Fibronectin Adsorption on Electrospun Synthetic Vascular Grafts Attracts Endothelial Progenitor Cells and Promotes Endothelialization in Dynamic In Vitro Culture

Abstract

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.

Comparative Evaluation on Impacts of Fibronectin, Heparin–Chitosan, and Albumin Coating of Bacterial Nanocellulose Small-Diameter Vascular Grafts on Endothelialization In Vitro

“…They found increased endothelialization for the modified BNC constructs in comparison to uncoated constructs and concluded that the RGD modification was the key factor for the improved cell adherence. We observed similar behaviors of EPCs on our fibronectin-coated grafts, which is also in line with the literature, as it is known that fibronectin coating of vascular grafts induces the homing of CD34+ endothelial progenitor cells [ 87 ] and promotes VEGF-induced CD34 + cell differentiation into ECs [ 88 ]. Consistent with that, our EPCs were characterized as CD34 + by FACS.…”

Engineering bioactive synthetic polymers for biomedical applications: a review with emphasis on tissue engineering and controlled release

“…Adsorbing FN onto or absorbing it into cell scaffolds is a strategy extensively used to promote cell attachment. [39][40][41][42] Recent reports show that recombinant engineered FN fragments can be even more efficient than full-length FN at promoting cell attachment and growth. 43,44 Licht et al 38 engineered an injectable PEG-based hydrogel functionalized with a recombinant FN fragment (FNIII9*-10/12-14) that contained cell adhesive motifs and a growth factor domain for nerve tissue regeneration.…”

Surface Engineering of Cardiovascular Devices for Improved Hemocompatibility and Rapid Endothelialization

“…Adhesive Proteins: To inhibit blood coagulation and strengthen cell affinity for ECs/EPCs, cell-adhesive proteins have been incorporated into the vascular biomaterials. Among these proteins, collagen, [182] gelatin, [183] fibronectin, [184] and keratin [185] can effectively improve endothelialization and vascular remodeling of the polymeric vascular grafts. However, proteins usually exhibit low stabilities and possess complex structure relative to peptides, which may limit their biomedical application.…”