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Objective.Schwann cells (SCs) transplanted in damaged nervous tissue promote axon growth, which may support the recovery of function lost after injury. However, SC transplant-mediated axon growth is often limited and lacks direction.Approach.We have developed a zinc oxide (ZnO) containing fibrous scaffold consisting of aligned fibers of polycaprolactone (PCL) with embedded ZnO nanoparticles as a biodegradable, bifunctional scaffold for promoting and guiding axon growth. This scaffold has bifunctional properties wherein zinc is released providing bioactivity and ZnO has well-known piezoelectric properties where piezoelectric materials generate electrical activity in response to minute deformations. In this study, SC growth, SC-mediated axon extension, and the presence of myelin basic protein (MBP), as an indicator of myelination, were evaluated on the scaffolds containing varying concentrations of ZnOin vitro. SCs and dorsal root ganglion (DRG) neurons were cultured, either alone or in co-culture, on the scaffolds.Main results.Findings demonstrated that scaffolds with 1 wt.% ZnO promoted the greatest SC growth and SC-mediated axon extension. The presence of brain-derived neurotrophic factor (BDNF) was also determined. BDNF increased in co-cultures for all scaffolds as compared to SCs or DRGs cultured alone on all scaffolds. For co-cultures, cells on scaffolds with low levels of ZnO (0.5 wt.% ZnO) had the highest amount of BDNF as compared to cells on higher ZnO-containing scaffolds (1 and 2 wt.%). MBP immunostaining was only detected in co-cultures on PCL control scaffolds (without ZnO).Significance.The results of this study demonstrate the potential of the ZnO-containing scaffolds for SC-mediated axon growth and its potential for use in nervous tissue repair.
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Óxido de Zinc , Óxido de Zinc/metabolismo , Factor Neurotrófico Derivado del Encéfalo , Andamios del Tejido , Células de Schwann/fisiología , Axones/fisiología , Células Cultivadas , Ganglios EspinalesRESUMEN
Stem cells have been sought as a promising cell source in the tissue engineering field due to their proliferative capacity as well as differentiation potential. Biomaterials have been utilized to facilitate the delivery of stem cells in order to improve their engraftment and long-term viability upon implantation. Biomaterials also have been developed as scaffolds to promote stem cell induced tissue regeneration. This review focuses on the latter where the biomaterial scaffold is designed to provide physical cues to stem cells in order to promote their behavior for tissue formation. Recent work that explores the effect of scaffold physical properties, topography, mechanical properties and electrical properties, is discussed. Although still being elucidated, the biological mechanisms, including cell shape, focal adhesion distribution, and nuclear shape, are presented. This review also discusses emerging areas and challenges in clinical translation.
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Materiales Biocompatibles , Señales (Psicología) , Diferenciación Celular , Células Madre , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
Stem cell strategies and the use of electrical stimulation (ES) represent promising new frontiers for peripheral nerve regeneration. Composite matrices were fabricated by coating electrospun polycaprolactone/cellulose acetate micro-nanofibers with chitosan and ionically conductive (IC) polymers including, sulfonated polyaniline, and lignin sulfonate. These composite matrices were characterized for surface morphology, coating uniformity, ionic conductivity, and mechanical strength to explore as scaffold materials for nerve regeneration in conjunction with ES. Composite matrices measured conductivity in the range of 0.0049-0.0068 mS/m due to the uniform coating of sulfonated polymers on the micro-nanofibers. Thin films (2D) and composite fiber matrices (3D) of IC polymers seeded with human mesenchymal stem cells (hMSCs) were electrically stimulated at 0.5 V, 20 Hz for 1 h daily for 14 days to study the changes in cell viability, morphology, and expression of the neuronal-like phenotype. In vitro ES lead to changes in hMSCs' fibroblast morphology into elongated neurite-like structures with cell bodies for ES-treated and positive control growth factor-treated groups. Immunofluorescent staining revealed the presence of neuronal markers including ß3-tubulin, microtubule-associated protein 2, and nestin in response to ES. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1792-1805, 2019.
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Terapia por Estimulación Eléctrica , Matriz Extracelular/química , Células Madre Mesenquimatosas/metabolismo , Regeneración Nerviosa , Neuritas/metabolismo , Polímeros/química , Antígenos de Diferenciación/metabolismo , Conductividad Eléctrica , HumanosRESUMEN
3D printing, or rapid prototyping, is a fabrication technique that is used for various engineering applications with advantages such as mass production and fine tuning of spatial-dimensional properties. Recently, this fabrication method has been adopted for tissue engineering applications due to its ability to finely tune porosity and create precise, uniform, and repeatable structures. This review aims to introduce 3D printing applications in soft tissue engineering and regenerative medicine including state-of-the-art scaffolds and key future challenges. Furthermore, 3D printing of individual cells, an evolution of traditional 3D printing technology which represents a cutting-edge technique for the creation of cell seeded scaffolds in vitro, is discussed. Key advances demonstrate the advantages of 3D printing, while also highlighting potential shortcomings to improve upon. It is clear that as 3D printing technology continues to develop, it will serve as a truly revolutionary means for fabrication of structures and materials for regenerative applications.
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A variety of engineered scaffolds have been created for tissue engineering using polymers, ceramics and their composites. Biomimicry has been adopted for majority of the three-dimensional (3D) scaffold design both in terms of physicochemical properties, as well as bioactivity for superior tissue regeneration. Scaffolds fabricated via salt leaching, particle sintering, hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo. Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity. Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution, not reproducible and involved multiple steps. The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery. This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores, bioactivity and degradation rate to enable tissue regeneration. Review highlights few examples of bioactive scaffold mediated nerve, muscle, tendon/ligament and bone regeneration. Regardless of the efforts required for optimization, a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.
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PURPOSE: Noncompliance with adjuvant hormonal therapy among women with breast cancer is common. Little is known about the impact of financial factors, such as co-payments, on noncompliance. PATIENTS AND METHODS: We conducted a retrospective cohort study by using the pharmacy and medical claims database at Medco Health Solutions. Women older than age 50 years who were taking aromatase inhibitors (AIs) for resected breast cancer with two or more mail-order prescriptions, from January 1, 2007, to December 31, 2008, were identified. Patients who were eligible for Medicare were analyzed separately. Nonpersistence was defined as a prescription supply gap of more than 45 days without subsequent refill. Nonadherence was defined as a medication possession ratio less than 80% of eligible days. RESULTS: Of 8110 women younger than age 65 years, 1721 (21.1%) were nonpersistent and 863 (10.6%) were nonadherent. Among 14,050 women age 65 years or older, 3476 (24.7%) were nonpersistent and 1248 (8.9%) were nonadherent. In a multivariate analysis, nonpersistence (ever/never) in both age groups was associated with older age, having a non-oncologist write the prescription, and having a higher number of other prescriptions. Compared with a co-payment of less than $30, a co-payment of $30 to $89.99 for a 90-day prescription was associated with less persistence in women age 65 years or older (odds ratio [OR], 0.69; 95% CI, 0.62 to 0.75) but not among women younger than age 65, although a co-payment of more than $90 was associated with less persistence both in women younger than age 65 (OR, 0.82; 95% CI, 0.72 to 0.94) and those age 65 years or older (OR, 0.72; 95% CI, 0.65 to 0.80). Similar results were seen with nonadherence. CONCLUSION: We found that higher prescription co-payments were associated with both nonpersistence and nonadherence to AIs. This relationship was stronger in older women. Because noncompliance is associated with worse outcomes, future policy efforts should be directed toward interventions that would help patients with financial difficulties obtain life-saving medications.