Center for Biomedical Engineering

Sun City Center, United States

Center for Biomedical Engineering

Sun City Center, United States
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Naz F.,All India Institute of Medical Sciences | Koul V.,Center for Biomedical Engineering | Srivastava A.,All India Institute of Medical Sciences | Gupta Y.K.,All India Institute of Medical Sciences | Dinda A.K.,All India Institute of Medical Sciences
Journal of Drug Targeting | Year: 2016

Gold nanoparticles (AuNPs) of ultrafine size have drawn attention for their use in drug delivery systems. Tissue toxicity may be an issue when AuNPs are used for such applications. We investigated the long-term biokinetics (90 d), redistribution, and urinary excretion of three different-sized (2 ± 0.5 nm, 5 ± 1 nm, and 10 ± 2 nm) AuNPs after a single intravenous (i.v.) administration of 1250 µg/kg dose in mice. ICP-AES analysis of lungs, liver, spleen, heart, kidney, brain, blood, and urine revealed highest accumulation of gold in spleen around 15 d after injection. A low concentration was detected in brain after 1 d without any residual AuNPs after 30 d. Ultrastructural study of brain tissue also showed few AuNPs in lysosome with no changes in cellular architecture. Renal retention of AuNPs was limited indicating low nephrotoxic potential. AuNPs were detectable in urine till 30 d after single injection indicating slow excretion from the body. No evidence of significant toxicity was observed in hemogram, serum biochemistry, and tissue histology. No mortality, changes in behavior, hair color, weight, and food intake was observed as compared to control mice. Therefore, we conclude that the ultrafine AuNPs are predominantly excreted in urine without any systemic toxicity following i.v. administration and are hence safe for use in drug delivery systems. © 2016 Informa UK Limited, trading as Taylor & Francis Group.


Tang Y.,Center for Biomedical Engineering | Hill E.H.,Center for Biomedical Engineering | Zhou Z.,Center for Biomedical Engineering | Zhou Z.,University of New Mexico | And 3 more authors.
Langmuir | Year: 2011

Three series of cationic oligo p-phenyleneethynylenes (OPEs) have been synthesized to study their structure-property relationships and gain insights into the transition from molecular to macromolecular properties. The absorbance maxima and molar extinction coefficients in all three sets increase with increasing number of repeat units; however, the increase in Imax between the oligomers having 2 and 3 repeat units is very small, and the oligomer having 3 repeat units shows virtually the same spectra as a p-phenyleneethynylene polymer having 49 repeat units. A computational study of the oligomers using density functional theory calculations indicates that while the simplest oligomers (OPE-1) are fully conjugated, the larger oligomers are nonplanar and the limiting "segment chromophore" may be confined to a near-planar segment extending over three or four phenyl rings. Several of the OPEs self-assemble on anionic "scaffolds", with pronounced changes in absorption and fluorescence. Both experimental and computational results suggest that the planarization of discrete conjugated segments along the phenylene-ethynylene backbone is predominantly responsible for the photophysical characteristics of the assemblies formed from the larger oligomers. The striking differences in fluorescence between methanol and water are attributed to reversible nucleophilic attack of structured interfacial water on the excited singlet state. © 2011 American Chemical Society.


Bajpayee A.G.,Massachusetts Institute of Technology | Bajpayee A.G.,Center for Biomedical Engineering | Scheu M.,Beth Israel Deaconess Medical Center | Grodzinsky A.J.,Massachusetts Institute of Technology | And 2 more authors.
Journal of Orthopaedic Research | Year: 2014

Intra-articular (i.a.) drug delivery for local treatment of osteoarthritis remains inadequate due to rapid clearance by the vasculature or lymphatics. Local therapy targeting articular cartilage is further complicated by its dense meshwork of collagen and negatively charged proteoglycans, which can prevent even nano-sized solutes from entering. In a previous in vitro study, we showed that Avidin, due to its size (7-nm diameter) and high positive charge (pI 10.5), penetrated the full thickness of bovine cartilage and was retained for 15 days. With the goal of using Avidin as a nano-carrier for cartilage drug delivery, we investigated its transport properties within rat knee joints. Avidin penetrated the full thickness of articular cartilage within 6-h, with a half-life of 29-h, and stayed inside the joint for 7 days after i.a. injection. The highest concentration of Avidin was found in cartilage, the least in patellar tendon and none in the femoral bone; in contrast, negligible Neutravidin (neutral counterpart of Avidin) was present in cartilage after 24-h. A positive correlation between tissue sGAG content and Avidin uptake (R2-=-0.83) confirmed the effects of electrostatic interactions. Avidin doses up to at least 1-μM did not affect bovine cartilage explant cell viability, matrix catabolism or biosynthesis. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.


