Small-diameter vascular graft using co-electrospun composite PCL/PU nanofibers.

Small-diameter vascular scaffolds have been developed by a co-electrospinning method using polyethylene terephthalate (PCL) and elastic polytetrafluoroethylene (PU) as biopolymers with long degradation time. Although they possess favorable properties, individually these two polymers do not meet the requirements for the production of synthetic vascular scaffolds. The co-electrospinning method was adopted to develop and mechanically improve the composite PCL/PU vascular scaffolds. The morphological, mechanical and biological properties of these vascular scaffolds were evaluated through scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, compliance, tensile testing and MTT assay. The in vivo study of the vascular scaffolds was performed by implanting them on rat and sheep models. The compliance of the composite vascular scaffolds improved by up to 43% through an increased percentage of PU from 10%-90%. The obtained UTS of the scaffolds at 10%, 25%, 50%, 75% and 90% of PU were 4.7 ± 0.34, 3.4 ± 0.6, 4.8 ± 0.62, 2.2 ± 0.34 and 4.4 ± 1.9 MPa, respectively. The results of MTT assays indicated that the cell growth on the scaffolds was augmented when compared to the control, from day one to day seven. Mild edema, mild foreign-body granulomatous reaction and mild fibrosis were observed by pathology test as the side effects in the composite scaffold with 50% PCL. Doppler ultrasound and angiography images confirm that no aneurysm, thrombogenesis, neointimal hyperplasia or occlusion exist, and there is complete patency at the end of an eight month investigation. The fabricated composite vascular scaffolds provide appropriate mechanical and biological properties and clinical requirements, indicating their required potential to be applied as a small-diameter vascular graft.

Synthesis, Characterization, and in Vitro Biological Evaluation of Copper-Containing Magnetic Bioactive Glasses for Hyperthermia in Bone Defect Treatment.

Hyperthermia treatment induced by magnetic mesoporous glasses has been applied as a potential therapeutic approach for bone defects due to malignant tumors. The objective of this study was to synthesize and characterize the structural and biological properties of magnetic bioactive glasses (BGs) for producing multifunctional materials. The effect of the addition of copper (Cu) to the bioactive glass composition was also evaluated. Fe BG and FeCu BG as magnetic mesoporous BGs, and Cu BG as mesoporous BG were synthesized and dried by template sol-gel method. Then the synthesized bioglasses were characterized and analyzed using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive electron disperse spectroscopy (EDS), Brunauer-Emmett-Teller (BET), and vibrating sample magnetometer (VSM). In addition, the antibacterial behavior, cytotoxicity assay (MTT test), proliferation assay of HUVEC cell assay, and bioactivity (ALP activity test) of the synthesized BGs were evaluated. The characterization results exhibited that the synthesized powders formed mesoporous glasses with nanoparticle morphology, good surface area, and magnetic properties. The synthesized BGs also demonstrated suitable biological behavior. The magnetic saturation of bioactive glasses was increased by the addition of copper oxide. A two-phase structure was observed for the magnetic glasses compared to the copper-containing glasses, thus making them suitable for drug delivery systems. The antibacterial behavior was found to be better for the Cu BG and Fe BG compared to the FeCu BG. However, the least amount of cytotoxicity was observed for the Fe BG and FeCu BG, compared to the Cu BG. In addition, the Fe-containing BGs compared with the control group showed a lack of HUVEC cell proliferation and angiogenesis motivation. From the ALP assay, higher bioactivity for the magnetic bioglasses in the presence of mesenchymal cells was found. From the results of this in vitro study, the Cu-containing magnetic bioglass (FeCu BG) could be considered as a new generation of magnetic glasses for inducing hyperthermia in treatment of bone defects due to malignant tumors. However, further in vitro and in vivo studies are required to confirm their applications in healing of bone defects and tissue engineering.

An experimental-numerical investigation on the effects of macroporous scaffold geometry on cell culture parameters.

INTRODUCTION: Perfused bioreactors have been demonstrated to be effective in the delivery of nutrients and in the removal of waste products to and from the interior of cell-populated three-dimensional scaffolds. In this paper, a perfused bioreactor hosting a macroporous scaffold provided with a channel is used to investigate transport phenomena and culture parameters on cell growth. METHODS: MG63 human osteosarcoma cells were seeded on macroporous poly​(ε-caprolactone) scaffolds provided with a channel. The scaffolds were cultured in a perfused bioreactor and in static conditions for 5 days. Cell viability and growth were assessed while the concentration of oxygen, glucose and lactate were measured. An in silico, multiphysics, numerical model was set up to study the fluid dynamics and the mass transport of the nutrients in the perfused bioreactor hosting different scaffold geometries. RESULTS: The experimental and numerical results indicated that the specific cell metabolic activity in scaffolds cultured under perfusion was 30% greater than scaffolds cultured under static conditions. In addition, the scaffold provided with a channel enabled the shear stress to be controlled, the initial seeding density to be retained, and adequate mass transport and waste removal. CONCLUSIONS: We show that the macroporous scaffold provided with a channel cultured in a macroscale bioreactor can be a robust reference experimental model system to systematically investigate and assess crucial culture parameters. We also show that such an experimental model system can be employed as a simplified "representative unit" to improve the performance of both perfused culture systems and hollow, fiber-integrated scaffolds for large-scale tissue engineering.

Computational modeling of adherent cell growth in a hollow-fiber membrane bioreactor for large-scale 3-D bone tissue engineering.

The use of hollow-fiber membrane bioreactors (HFMBs) has been proposed for three-dimensional bone tissue growth at the clinical scale. However, to achieve an efficient HFMB design, the relationship between cell growth and environmental conditions must be determined. Therefore, in this work, a dynamic double-porous media model was developed to determine nutrient-dependent cell growth for bone tissue formation in a HFMB. The whole hollow-fiber scaffold within the bioreactor was treated as a porous domain in this model. The domain consisted of two interpenetrating porous regions, including a porous lumen region available for fluid flow and a porous extracapillary space filled with a collagen gel that contained adherent cells for promoting long-term growth into tissue-like mass. The governing equations were solved numerically and the model was validated using previously published experimental results. The contributions of several bioreactor design and process parameters to the performance of the bioreactor were studied. The results demonstrated that the process and design parameters of the HFMB significantly affect nutrient transport and thus cell behavior over a long period of culture. The approach presented here can be applied to any cell type and used to develop tissue engineering hollow-fiber scaffolds.