Fibrin-Infiltrated Small Intestine Submucosa as a Scaffold for Tissue Engineered Vessels Using Hair-Follicle Derived Smooth Muscle Progenitor Cells

Our laboratory recently demonstrated that fibrin-based tissue engineered vessels (TEVs) can be prepared from bone marrow derived smooth muscle and endothelial cells. These cells demonstrated high proliferation potential and contractile function as well as great ability for matrix remodeling after implantation as interpositional grafts into the jugular veins of an ovine animal model. More recently we obtained contractile smooth muscle progenitor cells from ovine hair follicles (HF-SMPC), thereby identifying another source of stem cells for vascular tissue engineering. In this paper we aimed at improving the strength of TEVs while retaining some of the functional advantages of fibrin. To this end, we constructed a vascular matrix composite comprised of small intestinal submucosa (SIS) infiltrated with fibrin. Scanning electron microscopy showed that adhesion and spreading of HF-SMPCs were enhanced on the surface of fibrin-infiltrated compared to control SIS. In addition, fibrin promoted migration of cells into the matrix and increased proliferation significantly after 2 weeks in culture. At that time, fibrin-SIS was significantly compacted and cells expressed and secreted collagen and elastin. Notably, despite the increased strength of SIS, HF-SMPC were able constrict the matrix in response to vasoactive agonists. Taken together our data showed that fibrin-SIS composite enhanced cellular function and improved the mechanical properties of TEVs, suggesting that this composite of natural biomaterials may be used for arterial implantation of HF-SMPC based TEVs.