Building On-Demand Customizable Cardiovascular Implants

Abstract

Cardiovascular disease and injury frequently necessitate structural replacement of heart valves and blood vessels. As current clinical options often require repeat interventions, regenerative implants are of particular interest as they may enable lifelong solutions. To successfully regenerate cardiovascular components, implanted scaffolds should interact with the native environment across multiple length scales, ranging from the nanoscale of the cellular microenvironment to the centimeter scale relevant to valvular and vascular function. Current manufacturing platforms struggle to fabricate implants with concurrent control across these hierarchical length scales. This work presents Focused Rotary Jet Spinning (FRJS) as a rapid cell-free fabrication strategy capable of producing customizable cardiovascular implants comprised of nano- and microscale structural cues in just minutes. The nanofiber components of the textile scaffolds recapitulate fibrous extracellular matrix, interacting with cells at familiar length scales. When seeding representative cardiovascular cell types onto scaffolds with different alignments, the self-organizing behavior of the different cells displayed the ability to form anisotropic tissue configurations dependent on the degree of scaffold alignment. Extending these textile scaffolds to cardiovascular implants, vascular grafts were fabricated with control and customizability across nanometer to centimeter scales. When the acellular scaffolds were implanted for four weeks in rat femoral vasculature, the vascular grafts maintained patency, tissue perfusion, and initial cellular infiltration. With FRJS produced implants demonstrating the ability to convey blood flow, their ability to control these flows was examined. Pulmonary valve replacements were formed with rapid fabrication of customized scaffolds. Valve leaflet geometry parameters were adjusted, producing a valve capable of sufficiently controlling hemodynamic flows in vitro. The implant’s functionality was confirmed in a large animal model after a minimally invasive transcatheter delivery. Both valves and vascular grafts were produced in just minutes with manufacturing control across a wide range of necessary length scales. FRJS as a cell-free fabrication method provides speed and control advantages that can enable on-demand and customizable regenerative implants and lifelong solutions for patients.