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Bioengineering & Translational Medicine

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https://read.qxmd.com/read/30680327/interpretation-of-the-mechanism-of-action-of-antituberculosis-drug-bedaquiline-based-on-a-novel-two-ion-theory-of-energy-coupling-in-atp-synthesis
#1
Sunil Nath
Tuberculosis (TB) claims the lives of 1.3 million people each year, more than any other bacterial infection. Hence great interest was generated in health communities upon the recent introduction of the new diarylquinoline anti-TB drug, bedaquiline. Bedaquiline acts by binding to the c-subunit in the membrane-bound FO portion of the F1 FO -adenosine triphosphate (ATP) synthase, the universal enzyme that produces the ATP needed by cells. However, the mechanism of killing by bedaquiline is not fully understood...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680326/device-design-methodology-and-formulation-of-a-protein-therapeutic-for-sustained-release-intraocular-delivery
#2
Erica B Schlesinger, Daniel A Bernards, Hunter H Chen, James Feindt, Jingtai Cao, Daniel Dix, Carmelo Romano, Robert B Bhisitkul, Tejal A Desai
Despite years of effort, sustained delivery of protein therapeutics remains an unmet need due to three primary challenges - dose, duration, and stability. The work presented here provides a design methodology for polycaprolactone reservoir-based thin film devices suitable for long-acting protein delivery to the back of the eye. First, the challenge of formulating highly concentrated protein in a device reservoir was addressed by improving stability with solubility-reducing excipients. Next, predictive correlations between design parameters and device performance were developed to provide a methodology to achieve a target product profile...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680325/polymeric-curcumin-nanoparticles-by-a-facile-in-situ-method-for-macrophage-targeted-delivery
#3
Priyanka S Jahagirdar, Pramod K Gupta, Savita P Kulkarni, Padma V Devarajan
Targeting macrophages is a promising strategy for improved therapy of intracellular infections as macrophages exhibit rapid phagocytosis of particles >200 nm. Entrapment of Curcumin (CUR) in nanocarriers could provide bioenhancement and macrophage targeting. We present a simple and facile in situ nanoprecipitation approach for instantaneous and on-site generation of curcumin nanoparticles (ISCurNP). ISCurNP optimised by Box-Behnken design exhibited average size of 208.25 ± 7.55 nm and entrapment efficiency of 90...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680324/biodegradable-bioadhesive-nanoparticle-incorporation-of-broad-spectrum-organic-sunscreen-agents
#4
Hee-Won Suh, Julia Lewis, Linda Fong, Julie Ying Ramseier, Kacie Carlson, Zheng-Hong Peng, Emily Sara Yin, W Mark Saltzman, Michael Girardi
Conventional emulsion-based sunscreen formulations are limited by postapplication epicutaneous penetration that increases the risk of allergic dermatitis, cellular damage, and filter photodegradation upon ultraviolet radiation (UVR) exposure. Encapsulation of the UVB filter padimate O within bioadhesive biodegradable nanoparticles (BNPs) composed of poly(d,l-lactic acid)-hyperbranched polyglycerol was previously shown to enhance UVR protection while preventing skin absorption. Herein, we assess the capacity of BNP co-incorporation of avobenzone and octocrylene to provide broad-spectrum UVR protection...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680323/self-healing-encapsulation-and-controlled-release-of-vaccine-antigens-from-plga-microparticles-delivered-by-microneedle-patches
#5
J Maxwell Mazzara, Lukasz J Ochyl, Justin K Y Hong, James J Moon, Mark R Prausnitz, Steven P Schwendeman
There is an urgent need to reduce reliance on hypodermic injections for many vaccines to increase vaccination safety and coverage. Alternative approaches include controlled release formulations, which reduce dosing frequencies, and utilizing alternative delivery devices such as microneedle patches (MNPs). This work explores development of controlled release microparticles made of poly (lactic- co -glycolic acid) (PLGA) that stably encapsulate various antigens though aqueous active self-healing encapsulation (ASE)...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680322/gelatin-polysaccharide-composite-scaffolds-for-3d-cell-culture-and-tissue-engineering-towards-natural-therapeutics
#6
REVIEW
Samson Afewerki, Amir Sheikhi, Soundarapandian Kannan, Samad Ahadian, Ali Khademhosseini
Gelatin is a promising material as scaffold with therapeutic and regenerative characteristics due to its chemical similarities to the extracellular matrix (ECM) in the native tissues, biocompatibility, biodegradability, low antigenicity, cost-effectiveness, abundance, and accessible functional groups that allow facile chemical modifications with other biomaterials or biomolecules. Despite the advantages of gelatin, poor mechanical properties, sensitivity to enzymatic degradation, high viscosity, and reduced solubility in concentrated aqueous media have limited its applications and encouraged the development of gelatin-based composite hydrogels...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680321/applications-of-decellularized-extracellular-matrix-in-bone-and-cartilage-tissue-engineering
#7
REVIEW
Yu Seon Kim, Marjan Majid, Anthony J Melchiorri, Antonios G Mikos
Regenerative therapies for bone and cartilage injuries are currently unable to replicate the complex microenvironment of native tissue. There are many tissue engineering approaches attempting to address this issue through the use of synthetic materials. Although synthetic materials can be modified to simulate the mechanical and biochemical properties of the cell microenvironment, they do not mimic in full the multitude of interactions that take place within tissue. Decellularized extracellular matrix (dECM) has been established as a biomaterial that preserves a tissue's native environment, promotes cell proliferation, and provides cues for cell differentiation...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680320/lipid-nanoparticles-silence-tumor-necrosis-factor-%C3%AE-to-improve-wound-healing-in-diabetic-mice
