Electrospraying Electrospun Nanofiber Segments into Injectable Microspheres for Potential Cell Delivery

Nanofiber microspheres have attracted a lot of attention for biomedical applications because of their injectable and biomimetic properties. Herein, we report for the first time a new method for fabrication of nanofiber microspheres by combining electrospinning and electrospraying and explore their potential applications for cell therapy. Electrospraying of aqueous dispersions of electrospun nanofiber segments with desired length obtained by either cryocutting or homogenization into liquid nitrogen followed by freeze-drying and thermal treatment can form nanofiber microspheres. The microsphere size can be controlled by varying the applied voltage during the electrospray process. A variety of morphologies were achieved including solid, nanofiber, porous and nanofiber microspheres, and hollow nanofiber microspheres. Furthermore, a broad range of polymer and inorganic bioactive glass nanofiber-based nanofiber microspheres could be fabricated by electrospraying of their short nanofiber dispersions, indicating a comprehensive applicability of this method. A higher cell carrier efficiency of nanofiber microspheres as compared to solid microspheres was demonstrated with rat bone marrow-derived mesenchymal stem cells, along with the formation of microtissue-like structures in situ, when injected into microchannel devices. Also, mouse embryonic stem cells underwent neural differentiation on the nanofiber microspheres, indicated by positive staining of β-III-tubulin and neurite outgrowth. Taken together, we developed a new method for generating nanofiber microspheres that are injectable and have improved viability and maintenance of stem cells for potential application in cell therapy

Electrospraying Electrospun Nanofiber Segments into Injectable Microspheres for Potential Cell Delivery

Nanofiber microspheres have attracted a lot of attention for biomedical applications because of their injectable and biomimetic properties. Herein, we report for the first time a new method for fabrication of nanofiber microspheres by combining electrospinning and electrospraying and explore their potential applications for cell therapy. Electrospraying of aqueous dispersions of electrospun nanofiber segments with desired length obtained by either cryocutting or homogenization into liquid nitrogen followed by freeze-drying and thermal treatment can form nanofiber microspheres. The microsphere size can be controlled by varying the applied voltage during the electrospray process. A variety of morphologies were achieved including solid, nanofiber, porous and nanofiber microspheres, and hollow nanofiber microspheres. Furthermore, a broad range of polymer and inorganic bioactive glass nanofiber-based nanofiber microspheres could be fabricated by electrospraying of their short nanofiber dispersions, indicating a comprehensive applicability of this method. A higher cell carrier efficiency of nanofiber microspheres as compared to solid microspheres was demonstrated with rat bone marrow-derived mesenchymal stem cells, along with the formation of microtissue-like structures in situ, when injected into microchannel devices. Also, mouse embryonic stem cells underwent neural differentiation on the nanofiber microspheres, indicated by positive staining of β-III-tubulin and neurite outgrowth. Taken together, we developed a new method for generating nanofiber microspheres that are injectable and have improved viability and maintenance of stem cells for potential application in cell therapy

Electrospraying Electrospun Nanofiber Segments into Injectable Microspheres for Potential Cell Delivery

Nanofiber microspheres have attracted a lot of attention for biomedical applications because of their injectable and biomimetic properties. Herein, we report for the first time a new method for fabrication of nanofiber microspheres by combining electrospinning and electrospraying and explore their potential applications for cell therapy. Electrospraying of aqueous dispersions of electrospun nanofiber segments with desired length obtained by either cryocutting or homogenization into liquid nitrogen followed by freeze-drying and thermal treatment can form nanofiber microspheres. The microsphere size can be controlled by varying the applied voltage during the electrospray process. A variety of morphologies were achieved including solid, nanofiber, porous and nanofiber microspheres, and hollow nanofiber microspheres. Furthermore, a broad range of polymer and inorganic bioactive glass nanofiber-based nanofiber microspheres could be fabricated by electrospraying of their short nanofiber dispersions, indicating a comprehensive applicability of this method. A higher cell carrier efficiency of nanofiber microspheres as compared to solid microspheres was demonstrated with rat bone marrow-derived mesenchymal stem cells, along with the formation of microtissue-like structures in situ, when injected into microchannel devices. Also, mouse embryonic stem cells underwent neural differentiation on the nanofiber microspheres, indicated by positive staining of β-III-tubulin and neurite outgrowth. Taken together, we developed a new method for generating nanofiber microspheres that are injectable and have improved viability and maintenance of stem cells for potential application in cell therapy

Targeted Chemo-Photothermal Treatments of Rheumatoid Arthritis Using Gold Half-Shell Multifunctional Nanoparticles

We have developed RGD-attached gold (Au) half-shell nanoparticles containing methotrexate (MTX) for the treatment of rheumatoid arthritis (RA), where MTX is the most widely used disease-modifying anti-rheumatic drug (DMARD) for the treatment of RA, and RGD peptide is a targeting moiety for inflammation. Upon near-infrared (NIR) irradiation, heat is locally generated due to Au half-shells, and the drug release rate is enhanced, delivering heat and drug to the inflamed joints simultaneously. RA is a chronic inflammatory disease characterized by synovial inflammation in multiple joints within the penetration depth of NIR light. When combined with NIR irradiation, these nanoparticles containing a much smaller dosage of MTX (1/930 of MTX solution) showed greater therapeutic effects than that of a conventional treatment with MTX solution in collagen-induced arthritic mice. This novel drug delivery system is a good way to maximize therapeutic efficacy and minimize dosage-related MTX side effects in the treatment of RA. Furthermore, these multifunctional nanoparticles could be applied to other DMARDs for RA or other inflammatory diseases

