ASHLAND, MA, United States
ASHLAND, MA, United States

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Patent
Biosurfaces, Clemson University and Rhode Island Board Of Education | Date: 2016-02-18

The present invention is a bioactive, nanofibrous material construct which is manufactured using a unique electrospinning perfusion methodology. One embodiment provides a nanofibrous biocomposite material formed as a discrete textile fabric from a prepared liquid admixture of (i) a non-biodegradable durable synthetic polymer; (ii) a biologically active agent; and (iii) a liquid organic carrier. These biologically-active agents are chemical compounds which retain their recognized biological activity both before and after becoming non-permanently bound to the formed textile material; and will become subsequently released in-situ as discrete freely mobile agents front the fabric upon uptake of water from the ambient environment.


Patent
Biosurfaces, Clemson University and Rhode Island Board Of Education | Date: 2014-06-02

The present invention is a bioactive, nanofibrous material construct which is manufactured using a unique electrospinning perfusion methodology. One embodiment provides a nanofibrous biocomposite material formed as a discrete textile fabric from a prepared liquid admixture of (i) a non-biodegradable durable synthetic polymer; (ii) a biologically active agent; and (iii) a liquid organic carrier. These biologically-active agents are chemical compounds which retain their recognized biological activity both before and after becoming non-permanently bound to the formed textile material; and will become subsequently released in-situ as discrete freely mobile agents from the fabric upon uptake of water from the ambient environment.


Eisele N.B.,Biosurfaces | Eisele N.B.,Max Planck Institute for Biophysical Chemistry | Frey S.,Max Planck Institute for Biophysical Chemistry | Piehler J.,University of Osnabrück | And 3 more authors.
EMBO Reports | Year: 2010

Nuclear pore complexes (NPCs) are highly selective gates that mediate the exchange of all proteins and nucleic acids between the cytoplasm and the nucleus. Their selectivity relies on a supramolecular assembly of natively unfolded nucleoporin domains containing phenylalanine-glycine (FG)-rich repeats (FG repeat domains), in a way that is at present poorly understood. We have developed ultrathin FG domain films that reproduce the mode of attachment and the density of FG repeats in NPCs, and that exhibit a thickness that corresponds to the nanoscopic dimensions of the native permeability barrier. By using a combination of biophysical characterization techniques, we quantified the binding of nuclear transport receptors (NTRs) to such FG domain films and analysed how this binding affects the swelling behaviour and mechanical properties of the films. The results extend our understanding of the interaction of FG domain assemblies with NTRs and contribute important information to refine the model of transport across the permeability barrier. © 2010 EuropeEan MoleEcular Biology Oorganization.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase II | Award Amount: 748.95K | Year: 2011

