Diseases of the heart remain the leading cause of death for Americans.¹ At Duke University in Durham, North Carolina, a multidisciplinary team of surgeons, biomedical engineers, medical personnel, and graduate students hopes to change the way heart disease is treated—and perhaps even affect clinical outcomes.
In their research, led by Assistant Professor of Surgery, Hardean Achneck, MD, the team is using blood-derived endothelial progenitor cells (EPCs) to create a biocompatible lining for titanium surfaces. In other words, they are testing the possibility of using a coating of the patient’s own endothelial cells within a titanium stent so that the device becomes fully biocompatible. Because commonly used drug-eluting stents impede the growth of healthy endothelium and can activate coagulation, this lining, if proven successful, would prevent the occurrence of late-stent thrombosis (or blood clots) and occlusion (or blockage) of the stented artery.
“This research has the potential to change the way we practice medicine today,” said Dr. Achneck. “Currently coronary artery disease (decreased blood supply due to blockages in the blood vessels of the heart) is treated with angioplasty and stenting or coronary artery bypass graft surgery (CABG). To perform a CABG, a vein is harvested from the patient’s leg as a conduit to bypass a blocked artery. Yet, the vein itself—or more precisely its inner lining, the endothelium—sustains damage when removed and exposed to the much higher pressures in the arterial system. Supplementing the lining with the patient’s own EPCs might mitigate this damage”.
“Further, when stents are placed in the heart, the blood vessel is dilated with a balloon. This process damages the endothelial lining and results in endothelial dysfunction. Our proposed technology lines the stent with healthy EPCs that would replace damaged endothelial cells. Lastly, we are working to utilize a similar approach to coat the titanium surfaces of implantable pumps and artificial hearts with EPCs to create a more biocompatible surface that prevents clot formation.”
The research, which has been in process for four years, has now successfully completed its first proof of concept stage. The team has implanted solid titanium tubes into pigs in their inferior venae cavae, the large veins carrying de-oxygenated blood into the right atria of the pigs’ hearts. The team discovered that the bare metal tubes became fully occluded after only three days. However, those tubes seeded with an EPC lining remained open and functional, thus allowing blood flow. It is a promising result.
“The next step is using self-expanding nitinol (nickel titanium alloy) stents that are commonly deployed in humans,” said Dr. Achneck. “We hope that our patented QuickSeed technology moves into humans within two to three years. In the interim, we will evaluate the performance of the cells on stent surfaces that are exposed to physiological shear stresses in order to adequately imitate biological conditions in the lab. We can create flow conditions that mimic the shear stresses cells experience in blood vessels using our flow chamber and flow circuit.”
Integral to creating these flow conditions is a Masterflex® tubing pump with L/S® digital drive and L/S® Easy-Load® pump head. The peristaltic pump system drives the cell medium into the flow circuit, enabling researchers to evaluate the EPCs under flow conditions similar to those within the body. “The digital drive makes it easy to program the flow rate,” stated Dr. Achneck. “It has proven to be a very reliable research tool.”
The team uses a system that employs both Masterflex peroxide-cured silicone tubing and Masterflex PharMed® BPT tubing with female and male luer adapters and barbed polypropylene fittings. Additional instruments used in the research include polypropylene pulse dampeners to create a laminar flow and Masterflex programmable syringe pumps.
If the research continues on its current path and proves successful, it has potential impact beyond the treatment of heart disease.
“It may also be applied to peripheral vascular disease, or treating blood vessels outside the heart region,” said Dr. Achneck. For example, arteries in the lower legs can become obstructed by thrombosis or embolism, potentially resulting in an amputation. “The same principles of tricking the blood into thinking it is in a blood vessel instead of an artificial device can be used to repair major arteries throughout the body.”
¹National Institutes of Health. Retrieved from http://www.nih.gov/about/discovery/chronicdiseases/cardio.htmDisclaimer: Masterflex products are not approved or intended for, and should not be used for medical, clinical, surgical or other patient-oriented applications.