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Baltimore Highlands, MD, United States

Williford J.-M.,Johns Hopkins University | Wu J.,Johns Hopkins University | Ren Y.,Johns Hopkins University | Archang M.M.,Johns Hopkins University | And 3 more authors.
Annual Review of Biomedical Engineering | Year: 2014

Inhibiting specific gene expression by short interfering RNA (siRNA) offers a new therapeutic strategy to tackle many diseases, including cancer, metabolic disorders, and viral infections, at the molecular level. The macromolecular and polar nature of siRNA hinders its cellular access to exert its effect. Nanoparticulate delivery systems can promote efficient intracellular delivery. Despite showing promise in many preclinical studies and potential in some clinical trials, siRNA has poor delivery efficiency, which continues to demand innovations, from carrier design to formulation, in order to overcome transport barriers. Previous findings for optimal plasmid DNA delivery cannot be generalized to siRNA delivery owing to significant discrepancy in size and subtle differences in chain flexibility between the two types of nucleic acids. In this review, we highlight the recent advances in improving the stability of siRNA nanoparticles, understanding their intracellular trafficking and release mechanisms, and applying judiciously the promising formulations to disease models. Copyright © 2014 by Annual Reviews. All rights reserved. Source

Jiang X.,Johns Hopkins University | Mao H.-Q.,Johns Hopkins University | Mao H.-Q.,Translational Tissue Engineering Center | Wang T.-H.,Johns Hopkins University
Nano Letters | Year: 2014

Nonviral gene delivery holds great promise not just as a safer alternative to viral vectors in traditional gene therapy applications, but also for regenerative medicine, induction of pluripotency in somatic cells, and RNA interference for gene silencing. Although it continues to be an active area of research, there remain many challenges to the rational design of vectors. Among these, the inability to characterize the composition of nanoparticles and its distribution has made it difficult to probe the mechanism of gene transfection process, since differences in the nanoparticle-mediated transfection exist even when the same vector is used. There is a lack of sensitive methods that allow for full characterization of DNA content in single nanoparticles and its distribution among particles in the same preparation. Here we report a novel spectroscopic approach that is capable of interrogating nanoparticles on a particle-by-particle basis. Using PEI/DNA and PEI-g-PEG/DNA nanoparticles as examples, we have shown that the distribution of DNA content among these nanoparticles was relatively narrow, with the average numbers of DNA of 4.8 and 6.7 per particle, respectively, in PEI/DNA and PEI-g-PEG/DNA nanoparticles. This analysis enables a more accurate description of DNA content in polycation/DNA nanoparticles. It paves the way toward comparative assessments of various types of gene carriers and provides insights into bridging the efficiency gap between viral and nonviral vehicles. © 2014 American Chemical Society. Source

Yu A.-Q.,Zhejiang University | Jiang X.-S.,Translational Tissue Engineering Center | Jiang X.-S.,Johns Hopkins University | Gao S.,Zhejiang University | And 7 more authors.
Journal of Biomedical Nanotechnology | Year: 2014

Vascular endothelial growth factor (VEGF) is a potent regulator for liver regeneration following partial hepatectomy. However, intravenous delivery of VEGF has yielded limited success in promoting the regeneration of remnant liver. Here we report a new approach to locally deliver recombinant VEGF from an electrospun poly-ε-caprolactone nanofiber mesh and its effect on improving rat liver regeneration after 70% hepatectomy. After applying the VEGF-releasing nanofiber mesh to the remnant liver lobes following hepatectomy in rats, the fractions of proliferating hepatocytes increased markedly at 48 h and 72 h in comparison with the control group receiving nanofiber meshes without VEGF. The expression of endogenous VEGF in liver tissue was also higher in the VEGF-nanofiber group than those in the control group. These results demonstrate that biodegradable nanofiber meshes offer a convenient and effective approach for local and sustained delivery of VEGF to the remnant liver following partial hepatectomy. Copyright © 2014 American Scientific Publishers All rights reserved. Source

Jiang X.,Johns Hopkins University | Jiang X.,Translational Tissue Engineering Center | Christopherson G.T.,Johns Hopkins University | Mao H.-Q.,Johns Hopkins University | And 2 more authors.
Interface Focus | Year: 2011

Previous studies have shown that substrate surface chemistry and topography exhibit significant impact on haematopoietic progenitor cell adhesion, proliferation and differentiation. In the present study, the effect of surface amine density and structure of grafted polymer chains on the adhesion and expansion of haematopoietic progenitor cells was investigated. Cryopreserved human umbilical cord blood CD133 + cells were expanded in cytokine-supplemented medium on ethylenediamine (EDA)- or 2-aminoethyl methacrylate hydrochloride (AEMA)-grafted polyethersulphone (PES) nanofibre scaffolds for 10 days. Although the percentage of CD34 + cells among the expanded cells increased with the surface amine density, the maximum fold expansion of CD34 + cells was obtained at a moderate amine density of 20-80 nmol cm -2.When comparing nanofibre matrices with similar amine densities, but prepared with two different methods, cells cultured on the AEMA-grafted PES nanofibre matrix showed lower fold expansion in terms of total cell number (300+84 fold) and CD34{thorn} cell number (68+19-fold) in comparison with those cultured on EDA-grafted nanofibres (787+84-fold and 185+84-fold, respectively). These results indicate that the surface amine density and the conjugate structure are important determinants for the preservation of CD34 surface marker and expansion efficiency of CD34 + cells. © 2011 The Royal Society. Source

Barreto-Ortiz S.F.,Johns Hopkins University | Fradkin J.,Johns Hopkins University | Eoh J.,Johns Hopkins University | Trivero J.,Johns Hopkins University | And 6 more authors.
FASEB Journal | Year: 2015

Despite current advances in engineering blood vessels over 1mmin diameter and the existing wealth of knowledge regarding capillary bed formation, studies for the development of microvasculature, the connecting bridge between them, have been extremely limited so far. Here, we evaluate the use of 3-dimensional (3D) microfibers fabricated by hydrogel electrospinning as templates formicrovascular structure formation.Wehypothesize that 3D microfibers improve extracellular matrix (ECM) deposition from vascular cells, enabling the formation of freestanding luminal multicellularmicrovasculature. Compared to 2-dimensional cultures, we demonstrate with confocal microscopy and RT-PCR that fibrin microfibers induce an increased ECM protein deposition by vascular cells, specifically endothelial colony-forming cells, pericytes, and vascular smooth muscle cells. These ECM proteins comprise different layers of the vascular wall including collagen types I, III, and IV, as well as elastin, fibronectin, and laminin. We further demonstrate the achievement ofmulticellular microvascular structures with an organized endothelium and a robust multicellular perivascular tunica media. This, along with the increased ECM deposition, allowed for the creation of self-supporting multilayered microvasculature with a distinct circular lumen following fibrin microfiber core removal. This approach presents an advancement toward the development of human microvasculature for basic and translational studies. Barreto-Ortiz, S. F., Fradkin, J., Eoh, J., Trivero, J., Davenport, M., Ginn, B., Mao, H.-Q., Gerecht, S. Fabrication of 3-dimensional multicellular microvascular structures. Source

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