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1.
Nano Lett ; 18(11): 7314-7322, 2018 11 14.
Article in English | MEDLINE | ID: mdl-30380888

ABSTRACT

Nano- and microscale topographical cues have become recognized as major regulators of cell growth, migration, and phenotype. In tissue engineering, the complex and anisotropic architecture of culture platforms is aimed to imitate the high degree of spatial organization of the extracellular matrix and basement membrane components. Here, we developed a method of creating a novel, magnetically aligned, three-dimensional (3D) tissue culture matrix with three distinct classes of anisotropy-surface topography, microstructure, and physical properties. Alginate-stabilized magnetic nanoparticles (MNPs) were added to a cross-linked alginate solution, and an external magnetic field of about 2400 G was applied during freezing to form the aligned macroporous scaffold structure. The resultant scaffold exhibited anisotropic topographic features on the submicron scale, the directionality of the pore shape, and increased scaffold stiffness in the direction of magnetic alignment. These scaffold features were modulated by an alteration in the impregnated MNP size and concentration, as quantified by electron microscopy, advanced image processing analyses, and rheological methods. Mouse myoblasts (C2C12) cultured on the magnetically aligned scaffolds, demonstrated co-oriented morphology in the direction of the magnetic alignment. In summary, magnetic alignment introduces several degrees of anisotropy in the scaffold structure, providing diverse mechanical cues that can affect seeded cells and further tissue development. Multiscale anisotropy together with the capability of the MNP-containing alginate scaffolds to undergo reversible shape deformation in an oscillating magnetic field creates interesting opportunities for multifarious stimulation of cells and functional tissue development.

2.
J Control Release ; 232: 215-27, 2016 06 28.
Article in English | MEDLINE | ID: mdl-27117458

ABSTRACT

Therapeutic implementation of RNA interference (RNAi) through delivery of short interfering RNA (siRNA) is still facing several critical hurdles, which mostly can be solved through the use of an efficient delivery system. We hereby introduce anionic siRNA nanoparticles (NPs) co-assembled by the electrostatic interactions of the semi-synthetic polysaccharide hyaluronan-sulfate (HAS), with siRNA, mediated by calcium ion bridges. The NPs have an average size of 130nm and a mild (-10mV) negative surface charge. Transmission electron microscopy (TEM) using gold-labeled components and X-ray photoelectron spectroscopy (XPS) demonstrated the spatial organization of siRNA molecules in the particle core, surrounded by a layer of HAS. The anionic NPs efficiently encapsulated siRNA, were stable in physiological-relevant environments and were cytocompatible, not affecting cell viability or homeostasis. Efficient cellular uptake of the anionic siRNA NPs, associated with potent gene silencing (>80%), was observed across multiple cell types, including murine primary peritoneal macrophages and human hepatocellular carcinoma cells. In a clinically-relevant model of acute inflammatory response in IL-6-stimulated human hepatocytes, STAT3 silencing induced by HAS-Ca(2+)-siRNA NPs resulted in marked decrease in the total and activated STAT3 protein levels, as well as in the expression levels of downstream acute phase response genes. Collectively, anionic NPs prove to be an efficient and cytocompatible delivery system for siRNA.


Subject(s)
Calcium/metabolism , Hyaluronic Acid/administration & dosage , Nanoparticles/administration & dosage , RNA, Small Interfering/administration & dosage , Animals , Cell Line, Tumor , Cell Survival , Cells, Cultured , Fibroblasts/metabolism , Gene Silencing , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Hepatocytes/metabolism , Humans , Macrophages, Peritoneal/metabolism , Male , Mice, Inbred BALB C , STAT3 Transcription Factor/genetics
3.
Occup Ther Int ; 12(3): 123-36, 2005.
Article in English | MEDLINE | ID: mdl-16398202

ABSTRACT

Although the use of evidence-based practice (EBP) is presently on the rise, there have been limited studies examining its use by occupational therapists within the US. The purpose of this study was to examine the use of EBP among registered occupational therapists in the occupational therapy intervention planning process. This descriptive study surveyed 500 members of the American Occupational Therapy Association (AOTA), of which 131 participants responded (26%). The results of the study supported the hypothesis that, within the sample studied, a minority of registered occupational therapists in the US utilize EBP in the intervention planning process. Other results included: (1) As level of academic education increased, the view of the importance of research to occupational therapy decreased. (2) As the years of practice increased, the use of research evidence in making clinical decisions decreased. As the occupational therapy profession moves towards utilization of EBP as a professional standard, it is imperative that the profession examines specific strategies to promote the adoption of such practice by its members, including the promotion of competency in evidence utilization, and the valuing of the established clinical reasoning skills of the practitioner while integrating research evidence into intervention planning to support professional practice.


Subject(s)
Evidence-Based Medicine/statistics & numerical data , Occupational Therapy , Health Care Surveys , Humans , United States
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