Immobilization of Heparin on Bacterial Nanocellulose Hydrogels Induces Tubulogenesis of Human Endothelial Cells

Abstract

Models that mimic the angiogenesis initial processes, as adhesion, migration, proliferation and tubulogenesis, are extremely valuable for investigating the action of new anti-cancer drugs. There still is a need for an angiogenesis model that reflects in vivo environment. To address this challenge, we developed a 3D matrix well-defined based on covalently immobilization of heparin (HEP) on bacterial nanocellulose (BNC) hydrogels. Successful immobilization was confirmed by qualitative and quantification analysis. Human umbilical vein endothelial cells (HUVECs) were seeded on bottom and top surfaces of BNC and BNC-HEP hydrogels and cells behavior were analyzed. The bottom surfaces of BNC-HEP hydrogels were able to support cell adhesion and promote proliferation and tubulogenesis formation. Results here presented indicate that the tubulogenesis process could be controlled by physico-chemical properties of the developed hydrogel. The interaction between the bioactive molecule, heparin, and the particular microstructure of BNC induced tubulogenenic behavior of HUVECs in vitro.