Kumar M.,Center for Biomedical Engineering | Gupta D.,Center for Biomedical Engineering | Singh G.,Center for Biomedical Engineering | Sharma S.,Center for Biomedical Engineering | And 6 more authors.
Cancer Research | Year: 2014

The preclinical development of peptidyl drugs for cancer treatment is hampered by their poor pharmacologic properties and cell penetrative capabilities in vivo . In this study, we report a nanoparticle-based formulation that overcomes these limitations, illustrating their utility in studies of the anticancer peptide NuBCP-9, which converts BCL-2 from a cell protector to a cell killer. NuBCP-9 was encapsulated in polymeric nanoparticles composed of a polyethylene glycol (PEG)-modified polylactic acid (PLA) diblock copolymer (NuBCP-9/PLA-PEG) or PEGpolypropylene glycol-PEG-modified PLA - tetrablock copolymer (NuBCP-9/PLA-PEG-PPG-PEG). We found that peptide encapsulation was enhanced by increasing the PEG chain length in the block copolymers. NuBCP-9 release from the nanoparticles was controlled by both PEG chain length and the PLA molecular weight, permitting time-release over sustained periods. Treatment of human cancer cells with these nanoparticles in vitro triggered apoptosis by NuBCP-9-mediated mechanism, with a potency similar to NuBCP-9 linked to a cell-penetrating poly-Arg peptide. Strikingly, in vivo administration of NuBCP-9/nanoparticles triggered complete regressions in the Ehrlich syngeneic mouse model of solid tumor. Our results illustrate an effective method for sustained delivery of anticancer peptides, highlighting the superior qualities of the novel PLA-PEG-PPG-PEG tetrablock copolymer formulation as a tool to target intracellular proteins. ©2014 AACR.


News Article | November 9, 2015
Site: www.biosciencetechnology.com

Imitation may be the sincerest form of flattery but the best way to make something is often to co-opt the original process and make it work for you. In a sense, that’s how scientists at Brown University accomplished a new advance in tissue engineering. In the journal Biomaterials, the team reports culturing cells to make extracellular matrix (ECM) of two types and five different alignments with the strength found in natural tissue and without using any artificial chemicals that could make it incompatible to implant. ECM is the fibrous material between cells in tissues like skin, cartilage, or tendon that gives them their strength, stretchiness, squishiness, and other mechanical properties. To help patients heal wounds and injuries, engineers and physicians have strived to make ECM in the lab that’s aligned as well as it is when cells make it in the body. So far, though, they’ve struggled to recreate ECM. Using artificial materials provides strength, but those don’t interact well with the body. Attempts to extract and build upon natural ECM have yielded material that’s too weak to reimplant. The Brown team tried a different approach to making both collagen, which is strong, and elastin, which is stretchy, with different alignments of their fibers. They cultured ECM-making cells in specially designed molds that promoted the cells to make their own natural but precisely guided ECM. “What we hypothesized is that the cells are making it the same way they do in the body, because we’re starting them in a more natural environment,” said lead author Jacquelyn Schell, assistant professor (research) of molecular pharmacology, physiology and biotechnology. “We’re not adding exogenous materials.” The strategy built on the insight that when cells clump together and grow in culture, they pull on each other and communicate as they would in the body, Schell said. The molds therefore were made from agarose so that cells wouldn’t stick to the sides or bottom. Instead they huddled together. To guide ECM growth in particular alignments, the researchers used molds with very specific shapes, often constrained by pegs the cells had to grow around. For instance, to make a rod with collagen fibers aligned along its length (like a tendon) they cultured chondrocyte cells in a dog bone-shaped mold with loops on either end. To make a skin-like “trampoline” of elastin, where the ECM fibers run in all directions, they cultured fibroblast cells to grow in an open area suspended at the center of a honeycomb shape. “The placement of the pegs that this group of cells wraps itself around and then exerts force on each other is what dictates their alignment and the direction of the ECM they are going to synthesize,” said senior author Jeffrey Morgan, professor of medical science and engineering and co-director of Brown’s Center for Biomedical Engineering. “That’s a new ability to control the cells’ synthesis of extracellular matrix.” After the researchers grew various forms of ECM, they did some stress testing. They took the dog bone-shaped tissues to the lab of Christian Franck, assistant professor of engineering, and together made precise measurements of the tissue strength under the force of being pulled apart. The measurements confirmed the self-assembled tissue was about as strong as that found in some of the body’s tissues, such as skin, cartilage or blood vessels. The team’s next goal is to identify a prospective clinical application, Morgan said. The lab will pursue the needed testing to see if this new way of growing ECM can help future patients. The Department of Defense and the National Science Foundation funded the study.