DESCRIPTION (provided by applicant): Over 60,000 prosthetic grafts, which are primarily comprised of polyethylene terephthalate (polyester) or expanded polytetrafluoroethylene (ePTFE), are implanted in the United States each year. Unfortunately, these grafts continue to have high failure rates due to secondary complications associated with acute thromboses and incomplete, unregulated cellular proliferation. These complications are only more profound and severe as the diameter of the prosthetic vascular graft decreases (6-8mm internal diameter or ID). To date, there are no small vascular grafts (lt 5mm ID) that are FDA-approved for clinical use in the United States. Our hypothesis is covalent immobilization of APC onto the functionalized polyester vascular graft surface will prevent surface thrombus formation via renewably inactivating FVa and FVIIIa upon graft implantation. Additionally, surface bound APC would promote adherence of mature and progenitor endothelial cells circulating in the blood to the polyester graft surface through a highly specific, high affinity ligand-receptor binding reaction and signal graft-adherent cells or cells from adjacent endothelium to proliferate and migrate on the surface, thus having a direct effect in controlling cellular proliferation in the adjacent tissue. In surface I, Phase functional groups were created within an existing small-diameter woven polyester graft matrix, (BioFunc) graft functionalized the of properties chemical and physical with characterized. Additionally,the natural anticoagulant Activated Protein C (APC) was covalently immobilized to these surface functional groups, with APC binding optimized (BioFunc-APC significant maintained APC immobilized Surface material). Graft antithrombotic properties as well aspromoted increased endothelial cell adhesion to this bioactive graft surface. Lastly, APC was stable on the graft surface over an extended period of time under simulated arterial flow conditions. The goal of this Phase II STTR grant healing and antithrombotic for vivo in graft BioFunc-APC the assess to is characteristics using an arterial grafting model. canine The specific objectives of this Phase II study are to: 1) create functional groups on small diameter (4mm ID) tight woven 2) characterize graft), technology (BioFunc proprietary grafts using polyester physical/chemical properties of BioFunc graft, 3) immobilize APC onto BioFunc graft surface (BioFunc-APC graft), 4) evaluate surface antithrombotic and cell adhesion properties of BioFunc-APC graft,5) assess in vivo acute and chronic implantation periods using a canine arterial grafting model, and 6) examine macroscopically/microscopically explanted BioFunc-APC grafts. Development of a bioactive polyester vascular graft that would provide localized surface antithrombin properties and stimulate endothelial cell-specific attachment/proliferation would have a significant impact on arterial repair and replacement. These grafts could be utilized in peripheral bypass (specifically below-knee reconstruction)as well as for coronary artery bypass. Thus, the potential annual market value for an off-the-shelf bioactive synthetic arterial bypass graft that would be available for medium and small vessel reconstruction could exceed 1.5 billion. PUBLIC HEALTH RELEVANCE: Over 60,000 prosthetic grafts, which are primarily comprised of polyethylene terephthalate (polyester) or expanded polytetrafluoroethylene (ePTFE), are implanted in the United States each year. Unfortunately, these prosthetic arterial graftscontinue to have high failure rates due to secondary complications associated with acute thromboses and incomplete, unregulated cellular proliferation. These complications are only more profound and severe as the diameter of the prosthetic vascular graftdecreases. To date, there are no small vascular grafts (lt 5mm I.D.) that are FDA-approved for clinical use in the United States. Development of a novel artificial artery with a surface designed to prevent these types of failures from occurring would haveapplication for complex devices such as artificial arteries, total implantable heart and left ventricular assist devices as well as simple devices such as catheter cuffs. Thus, the potential annual market value for an off-the-shelf bioactive synthetic arterial bypass graft that would be available for medium and small vessel reconstruction could exceed 1.5 billion.


Osma J.F.,Rovira i Virgili University | Toca-Herrera J.L.,Biosurfaces | Rodriguez-Couto S.,Centro de estudios e investigaciones técnicas de Gipuzkoa | Rodriguez-Couto S.,Ikerbasque
Bioresource Technology | Year: 2010

This study deals with the biotransformation products obtained from the transformation of the anthraquinonic dye Remazol Brilliant Blue R (RBBR) by immobilised laccase from the white-rot fungus Trametes pubescens. A decolouration percentage of 44% was obtained in 42. h. RBBR transformation products were investigated using ultraviolet-visible (UV-vis) spectrum scan and High Performance Liquid Chromatography/Mass Spectrometry (LC-MS) analysis. Two compounds were identified as the transformation intermediates (m/. z 304.29 and m/. z 342.24) and other two as the final transformation products (m/. z 343.29 and m/. z 207.16). As a result a metabolic pathway for RBBR transformation by laccase was proposed. No backward polymerisation of the transformation products resulting in recurrent colouration was observed after laccase treatment of RBBR. It was also found that the biotransformation products of RBBR showed less phytotoxicity than the dye itself. © 2010 Elsevier Ltd.


Osma J.F.,Rovira i Virgili University | Toca-Herrera J.L.,Biosurfaces | Rodriguez-Couto S.,Centro de estudios e investigaciones técnicas de Gipuzkoa | Rodriguez-Couto S.,Ikerbasque
Applied Catalysis A: General | Year: 2010

Laccase from Trametes pubescens was immobilised on alumina pellets and coated with polyelectrolytes. It was shown that this approach enhanced both laccase stability and reusability. Further, the immobilised-coated laccase was applied to the decolouration of a simulated textile effluent in laboratory-scale reactors. The simulated textile effluent was based on the recalcitrant diazo dye Reactive Black 5 (0.5 g/L). It was found that the decolouration was due to two processes: dye adsorption on the immobilisation support and coating and dye degradation by the laccase enzyme. The adsorption process represented less than 10% of colour removal for all cases, so decolouration was mainly due to laccase action. The decolouration was performed in both batch and continuous modes. A complete decolouration of the effluent was obtained in 30-36 h for the former and 48 h for the latter without the addition of redox mediators. In addition, the decolourised effluent showed lower phytotoxicity than the original one. These encouraging results make the process suitable for its potential implementation at industrial scale. © 2009 Elsevier B.V. All rights reserved.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 111.08K | Year: 2010

