Fabrication of mesenchymal stem cells-integrated vascular constructs mimicking multiple properties of the native blood vessels

Abstract

Mesenchymal stem cells (MSCs)-populated small diameter (6 mm) vascular constructs were fabricated. The constructs mimicked the native vessels in multiple levels, i.e. having similar structure and morphology to that of the extracellular matrix in the native blood vessels; recapitulating mechanical properties such as compliance and burst pressure of the native blood vessels; simulating the highly cellularized nature of the native blood vessels; and having an antithrombogenic lumen. The constructs were fabricated by simultaneously assembling poly(ester carbonate urethane) urea nanofibers and MSCs in an electrical field. The nanofibers had a diameter similar to that of the collagen and elastin fibers in the native blood vessels. MSCs were distributed evenly in the constructs. The constructs were highly cellularized when the cell loading density was exceeded 6 million/ml. The vascular constructs were strong and flexible with breaking strains of 144–202%, tensile strengths of 0.80–1.29 MPa, compliances of 13.23–21.96 × 10⁻⁴mmHg⁻¹, stiffness indexes of 7.3–9.8, and burst pressures greater than 1700 mmHg. These mechanical properties were similar to those of the native blood vessels. In vitro platelet deposition experiments showed that platelet adhesion was remarkably decreased in the MSCs-populated constructs compared to that in the construct without MSCs. An increase in MSC density in the constructs further decreased platelet adhesion. When cultured in a spinner flask, MSCs maintained their mitochondria viability and cell number during a two-week culture period, as confirmed by MTT and dsDNA assays. These vascular constructs may hold the potential to regenerate functional small diameter vessels for cardiovascular tissue repair.

Keywords:

• vascular constructs
• nanofibers
• mesenchymal stem cells
• mechanical properties
• platelet adhesion

Acknowledgments

This work was supported by National Science Foundation (DMR1006734) and seed grants of Institute of Materials Research at The Ohio State University.