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Richmond, VA, United States

Guiseppi-Elie A.,ABTECH Scientific Inc. | Guiseppi-Elie A.,Clemson University
Biomaterials | Year: 2010

Electroconductive hydrogels (ECHs) are composite biomaterials that bring together the redox switching and electrical properties of inherently conductive electroactive polymers (CEPs) with the facile small molecule transport, high hydration levels and biocompatibility of cross-linked hydrogels. General methods for the synthesis of electroconductive hydrogels as polymer blends and as polymer co-networks via chemical oxidative, electrochemical and/or a combination of chemical oxidation followed by electrochemical polymerization techniques are reviewed. Specific examples are introduced to illustrate the preparation of electroconductive hydrogels that were synthesized from poly(HEMA)-based hydrogels with polyaniline and from poly(HEMA)-based hydrogels with polypyrrole. The key applications of electroconductive hydrogels; as biorecognition membranes for implantable biosensors, as electro-stimulated drug release devices for programmed delivery, and as the low interfacial impedance layers on neuronal prostheses are highlighted. These applications provide great new horizons for these stimuli responsive, biomimetic polymeric materials. © 2009 Elsevier Ltd. All rights reserved.


Guiseppi-Elie A.,Clemson University | Guiseppi-Elie A.,ABTECH Scientific Inc.
Analytical and Bioanalytical Chemistry | Year: 2011

Following hemorrhage-causing injury, lactate levels rise and correlate with the severity of injury and are a surrogate of oxygen debt. Posttraumatic injury also includes hyperglycemia, with continuously elevated glucose levels leading to extensive tissue damage, septicemia, and multiple organ dysfunction syndrome. A temporary, implantable, integrated glucose and lactate biosensor and communications biochip for physiological status monitoring during hemorrhage and for intensive care unit stays has been developed. The dual responsive, amperometric biotransducer uses the microdisc electrode array format upon which were separately immobilized glucose oxidase and lactate oxidase within biorecognition layers, 1.0-5.0 μm thick, of 3 mol% tetraethyleneglycol diacrylate cross-linked p(HEMA-co-PEGMA-co-HMMA-co-SPA)-p(Py-co-PyBA) electroconductive hydrogels. The device was then coated with a bioactive hydrogel layer containing phosphoryl choline and polyethylene glycol pendant moieties [p(HEMA-co-PEGMA-co-HMMA-co-MPC)] for indwelling biocompatibility. In vitro cell proliferation and viability studies confirmed both polymers to be non-cytotoxic; however, PPy-based electroconductive hydrogels showed greater RMS 13 and PC12 proliferation compared to controls. The glucose and lactate biotransducers exhibited linear dynamic ranges of 0.10-13.0 mM glucose and 1.0-7.0 mM and response times (t 95) of 50 and 35-40 s, respectively. Operational stability gave 80% of the initial biosensor response after 5 days of continuous operation at 37 °C. Preliminary in vivo studies in a Sprague-Dawley hemorrhage model showed tissue lactate levels to rise more rapidly than systematic lactate. The potential for an implantable biochip that supports telemetric reporting of intramuscular lactate and glucose levels allows the refinement of resuscitation approaches for civilian and combat trauma victims. © 2010 Springer-Verlag.


Kotanen C.N.,Clemson University | Tlili C.,Clemson University | Guiseppi-Elie A.,Clemson University | Guiseppi-Elie A.,ABTECH Scientific Inc.
Talanta | Year: 2013

Fabrication of an enzyme amperometric biosensor for glucose via electropolymerization of pyrrole in the presence of glucose oxidase onto a hydrogel coated platinum electrode is hereby established as a viable biotransducer fabrication method. Platinum micro- (φ=25 mm) and macro- (φ=100 μm) electrodes were electrochemically activated and chemically modified with 3-aminopropyl-trimethoxysilane (APTMS), functionalized with acryloyl(polyethyleneglycol)-N-hydroxysuccinamide (ACRL-PEG-NHS), dipped into a polyHEMA based hydrogel cocktail and UV cross-linked. Electropolymerization of Py in the presence of GOx produced glucose responsive biotransducers that showed; (i) a 4-fold reduction in sensitivity compared with directly electropolymerized PPy films, (ii) an electropolymerization charge density dependence of biotransducer sensitivity and enzyme activity that was maximal at 1.0 mC/cm2 with an apparent KM of 33 mM, (iii) interference screening of ascorbic acid and (iv) a temporal increase in sensitivity with storage over a 17 days period. This method has the ability to precisely and quantitatively add enzyme catalytic bioactivity to metal or semiconductor biointerfaces for applications in biosensors, bioelectronics and bionics. © 2012 Elsevier B.V. All rights reserved.


Kotanen C.N.,Clemson University | Moussy F.G.,Brunel University | Carrara S.,Ecole Polytechnique Federale de Lausanne | Guiseppi-Elie A.,Clemson University | Guiseppi-Elie A.,ABTECH Scientific Inc.
Biosensors and Bioelectronics | Year: 2012

The implantable enzyme amperometric biosensor continues as the dominant in vivo format for the detection, monitoring and reporting of biochemical analytes related to a wide range of pathologies. Widely used in animal studies, there is increasing emphasis on their use in diabetes care and management, the management of trauma-associated hemorrhage and in critical care monitoring by intensivists in the ICU. These frontier opportunities demand continuous indwelling performance for up to several years, well in excess of the currently approved seven days. This review outlines the many challenges to successful deployment of chronically implantable amperometric enzyme biosensors and emphasizes the emerging technological approaches in their continued development. The foreign body response plays a prominent role in implantable biotransducer failure. Topics considering the approaches to mitigate the inflammatory response, use of biomimetic chemistries, nanostructured topographies, drug eluting constructs, and tissue-to-device interface modulus matching are reviewed. Similarly, factors that influence biotransducer performance such as enzyme stability, substrate interference, mediator selection and calibration are reviewed. For the biosensor system, the opportunities and challenges of integration, guided by footprint requirements, the limitations of mixed signal electronics, and power requirements, has produced three systems approaches. The potential is great. However, integration along the multiple length scales needed to address fundamental issues and integration across the diverse disciplines needed to achieve success of these highly integrated systems, continues to be a challenge in the development and deployment of implantable amperometric enzyme biosensor systems. © 2012 Elsevier B.V.


Wilson A.N.,Clemson University | Guiseppi-Elie A.,Clemson University | Guiseppi-Elie A.,ABTECH Scientific Inc.
Advanced Healthcare Materials | Year: 2013

Bioresponsive hydrogels are emerging with technological significance in targeted drug delivery, biosensors, and regenerative medicine. Their ability to respond to specific biologically derived stimuli creates a design challenge in effectively linking the conferred biospecificity with an engineered response tailored to the needs of a particular application. Moreover, the fundamental phenomena governing the response must support an appropriate dynamic range, limit of detection, and the potential for feedback control. The design of these systems is inherently complicated due to the high interdependency of the governing phenomena that guide sensing, transduction, and actuation of the hydrogel. Future advancements in bioresponsive hydrogels will out of necessity contain control loops similar to synthetic metabolic pathways. The use of these materials will continue to expand as they become coupled and integrated with new technologies. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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