Ithaca, NY, United States
Ithaca, NY, United States

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This paper describes a layer-by-layer (LBL) electrostatic self-assembly process for fabricating highly efficient antimicrobial nanocoatings on a natural cellulose substrate. The composite materials comprise a chemically modified cotton substrate and a layer of sub-5 nm copper-based nanoparticles. The LBL process involves a chemical preconditioning step to impart high negative surface charge on the cotton substrate for chelation controlled binding of cupric ions (Cu 2+), followed by chemical reduction to yield nanostructured coatings on cotton fibers. These model wound dressings exhibit rapid and efficient killing of a multidrug resistant bacterial wound pathogen, A. baumannii, where an 8-log reduction in bacterial growth can be achieved in as little as 10 min of contact. Comparative silver-based nanocoated wound dressings-a more conventional antimicrobial composite material-exhibit much lower antimicrobial efficiencies; a 5-log reduction in A. baumannii growth is possible after 24 h exposure times to silver nanoparticle-coated cotton substrates. The copper nanoparticle-cotton composites described herein also resist leaching of copper species in the presence of buffer, and exhibit an order of magnitude higher killing efficiency using 20 times less total metal when compared to tests using soluble Cu 2+. Together these data suggest that copper-based nanoparticle-coated cotton materials have facile antimicrobial properties in the presence of A. baumannii through a process that may be associated with contact killing, and not simply due to enhanced release of metal ion. The biocompatibility of these copper-cotton composites toward embryonic fibroblast stem cells in vitro suggests their potential as a new paradigm in metal-based wound care and combating pathogenic bacterial infections. Nanostructured copper coatings on natural cellulose (woven cotton substrate; left) are produced using a layer-by-layer electrostatic self-assembly process. The resulting copper nanoparticle-coated cotton fiber composites exhibit extremely efficient antimicrobial activity against a multi-drug resistant bacterial pathogen through a putative contact-killing mechanism at the nanostructured cotton interface. The substrates exhibit an 8-log reduction in bacterial growth in as little as ten minutes. These unique materials also show mammalian cell biocompatibility as indicated in the confocal fluorescence microscopy image showing healthy mouse fibroblast cells growing in the presence of nanostructured copper-coated cotton substrates after 48 hours. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 231.70K | Year: 2012

DESCRIPTION (provided by applicant): Seromas are a common post-operative complication particularly prevalent following ablative and reconstructive surgeries. Without timely intervention post-operative seromas can lead to significant patient morbidity including infection, tissue necrosis, permanent cystic cavities, reduced limb mobility and permanent disfigurement. The high incidence of seroma formation and the resulting increase in patient morbidity has led to the widespread use of drainage to treat seromaafter formation. The last several decades have also seen the development and implementation of several clinical and experimental preventative treatment strategies; however, to date no preventative strategy has shown clinically relevant efficacy and seromarates remain at unacceptably high levels. Consequently, there is a clear need for a clinically effective, preventative seroma treatment. The current STTR funded research effort will lay the foundation for the commercialization of a new class of biomaterialfor the prevention of seroma, thereby enhancing patient health through improved patient outcomes and reduced patient morbidity. Preliminary studies have shown that a novel coblock polymer in hydrogel form, consisting of a methoxy polyethylene glycol (MPEG) block and a block of the polycarbonate form of dihidroxyacetone (pDHA), has shown efficacy in preventing seroma formation. Through the completion of research and development tasks during Phase I/II efforts, a compelling data set will be compiled on thebiocompatibility, the efficacy and the mode of action of MPEG-pDHA in seroma prevention. This data set will support the entry of MPEG-pDHA into the FDA's regulatory process. A significant preliminary data set demonstrating the clinical utility of MPEG-pDHA hydrogels in seroma prevention has been developed. Key features of this biomaterial are: in vitro and in vivo biodegradation (within 24h in vitro and 3 das in vivo) into biocompatible products, and successful elimination of seroma in an accepted animal model of radical mastectomy. Phase I efforts will focus on determining the range of efficacy of MPEG-pDHA in vivo and on evaluating its biocompatibility using FDA accepted in vitro and in vivo biocompatibility testing standards. The key tasks are listed below: Task 1 - Synthesize and characterize the MPEG-pDHA polymers to be used during the Phase I study. Task 2 - Determine the range of efficacy in vivo using a model involving the harvesting of the rat latissimus dorsi muscle. Task 3 - Use FDA accepted ISO 10993 standards to quantify biocompatibility through in vitro cytotoxicity, genotoxicity, systemic toxicity, and hemocompatibility studies and local toxic effects after implantation through in vivo animal studies. PUBLIC HEALTH RELEVANCE: Seroma formation is a common post-operative complication that diminishes patient health and for which there are no accepted preventative treatments. The current STTR funded research effort aims to advance the development of a new biodegradable material for the prevention of seroma and thereby improve patient health through improved surgical outcomes.


