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Studies of combined NO-eluting/CD47-modified polyurethane surfaces for synergistic enhancement of biocompatibility.
Zhang, Qi; Stachelek, Stanley J; Inamdar, Vaishali V; Alferiev, Ivan; Nagaswami, Chandrasekaran; Weisel, John W; Hwang, Jeong Hyun; Meyerhoff, Mark E.
Affiliation
  • Zhang Q; Department of Chemistry, The University of Michigan, Ann Arbor, MI 48109-1055, United States.
  • Stachelek SJ; Division of Cardiology-Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, United States; Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, 19104, United States.
  • Inamdar VV; Division of Cardiology-Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, United States; Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, 19104, United States.
  • Alferiev I; Division of Cardiology-Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, United States; Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, 19104, United States.
  • Nagaswami C; Department of Cell and Developmental Biology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, 19104, United States.
  • Weisel JW; Department of Cell and Developmental Biology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, 19104, United States.
  • Hwang JH; Department of Chemistry, The University of Michigan, Ann Arbor, MI 48109-1055, United States.
  • Meyerhoff ME; Department of Chemistry, The University of Michigan, Ann Arbor, MI 48109-1055, United States.
Colloids Surf B Biointerfaces ; 192: 111060, 2020 Apr 18.
Article in En | MEDLINE | ID: mdl-32450498
The blood compatibility of various intravascular (IV) devices (e.g., catheters, sensors, etc.) is compromised by activation of platelets that can cause thrombus formation and device failure. Such devices also carry a high risk of microbial infection. Recently, nitric oxide (NO) releasing polymers/devices have been proposed to reduce these clinical problems. CD47, a ubiquitously expressed transmembrane protein with proven anti-inflammation/anti-platelet properties when immobilized on polymeric surfaces, is a good candidate to complement NO release in both effectiveness and longevity. In this work, we successfully appended CD47 peptides (pepCD47) to the surface of biomedical grade polyurethane (PU) copolymers. SIRPα binding and THP-1 cell attachment experiments strongly suggested that the pepCD47 retains its biological properties when bound to PU films. In spite of the potentially high reactivity of NO toward various amino acid residues in CD47, the efficacy of surface-immobilized pepCD47 to prevent inflammatory cell attachment was not inhibited after being subjected to a high flux of NO for three days, demonstrating excellent compatibility of the two species. We further constructed a CD47 surface immobilized silicone tubing filled with NO releasing S-nitrosoglutathione/ascorbic acid (GSNO/AA) solution for synergistic biocompatibility evaluation. Via an ex vivo Chandler loop model, we demonstrate for the first time that NO release and CD47 modification could function synergistically at the blood/material interface and produce greatly enhanced anti-inflammatory/anti-platelet effects. This concept should be readily implementable to create a new generation of thromboresistant/antimicrobial implantable devices.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Colloids Surf B Biointerfaces Journal subject: QUIMICA Year: 2020 Document type: Article Affiliation country: United States Country of publication: Netherlands

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Colloids Surf B Biointerfaces Journal subject: QUIMICA Year: 2020 Document type: Article Affiliation country: United States Country of publication: Netherlands