#8
Lisa N Kasiewicz, Kathryn A Whitehead
Diabetes mellitus is a mounting concern in the United States, as are the mortality and morbidity that result from its complications. Of particular concern, diabetes patients frequently suffer from impaired wound healing and resultant nonhealing diabetic foot ulcers. These ulcers overproduce tumor necrosis factor α (TNFα), which reduces wound bed cell migration and proliferation while encouraging apoptosis. Herein, we describe the use of siRNA-loaded lipid nanoparticles (LNPs) as a potential wound treatment to combat an overzealous immune response and facilitate wound closure...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680319/multivariate-learning-framework-for-long-term-adaptation-in-the-artificial-pancreas
#9
Dawei Shi, Eyal Dassau, Francis J Doyle
The long-term use of the artificial pancreas (AP) requires an automated insulin delivery algorithm that can learn and adapt with the growth, development, and lifestyle changes of patients. In this work, we introduce a data-driven AP adaptation method for improved glucose management in a home environment. A two-phase Bayesian optimization assisted parameter learning algorithm is proposed to adapt basal and carbohydrate-ratio profile, and key feedback control parameters. The method is evaluated on the basis of the 111-adult cohort of the FDA-accepted UVA/Padova type 1 diabetes mellitus simulator through three scenarios with lifestyle disturbances and incorrect initial parameters...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680318/rescuing-mesenchymal-stem-cell-regenerative-properties-on-hydrogel-substrates-post-serial-expansion
#10
Varsha V Rao, Michael K Vu, Hao Ma, Anouk R Killaars, Kristi S Anseth
The use of human mesenchymal stem/stromal cells (hMSCs) in most clinical trials requires millions of cells/kg, necessitating ex vivo expansion typically on stiff substrates (tissue culture polystyrene [TCPS]), which induces osteogenesis and replicative senescence. Here, we quantified how serial expansion on TCPS influences proliferation, expression of hMSC-specific surface markers, mechanosensing, and secretome. Results show decreased proliferation and surface marker expression after five passages (P5) and decreased mechanosensing ability and cytokine production at later passages (P11-P12)...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680317/engineering-on-demand-manufacturing-and-scaling-up-of-polymeric-nanocapsules
#11
José Crecente-Campo, María José Alonso
Polymeric nanocapsules are versatile delivery systems with the capacity to load lipophilic drugs in their oily nucleus and hydrophilic drugs in their polymeric shell. The objective of this work was to expand the technological possibilities to prepare customized nanocapsules. First, we adapted the solvent displacement technique to modulate the particle size of the resulting nanocapsules in the 50-500 nm range. We also produced nanosystems with a shell made of one or multiple polymer layers i.e. chitosan, dextran sulphate, hyaluronate, chondroitin sulphate, and alginate...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680316/method-of-establishing-breast-cancer-brain-metastases-affects-brain-uptake-and-efficacy-of-targeted-therapeutic-nanoparticles
#12
Emily A Wyatt, Mark E Davis
HER2-targeted therapies effectively control systemic disease, but their efficacy against brain metastases is hindered by their low penetration of the blood-brain and blood-tumor barriers (BBB and BTB). We investigate brain uptake and antitumor efficacy of transferrin receptor (TfR)-targeted, therapeutic nanoparticles designed to transcytose the BBB/BTB in three murine models. Two known models involving intracranial (IC) or intracardiac (ICD) injection of human breast cancer cells were employed, as was a third model developed here involving intravenous (IV) injection of the cells to form whole-body tumors that eventually metastasize to the brain...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680315/uptake-and-function-of-membrane-destabilizing-cationic-nanogels-for-intracellular-drug-delivery
#13
William B Liechty, Rebekah L Scheuerle, Julia E Vela Ramirez, Nicholas A Peppas
The design of intracellular drug delivery vehicles demands an in-depth understanding of their internalization and function upon entering the cell to tailor the physicochemical characteristics of these platforms and achieve efficacious treatments. Polymeric cationic systems have been broadly accepted to be membrane disruptive thus being beneficial for drug delivery inside the cell. However, if excessive destabilization takes place, it can lead to adverse effects. One of the strategies used to modulate the cationic charge is the incorporation of hydrophobic moieties, thus increasing the hydrophobic content...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680314/nanocrystals-a-perspective-on-translational-research-and-clinical-studies
#14
REVIEW
Maria Jarvis, Vinu Krishnan, Samir Mitragotri
Poorly soluble small molecules typically pose translational hurdles owing to their low solubility, low bioavailability, and formulation challenges. Nanocrystallization is a versatile method for salvaging poorly soluble drugs with the added benefit of a carrier-free delivery system. In this review, we provide a comprehensive analysis of nanocrystals with emphasis on their clinical translation. Additionally, the review sheds light on clinically approved nanocrystal drug products as well as those in development...
