In Vitro and Pilot In Vivo Evaluation of a Bioactive Coating for Stent Grafts Based on Chondroitin Sulfate and Epidermal Growth Factor

Abstract

2 AbstractPurpose: To evaluate the potential of a bioactive coating based on chondroitin sulfate (CS) and tethered epidermal growth factor (EGF) for the improvement of healing around stent-grafts (SG). Methods:The impact of the bioactive coating on cell survival was tested in vitro on human vascular cells using polyethylene terephtalate films (PET) as a substrate. After being transferred onto a more "realistic" material (expanded poly(tetrafluoroethylene), ePTFE), the durability and mechanical behavior of the coating in addition to cell survival were studied. Preliminary in vivo testing was performed in a canine iliac aneurysm model reproducing type I endoleaks (3 animals with 1 control and 1 bioactive SG for each). Results:The CS and EGF coatings significantly increased survival of human smooth muscle cells and fibroblasts, compared with bare PET or ePTFE (P<.05). The coating also displayed good durability over 30 days according to ELISA and cell-survival tests.The coating did not affect the mechanical properties of ePTFE and was successfully transferred onto commercial SG for in vivo testing. According to CT-scan and macroscopic examinations, no difference was observed in endoleak persistence at three months, but the bioactive coating deposited on the abluminal surface of the SG (exposed to the vessel wall) increased the percentage of healed tissue in the aneurysm. Moreover, no adverse effect such as neointima formation or thrombosis was observed. Conclusion:The bioactive coating promoted in vitro cell survival, displayed good durability and was successfully transferred onto a commercial SG. Preliminary in vivo results suggest improved healing around bioactive SG.3

Negative In Vivo Results Despite Promising In Vitro Data With a Coated Compliant Electrospun Polyurethane Vascular Graft

“…An average sulfur concentration of 1.3 ± 0.2 % was measured at the surface of coated electrospun grafts though XPS technique, while no sulfur was found on bare grafts. This was consistent to previous results on electrospun PET [24,34] and confirmed the presence of CS at the intraluminal surface of eVG-CS. Tensile testing of circumferential samples of eVG and eVG-CS demonstrated their quite linear elastic behavior until rupture (Figure 3), with a similar Young's modulus (4.6 ± 0.9 MPa and 4.7 ± 1.0 MPa for bare and coated materials, respectively).…”

Combining Electrospun Fiber Mats and Bioactive Coatings for Vascular Graft Prostheses

“…In addition, the oriented immobilization of EGF enabled strong increase in VSMC survival in serum-free media, mimicking the lack of nutrients on the abluminal side of the graft. Immobilization of biomolecules has demonstrated great promise by their resulting durability and stability, which in turn lead to enhanced and continuous cell response. , …”

“…Immobilization of biomolecules has demonstrated great promise by their resulting durability and stability, which in turn lead to enhanced and continuous cell response. 43,44 An additional advantage of these coatings is their versatility, since they can be created on any electrospun material thanks to the plasma polymerization process, in contrast to chemical modifications that require optimization as a function of substrate chemistry. In this project, electrospun PET was used for practical and regulatory reasons.…”

Promotion of Endothelial Cell Adhesion and Antithrombogenicity of Polytetrafluoroethylene by Chemical Grafting of Chondroitin Sulfate

“…On PTFE-CS membrane, the platelets were not activated suggesting that the anticoagulant was functioning which enhanced the thrombus prevention. Moreover, the endothelial cells showed a promoted proliferation might also indicate that the endothelialization on PTFE-CS membrane was facilitated. , Overall, PTFE-CS was proved to possess high biocompatibility and excellent anticoagulant properties and, thus, represents an ideal candidate for the fabrication of SDVGs.…”