Poly(ϵ-caprolactone) Scaffolds Doped with c-Jun N-terminal Kinase Inhibitors Modulate Phagocyte Activation

Ksenia S. Stankevich, Igor A. Schepetkin, Semen I. Goreninskii, Anastasia K. Lavrinenko, Evgeniy N. Bolbasov, Anastasia R. Kovrizhina, Liliya N. Kirpotina, Victor D. Filimonov, Andrei I. Khlebnikov, Sergei I. Tverdokhlebov, Mark T. Quinn

Research output: Contribution to journalArticle

Abstract

The modulation of phagocyte responses is essential for successful performance of biomaterials in order to prevent negative outcomes associated with inflammation. Herein, we developed electrospun poly(ϵ-caprolactone) (PCL) scaffolds doped with the novel potent c-Jun N-terminal kinase (JNK) inhibitors 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) and 11H-indeno[1,2-b]quinoxalin-11-one O-(O-ethylcarboxymethyl) oxime(IQ-1E) as a promising approach for modulating phagocyte activation. Optimized electrospinning parameters allowed us to produce microfiber composite materials with suitable mechanical properties. We found that embedded compounds were bound to the polymer matrix via hydrophobic interactions and released in two steps, with release mostly controlled by Fickian diffusion. The fabricated scaffolds doped with active compounds IQ-1 and IQ-1E effectively inhibited phagocyte inflammatory responses. For example, they suppressed human neutrophil activation by the biomaterials, as indicated by decreased neutrophil reactive oxygen species (ROS) production and Ca2+ mobilization. In addition, they inhibited lipopolysaccharide (LPS)-induced NF-κB/AP-1 reporter activity in THP-1Blue cells and interleukin (IL)-6 production in MonoMac-6 cells without affecting cell viability. These effects were attributed to the released compounds rather than cell-surface interactions. Therefore, our study demonstrates that doping tissue engineering scaffolds with novel JNK inhibitors represents a powerful tool for preventing adverse immune responses to biomaterials as well as serves as a platform for drug delivery.

Original languageEnglish
Pages (from-to)5990-5999
Number of pages10
JournalACS Biomaterials Science and Engineering
Volume5
Issue number11
DOIs
Publication statusPublished - 11 Nov 2019

Fingerprint

JNK Mitogen-Activated Protein Kinases
Biocompatible Materials
Biomaterials
Scaffolds
Chemical activation
Tissue Scaffolds
Quinoxalines
Oximes
Transcription Factor AP-1
Electrospinning
Scaffolds (biology)
Polymer matrix
Drug delivery
Tissue engineering
Lipopolysaccharides
Interleukin-6
Reactive Oxygen Species
Phosphotransferases
Cells
Doping (additives)

Keywords

  • biomaterial
  • c-Jun-N-terminal kinase
  • electrospinning
  • immune response
  • JNK inhibitor
  • neutrophil
  • poly(ϵ-caprolactone)

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

Cite this

Poly(ϵ-caprolactone) Scaffolds Doped with c-Jun N-terminal Kinase Inhibitors Modulate Phagocyte Activation. / Stankevich, Ksenia S.; Schepetkin, Igor A.; Goreninskii, Semen I.; Lavrinenko, Anastasia K.; Bolbasov, Evgeniy N.; Kovrizhina, Anastasia R.; Kirpotina, Liliya N.; Filimonov, Victor D.; Khlebnikov, Andrei I.; Tverdokhlebov, Sergei I.; Quinn, Mark T.

In: ACS Biomaterials Science and Engineering, Vol. 5, No. 11, 11.11.2019, p. 5990-5999.

Research output: Contribution to journalArticle

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AU - Stankevich, Ksenia S.

AU - Schepetkin, Igor A.

AU - Goreninskii, Semen I.

AU - Lavrinenko, Anastasia K.

AU - Bolbasov, Evgeniy N.

AU - Kovrizhina, Anastasia R.

AU - Kirpotina, Liliya N.

AU - Filimonov, Victor D.

AU - Khlebnikov, Andrei I.

AU - Tverdokhlebov, Sergei I.

AU - Quinn, Mark T.

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