Poly(ε-caprolactone) Scaffolds Doped with c-Jun N-terminal Kinase Inhibitors Modulate Phagocyte Activation / K. S. Stankevich, I. A. Schepetkin (Shchepyotkin), S. I. Goreninsky (Goreninskii) [et al.]

Уровень набора: ACS Biomaterials Science and EngineeringАльтернативный автор-лицо: Stankevich, K. S., Physicist, Engineer Tomsk Polytechnic University, 1992-, Ksenia Sergeevna;Schepetkin (Shchepyotkin), I. A., doctor-biophysicist, leading researcher of Tomsk Polytechnic University, candidate of medical science, 1962-, Igor Aleksandrovich;Goreninsky (Goreninskii), S. I., chemist, engineer of Tomsk Polytechnic University, 1993-, Semen Igorevich;Lavrinenko, A. K., Anastasiya Konstantinovna;Bolbasov, E. N., physicist, Associate Scientist of Tomsk Polytechnic University, Candidate of Sciences, 1981-, Evgeny Nikolaevich;Kovrizhina, A. R., biotechnology specialist, Research Engineer of Tomsk Polytechnic University, 1995-, Anastasia Ruslanovna;Kirpotina, L. N., Liliya Nikolaevna;Filimonov, V. D., Russian chemist, Professor of the TPU, 1945-, Viktor Dmitrievich;Khlebnikov, A. I., Chemist, Professor of Tomsk Polytechnic University, 1963-, Andrey Ivanovich;Tverdokhlebov, S. I., physicist, Associate Professor of Tomsk Polytechnic University, Candidate of physical and mathematical science, 1961-, Sergei Ivanovich;Quinn, M. T., MarkКоллективный автор (вторичный): Национальный исследовательский Томский политехнический университет, Инженерная школа новых производственных технологий, Научно-образовательный центр Н. М. Кижнера;Национальный исследовательский Томский политехнический университет, Инженерная школа ядерных технологий, Лаборатория плазменных гибридных систем;Национальный исследовательский Томский политехнический университет, Инженерная школа ядерных технологий, Научно-образовательный центр Б. П. ВейнбергаЯзык: английский.Страна: .Резюме или реферат: 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..Аудитория: .Тематика: электронный ресурс | труды учёных ТПУ | poly(e-caprolactone) | electrospinning | c-Jun-N-terminal kinase | JNK inhibitor | neutrophil | immune response | biomaterial Ресурсы он-лайн:Щелкните здесь для доступа в онлайн
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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.

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