Changes in gene expression profile of normal human fibroblasts on P (VDF-TrFE) scaffolds highly doped with Fe3O4-CA nanoparticles under alternating magnetic field stimulation

resumo

The design of novel hybrid magnetoactive scaffolds based on biocompatible piezopolymers and magnetic nanoparticles is of interest for medicine, mainly for tissue regeneration, because application of an external either static or alternating magnetic field to cells that settled on a magnetoactive scaffold offers an opportunity for remote control of cellular functions. This study describes fabrication of electrospun magnetoactive poly(vinylidene fluoride-co-trifluoroethylene) [P(VDF-TrFE)] scaffolds highly doped with 20 wt% of magnetite nanoparticles modified with citric acid (Fe3O4-CA). The electrospun P(VDF-TrFE)/Fe3O4-CA scaffolds have defect-free morphology with a fiber diameter of approximately 1 mu m and contain both an electroactive beta-phase (predominantly) and a lesser amount of an gamma-phase. A high content of uniformly distributed Fe3O4-CA nanoparticles within P(VDF-TrFE) fibrous scaffolds resulted in a high saturation magnetization of 12.1 emu/g and ferrimagnetic behavior of the composite P(VDF-TrFE)/Fe3O4-CA scaffolds. They were proved to be biocompatible with normal human cells: normal human fibroblasts and human mesenchymal stem cells adhered to the scaffold and retained their viability. According to high-throughput RNA-sequencing data, the adhesion of fibroblasts to the scaffolds upregulated genes related to key stages of tissue regeneration such as coagulation (genes THBD and SERPINB2) and wound healing (IL24, PDGFB, F3, and PLAU) and affected TGF beta, BMP, and Wnt signaling pathways. Alternating-magnetic-field exposure of the magnetoactive P(VDF-TrFE)/Fe3O4-CA scaffolds with fibroblasts settled on the surface activated extracellular and intracellular cell signaling pathways.

palavras-chave

POLY(VINYLIDENE FLUORIDE); SIGNALING PATHWAY; GROWTH-FACTOR; STEM-CELLS; IN-VITRO; DIFFERENTIATION; P(VDF-TRFE); NANOFIBERS; PHASES; OSTEOGENESIS

categoria

Polymer Science

autores

Botvin, VV; Sukhinina, E; Fetisova, AA; Wagner, D; Vedyashkina, MY; Pryadko, A; Pershina, AG; Surmeneva, MA; Kholkin, AL; Surmenev, RA

nossos autores

agradecimentos

The authors thank the central laboratories of Tomsk Polytechnic University (Analytical Center) for the XPS measurements. Financial support from the Russian Science Foundation (grant number 22-73-00228, synthesis and characterization of materials) and from the Ministry of Science and Higher Education of Russia (grant agreement #075-15-2021-588 of 1 June 2021, biological study) is acknowledged. The authors thank Albert Muslimov for MSCs isolation and Prof. Dmitry Kuprash for carrying out the RNA sequencing at the Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Medical University.

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