Osteogenic Potential and Long-Term Enzymatic Biodegradation of PHB-based Scaffolds with Composite Magnetic Nanofillers in a Magnetic Field

resumo

Millions of people worldwide suffer from musculoskeletal damage, thus using the largest proportion of rehabilitation services. The limited self-regenerative capacity of bone and cartilage tissues necessitates the development of functional biomaterials. Magnetoactive materials are a promising solution due to clinical safety and deep tissue penetration of magnetic fields (MFs) without attenuation and tissue heating. Herein, electrospun microfibrous scaffolds were developed based on piezoelectric poly(3-hydroxybutyrate) (PHB) and composite magnetic nanofillers [magnetite with graphene oxide (GO) or reduced GO]. The scaffolds' morphology, structure, mechanical properties, surface potential, and piezoelectric response were systematically investigated. Furthermore, a complex mechanism of enzymatic biodegradation of these scaffolds is proposed that involves (i) a release of polymer crystallites, (ii) crystallization of the amorphous phase, and (iii) dissolution of the amorphous phase. Incorporation of Fe3O4, Fe3O4-GO, or Fe3O4-rGO accelerated the biodegradation of PHB scaffolds owing to pores on the surface of composite fibers and the enlarged content of polymer amorphous phase in the composite scaffolds. Six-month biodegradation caused a reduction in surface potential (1.5-fold) and in a vertical piezoresponse (3.5-fold) of the Fe3O4-GO scaffold because of a decrease in the PHB beta-phase content. In vitro assays in the absence of an MF showed a significantly more pronounced mesenchymal stem cell proliferation on composite magnetic scaffolds compared to the neat scaffold, whereas in an MF (68 mT, 0.67 Hz), cell proliferation was not statistically significantly different when all the studied scaffolds were compared. The PHB/Fe3O4-GO scaffold was implanted into femur bone defects in rats, resulting in successful bone repair after nonperiodic magnetic stimulation (200 mT, 0.04 Hz) owing to a synergetic influence of increased surface roughness, the presence of hydrophilic groups near the surface, and magnetoelectric and magnetomechanical effects of the material.

palavras-chave

STEM-CELLS; OXIDE SCAFFOLDS; POLY(3-HYDROXYBUTYRATE); FILMS; DIFFERENTIATION; NANOPARTICLES; PROLIFERATION; LIPASE; CO

categoria

Science & Technology - Other Topics; Materials Science

autores

Shlapakova, LE; Pryadko, AS; Zharkova, II; Volkov, A; Kozadaeva, M; Chernozem, RV; Mukhortova, YR; Chesnokova, D; Zhuikov, VA; Zeltser, A; Dudun, AA; Makhina, T; Bonartseva, GA; Voinova, VV; Shaitan, KV; Romanyuk, K; Kholkin, AL; Bonartsev, AP; Surmeneva, MA; Surmenev, RA

Grupos

G2 - Materiais Fotónicos, Eletrónicos e Magnéticos

Projectos

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

agradecimentos

This research is supported by Tomsk Polytechnic University. This research was funded by the Russian Science Foundation project # 20-63-47096 (material preparation and characterization), project # 20-64-47008 (in vitro study on mesenchymal stem cells and in vivo study on rats), and was carried out within the framework of government assignment of the Ministry of Science and Higher Education of the Russian Federation (in part of the biosynthesis of poly(3-hydroxybutyrate, affiliation: Research Center of Biotechnology RAS). Equipment of the Multi-Access Equipment Centers of M.V.Lomonosov Moscow State University and Research Center of Biotechnology RAS were used in the work. Scanning electron microscopy was performed using a unique equipment setup "3D-EMS" of MSU. The authors thank the central laboratories of TPU (Analytical Center) for the XPS measurements. Experiments were partly performed on the infrastructure and facilities of Tomsk State University and of the Institute of Physics of Strength and Materials Science (Tomsk, Russia). Part of this work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 (DOI 10.54499/UIDB/50011/2020), UIDP/50011/2020 (DOI 10.54499/UIDP/50011/2020) & LA/P/0006/2020 (DOI 10.54499/LA/P/0006/2020), financed by national funds through the FCT/MCTES (PIDDAC). It is also funded by national funds (OE), through FCT-Fundacao para a Ciencia e a Tecnologia, I.P., in the scope of the framework contract foreseen in the numbers 4, 5, and 6 of article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19.