New 3D printed mechanical and microfluid dynamic medical devices for injection into cardiac muscle tissue and ultrasound imaging.

Heart failure is still one of the most common and costly hospitalizations in the United States. The goal is to enable patients, who survive a myocardial infarction, to live longer by limiting the effects of damaged myocardium. Scientific and clinical attention has focused on regenerative medicine, which uses stem cell therapies and cardiac ablation to correct heart rhythm disorders. This has fueled research on new advanced intramyocardial delivery devices. They are useful for the direct administration into the myocardium, via injection in open-chest procedures, of various drug compounds, an action that requires certain methods of mixing, administration, precision, timing, and monitoring. Implementation difficulties, however, remain a crucial challenge for further development, especially in therapies that require mixing of the two fluids close to myocardial tissue. The aim of this study is to enable the injection and creation of a calcium alginate gel in the heart muscle tissue, both in open-chest procedures and via left ventricular catheterism. The chemical species used and mixed , shortly before injection to obtain the gel, are sodium alginate and calcium chloride, creating a containment system, the gel, for goldnanoshells. This gel is located in the tissue and is not affected by cardiac washout, to focus the cardiac ablation and at the same time create a versatile and effective delivery system for future cardiac therapies. In the first part of the study, a commercial adapter for syringes was optimized to allow the mixing of two liquids contained in two syringes. Taking advantage of the fluid dynamic properties and various pathways shapes/sections I tried to introduce Dean flow into the initial laminar flow of the device. In this way, I maximize the yield of the calcium alginate gel polymerization inside injection needles of different diameters. Thanks to the excellent results achieved, I have designed a multiple syringe injection mechanical system to further increase the amount of gel injected because the consistency of injection being crucial. This has led to the development of a more compact, manageable, and versatile syringe pump system than the current laboratory pumps, equipping my device with Bluetooth BLE connectivity for controlling and modifying parameters from smartphone. The next project involved the creation of a double- and triple-lumen catheter for injecting sodium alginate and calcium chloride into the left ventricular cardiac muscle through the carotid artery. The device uses a 22G needle printed in 3D that was visible in CT and fluoroscopy. It was tested on porcine models in vivo studies and the injections were performed both manually and through an automated system designed by the team. Lastly, I also designed an ultrasound probe adapter device that leveraged the effect of negative pressure to anchor the transducer to the myocardial surface during signal acquisition. The entire model was designed in 3D, printed with biocompatible flexible and non-flexible resins, and tested in vivo on a porcine model. In conclusion, all devices achieved excellent results, ensuring new, safe and effective methods of delivering multiple solutions simultaneously.