DESCRIPTION (provided by applicant): Current gold standards for hemodialysis access, radial cephalic vein fistulas and autogenous saphenous veins, have significant problems associated with their use. Many patients do not have a healthy vein to spare due to disease progression or prior/future use for a different surgical procedure (i.e. for a distal or coronary bypass). These surgical procedures also require greater time than a prosthetic graft implant due to vein harvesting. Synthetic grafts have issues with patency and inability to provide instant access. Our hypothesis is that the next generation of prosthetic hemodialysis grafts should possess multiple structural and biological properties that mimic some of those processes inherent to native arteries in order to prevent these complications from occurring. The goal of the Phase I study is to develop a first of its kind hemodialysis access graft comprised of polyester (PET) and polyurethane (PU) blend via electrospinning technology (BioAccess). Incorporation of these polymers as this unique blend will impart both strength and compliance to the graft. Specific biologic agents for preventing thrombosis (recombinant hirudin or rHir), infection (Moxifloxacin) and hyperplasia (Paclitaxel), will be blended in the graft. The incorporation of these agents should aid in the healing of the graft by preventing acute thrombosis, chronic infection and stenosis of the conduits during the repeated cannulation of the graft. The specific objectives of our proposed study are to: 1) optimize electrospinning conditions for the nanofibrous BioAccess graft, 2) characterize physical, chemical and surface properties of the graft, 3) evaluate release pharmacokinetics of rHir, Moxifloxacin and Paclitaxel from the BioAccess graft via a stringent washing study and 4) examine antithrombotic, antimicrobial and anti-proliferative properties of the graft using established biologic assays. The overall annual cost of ESRD treatment in the US is 23 billion, which is projected to increase 3.6% every year. About 2 million patients worldwide (355,000, currently in US alone) will receive hemodialysis treatment by 2010. With increasing age of dialysis patients and higher occurrence of diabetes and obesity, there is an urgent need for hemodialysis grafts with immediate access and better healing properties. PUBLIC HEALTH RELEVANCE: End Stage Renal Disease (ESRD) affects millions of people worldwide with the total cost of treatment in US alone standing at 23 billion. With increasing age, diabetes and obesity associated with the patients, there is a need for better hemodialysis access grafts that provide instant access and faster healing. The goal of this Phase I grant is to develop a novel hemodialysis graft from polyester (PET) and polyurethane (PU) through the process of electrospinning, incorporating antithrombotic (recombinant hirudin), antimicrobial and antineoplastic (Paclitaxel) agents directly into the fibrous (Moxifloxacin) construct. Our hypothesis is that the strength and elasticity of the polymers combined with the synergisticbiological effects of the selected drugs should lead to a synthetic graft with improved healing, better long-term patency and instant access.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2014

PROJECT SUMMARY Cardiac valve repair or replacement is indicated when progression of degenerative disease or bacterial infection of the native valve results in valvular dysfunction, thereby impacting cardiac output. Both procedures require the use of a woven or knitted polyester material with an internal reinforcement (Teflon, silicone or metal) to either stabilize the native valve (annuloplasty ring) or to attach a prosthetic heart valve (sewing cuff). Bacterial infection (prosthetic valve endocarditis orPVE) is a major complication associated with implantation of these devices. Bacteremia seeded at the site prior to surgery or nosocomial infection acquired during the surgery or post-operatively are the primary routes of inoculation, resulting in significant morbidity and mortality. Since the functional parts of the mechanical valves are composed of metals, they are incapable of providing the environment for bacterial growth. Infection is typically localized to the prosthesis/tissue interface at the sewing


