Advanced Biomaterials and Devices in Medicine
December 2014, Volume 1, Issue 1, pp 28-37

Fibrin-based hydrogel scaffolds for controlling cell-matrix interaction in vascular tissue engineering

I. Mironi-Harpaz, S. Zigerson, D. Seliktar*

Faculty of Biomedical Engineering, Technion–Israel Institute of Technology, Haifa 32000 Israel

* Corresponding author: Prof. Dror Seliktar, e-mail: dror@bm.technion.ac.il

Abstract
Hydrogel biomaterials are used as scaffolds in vascular tissue engineering with the purpose of creating tissue mimics as replacement blood vessels. A tissue engineered vascular construct must be capable of supporting the growth and proliferation of different cell types, including endothelial cells, vascular smooth muscle cells and fibroblasts. The purpose of this investigation was to explore the use of a biocomposite hydrogel biomaterial for vascular tissue engineering, made from a network of fibrillar fibrin and amorphous semisynthetic polyethylene glycol (PEG) – fibrinogen. Both phases of the biocomposite provide distinct biophysical interactions between the material and the cultivated vascular cells. Several properties of the tissue engineered vascular constructs were controlled, including the scaffold composition (fibrin versus PEG-fibrinogen), matrix mechanical properties (shear storage modulus), and cell composition. The constructs were grown for up to 7 days in vitro, and examined by fluorescence microscopy for cell viability and cell morphogenesis. The endothelial cells survived poorly in the absence of smooth muscle cells or fibroblasts on the PEG-fibrinogen hydrogels. The fibrillar fibrin constituent promoted better survival and spreading of the endothelial cells on top of the scaffold, even in the absence of smooth muscle cells or fibroblasts. The greatest impact on endothelial cell viability and spreading was observed with the highest fibrin concentrations. The mechanical properties of the composite, as well as different crosslinking protocols had a minor influence on the morphology and longevity of the endothelial cells. However, the addition of PEG-fibrinogen to the fibrin decreased the matrix degradation rate, supporting endothelial cell morphogenesis for longer durations. In conclusion we have demonstrated that a biocomposite fibrin-based material, containing both fibrillar and amorphous phases, may be optimized to enhance endothelial cell survival in vascular tissue engineering.

Keywords: fibrinogen, endothelial cells, hydrogels, biomaterials, vascular grafts, angiogenesis, tissue engineering