Cover Picture: Organ Repair, Hemostasis, and In Vivo Bonding of Medical Devices by Aqueous Solutions of Nanoparticles (Angew. Chem. Int. Ed. 25/2014)

Thermoresponsive materials have the ability to respond to a small change in temperature—a property that makes them useful in a wide range of applications and medical devices. Although very promising, there is only little conclusive data about the cytotoxicity and tissue toxicity of these materials. This work studied the biocompatibility of three Food and Drug Administration approved thermoresponsive polymers: poly( N-isopropyl acrylamide), poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) tri-block copolymer, and poly(lactic acid-co-glycolic acid) and poly(ethylene glycol) tri-block copolymer. Fibroblast NIH 3T3 and HaCaT keratinocyte cells were used for the cytotoxicity testing and a mouse model for the in vivo evaluation. In vivo results generally showed similar trends as the results seen in vitro, with all tested materials presenting a satisfactory biocompatibility in vivo. pNIPAM, however, showed the highest toxicity both in vitro and in vivo, which was explained by the release of harmful monomers and impurities. More data focusing on the biocompatibility of novel thermoresponsive biomaterials will facilitate the use of existing and future medical devices.

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DNA KNOT FORMATION IN AQUEOUS SOLUTIONS

Journal of Knot Theory and Its Ramifications ◽

10.1142/s0218216594000228 ◽

1994 ◽

Vol 03 (03) ◽

pp. 287-298 ◽

Cited By ~ 8

Author(s):

STANLEY Y. SHAW ◽

JAMES C. WANG

Keyword(s):

Aqueous Solutions ◽

Experimental Test ◽

Attractive Potential ◽

Sodium Ions ◽

Magnesium Ions ◽

Close Apposition ◽

Closed Chain ◽

Solvent Properties

The knotting probability of a closed chain has been calculated as a function of chain dimensions and solvent properties in a number of studies. We have measured the probability of DNA knot formation upon random cyclization of linear DNA in vitro to provide an experimental test of the various theoretical treatments of the problem; parameters of these models, such as the effective chain diameter of DNA, were calculated in different concentrations of counterions. Our results in the presence of sodium ions agree well with theoretical treatments of DNA as a polyelectrolyte; knotting data in the presence of divalent magnesium ions indicate that moderate concentrations of magnesium ions can induce an attractive potential between DNA segments, resulting in negative values of the calculated effective DNA helix diameter. We discuss structures in which the divalent magnesium counterion facilitates the close apposition of two DNA segments, and review the effect of chemical- and protein-mediated crosslinks between DNA segments on DNA knot formation. Finally, we consider DNA knot formation in vivo.

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In Vivo Bioreactor: New Type of Implantable Medical Devices

Security and Privacy for Implantable Medical Devices ◽

10.1007/978-1-4614-1674-6_5 ◽

2013 ◽

pp. 129-152

Author(s):

Qiang Tan

Keyword(s):

Medical Devices ◽

Implantable Medical Devices ◽

New Type

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Modern Strategies in the Prevention of Implant-Associated Infections

The International Journal of Artificial Organs ◽

10.1177/039139880502801112 ◽

2005 ◽

Vol 28 (11) ◽

pp. 1146-1156 ◽

Cited By ~ 32

Author(s):

C. Von Eiff ◽

W. Kohnen ◽

K. Becker ◽

B. Jansen

Keyword(s):

Medical Devices ◽

Fungal Infections ◽

Material Surface ◽

Strict Adherence ◽

Antimicrobial Substances ◽

Substantial Risk ◽

Considerable Impact ◽

Almost All ◽

Microbial Adherence

The application of medical devices either for temporary or permanent use has become an indispensible part of almost all fields of medicine. However, foreign bodies are associated with a substantial risk of bacterial and fungal infections. Implant-associated infections significantly contribute to the still increasing problem of nosocomial infections. To reduce the incidence of such infections, specific guidelines providing evidence-based recommendations and comprising both technological and nontechnological strategies for prevention have been established. Strict adherence to hygienic rules during insertion or implantation of the device are aspects of particular importance. Besides such basic and indispensable aspects, the development of new materials which could withstand microbial adherence and colonization has become a major topic in recent years. Modification of surface by primarily physico-chemical methods may lead to a change in specific and unspecific interactions with microorganisms and, thus, to a reduction in microbial adherence. Medical devices made out of a material that would be ideally antiadhesive or at least colonization-resistant would be the most suitable candidates to avoid colonization and subsequent infection. However, it appears impossible to create a surface with an absolute “zero”-adherence due to thermodynamical reasons and due to the fact that a modified material surface is in vivo rapidly covered by plasma and connective tissue proteins. Therefore, another concept for the prevention of implant-associated infections involves the impregnation of devices with various antimicrobial substances such as antibiotics, antiseptics, and/or metals. In fact, already commercially available materials for clinical use such as antimicrobial catheters have been introduced, in part with considerable impact on subsequent infections. However, future studies are warranted to translate the knowledge on the pathogenesis of device-associated infections into applicable prevention strategies.

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Hematin-derived anticoagulant. Generation in vitro and in vivo.