Targeted Chemo-Photothermal Treatments of Rheumatoid Arthritis Using Gold Half-Shell Multifunctional Nanoparticles

We have developed RGD-attached gold (Au) half-shell nanoparticles containing methotrexate (MTX) for the treatment of rheumatoid arthritis (RA), where MTX is the most widely used disease-modifying anti-rheumatic drug (DMARD) for the treatment of RA, and RGD peptide is a targeting moiety for inflammation. Upon near-infrared (NIR) irradiation, heat is locally generated due to Au half-shells, and the drug release rate is enhanced, delivering heat and drug to the inflamed joints simultaneously. RA is a chronic inflammatory disease characterized by synovial inflammation in multiple joints within the penetration depth of NIR light. When combined with NIR irradiation, these nanoparticles containing a much smaller dosage of MTX (1/930 of MTX solution) showed greater therapeutic effects than that of a conventional treatment with MTX solution in collagen-induced arthritic mice. This novel drug delivery system is a good way to maximize therapeutic efficacy and minimize dosage-related MTX side effects in the treatment of RA. Furthermore, these multifunctional nanoparticles could be applied to other DMARDs for RA or other inflammatory diseases

Viral load showed a significant inverse correlation with serum peak PT levels (A, <i>r</i> = -0.453, <i>P</i> = 0.001) and a significant direct correlation with serum peak ALT (B, <i>r</i> = 0.417, <i>P</i> = 0.003).

<p>Viral load showed a significant inverse correlation with serum peak PT levels (A, <i>r</i> = -0.453, <i>P</i> = 0.001) and a significant direct correlation with serum peak ALT (B, <i>r</i> = 0.417, <i>P</i> = 0.003).</p

Multivariate analysis of predictive factors associated with severe acute hepatitis A.

<p>NOTE. ^*P-value from logistic regression models</p><p>Abbreviation: HR, hazard ratio; CI, confidence interval; ALT, alanine aminotransferase; CRP, C-reactive protein; LDH, lactate dehydrogenase.</p><p>Multivariate analysis of predictive factors associated with severe acute hepatitis A.</p

Targeted Chemo-Photothermal Treatments of Rheumatoid Arthritis Using Gold Half-Shell Multifunctional Nanoparticles

We have developed RGD-attached gold (Au) half-shell nanoparticles containing methotrexate (MTX) for the treatment of rheumatoid arthritis (RA), where MTX is the most widely used disease-modifying anti-rheumatic drug (DMARD) for the treatment of RA, and RGD peptide is a targeting moiety for inflammation. Upon near-infrared (NIR) irradiation, heat is locally generated due to Au half-shells, and the drug release rate is enhanced, delivering heat and drug to the inflamed joints simultaneously. RA is a chronic inflammatory disease characterized by synovial inflammation in multiple joints within the penetration depth of NIR light. When combined with NIR irradiation, these nanoparticles containing a much smaller dosage of MTX (1/930 of MTX solution) showed greater therapeutic effects than that of a conventional treatment with MTX solution in collagen-induced arthritic mice. This novel drug delivery system is a good way to maximize therapeutic efficacy and minimize dosage-related MTX side effects in the treatment of RA. Furthermore, these multifunctional nanoparticles could be applied to other DMARDs for RA or other inflammatory diseases

Clinical characteristics of 770 patients with acute hepatitis A.

<p>NOTE. Values are given as mean (range)</p><p>Abbreviation: s-AH, severe acute hepatitis A; m-AH, mild acute hepatitis; ALT, alanine aminotransferase; CRP, C-reactive protein; LDH, lactate dehydrogenase.</p><p>Clinical characteristics of 770 patients with acute hepatitis A.</p

Establishment of a Human iPSC- and Nanofiber-Based Microphysiological Blood–Brain Barrier System

The blood–brain barrier (BBB) is an active and complex diffusion barrier that separates the circulating blood from the brain and extracellular fluid, regulates nutrient transportation, and provides protection against various toxic compounds and pathogens. Creating an in vitro microphysiological BBB system, particularly with relevant human cell types, will significantly facilitate the research of neuropharmaceutical drug delivery, screening, and transport, as well as improve our understanding of pathologies that are due to BBB damage. Currently, most of the in vitro BBB models are generated by culturing rodent astrocytes and endothelial cells, using commercially available transwell membranes. Those membranes are made of plastic biopolymers that are nonbiodegradable, porous, and stiff. In addition, distinct from rodent astrocytes, human astrocytes possess unique cell complexity and physiology, which are among the few characteristics that differentiate human brains from rodent brains. In this study, we established a novel human BBB microphysiologocal system, consisting of a three-dimensionally printed holder with a electrospun poly­(lactic-<i>co</i>-glycolic) acid (PLGA) nanofibrous mesh, a bilayer coculture of human astrocytes, and endothelial cells, derived from human induced pluripotent stem cells (hiPSCs), on the electrospun PLGA mesh. This human BBB model achieved significant barrier integrity with tight junction protein expression, an effective permeability to sodium fluorescein, and higher transendothelial electrical resistance (TEER) comparing to electrospun mesh-based counterparts. Moreover, the coculture of hiPSC-derived astrocytes and endothielial cells promoted the tight junction protein expression and the TEER value. We further verified the barrier functions of our BBB model with antibrain tumor drugs (paclitaxel and bortezomib) and a neurotoxic peptide (amyloid β 1-42). The human microphysiological system generated in this study will potentially provide a new, powerful tool for research on human BBB physiology and pathology