support for the cells, localizes the cells and their signaling factors, and allows for diffusion through the porous matrix [2]. TE fibrous scaffolds made from synthetic biodegradable elastomer polymers stand out as the promising constructs for heart valve replacements because they can sustain the dynamic mechanical environment of the heart and mimic the native extracellular matrix (ECM) to support cell growth. Synthetic, biomimetic scaffolds have been made in various ways, but electrospinning is considered to be one of the simplest and most tunable methods of fabrication [2]. Electrospinning, which involves pumping a polymer solution through a syringe at an applied voltage, is so tunable because the experimenter can adjust properties of the polymer solution as well as the physical setup of the electrospinning apparatus. In addition, depending on the setup, the electrospinning technique can be used to make isotropic or anisotropic fiber alignments. APS (amino polyol sebacates) were a family of relatively hydrophobic, slow-degrading elastomers synthesized recently [3]. APS polymers cannot be electrospun, but mixtures of APS and PCL (ε-polycaprolactone) can be. However, little research has been done on fabricating APS-based elastomeric scaffolds for TE purposes. In addition, the relatively hydrophobic backbone of APS is undesirable for TE purposes. In light of this, our lab has synthesized novel APS-co-PEG polymers (copolymers of APS and PEG, or polyethylene glycol, a hydrophilic polymer) to increase the processability and widen the property spectrum of current biodegradable elastomers.