Matrigel as a Basement Membrane: A Feasibility Study

Abstract

Peripheral arterial disease (PAD), a circulatory problem in which narrowed arteries reduce blood flow to the limbs, affects approximately 8 million people in the United States alone. This is a chronic disease that is negatively impacted by damage due to unavoidable treatment, such as balloon angioplasty and atherectomy. The use of drugs combined with these treatments is becoming the gold standard of clinical treatment as they lengthen time between restenosis, or the repeated accumulation of buildup (Fig. 1). To date, very few studies have been performed to create an in vitro model that can be used to assess the effects of damaging treatments on drug delivery and retention following clinical standard of care. Therefore, we propose to take steps in the development and advancement of a benchtop 3-D structure in which cells can be grown to mimic an occluded artery (Fig 1.). This model can then be used to allow for the visualization and quantification of drug adhesion and transport and provide a platform to quantify biological changes. This will allow for the best conditions for optimizing drug delivery to be determined. The goal of this study is to establish a protocol that can be used to prevent the degradation of Matrigel, a basement membrane matrix, by crosslinking it with glutaraldehyde in order to grow smooth muscle cells (SMCs) into a 3-D structure, which can then be built upon with the addition of macrophages, collagen, fibrin, and calcification to form an in vitro model of an occluded artery. The preliminary results indicate the crosslinking of glutaraldehyde with the Matrigel is effective in prolonging the lifespan of Matrigel, with an increased amount of glutaraldehyde resulting in a slower rate of degradation.