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30680313/biotm-buzz-volume-4-issue-1
#15
Aaron C Anselmo
No abstract text is available yet for this article.
January 2019: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30377665/encapsulation-of-mesenchymal-stem-cells-in-glycosaminoglycans-chitosan-polyelectrolyte-microcapsules-using-electrospraying-technique-investigating-capsule-morphology-and-cell-viability
#16
Amin Vossoughi, Howard W T Matthew
Polyelectrolyte microcapsules are modular constructs which facilitate cell handling and assembly of cell-based tissue constructs. In this study, an electrospray (ES) encapsulation apparatus was developed for the encapsulation of mesenchymal stem cells (MSCs). Ionic complexation between glycosaminoglycans (GAGs) and chitosan formed a polyelectrolyte complex membrane at the interface. To optimize the capsules, the effect of voltage, needle size and GAG formulation on capsule size were investigated. It was observed that by increasing the voltage and decreasing the needle size, the capsule size would decrease but at voltages above 12 kV, capsule size distribution broadened significantly which yields lower circularity...
September 2018: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30377664/derivation-of-neural-crest-stem-cells-from-human-epidermal-keratinocytes-requires-fgf-2-igf-1-and-inhibition-of-tgf-%C3%AE-1
#17
Georgios Tseropoulos, Samaneh Moghadasi Boroujeni, Vivek K Bajpai, Pedro Lei, Stelios T Andreadis
Neural crest (NC) cells play a central role in forming the peripheral nervous system, the craniofacial skeleton, and the pigmentation of the skin during development due to their broad multilineage differentiation potential into neurons, Schwann cells, melanocytes, and mesenchymal stem cells. Recently, we identified an easily accessible source of pluripotent NC stem cells from human inter-follicular keratinocyte (KC) cultures (KC-NC). In this work, we examined specific conditions for the derivation of NC from KC cultures...
September 2018: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30377663/engineering-molecular-imaging-strategies-for-regenerative-medicine
#18
REVIEW
Matthew Willadsen, Marc Chaise, Iven Yarovoy, An Qi Zhang, Natesh Parashurama
The reshaping of the world's aging population has created an urgent need for therapies for chronic diseases. Regenerative medicine offers a ray of hope, and its complex solutions include material, cellular, or tissue systems. We review basics of regenerative medicine/stem cells and describe how the field of molecular imaging, which is based on quantitative, noninvasive, imaging of biological events in living subjects, can be applied to regenerative medicine in order to interrogate tissues in innovative, informative, and personalized ways...
September 2018: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30377662/in-silico-analytico-mathematical-interpretation-of-biopolymeric-assemblies-quantification-of-energy-surfaces-and-molecular-attributes-via-atomistic-simulations
#19
REVIEW
Pradeep Kumar, Yahya E Choonara, Viness Pillay
Static-lattice atomistic simulations, in vacuum and solvent phase, have been recently employed to quantify the "in vitro-in vivo-in silico" performance-correlation profile of various drug delivery systems and biomaterial scaffolds. The reactional profile of biopolymers was elucidated by exploring the spatial disposition of the molecular components with respect to the formulation conditions and the final release medium. This manuscript provides a brief overview of recently completed and published studies related to molecular tectonics of: (a) the nanoformation and solvation properties of the surfactant-emulsified polymeric systems; (b) the formation and chemistry of polyelectrolyte complexes; (c) the effect of a plasticizer and/or drug on the physicomechanical properties of biomedical archetypes; (d) the molecular modeling templates to predict stimuli- and environmentally esponsive systems; and (e) the polymer-mucopeptide complexes and intermacromolecular networks...
September 2018: Bioengineering & Translational Medicine
https://read.qxmd.com/read/30377661/a-platform-of-genetically-engineered-bacteria-as-vehicles-for-localized-delivery-of-therapeutics-toward-applications-for-crohn-s-disease
#20
Ryan McKay, Monil Ghodasra, John Schardt, David Quan, Alex Eli Pottash, Wu Shang, Steven M Jay, Gregory F Payne, Matthew Wook Chang, John C March, William E Bentley
For therapies targeting diseases of the gastrointestinal tract, we and others envision probiotic bacteria that synthesize and excrete biotherapeutics at disease sites. Toward this goal, we have engineered commensal E. coli that selectively synthesize and secrete a model biotherapeutic in the presence of nitric oxide (NO), an intestinal biomarker for Crohn's disease (CD). This is accomplished by co-expressing the pore forming protein TolAIII with the biologic, granulocyte macrophage-colony stimulating factor (GM-CSF)...
September 2018: Bioengineering & Translational Medicine
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