Fibronectin Adsorption on Electrospun Synthetic Vascular Grafts Attracts Endothelial Progenitor Cells and Promotes Endothelialization in Dynamic In Vitro Culture.
Ruben DaumDmitri VisserConstanze WildLarysa KutuzovaMaria SchneiderGünter LorenzMartin WeissSvenja HindererUlrich A StockMartina SeifertKatja Schenke-LaylandPublished in: Cells (2020)
Appropriate mechanical properties and fast endothelialization of synthetic grafts are key to ensure long-term functionality of implants. We used a newly developed biostable polyurethane elastomer (TPCU) to engineer electrospun vascular scaffolds with promising mechanical properties (E-modulus: 4.8 ± 0.6 MPa, burst pressure: 3326 ± 78 mmHg), which were biofunctionalized with fibronectin (FN) and decorin (DCN). Neither uncoated nor biofunctionalized TPCU scaffolds induced major adverse immune responses except for minor signs of polymorph nuclear cell activation. The in vivo endothelial progenitor cell homing potential of the biofunctionalized scaffolds was simulated in vitro by attracting endothelial colony-forming cells (ECFCs). Although DCN coating did attract ECFCs in combination with FN (FN + DCN), DCN-coated TPCU scaffolds showed a cell-repellent effect in the absence of FN. In a tissue-engineering approach, the electrospun and biofunctionalized tubular grafts were cultured with primary-isolated vascular endothelial cells in a custom-made bioreactor under dynamic conditions with the aim to engineer an advanced therapy medicinal product. Both FN and FN + DCN functionalization supported the formation of a confluent and functional endothelial layer.
Keyphrases
- tissue engineering
- endothelial cells
- high glucose
- immune response
- single cell
- cell therapy
- vascular endothelial growth factor
- induced apoptosis
- diabetic rats
- inflammatory response
- oxidative stress
- emergency department
- cell proliferation
- type iii
- dendritic cells
- signaling pathway
- endoplasmic reticulum stress
- soft tissue