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Original research
In situ tissue engineering: endothelial growth patterns as a function of flow diverter design
  1. Miklos Marosfoi1,
  2. Erin T Langan1,
  3. Lara Strittmatter2,
  4. Kajo van der Marel1,
  5. Srinivasan Vedantham1,
  6. Jennifer Arends3,
  7. Ivan R Lylyk4,
  8. Siddharth Loganathan3,
  9. Gregory M Hendricks2,
  10. Istvan Szikora5,
  11. Ajit S Puri1,
  12. Ajay K Wakhloo1,
  13. Matthew J Gounis1
  1. 1Department of Radiology, New England Center for Stroke Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  2. 2Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  3. 3Preclinical Science and Research and Development, Stryker Neurovascular, Fremont, California, USA
  4. 4Clínica La Sagrada Familia, Buenos Aires, Argentina
  5. 5Department of Neurointervention, National Institute of Neurosciences, Budapest, Hungary
  1. Correspondence to Dr Matthew J Gounis, Department of Radiology, New England Center for Stroke Research, University of Massachusetts Medical School, 55 Lake Ave N, SA-107R, Worcester, MA 01655, USA; matt.gounis{at}umassmed.edu

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.

  • Aneurysm
  • Flow Diverter

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Footnotes

  • Contributors Study design: MJG, ASP, AKW, GMH, JA and MM. Data acquisition: MM, ETL, LS, KvdM and IRL. Literature research: MM, MJG and AKW. Data analysis and interpretation: MM, AKW, MJG, ASP and SV. Manuscript preparation: MM and MJG. Revision of manuscript for important intellectual content: LS, SV, JA, SL, GMH, ASP, IS, AKW and MJG. Approval of final version of manuscript: all authors.

  • Funding This work was supported by Stryker Neurovascular.

  • Competing interests MJG has been a consultant on a fee-per-hour basis for Codman Neurovascular and Stryker Neurovascular; holds stock in InNeuroCo; and has received research support from the National Institutes of Health (NIH), Codman Neurovascular, Stryker Neurovascular, Microvention, Medtronic Neurovascular, Philips Healthcare, InNeuroCo, Neuronal Protection Systems, the Wyss Institute and Silk Road. ASP has received research grants from Medtronic Neurovascular and Stryker Neurovascular. AKW: Consultant for Codman Neurovascular and Stryker Neurovascular; research grant: NIH, Philips Healthcare, Wyss Institute; speaker: Harvard Postgraduate Course, Miami Cardiovascular Institute; co-founder of InNeuroCo and major stockholder; stocks in EpiEB and Pulsar Medical. IS: Consultant for Stryker Neurovascular and ev3/ Covidien, Chestnut Medical. JA and SL are employed by Stryker Neurovascular.

  • Ethics approval Ethics approval was obtained from the university's Institutional Animal Care and Use Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement For access to the raw images obtained in this study, please contact the corresponding author.

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