Building and testing multi-layered fully biological blood vessel substitutes

DESCRIPTION (provided by applicant): Given the growing need for replacement tissues, organs and grafts tissue engineering has emerged as a viable regenerative/reconstructive technology. Recent spectacular results in the field suggest that it is possible to fabricate functional organ modules under laboratory conditions. The present application introduces a versatile, novel approach to engineer fully biological tissue constructs. Present efforts are focused primarily on building tubular modules. Here we detail our Phase I program with the principal objective to construct suturable, small diameter blood vessel substitutes, a critical domain within vascular medicine. Whereas synthetic materials have been successful for large diameter high flow grafts, these fail in the intermediate and small diameter sizes due to thrombogenicity and compliance mismatch. Limitations of presently used strategies to engineer small diameter conduits resulted in grafts with mechanical properties inferior to those of native blood vessels. To overcome the limitations of the classical approach we have implemented a patent-pending print-based tissue engineering technology. The technology on one hand relies on established principles of biological shape formation (i.e. morphogenesis), such as tissue fusion and cell sorting. On the other hand it utilizes engineering methods to speed up the process and make it reliable, thus rendering it commercially viable. The principal objective will be pursued through two specific aims. The first is to fabricate perfusable conduits and to condition them in bioreactors. The second aim is to measure the biomechanical properties (i.e. suture retention strength, burst pressure and compliance) of the conditioned conduits over time. A milestone will be to achieve physiologically relevant biomechanical properties, necessary for implantation. PUBLIC HEALTH RELEVANCE: The objective of this proposal is to construct fully biological small diameter blood vessel substitutes by a novel and versatile tissue engineering technology, and assess their biomechanical properties and structure. The proposed studies could lead to nearly physiological and implantable blood vessels composed of the patient's own cells (i.e. autologous).