Chaudhuri P.,Center for Biomedical Engineering | Harfouche R.,Center for Biomedical Engineering | Soni S.,Center for Biomedical Engineering | Hentschel D.M.,Harvard University | Sengupta S.,Center for Biomedical Engineering
ACS Nano | Year: 2010

Physically diverse carbon nanostructures are increasingly being studied for potential applications in cancer chemotherapy. However, limited knowledge exists on the effect of their shape in tuning the biological outcomes when used as nanovectors for drug delivery. In this study, we evaluated the effect of doxorubicinconjugated single walled carbon nanotubes (CNT-Dox) and doxorubicin-conjugated spherical polyhydroxylated fullerenes or fullerenols (Ful-Dox) on angiogenesis. We report that CNTs exert a pro-angiogenic effect in vitro and in vivo. In contrast, the fullerenols or doxorubicin-conjugated fullerenols exerted a dramatically opposite antiangiogenic activity in zebrafish and murine tumor angiogenesis models. Dissecting the angiogenic phenotype into discrete cellular steps revealed that fullerenols inhibited endothelial cell proliferation, while CNTs attenuated the cytotoxic effect of doxorubicin on the endothelial cells. Interestingly, CNT promoted endothelial tubulogenesis, a late step during angiogenesis. Further, mechanistic studies revealed that CNTs, but not fullerenols, induced integrin clustering and activated focal adhesion kinase and downstream phosphoinositide-3-kinase (PI3K) signaling in endothelial cells, which can explain the distinct angiogenic outcomes. The results of the study highlight the function of physical parameters of nanoparticles in determining their activity in biological settings. © 2010 American Chemical Society.


Ista L.K.,Center for Biomedical Engineering | Lopez G.P.,Center for Biomedical Engineering
Biointerphases | Year: 2013

Colloidal models are frequently used to model the thermodynamics of bacterial attachment to surfaces. The most commonly used of such models is that proposed by van Oss, Chaudhury and Good, which includes both non-polar and polar (including hydrogen bonding) interactions between the attaching bacterium, the attachment substratum and the aqueous environment. We use this model to calculate the free energy of adhesion, ∆Gadh, for attachment of the marine bacterium Cobetia marina to well defined attachment substrata that systematically vary in their chemistry and their ability to attach bacteria, namely a series of oligo(ethylene glycol) (OEG) terminated self-assembled monolayers that vary in the number of OEG moieties. For this system, the values of ∆Gadh calculated using VCG do not correlate with observed attachment profiles. We examine the validity of a number of assumptions inherent in VCG and other colloidal models of adhesion, with special attention paid to those regarding bacterial surfaces.


Ting C.M.,Center for Biomedical Engineering
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference | Year: 2012

This paper applies an expectation-maximization (EM) based Kalman smoother (KS) approach for single-trial event-related potential (ERP) estimation. Existing studies assume a Markov diffusion process for the dynamics of ERP parameters which is recursively estimated by optimal filtering approaches such as Kalman filter (KF). However, these studies only consider estimation of ERP state parameters while the model parameters are pre-specified using manual tuning, which is time-consuming for practical usage besides giving suboptimal estimates. We extend the KF approach by adding EM based maximum likelihood estimation of the model parameters to obtain more accurate ERP estimates automatically. We also introduce different model variants by allowing flexibility in the covariance structure of model noises. Optimal model selection is performed based on Akaike Information Criterion (AIC). The method is applied to estimation of chirp-evoked auditory brainstem responses (ABRs) for detection of wave V critical for assessment of hearing loss. Results shows that use of more complex covariances are better estimating inter-trial variability.