Disclosed in this specification is a method for detecting an analyte using buoyant particles and chemical moieties to give buoyant particle composites that exhibit SERS and can be used for detecting the analytes in a liquid sample. A method is provided for detecting analytes of interest by contacting the analyte with a buoyant particle that comprises a first chemical moiety, such as a SERS-active component, allowing the analyte of interest to bind to the first chemical moiety. The resulting composite localizes in a discrete location of the liquid sample through a buoyant force. The composite is then detected by measuring the Raman scattered light in the discrete location of the liquid sample.


Grant
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2011

This Small Business Innovation Research Phase I project addresses the important problem of combating hospital acquired infections with the development of novel tissue matrices aimed at preventing nosocomial microbial infection. The aim of this project is to combine antimicrobial nanomaterials and a natural dermis product to help prevent infections that occur during reconstructive surgeries. This proof-of-concept study will develop methods for the production of uniform and conformal coatings on natural tissue matrices using layer-by-layer assembly of antimicrobial nanoparticles. Importantly, this project will evaluate the efficacy of nanocoated natural dermis in eliminating or inhibiting bacterial growth in liquid and solid media. In vitro studies also will be conducted to establish mammalian cell toxicity and viability of the engineered dermis in supporting mammalian cell growth. Phase I results are expected to produce an optimized antimicrobial dermis scaffold that will be carried onto a focused Phase II evaluation in animal experimental wounds. The broader impact/commercial potential of this project will address the growing problem of hospital acquired infections from antibiotic resistant pathogens. With nearly 1.7 million hospital-acquired infections and 99,000 deaths per year, increases in antibiotic-resistant bacterial strains represent a critical safety concern and a significant cost burden to our nation's health care system. The proposed technology is a versatile option that provides a broad spectrum solution in combating bacterial infections and the prevalence of antibiotic resistance. Furthermore, the methods used to characterize the proposed composite materials will add valuable insight into mechanisms associated with nanoparticle-derived antimicrobial activity, and will help guide future efforts in the arena of nanobiotechnology.


Grant
Agency: Department of Defense | Branch: Army | Program: SBIR | Phase: Phase I | Award Amount: 69.90K | Year: 2011

iFyber LLC, the lead company for this project, will partner with Prof. CC Chu from Cornell University, a recognized expert in the development and study of new drug-eluting biomaterials for wound healing, to develop a platform technology for controlled release of nitric using a newly invented family of novel biodegradable amino acid-based poly(ester amide)s (AA-PEAs). These pseudo-protein biomaterials have been engineered into different physical forms including gels, fibrous membranes, micro/nanospheres. These novel pseudo-protein biomaterials have already been demonstrated in vitro and in vivo to elicit far lower levels of inflammation than existing FDA-approved commercial biomaterials. The current efforts will exploit AA-PEA-based biodegradable biomaterials that are enzymatically biodegradable and have pendant functional groups that can be used to conjugate condensed-phase nitric oxide (NO) moieties. Controlled release of nitric oxide with be fine-tuned using a combination of NO moiety breakdown and enzymatic biodegradation of the NO-containing AA-PEA biomaterials.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 150.00K | Year: 2013

This Small Business Innovation Research (SBIR) Phase I project aims to develop a topical formulation incorporating a polymeric platform that releases therapeutic levels of nitric oxide gas, and assess its efficacy in dispersing wound-relevant bacterial biofilms. The intellectual merit of the proposed project is built around the remarkable characteristics of the polymeric system, where under appropriate conditions this polymer can provide sustained release of nitric oxide over long periods of time and at low concentrations that are biocompatible. The benefit of this characteristic is substantial. Firstly, it avoids the toxicity problems associated with high levels of reactive species formed in response to concentrated nitric oxide release. Secondly, the low levels of nitric oxide release from the polymer will result in increased bioavailability of nitric oxide for promotion of wound healing. Taken together, the characteristics of the proposed nitric oxide releasing polymer prodrug may offer a significant improvement over current approaches to chronic wound treatment.