Journal of Experimental Medicine ◽

10.1084/jem.163.3.724 ◽

1986 ◽

Vol 163 (3) ◽

pp. 724-739 ◽

Cited By ~ 15

Author(s):

R L Jones

Keyword(s):

Aqueous Solutions ◽

Anticoagulant Activity ◽

Parent Compound ◽

Iron Chelator ◽

Ferric Citrate ◽

Anticoagulant Effect ◽

Single Peak

Prolongation of clotting times produced by hematin was investigated both in vitro and in vivo. Hematin-derived anticoagulant (HDA) was found to be due to a degradative product or derivative of hematin, and was generated in vitro in standing (aging) aqueous solutions of the parent compound. Generation of HDA in vitro was inhibited by antioxidants. The anticoagulant effect of HDA was inhibited by freshly prepared hematin, fresh Sn-protoporphyrin, imidazole, or the iron chelator desferrioxamine. Ferrioxamine did not inhibit HDA, and inhibition by imidazole was reversed with ferric citrate, suggesting a role for iron in the mechanism of HDA activity. HDA activity was dissociated from hematin in plasma by clotting with thrombin. HDA segregated into the clot fraction, whereas hematin remained largely in the serum fraction, suggesting that HDA may preferentially bind to fibrinogen. TLC and HPLC showed a single peak of HDA activity that was not associated with the parent compound. Evidence for HDA generation in vivo was found when rats were injected with fresh (no HDA) hematin. Prolongation of clotting times appeared after hematin appeared in the plasma, and anticoagulant activity persisted after a fall in plasma hematin concentration. Thus, there was a temporal dissociation between hematin and HDA, suggesting that a modification of hematin must occur in vivo before an anticoagulant effect is produced. Generation of HDA in vitro has implications for hematin preparation and administration. Generation of HDA in vivo suggests that similar modifications of endogenous heme or other porphyrins may occur to produce HDA under physiologic or pathophysiologic conditions.

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High Resolution NMR Spectroscopy on Whole-Body Imagers:Optimized Single-and Multi-Pulse Experiments in Vitro

Zeitschrift für Naturforschung A ◽

10.1515/zna-1995-1006 ◽

1995 ◽

Vol 50 (10) ◽

pp. 942-948

Author(s):

Fritz Schick

Keyword(s):

Aqueous Solutions ◽

Spin Echo ◽

Single Pulse ◽

Spin Systems ◽

The Body ◽

Coupling Constants ◽

Whole Body ◽

Receiver Coil

Abstract From 100 ml spherical glass bottles filled with aqueous solutions and suspended in a homogeneous magnetic field, NMR spectra with linewidths of about 0.7 Hz were achieved in single-pulse and multi-pulse spectra. A relatively wide receiver coil as the body coil or the standard head coil of the manufacturer were employed to acquire spectra after different non-localized pulse sequences. Examples of single-pulse spectra and double spin-echo spectra of aqueous solutions with lactate, citrate, or glucose are demonstrated and discussed. The fact that all experiments can be performed using well-defined pulse angles acting on the entire sample at the field strenght of the whole-body unit allows to determine the characteristics (e.g. chemical shift differences, coupling constants) of spin systems of biologically important molecules precisely, without need for additional spectrometers. Constant flip angles are advantageous for adequate theoretical analysis of spectra from coupled spin systems. The effects of a defined "misadjustment" of the transmitter on the spectra can be measured directly, whereas localized methods always yield a superposition of signals due to the distribution of flip angles inside the selected volume. In some cases, optimized sequence parameters for localized examinations in vivo can be derived numerically from the analyzed coupling data.

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Recommendations for Nanomedicine Human Subjects Research Oversight: An Evolutionary Approach for an Emerging Field

The Journal of Law Medicine & Ethics ◽

10.1111/j.1748-720x.2012.00703.x ◽

2012 ◽

Vol 40 (4) ◽

pp. 716-750 ◽

Cited By ~ 17

Author(s):

Leili Fatehi ◽

Susan M. Wolf ◽

Jeffrey McCullough ◽

Ralph Hall ◽

Frances Lawrenz ◽

...

Keyword(s):

Medical Devices ◽

Human Subjects ◽

High Surface ◽

The Body ◽

Biologically Active ◽

Implantable Medical Devices ◽

Research Oversight ◽

Insoluble Drugs ◽

Drug Eluting

Nanomedicine is yielding new and improved treatments and diagnostics for a range of diseases and disorders. Nanomedicine applications incorporate materials and components with nanoscale dimensions (often defined as 1-100 nm, but sometimes defined to include dimensions up to 1000 nm, as discussed further below) where novel physiochemical properties emerge as a result of size-dependent phenomena and high surface-to-mass ratio. Nanotherapeutics and in vivo nanodiagnostics are a subset of nanomedicine products that enter the human body. These include drugs, biological products (biologics), implantable medical devices, and combination products that are designed to function in the body in ways unachievable at larger scales. Nanotherapeutics and in vivo nanodiagnostics incorporate materials that are engineered at the nanoscale to express novel properties that are medicinally useful. These nanomedicine applications can also contain nanomaterials that are biologically active, producing interactions that depend on biological triggers. Examples include nanoscale formulations of insoluble drugs to improve bioavailability and pharmacokinetics, drugs encapsulated in hollow nanoparticles with the ability to target and cross cellular and tissue membranes (including the bloodbrain barrier) and to release their payload at a specific time or location, imaging agents that demonstrate novel optical properties to aid in locating micrometastases, and antimicrobial and drug-eluting components or coatings of implantable medical devices such as stents.

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