A biological hybrid model for collagen-based tissue engineered vascular constructs

Abstract

Various approaches to tissue engineering a small diameter blood vessel have historically relied upon extended culturing periods and/or synthetic materials to create mechanical properties suitable to withstand the hemodynamic stresses of the vasculature. In this work, we present the concept of a construct-sleeve hybrid (CSH) graft, which uses a biological support to provide temporary reinforcement while cell-mediated remodeling of the construct occurs. Support sleeves were fabricated from Type I collagen gels and crosslinked with glutaraldehyde, ultraviolet, or dehydrothermal treatments. Uniaxial tensile testing of acellular sleeves revealed increased stiffness moduli and tensile stresses with crosslinking treatments. A second collagen layer containing cells was molded about the sleeve to create a CSH. After in vitro culture, CHSs with uncrosslinked (UnXL) and glutaraldehyde treated (Glut) sleeves exhibited significant increases in mechanical strength (20.4-fold and 121-fold increases in ultimate stress, respectively) compared to unreinforced control constructs. Burst testing produced similar findings with peak pressures of 100 and 650 mmHg in the UnXL and Glut CSHs, respectively. Construct compaction, cell viability, and histological examination demonstrated that the function of most cells remained unimpaired with the incorporation of the biological support sleeve.