News Article | November 9, 2015
Site: www.rdmag.com

Imitation may be the sincerest form of flattery, but the best way to make something is often to co-opt the original process and make it work for you. In a sense, that’s how scientists at Brown Univ. accomplished a new advance in tissue engineering. In Biomaterials, the team reports culturing cells to make extracellular matrix (ECM) of two types and five different alignments with the strength found in natural tissue and without using any artificial chemicals that could make it incompatible to implant. ECM is the fibrous material between cells in tissues like skin, cartilage, or tendon that gives them their strength, stretchiness, squishiness and other mechanical properties. To help patients heal wounds and injuries, engineers and physicians have strived to make ECM in the lab that’s aligned, as well as it is when cells make it in the body. So far, though, they’ve struggled to recreate ECM. Using artificial materials provides strength, but those don’t interact well with the body. Attempts to extract and build upon natural ECM have yielded material that’s too weak to re-implant. The Brown team tried a different approach to making both collagen, which is strong, and elastin, which is stretchy, with different alignments of their fibers. They cultured ECM-making cells in specially designed molds that promoted the cells to make their own natural but precisely guided ECM. “What we hypothesized is that the cells are making it the same way they do in the body, because we’re starting them in a more natural environment,” said lead author Jacquelyn Schell, assistant professor (research) of molecular pharmacology, physiology and biotechnology. “We’re not adding exogenous materials.” The strategy built on the insight that when cells clump together and grow in culture, they pull on each other and communicate as they would in the body, Schell said. The molds therefore were made from agarose so that cells wouldn’t stick to the sides or bottom. Instead they huddled together. To guide ECM growth in particular alignments, the researchers used molds with very specific shapes, often constrained by pegs the cells had to grow around. For instance, to make a rod with collagen fibers aligned along its length (like a tendon) they cultured chondrocyte cells in a dog bone-shaped mold with loops on either end. To make a skin-like “trampoline” of elastin, where the ECM fibers run in all directions, they cultured fibroblast cells to grow in an open area suspended at the center of a honeycomb shape. “The placement of the pegs that this group of cells wraps itself around and then exerts force on each other is what dictates their alignment and the direction of the ECM they are going to synthesize,” said senior author Jeffrey Morgan, professor of medical science and engineering and co-director of Brown’s Center for Biomedical Engineering. “That’s a new ability to control the cells’ synthesis of extracellular matrix.” After the researchers grew various forms of ECM, they did some stress testing. They took the dog bone-shaped tissues to the lab of Christian Franck, assistant professor of engineering, and together made precise measurements of the tissue strength under the force of being pulled apart. The measurements confirmed the self-assembled tissue was about as strong as that found in some of the body’s tissues, such as skin, cartilage or blood vessels. The team’s next goal is to identify a prospective clinical application, Morgan said. The lab will pursue the needed testing to see if this new way of growing ECM can help future patients. The highly-anticipated educational tracks for the 2015 R&D 100 Awards & Technology Conference feature 28 sessions, plus keynote speakers Dean Kamen and Oak Ridge National Laboratory Director Thom Mason.  Learn more.


News Article | November 9, 2015
Site: phys.org

In the journal Biomaterials, the team reports culturing cells to make extracellular matrix (ECM) of two types and five different alignments with the strength found in natural tissue and without using any artificial chemicals that could make it incompatible to implant. ECM is the fibrous material between cells in tissues like skin, cartilage, or tendon that gives them their strength, stretchiness, squishiness, and other mechanical properties. To help patients heal wounds and injuries, engineers and physicians have strived to make ECM in the lab that's aligned as well as it is when cells make it in the body. So far, though, they've struggled to recreate ECM. Using artificial materials provides strength, but those don't interact well with the body. Attempts to extract and build upon natural ECM have yielded material that's too weak to reimplant. The Brown team tried a different approach to making both collagen, which is strong, and elastin, which is stretchy, with different alignments of their fibers. They cultured ECM-making cells in specially designed molds that promoted the cells to make their own natural but precisely guided ECM. "What we hypothesized is that the cells are making it the same way they do in the body, because we're starting them in a more natural environment," said lead author Jacquelyn Schell, assistant professor (research) of molecular pharmacology, physiology and biotechnology. "We're not adding exogenous materials." The strategy built on the insight that when cells clump together and grow in culture, they pull on each other and communicate as they would in the body, Schell said. The molds therefore were made from agarose so that cells wouldn't stick to the sides or bottom. Instead they huddled together. To guide ECM growth in particular alignments, the researchers used molds with very specific shapes, often constrained by pegs the cells had to grow around. For instance, to make a rod with collagen fibers aligned along its length (like a tendon) they cultured chondrocyte cells in a dog bone-shaped mold with loops on either end. To make a skin-like "trampoline" of elastin, where the ECM fibers run in all directions, they cultured fibroblast cells to grow in an open area suspended at the center of a honeycomb shape. "The placement of the pegs that this group of cells wraps itself around and then exerts force on each other is what dictates their alignment and the direction of the ECM they are going to synthesize," said senior author Jeffrey Morgan, professor of medical science and engineering and co-director of Brown's Center for Biomedical Engineering. "That's a new ability to control the cells' synthesis of extracellular matrix." After the researchers grew various forms of ECM, they did some stress testing. They took the dog bone-shaped tissues to the lab of Christian Franck, assistant professor of engineering, and together made precise measurements of the tissue strength under the force of being pulled apart. The measurements confirmed the self-assembled tissue was about as strong as that found in some of the body's tissues, such as skin, cartilage or blood vessels. The team's next goal is to identify a prospective clinical application, Morgan said. The lab will pursue the needed testing to see if this new way of growing ECM can help future patients. Explore further: Development of 'matrix' material controlling differentiation of stem cells

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