Effect of particle concentration on the microstructural and macromechanical properties of biocompatible magnetic hydrogels

We analyze the effect of nanoparticle concentration on the physical properties of magnetic hydrogels consisting of polymer networks of the human fibrin biopolymer with embedded magnetic particles, swollen by a water-based solution. We prepared these magnetic hydrogels by polymerization of mixtures consisting mainly of human plasma and magnetic nanoparticles with OH- functionalization. Microscopic observations revealed that magnetic hydrogels presented some cluster-like knots that were connected by several fibrin threads. By contrast, nonmagnetic hydrogels presented a homogeneous net-like structure with only individual connections between pairs of fibers. The rheological analysis demonstrated that the rigidity modulus, as well as the viscoelastic moduli, increased quadratically with nanoparticle content following a square-like function. Furthermore, we found that time for gel point was shorter in the presence of magnetic nanoparticles. Thus, we can conclude that nanoparticles favor the cross-linking process, serving as nucleation sites for the attachment of the fibrin polymer. Attraction between the positive groups of the fibrinogen, from which the fibrin is polymerized, and the negative OH- groups of the magnetic particle surface qualitatively justifies the positive role of the nanoparticles in the enhancement of the mechanical properties of the magnetic hydrogels. Indeed, we developed a theoretical model that semiquantitatively explains the experimental results by assuming the indirect attraction of the fibrinogen through the attached nanoparticles. Due to this attraction the monomers condense into nuclei of the dense phase and by the end of the polymerization process the nuclei (knots) of the dense phase cross-link the fibrin threads, which enhances their mechanical properties. This journal is © The Royal Society of Chemistry 2017

Rheological properties of magnetic biogels

We report an experimental and theoretical study of the rheological properties of magnetic biogels consisting of fibrin polymer networks with embedded magnetite nanoparticles, swollen by aqueous solutions. We studied two types of magnetic biogels, differenced by the presence or absence of an applied magnetic field during the initial steps of cross-linking. The experiments demonstrated very strong dependence of the elastic modulus of the magnetic biogels on the concentration of the magnetic particles. We finally developed some theoretical models that explain the observed strong concentration effects.This study was supported by projects FIS2013-41821-R (Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, MINECO, Spain, co-funded by ERDF, European Union) and FIS2017-85954-R (Ministerio de Economía, Industria y Competitividad, MINECO, andAgencia Estatal de Investigación, AEI, Spain, co-funded by Fondo Europeo de Desarrollo Regional, FEDER, European Union). A.Z. is grateful to the program of the Ministry of Education and Science of the Russian Federation, projects 02.A03.21.0006, 3.1438.2017/4.6, and 3.5214.2017/6.7, as well as to the Russian Fund of Basic Researches, project 18-08-00178

In vivo time-course biocompatibility assessment of biomagnetic nanoparticles-based biomaterials for tissue engineering applications.

Novel artificial tissues with potential usefulness in local-based therapies have been generated by tissue engineering using magnetic-responsive nanoparticles (MNPs). In this study, we performed a comprehensive in vivo characterization of bioengineered magnetic fibrin-agarose tissue-like biomaterials. First, in vitro analyses were performed and the cytocompatibility of MNPs was demonstrated. Then, bioartificial tissues were generated and subcutaneously implanted in Wistar rats and their biodistribution, biocompatibility and functionality were analysed at the morphological, histological, haematological and biochemical levels as compared to injected MNPs. Magnetic Resonance Image (MRI), histology and magnetometry confirmed the presence of MNPs restricted to the grafting area after 12 weeks. Histologically, we found a local initial inflammatory response that decreased with time. Structural, ultrastructural, haematological and biochemical analyses of vital organs showed absence of damage or failure. This study demonstrated that the novel magnetic tissue-like biomaterials with improved biomechanical properties fulfil the biosafety and biocompatibility requirements for future clinical use and support the use of these biomaterials as an alternative delivery route for magnetic nanoparticles