Point-of-care seeding of nitinol stents with blood-derived endothelial cells.
Nitinol-based vascular devices, for example, peripheral and intracranial stents, are limited by thrombosis and restenosis. To ameliorate these complications, we developed a technology to promote vessel healing by rapidly seeding (QuickSeeding) autologous blood-derived endothelial cells (ECs) onto modified self-expanding nitinol stent delivery systems immediately before implantation. Several thousand micropores were laser-drilled into a delivery system sheath surrounding a commercial nitinol stent to allow for exit of an infused cell suspension. As suspension medium flowed outward through the micropores, ECs flowed through the delivery system attaching to the stent surface. The QuickSeeded ECs adhered to and spread on the stent surface following 24-h in vitro culture under static or flow conditions. Further, QuickSeeded ECs on stents that were deployed into porcine carotid arteries spread to endothelialize stent struts within 48 h (n = 4). The QuickSeeded stent struts produced significantly more nitric oxide in ex vivo flow circuits after 24 h, as compared to static conditions (n = 5). In conclusion, ECs QuickSeeded onto commercial nitinol stents within minutes of implantation spread to form a functional layer in vitro and in vivo, providing proof of concept that the novel QuickSeeding method with modified delivery systems can be used to seed functional autologous endothelium at the point of care. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1658-1665, 2016.
Department of Biomedical Engineering, Duke University, Durham, North Carolina.
Alexandra E
AE
Jantzen
Department of Surgery, Duke University Medical Center, Durham, North Carolina.|Duke-National University of Singapore Graduate Medical School Singapore Cardiovascular & Metabolic Disorders Program, Singapore.
Maria
M
Noviani
Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
James S
JS
Mills
Department of Biology, Duke University, Durham, North Carolina.
Katherine M
KM
Baker
Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Fu-Hsiung
FH
Lin
Department of Biomedical Engineering, Duke University, Durham, North Carolina.
George A
GA
Truskey
Department of Surgery, Duke University Medical Center, Durham, North Carolina. hachneck@gmail.com.|Duke-National University of Singapore Graduate Medical School Singapore Cardiovascular & Metabolic Disorders Program, Singapore. hachneck@gmail.com.|Department of Pathology, Duke University Medical Center, Durham, North Carolina. hachneck@gmail.com.|Hemostemix Inc., Ness Ziona, Israel, Calgary, Alberta, Canada. hachneck@gmail.com.
Hardean E
HE
Achneck
D000497:Alloys / Q000494:pharmacology*; D000818:Animals; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D019095:Point-of-Care Systems; D015607:Stents; D013552:Swine
D000497:Alloys; C013616:nitinol
endothelial cells; endothelialization; stem/progenitor cells; stents; thrombogenicity