Designing Biocompatible Tissue Engineered Heart Valves In Situ: JACC Review Topic of the Week.

Valvular heart disease is a globally prevalent cause of morbidity and mortality, with both congenital and acquired clinical presentations. Tissue engineered heart valves (TEHVs) have the potential to radically shift the treatment landscape for valvular disease by functioning as life-long valve replacements that overcome the current limitations of bioprosthetic and mechanical valves. TEHVs are envisioned to meet these goals by functioning as bioinstructive scaffolds that guide the in situ generation of autologous valves capable of growth, repair, and remodeling within the patient. Despite their promise, clinical translation of in situ TEHVs has proven challenging largely because of the unpredictable and patient-specific nature of the TEHV and host interaction following implantation. In light of this challenge, we propose a framework for the development and clinical translation of biocompatible TEHVs, wherein the native valvular environment actively informs the valve's design parameters and sets the benchmarks by which it is functionally evaluated.

Recreating the heart's helical structure-function relationship with focused rotary jet spinning.

Helical alignments within the heart's musculature have been speculated to be important in achieving physiological pumping efficiencies. Testing this possibility is difficult, however, because it is challenging to reproduce the fine spatial features and complex structures of the heart's musculature using current techniques. Here we report focused rotary jet spinning (FRJS), an additive manufacturing approach that enables rapid fabrication of micro/nanofiber scaffolds with programmable alignments in three-dimensional geometries. Seeding these scaffolds with cardiomyocytes enabled the biofabrication of tissue-engineered ventricles, with helically aligned models displaying more uniform deformations, greater apical shortening, and increased ejection fractions compared with circumferential alignments. The ability of FRJS to control fiber arrangements in three dimensions offers a streamlined approach to fabricating tissues and organs, with this work demonstrating how helical architectures contribute to cardiac performance.