Human Aortic Cells in Research for National Heart Month

Evaluation of Biocompatible Materials for Cardiovascular Microsensors

February is National Heart Month, a time to bring awareness to cardiovascular health and heart disease–the leading cause of death in men and women in North America. It is estimated that 1 in 4 adults succumb to heart disease every year. One of the main risk factors for heart disease is high blood pressure. It can greatly increase the heart’s workload, causing the heart muscle to thicken and become stiffer, resulting in heart dysfunction. Steps to actively monitor blood pressure can provide valuable prognostic information about cardiovascular disease.

Technological advances in biocompatible polymers have garnered interest for developing novel medical devices, opening up new opportunities for implantable medical devices (IMDs) for diagnostic or therapeutic purposes. One area of focus is the development of implantable intravascular pressure microsensors that can provide real-time and continue blood pressure measurements for cardiovascular applications. Of course, for any implantable device, the safety of the composite materials warrants extensive evaluation. Relevant in vitro cellular models enable researchers to assess cytotoxicity that is predictive of in vivo outcomes. This strategy was used by the authors of our publication highlight to evaluate an investigational blood pressure sensor fabricated from polyimides.

The Lifeline® catalog has a variety of high-quality endothelial and cardiac cells from a variety of tissue sources to help answer a broad scope of research questions, which include the following:

• Cardiac microvascular endothelial cells
• Cardiac fibroblasts
• Pulmonary artery endothelial cells
• Aortic endothelial cells
• Coronary artery endothelial cells
• Lung microvascular endothelial cells
• Dermal microvascular endothelial cells (adult and neonatal)
• Iliac artery endothelial cells
• Umbilical cord endothelial cells (HUVECs; primary and 10-donor pool)

Research Using Lifeline’s Human Aortic Endothelial Cells

A wide range of microfabricated devices for biomedical use are currently being designed with polyimides as a primary structural material for cardiovascular applications, yet the biocompatibility and safety of polyimides with human endothelial cells–the primary cell type likely to be in direct contact with an intravascular IMD- has not been reported in the literature. Therefore, the focus of the studies conducted by Starr and Colleagues was to evaluate the biological safety of a new polyimide-based pressure microsensor by using an in vitro model of human endothelium, following protocols outlined in ISO 10993-5 for testing the in vitro cytotoxicity of medical devices.

Extract Tests

Three commonly used polyimides were evaluated in the extracts testing, including thermosetting 4,40-oxydiphenylene-pyromellitimide (PMDA-ODA), thermosetting biphenyldianhydride/ 1,4 phenylenediamine (BPDA-PPD), and a proprietary thermoplastic adhesive. These extracts were prepared by incubating the polyimides in cell culture media at 37°C for 48 hrs, at a ratio of 1 cm²/mL media.  Human capillary and microvascular endothelial cells (SV-HCEC) were used to evaluate the potential cytotoxicity resulting from any leachables from the polymers. After 24-hrs of exposure, cells were harvested and mitochondrial stress/toxicity and cell viability/apoptosis/necrosis was quantified using flow cytometry.

While the mechanisms for cytotoxicity are variable, the studies performed by the authors address the most common forms of acute cytotoxicity in vitro. The results of these in vitro extract studies showed little to no stress induction or cytotoxicity in the human endothelial cells (SV-HCEC), where neither the early marker of mitochondrial stress nor the markers of viability were significantly affected.

Direct Contact Test

Direct contact testing was conducted using an in vitro model of human endothelium, established by culturing Lifeline’s primary human aortic endothelial cells in 6-well tissue-culture plates. The polyimide sensors were placed in the center of each well. After 24-hrs exposure, cell response was quantified by microscopy with a fluorescent live-dead stain. There was no significant difference between the untreated endothelial cells and those exposed to either the HDPE negative control or the polyimide device. Conversely, cells exposed to the latex positive control showed significant cell death and loss of viability. Together, these results suggest that the assembled polyimide-based sensor is not cytotoxic to endothelial cells.

The results from this study, the first to evaluate the direct cytotoxic effects of polyimides on endothelial cells demonstrate their nontoxicity and biocompatibility. The authors concluded that the experimental polyimide sensor is suitable for safe, short-term use in the intravascular environment. However, they recognize the limitations of their studies for long-term usage, where chronic cellular toxicity will need further evaluation.