Electrospun Template Architecture and Composition Regulate Neutrophil NETosis in Vitro and in Vivo

Allison E. Fetz, Indira Neeli, Isaac A. Rodriguez, Marko Radic, Gary L. Bowlin

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Mounting evidence indicates that neutrophils, first responders to an implanted biomaterial, prime the microenvironment for recruited immune cells by secreting factors and releasing neutrophil extracellular traps (NETs) through NETosis. In this study, we investigated the role of electrospun template architecture and composition in regulating NETosis. Electrospun polydioxanone (PDO), collagen type I (COL), and blended PDO-COL templates (PC) were fabricated with small-diameter (0.25-0.35 μm) and large-diameter (1.0-2.00 μm) fibers. Neutrophil-template interactions were evaluated in vitro for 3 and 24 h with human neutrophils, and the PDO templates were studied in vivo (rat subcutaneous model) for 1 and 7 days. Template-bound NETs were quantified by fluorescent microscopy and an On-cell Western assay. The in vitro results indicate that larger fiber diameters reduced NETosis on PDO templates, whereas the incorporation of COL attenuated NETosis independent of fiber diameter. The in vivo results similarly revealed a lower degree of NETs on large-diameter PDO templates at 1 day, resulting in marginal tissue integration of the templates at 7 days. In contrast, the small-diameter PDO templates, which were coated in a large amount of NETs at 24 h in vivo, were surrounded by capsule-like tissue at 7 days. These preliminary in vivo results validate the in vitro model and signify NETosis as a potentially significant physiological response and a critical preconditioning event for the innate immune response to templates. In conclusion, these results demonstrate the importance of characterizing the neutrophil's acute confrontation with biomaterials to engineer templates capable of promoting in situ regeneration.

Original languageEnglish (US)
Pages (from-to)1054-1063
Number of pages10
JournalTissue Engineering - Part A
Volume23
Issue number19-20
DOIs
StatePublished - Oct 1 2017

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Polydioxanone
Neutrophils
Biomaterials
Fibers
Chemical analysis
Tissue
Biocompatible Materials
Mountings
Collagen
Rats
Assays
Microscopic examination
Engineers
Collagen Type I
Innate Immunity
Capsules
In Vitro Techniques
Regeneration
Microscopy
Extracellular Traps

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Cite this

Electrospun Template Architecture and Composition Regulate Neutrophil NETosis in Vitro and in Vivo. / Fetz, Allison E.; Neeli, Indira; Rodriguez, Isaac A.; Radic, Marko; Bowlin, Gary L.

In: Tissue Engineering - Part A, Vol. 23, No. 19-20, 01.10.2017, p. 1054-1063.

Research output: Contribution to journalArticle

Fetz, Allison E. ; Neeli, Indira ; Rodriguez, Isaac A. ; Radic, Marko ; Bowlin, Gary L. / Electrospun Template Architecture and Composition Regulate Neutrophil NETosis in Vitro and in Vivo. In: Tissue Engineering - Part A. 2017 ; Vol. 23, No. 19-20. pp. 1054-1063.
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