title: Point-of-Care Rapid-Seeding Ventricular Assist Device with Blood-Derived Endothelial Cells to Create a Living Antithrombotic Coating.
abstract: The most promising alternatives to heart transplantation are left ventricular assist devices and artificial hearts; however, their use has been limited by thrombotic complications. To reduce these, sintered titanium (Ti) surfaces were developed, but thrombosis still occurs in approximately 7.5% of patients. We have invented a rapid-seeding technology to minimize the risk of thrombosis by rapid endothelialization of sintered Ti with human cord blood-derived endothelial cells (hCB-ECs). Human cord blood-derived endothelial cells were seeded within minutes onto sintered Ti and exposed to thrombosis-prone low fluid flow shear stresses. The hCB-ECs adhered and formed a confluent endothelial monolayer on sintered Ti. The exposure of sintered Ti to 4.4 dynes/cm for 20 hr immediately after rapid seeding resulted in approximately 70% cell adherence. The cell adherence was not significantly increased by additional ex vivo static culture of rapid-seeded sintered Ti before flow exposure. In addition, adherent hCB-ECs remained functional on sintered Ti, as indicated by flow-induced increase in nitric oxide secretion and reduction in platelet adhesion. After 15 day ex vivo static culture, the adherent hCB-ECs remained metabolically active, expressed endothelial cell functional marker thrombomodulin, and reduced platelet adhesion. In conclusion, our results demonstrate the feasibility of rapid-seeding sintered Ti with blood-derived hCB-ECs to generate a living antithrombotic surface.
authors.affiliation: From the *Department of Surgery, Duke University Medical Center, Durham, North Carolina; †Cardiovascular & Metabolic Disorders Program, Duke - National University of Singapore Graduate Medical School, Singapore; ‡Department of Biomedical Engineering, Duke University, Durham, North Carolina; §Department of Pathology, Duke University Medical Center, Durham, North Carolina; ¶Hemostemix Inc., Toronto, Ontario, Canada; and ‖Hemostemix Inc., Ness Ziona, Israel.
authors.forename: Maria
authors.initials: M
authors.lastname: Noviani
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Jamiolkowski
authors.forename: Justin E
authors.initials: JE
authors.lastname: Grenet
authors.forename: Qiuyu
authors.initials: Q
authors.lastname: Lin
authors.forename: Tim A
authors.initials: TA
authors.lastname: Carlon
authors.forename: Le
authors.initials: L
authors.lastname: Qi
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Jantzen
authors.forename: Carmelo A
authors.initials: CA
authors.lastname: Milano
authors.forename: George A
authors.initials: GA
authors.lastname: Truskey
authors.forename: Hardean E
authors.initials: HE
authors.lastname: Achneck
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D005312:Fetal Blood / Q000166:cytology; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006801:Humans; D010973:Platelet Adhesiveness; D019095:Point-of-Care Systems; D013927:Thrombosis / Q000517:prevention & control*; D014025:Titanium
chemical_list: D014025:Titanium
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