Electro-optical Study of the Anomalous Rotational Diffusion in Polymer Solutions.

Brownian diffusion of spherical nanoparticles is usually exploited to ascertain the rheological properties of complex media. However, the behavior of the tracer particles is affected by a number of phenomena linked to the interplay between the dynamics of the particles and polymer coils. For this reason, the characteristic lengths of the dispersed entities, depletion phenomena, and the presence of sticking conditions have been observed to affect the translational diffusion of the probes. On the other hand, the retardation effect of the host fluid on the rotational diffusion of nonspherical particles is less understood. We explore the possibility of studying this phenomenon by analyzing the electro-orientation of the particles in different scenarios in which we vary the ratio between the particle and polymer characteristic size, and the geometry of the particles, including both elongated and oblate shapes. We find that the Stokes-Einstein relation only applies if the radius of gyration of the polymer is much shorter than the particle size and when some repulsive interaction between both is present.

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.

Generation of genipin cross-linked fibrin-agarose hydrogel tissue-like models for tissue engineering applications.

The generation of biomimetic and biocompatible artificial tissues is the basic research objective for tissue engineering (TE). In this sense, the biofabrication of scaffolds that resemble the tissues' extracellular matrix is an essential aim in this field. Uncompressed and nanostructured fibrin-agarose hydrogels (FAH and NFAH, respectively) have emerged as promising scaffolds in TE, but their structure and biomechanical properties must be improved in order to broaden their TE applications. Here, we generated and characterized novel membrane-like models with increased structural and biomechanical properties based on the chemical cross-linking of FAH and NFAH with genipin (GP at 0.1%, 0.25%, 0.5% and 0.75%). Furthermore, the scaffolds were subjected to rheological (G, G', G″ modulus), ultrastructural and ex vivo biocompatibility analyses. Results showed that all GP concentrations increased the stiffness (G) and especially the elasticity (G') of FAH and NFAH. Ultrastructural analyses demonstrated that GP and nanostructuration of FAH allowed us to control the porosity of FAH. In addition, biological studies revealed that higher concentration of GP (0.75%) started to compromise the cell function and viability. Finally, this study demonstrated the possibility to generate natural and biocompatible FAH and NFAH with improved structural and biomechanical properties by using 0.1%-0.5% of GP. However, further in vivo studies are needed in order to demonstrate the biocompatibility, biodegradability and regeneration capability of these cross-linked scaffolds.

Ex vivo characterization of a novel tissue-like cross-linked fibrin-agarose hydrogel for tissue engineering applications.

The generation of biomaterials with adequate biomechanical and structural properties remains a challenge in tissue engineering and regenerative medicine. Earlier research has shown that nanostructuration and cross-linking techniques improved the biomechanical and structural properties of different biomaterials. Currently, uncompressed and nanostructured fibrin-agarose hydrogels (FAH and NFAH, respectively) have been used successfully in tissue engineering. The aim of this study was to investigate the possibility of improving the structural and biomechanical properties of FAH and NFAH by using 0.25% and 0.5% (v/v) glutaraldehyde (GA) as a cross-linker. These non-cross-linked and cross-linked hydrogels were subjected to structural, rheological and ex vivo biocompatibility analyses. Our results showed that GA cross-linking induced structural changes and significantly improved the rheological properties of FAH and NFAH. In addition, ex vivo biocompatibility analyses demonstrated viable cells in all conditions, although viability was more compromised when 0.5% GA was used. Our study demonstrates that it is possible to control fiber density and hydrogel porosity of FAH and NFAH by using nanostructuration or GA cross-linking techniques. In conclusion, hydrogels cross-linked with 0.25% GA showed promising structural, biochemical and biological properties for use in tissue engineering.

Biocompatible magnetic core-shell nanocomposites for engineered magnetic tissues.

The inclusion of magnetic nanoparticles into biopolymer matrixes enables the preparation of magnetic field-responsive engineered tissues. Here we describe a synthetic route to prepare biocompatible core-shell nanostructures consisting of a polymeric core and a magnetic shell, which are used for this purpose. We show that using a core-shell architecture is doubly advantageous. First, gravitational settling for core-shell nanocomposites is slower because of the reduction of the composite average density connected to the light polymer core. Second, the magnetic response of core-shell nanocomposites can be tuned by changing the thickness of the magnetic layer. The incorporation of the composites into biopolymer hydrogels containing cells results in magnetic field-responsive engineered tissues whose mechanical properties can be controlled by external magnetic forces. Indeed, we obtain a significant increase of the viscoelastic moduli of the engineered tissues when exposed to an external magnetic field. Because the composites are functionalized with polyethylene glycol, the prepared bio-artificial tissue-like constructs also display excellent ex vivo cell viability and proliferation. When implanted in vivo, the engineered tissues show good biocompatibility and outstanding interaction with the host tissue. Actually, they only cause a localized transitory inflammatory reaction at the implantation site, without any effect on other organs. Altogether, our results suggest that the inclusion of magnetic core-shell nanocomposites into biomaterials would enable tissue engineering of artificial substitutes whose mechanical properties could be tuned to match those of the potential target tissue. In a wider perspective, the good biocompatibility and magnetic behavior of the composites could be beneficial for many other applications.