The broader impact/commercial potential of this project will be determined by market needs that the technology addresses. Colonization of surfaces by biofilms is a significant problem not only in the clinical field, but also across industry and environmental biotechnology sectors. As such, there is a growing requirement for technologies that can either prevent biofilm growth or disperse an existing biofilm, and that can be manufactured in a cost effective manner. The technology that is put forward for development in this Phase I proposal has characteristics that are in line with these requirements. By demonstrating successful development of a product for treatment of wound-related biofilms, a solid foundation will be put in place for exploring similar biofilm prevention or eradication needs across other market sectors.


Grant
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2013

This Small Business Innovation Research (SBIR) Phase I project aims to develop a topical formulation incorporating a polymeric platform that releases therapeutic levels of nitric oxide gas, and assess its efficacy in dispersing wound-relevant bacterial biofilms. The intellectual merit of the proposed project is built around the remarkable characteristics of the polymeric system, where under appropriate conditions this polymer can provide sustained release of nitric oxide over long periods of time and at low concentrations that are biocompatible. The benefit of this characteristic is substantial. Firstly, it avoids the toxicity problems associated with high levels of reactive species formed in response to concentrated nitric oxide release. Secondly, the low levels of nitric oxide release from the polymer will result in increased bioavailability of nitric oxide for promotion of wound healing. Taken together, the characteristics of the proposed nitric oxide releasing polymer prodrug may offer a significant improvement over current approaches to chronic wound treatment. The broader impact/commercial potential of this project will be determined by market needs that the technology addresses. Colonization of surfaces by biofilms is a significant problem not only in the clinical field, but also across industry and environmental biotechnology sectors. As such, there is a growing requirement for technologies that can either prevent biofilm growth or disperse an existing biofilm, and that can be manufactured in a cost effective manner. The technology that is put forward for development in this Phase I proposal has characteristics that are in line with these requirements. By demonstrating successful development of a product for treatment of wound-related biofilms, a solid foundation will be put in place for exploring similar biofilm prevention or eradication needs across other market sectors.


Grant
Agency: Department of Defense | Branch: Defense Advanced Research Projects Agency | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2011

iFyber LLC proposal define a novel solution for the Point-of-Care diagnostics market. Traditional In-Vitro Diagnostic testing most often requires multiple steps (sample purification and analyte separation, analyte concentration/amplification, and detection) to achieve even qualitative levels of detection. iFyber proposes to develop and commercialize an entirely new paradigm in the POC diagnostic market that utilizes a unique microsphere-based, passive proximity assay (PPA) for integrated sample purification and target analyte capture, concentration and detection


Grant
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2010

This Small Business Innovation Research (SBIR) Phase I project aims to develop a novel textile coating and reading device for positive identification applications such as anti-counterfeit, textile brand verification, etc. The basis of this project is to use a layer-by-layer self-assembly process to control the interface between engineered textile substrates and nanomaterials. The resulting nanostructured composite materials may display a unique property that can be detected by a reading device. This technology allows for the precise control over the deposition of metal nanoparticle materials onto the surface of natural and synthetic textiles, which can be implemented into standard industrial processes. The broader/commercial impacts of this project will be the potential to provide a technology for positive identification and anti-counterfeit of textile products, which ranges from the basic clothing industry to military applications.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 171.53K | Year: 2011

This Small Business Innovation Research Phase I project addresses the important problem of combating hospital acquired infections with the development of novel tissue matrices aimed at preventing nosocomial microbial infection. The aim of this project is to combine antimicrobial nanomaterials and a natural dermis product to help prevent infections that occur during reconstructive surgeries. This proof-of-concept study will develop methods for the production of uniform and conformal coatings on natural tissue matrices using layer-by-layer assembly of antimicrobial nanoparticles. Importantly, this project will evaluate the efficacy of nanocoated natural dermis in eliminating or inhibiting bacterial growth in liquid and solid media. In vitro studies also will be conducted to establish mammalian cell toxicity and viability of the engineered dermis in supporting mammalian cell growth. Phase I results are expected to produce an optimized antimicrobial dermis scaffold that will be carried onto a focused Phase II evaluation in animal experimental wounds.

The broader impact/commercial potential of this project will address the growing problem of hospital acquired infections from antibiotic resistant pathogens. With nearly 1.7 million hospital-acquired infections and 99,000 deaths per year, increases in antibiotic-resistant bacterial strains represent a critical safety concern and a significant cost burden to our nations health care system. The proposed technology is a versatile option that provides a broad spectrum solution in combating bacterial infections and the prevalence of antibiotic resistance. Furthermore, the methods used to characterize the proposed composite materials will add valuable insight into mechanisms associated with nanoparticle-derived antimicrobial activity, and will help guide future efforts in the arena of nanobiotechnology.

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