A Robustly Supported Extracellular Matrix Improves the Intravascular Delivery Efficacy of Endothelial Progenitor Cells

Abstract

A major barrier in the multi-purpose use of implantable materials is an incomplete integration with surrounding tissues, causing foreign body reactions, such as fibrous encapsulation and chronic inflammation. From its viewpoint, a universal method is suggested for cloaking any kind of substrate in specific cell-made extracellular matrices (ECMs) via robust linkages for delivery of therapeutic cells. In addition, the feasibility of ECM-coated substrates as endothelial progenitor cells (EPCs)-laden coronary stent platform for endovascular implantation is investigated. Characteristics and stability of cell-secreted ECMs anchored on a substrate are evaluated, and structural and componential features are revealed similar to those of native ECMs, with enough strength to enable practical uses. The in vitro experiments demonstrated that the ECM coating effectively supports the adhesion, proliferation, and viability of EPCs and has selectively opposite effects on smooth muscle cells. The in vivo experiments using a porcine coronary model supports that ECM-coated stents enable endothelial regeneration and inhibit neointimal growth, and the cell-laden form is more effective than other stents. These results will allow the preparation of tissue-integrating materials containing cellular microenvironments and safely coat surfaces with cells to enable long-term implantation and the continuous managing of chronic diseases.