Two dielectrophoresis systems are introduced where the induced dielectrophoretic force is constant throughout the experimental region, resulting in uniform (isomotive) microparticle translation. Isomotive dielectrophoresis (isoDEP) is accomplished through a unique geometry where the gradient of the field-squared (∇Erms2) is constant, a characteristic that is otherwise highly nonuniform in traditional DEP platforms. The governing isoDEP equations were derived herein and applied to two different isoDEP prototypes: (i) one fabricated from deep reactive ion etching (DRIE) of a conductive silicon wafer (1-10 Ω-cm) whose patterned features served as electrodes and microchannel sidewalls simultaneously; (ii) a second where the electric field is applied lengthwise through a PDMS microchannel whose geometry follows a specific curvature. Both positive and negative dielectrophoresis was demonstrated with the isoDEP devices using silver-coated hollow glass spheres and polystyrene particles, respectively. Particle tracking was used to compare particle trajectory with the expected dielectrophoretic response; further, particle velocity was used to measure the Clausius-Mossotti factor of individual polystyrene particles (18-24.9 μm) in both devices with a value of -0.40 ± 0.063 (n = 110) and -0.48 ± 0.055 (n = 18) for the DRIE and PDMS isoDEP platforms, respectively. The isoDEP platform is capable of analyzing multiple particles simultaneously, providing greater throughput than traditional electrorotation platforms.
The increasing global prevalence of endocrine diseases like type 1 diabetes mellitus (T1DM) elevates the need for cellular replacement approaches, which can potentially enhance therapeutic durability and outcomes. Central to any cell therapy is the design of delivery systems that support cell survival and integration. In T1DM, well-established fabrication methods have created a wide range of implants, ranging from 3D macro-scale scaffolds to nano-scale coatings. These traditional methods, however, are often challenged by their inherent limitations in reproducible and discrete fabrication, particularly when scaling to the clinic. Additive manufacturing (AM) techniques provide a means to address these challenges by delivering improved control over construct geometry and microscale component placement. While still early in development in the context of T1DM cellular transplantation, the integration of AM approaches serves to improve nutrient material transport, vascularization efficiency, and the accuracy of cell, matrix, and local therapeutic placement. This review highlights current methods in T1DM cellular transplantation and the potential of AM approaches to overcome these limitations. In addition, emerging AM technologies and their broader application to cell-based therapy are discussed. Cellular Implants for the Treatment of Type 1 DiabetesCell-based therapies provide a potential curative approach for resolving type 1 diabetes mellitus (T1DM) via the replacement of the insulin-producing cells lost to autoimmune destruction. [1][2][3] In the native pancreas, these insulin-producing cells, termed 𝛽-cells, work to modulate metabolism and blood sugar in
The simultaneous local delivery of anti-inflammatory and pro-angiogenic agents via biomaterial scaffolds presents a promising method for improving the engraftment of tissue-engineered implants while avoiding potentially detrimental systemic delivery. In this study, PDMS microbeads were loaded with either anti-inflammatory dexamethasone (Dex) or pro-angiogenic 17β-estradiol (E2) and subsequently integrated into a single macroporous scaffold to create a controlled, dual drug-delivery platform. Compared to a standard monolithic drug dispersion scaffold, macroporous scaffolds containing drug-loaded microbeads exhibited reduced initial burst release and increased the durability of drug release for both agents. Incubation of scaffolds with LPS-stimulated M1 macrophages found that Dex suppressed the production of pro-inflammatory and pro-angiogenic factors, when compared to drug-free control scaffolds; however, the co-incubation of macrophages with Dex and E2 scaffolds restored their pro-angiogenic features. Following implantation, Dex-loaded microbead scaffolds (Dex-µBS) suppressed host cell infiltration and integration, when compared to controls. In contrast, the co-delivery of dexamethasone with estrogen from the microbead scaffold (Dex/E2-µBS) dampened overall host cell infiltration but restored graft vascularization. These results demonstrate the utility of a microbead scaffold approach for the controlled, tailored, and local release of multiple drugs from an open framework implant. It further highlights the complementary impacts of local Dex and E2 delivery to direct the healthy integration of implants, which has broad applications to the field of tissue engineering and regenerative medicine.
The incidence of asthma and allergic diseases of the airways is constantly increasing, both in the industrialised and developing countries, due to harmful and excessive quantities of air pollution. Although some studies have shown an effect of dietary supplementation of specific nutrients (especially with anti-oxidant and anti-inflammatory properties) in reducing airways inflammatory response, the results are not yet conclusive and the science is still at its infancy. Our hypothesis is that combining such nutrients could provide more benefits than using them alone. The aim of the research project proposed here is to investigate whether specific combinations of nutrients (docosahexanoic acid, vitamin C and E, and Bifidobacterium lactis strain BB-12®, included in an engineered diet) can act synergistically to reduce inflammation given by high level of air pollution. Beside the role of docosahexanoic acid, vitamins C and E on airways inflammatory disease, no study examined the effect of the supplementation of this probiotic strain in pathological conditions caused by air pollution so far. Herein we used a well-established in vivo model for the study of pollution effects, which consists in female BALB/c mice receiving by pharyngeal aspiration either a sham or a particulate matter with diameter <2.5 μm (PM 2.5) containing aerosol. Before treatment, mice were fed either a chow or a supplemented diet. By performing histological analyses and gene expression profiles on lung sections and serum measurement of the cytokine interleukin 10, we found that a specific combination of all the aforementioned nutrients rather than nutrients alone had a synergistic protective effect against PM2.5-induced inflammation. In conclusion, our study support that a supplemental nutritional intervention based on a combination of the probiotic B. lactis BB-12, the anti-oxidant vitamin C and E, and the anti-inflammatory docosahexanoic acid represents a rational option for alleviating air pollution-related lung inflammation.
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