Shear-resistant hydrogels to control permeability of porous tubular scaffolds in vascular tissue engineering

摘要

Aiming to perfuse porous tubular scaffolds for vascular tissue engineering (VTE) with controlled flow rate, prevention of leakage through the scaffold lumen is required. A gel coating made of 8% w/v alginate and 6% w/v gelatin functionalized with fibronectin was produced using a custom-made bioreactor-based method. Different volumetric proportions of alginate and gelatin were tested (50/50, 70/30, and 90/10). Gel swelling and stability, and rheological, and uniaxial tensile tests reveal superior resistance to the aggressive biochemical microenvironment, and their ability to withstand physiological deformations (similar to 10%) and wall shear stresses (5-20 dyne/cm(2)). These are prerequisites to maintain the physiologic phenotypes of vascular smooth muscle cells and endothelial cells (ECs), mimicking blood vessels microenvironment. Gels can induce ECs proliferation and colonization, especially in the presence of fibronectin and higher percentages of gelatin. The custom-designed bioreactor enables the development of reproducible and homogeneous tubular gel coating. The permeability tests show the effectiveness of tubular scaffolds coated with 70/30 alginate/gelatin gel to occlude wadding pores, and therefore prevent leakages. The synthesized double-layered tubular scaffolds coated with alginate/gelatin gel and fibronectin represent both promising substrate for ECs and effective leakproof scaffolds, when subjected to pulsatile perfusion, for VTE applications.