Current treatments for brain aneurysms are invasive, traumatic, and not suitable in most patients with increased risks. A new alternative method is using scaffold stents to create a local and focal attraction force of cells for an in situ reconstruction of the tunica media. For this purpose, a nanostructured bioactive coating is designed to render an asymmetric region of the stent scaffold magnetic and biomimetic, which utilizes bacterial nanocellulose (BNC) as a platform for both magnetic and cell attraction as well as proliferation. The magnetization of the BNC is realized through the reaction of Fe III and II, precipitating superparamagnetic iron oxide nanoparticles (SPION). Subsequently, magnetic bacterial nanocellulose (MBNC) is coated with polyethylene glycol to improve its biocompatibility. Cytotoxicity and biocompatibility are evaluated using porcine aortic smooth muscle cells. Preliminary cellular migration assays demonstrate the behavior between MBNC and cells labeled with SPION. In this work, (1) synthesis of BNC impregnated with magnetic nanoparticles is successfully demonstrated; (2) a viable, resilient, and biocompatible hydrogel membrane is tested for neuroendovascular application using a stent scaffold; (3) cell viability and minimal cytotoxicity is achieved; (4) cell migration tests and examination of cellular magnetic attraction confirm the viability of MBNC as a multifunctional coating.
A new generation of biomaterials are evolving from being biologically inert toward bioactive surfaces, which can further interact with biological components at the nanoscale. Here, we present directed irradiation synthesis (DIS) as a novel technology to selectively apply plasma ions to bombard any type of biomaterial and tailor the nanofeatures needed for in vitro growth stimulation. In this work, we demonstrate for the first time, the influence of physiochemical cues (e.g., self-organized topography at nanoscale) of medical grade Ti6Al4V results in control of cell shape, adhesion, and proliferation of human aortic smooth muscle stem cells. The control of surface nanostructures was found to be correlated to ion-beam incidence angle linked to a surface diffusive regime during irradiation synthesis with argon ions at energies below 1 keV and a fluence of 2.5 × 1017 cm–2. Cell viability and cytoskeleton morphology were evaluated at 24 h, observing an advance cell attachment state on post-DIS surfaces. These modified surfaces showed 84% of cell biocompatibility and an increase in cytoplasmatic protusions ensuring a higher cell adhesion state. Filopodia density was promoted by a 3-fold change for oblique incidence angle DIS treatment compared to controls (e.g., no patterning) and lamellipodia structures were increased more than a factor of 2, which are indicators of cell attachment stimulation due to DIS modification. In addition, the morphology of the nanofeatures were tailored, with high fidelity control of the main DIS parameters that control diffusive and erosive regimes of self-organization. We have correlated the morphology and the influence in cell behavior, where nanoripple formation is the most active morphology for cell stimulation.
Surgical clipping and endovascular coiling are well recognized as conventional treatments of Penetrating Brain Injury aneurysms. These clinical approaches show partial success, but often result in thrombus formation and the rupture of aneurysm near arterial walls. The authors address these challenging brain traumas with a unique combination of a highly biocompatible biopolymer hydrogel rendered magnetic in a flexible and resilient membrane coating integrated to a scaffold stent platform at the aneurysm neck orifice, which enhances the revascularization modality. This work focuses on the in situ diagnosis of nano‐mechanical behavior of bacterial nanocellulose (BNC) membranes in an aqueous environment used as tissue reconstruction substrates for cerebral aneurysmal neck defects. Nano‐mechanical evaluation, performed using instrumented nano‐indentation, shows with very low normal loads between 0.01 to 0.5 mN, in the presence of deionized water. Mechanical testing and characterization reveals that the nano‐scale response of BNC behaves similar to blood vessel walls with a very low Young´s modulus, E (0.0025 to 0.04 GPa), and an evident creep effect (26.01 ± 3.85 nm s−1). These results confirm a novel multi‐functional membrane using BNC and rendered magnetic with local adhesion of iron‐oxide magnetic nanoparticles.
In this study, bacterial nanocellulose (BNC) produced by the bacteria Gluconacetobacter xylinus is synthesized and impregnated in situ with iron oxide nanoparticles (IONP) (Fe3O4) to yield a magnetic bacterial nanocellulose (MBNC). The synthesis of MBNC is a precise and specifically designed multi-step process. Briefly, bacterial nanocellulose (BNC) pellicles are formed from preserved G. xylinus strain according to our experimental requirements of size and morphology. A solution of iron(III) chloride hexahydrate (FeCl3·6H2O) and iron(II) chloride tetrahydrate (FeCl2·4H2O) with a 2:1 molar ratio is prepared and diluted in deoxygenated high purity water. A BNC pellicle is then introduced in the vessel with the reactants. This mixture is stirred and heated at 80 °C in a silicon oil bath and ammonium hydroxide (14%) is then added by dropping to precipitate the ferrous ions into the BNC mesh. This last step allows forming in situ magnetite nanoparticles (Fe3O4) inside the bacterial nanocellulose mesh to confer magnetic properties to BNC pellicle. A toxicological assay was used to evaluate the biocompatibility of the BNC-IONP pellicle. Polyethylene glycol (PEG) was used to cover the IONPs in order to improve their biocompatibility. Scanning electron microscopy (SEM) images showed that the IONP were located preferentially in the fibril interlacing spaces of the BNC matrix, but some of them were also found along the BNC ribbons. Magnetic force microscope measurements performed on the MBNC detected the presence magnetic domains with high and weak intensity magnetic field, confirming the magnetic nature of the MBNC pellicle. Young's modulus values obtained in this work are also in a reasonable agreement with those reported for several blood vessels in previous studies.
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