title: In situ tissue engineering: endothelial growth patterns as a function of flow diverter design.
abstract: BACKGROUND
  Vascular remodeling in response to implantation of a tissue engineering scaffold such as a flow diverter (FD) leads to the cure of intracranial aneurysms. We hypothesize that the vascular response is dependent on FD design, and CD34+ progenitor cells play an important role in the endothelialization of the implant.
  
  
  METHODS
  Sixteen rabbit aneurysms were randomly treated with two different single-layer braided FDs made of cobalt-chrome alloys. The FD-48 and FD-72 devices had 48 and 72 wires, respectively. Aneurysm occlusion rate was assessed during the final digital subtraction angiogram at 10, 20, 30, and 60 days (n=2 per device per time point). Implanted vessels were analyzed with scanning electron microscopy for tissue coverage, endothelialization, and immuno-gold labeling for CD34+ cells.
  
  
  RESULTS
  Complete aneurysm occlusion rates were similar between the devices; however, complete or near complete occlusion was more frequently observed in aneurysms with neck ≤4.2 mm (p=0.008). Total tissue coverage at 10 days over the surface of the FD-48 and FD-72 devices was 56.4±11.6% and 76.6±3.6%, respectively. Endothelial cell growth over the surface was time-dependent for the FD-72 device (Spearman's r=0.86, p=0.013) but not for the FD-48 device (Spearman's r=-0.59, p=0.094). The endothelialization score was marginally correlated with the distance from the aneurysm neck for the FD-48 device (Spearman's r=1, p=0.083) but not for the FD-72 device (Spearman's r=0.8, p=0.33). CD34+ cells were present along the entirety of both devices at all time points.
  
  
  CONCLUSIONS
  This study gives preliminary evidence that temporal and spatial endothelialization is dependent on FD design. Circulating CD34+ progenitor cells contribute to endothelialization throughout the healing process.
authors.affiliation: Department of Radiology, New England Center for Stroke Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Miklos
authors.initials: M
authors.lastname: Marosfoi
authors.affiliation: Department of Radiology, New England Center for Stroke Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Erin T
authors.initials: ET
authors.lastname: Langan
authors.affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Lara
authors.initials: L
authors.lastname: Strittmatter
authors.affiliation: Department of Radiology, New England Center for Stroke Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Kajo
authors.identifier: http://orcid.org/0000-0003-1099-9498
authors.initials: K
authors.lastname: van der Marel
authors.affiliation: Department of Radiology, New England Center for Stroke Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Vedantham
authors.affiliation: Preclinical Science and Research and Development, Stryker Neurovascular, Fremont, California, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Arends
authors.affiliation: Clínica La Sagrada Familia, Buenos Aires, Argentina.
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Lylyk
authors.affiliation: Preclinical Science and Research and Development, Stryker Neurovascular, Fremont, California, USA.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Loganathan
authors.affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Hendricks
authors.affiliation: Department of Neurointervention, National Institute of Neurosciences, Budapest, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Szikora
authors.affiliation: Department of Radiology, New England Center for Stroke Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Ajit S
authors.initials: AS
authors.lastname: Puri
authors.affiliation: Department of Radiology, New England Center for Stroke Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Wakhloo
authors.affiliation: Department of Radiology, New England Center for Stroke Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gounis
mesh_terms: D000497:Alloys; D000818:Animals; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging* / Q000254:growth & development* / Q000601:surgery; D005260:Female; D002532:Intracranial Aneurysm / Q000000981:diagnostic imaging / Q000601:surgery; D019736:Prostheses and Implants; D011474:Prosthesis Design / Q000379:methods*; D011817:Rabbits; D011897:Random Allocation; D015607:Stents; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D066253:Vascular Remodeling / Q000502:physiology
chemical_list: D000497:Alloys
keywords: Aneurysm; Flow Diverter