BACKGROUND: Antibody screening and identification panels are generally limited by the natural antigenic phenotypes present in their source donor population. However, the recent ability to attach peptides to the surface of cells has opened up the opportunity to create red blood cells (RBCs) with antigen profiles specifically designed for antibody screening and identification in a target population. STUDY DESIGN AND METHODS: Clinically significant antibodies to variant glycophorins (GPs) such as GP.Mur are more commonly seen in certain Asian populations. Using peptides representative of the MNS antigens MUT and Mur, RBC antibody screening cells were created using KODE cell surface engineering constructs. MUT-, Mur-, and MUT+Mur-modified RBCs, known as kodecytes, were tested against monoclonal reagents and polyclonal sera with specificity for epitopes on GP.Mur-positive RBCs. RESULTS: Kodecytes retained their normal expression of intrinsic blood group antigens while expressing the new epitopes attached by KODE technology. The MUT, Mur, and MUT+Mur kodecytes, although unreactive with the various monoclonal reagents, were appropriately reactive with polyclonal sera containing antibodies reactive with GP.Mur-positive RBCs. CONCLUSIONS: This study used selected MUT and Mur peptides and KODE cell surface engineering technology to create MUT+Mur kodecytes suitable for the detection and identification of RBC antibodies in human serum or plasma. This technology has the potential to create a large range of specialized RBCs for antibody screening and identification. © 2009 American Association of Blood Banks.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 988.07K | Year: 2012

DESCRIPTION (provided by applicant): Current gold standards for hemodialysis access to treat End-Stage Renal Disease (ESRD), radial cephalic vein fistulas and autogenous saphenous veins, have significant problems associated with their use. The issues rangefrom unavailability of a healthy vein the patient can spare complexity of harvesting and longevity of the surgical procedure to the long time (4-6 months) required for healing of the fistula. Synthetic grafts made of ePTFE and polyurethane (PU) have issues of low patency (20% for 2 years), delayed access time to first puncture (more than 3 weeks), infection, weeping (leading to hematomas/seroma formation) and kinking of the native vein resulting in graft thrombosis. Thus, there is a need to develop an off-the shelf prosthetic graft that would give comparable or higher patency to autologous grafts or fistulas, eliminate/reduce infection, prevent surface thrombus formation inhibit uncontrolled cellular proliferation throughout graft and most importantly, provide instant access to puncture. Research objectives proposed and accomplished in Phase I were: 1) synthesis of a novel nanofibrous bioactive hemodialysis graft (BioAccess) via electrospinning of polyester and polyurethane in combination with antithrombin,antimicrobial and anti-proliferative agents, 2) characterization of the physical and chemical properties of the BioAccess graft, 3) determination of the release pharmacokinetics from the BioAccess graft, and 4) evaluation of the biologic properties of theBioAccess grafts after undergoing stringent wash conditions. The goal of the Phase II study is to assess in vivo the BioAccess grafts (6mm ID) as well as clinically utilized ePTFE grafts in a canine arteriovenous (carotid artery to jugular vein) shunt access model. BioAccess grafts will be evaluated for patency, infection-resistance, gross hematoma formation, surface thrombus formation and hyperplasia formation after being punctured various times for 30 and 60 days. Our hypothesis is that the BioAccess Graft will become the new standard for hemodialysis access by outperforming ePTFE grafts in terms of immediate access, reduced hematoma formation, low incidences of infection and increased primary patency rates. The BioAccess graft will be superior to ePTFE grafts due to its better mechanical compliance in conjunction with localized release of antithrombotic, antimicrobial and anti- proliferative agents, thereby regulating any potential complications directly at the graft surface. The specific objectives for Phase II are to: 1) electrospin BioAccess grafts for implantation studies, qualify physical, chemical and surface properties of BioAccess grafts, 3) confirm biologic properties of BioAccess graft using established assays employed in Phase I, 4) implant BioAccess and control ePTFE grafts into a canine arteriovenous shunt access model for 30 and 60 days in conjunction with numerous needle punctures and 5) macroscopically and histologically analyze explanted BioAccess and ePTFE grafts. The overall annual cost ofESRD treatment in the US is 23 billion, which is projected to increase at an annual rate of 3.6%. About 2 million patients worldwide (355,000 in US alone) currently will receive hemodialysis treatment by 2012. Approximately 140,000 access grafts are currently implanted in the US at a total healthcare cost of 80 million. Temporary catheters are the most expensive of all the ESRD treatments for Medicare, costing about 77,000/person/year, a cost that can be avoided by immediate access through a permanent arteriovenous graft. With the increase in aging population of ESRD patients, higher occurrence of diabetes and obesity, the options for a patient are reduced to immediate hemodialysis. Thus, there is an increasing demand for hemodialysis grafts with immediate access and better healing properties. PUBLIC HEALTH RELEVANCE: Current gold standards for hemodialysis access to treat End-Stage Renal Disease (ESRD), radial cephalic vein fistulas and autogenous saphenous veins, have significant problems associated with their use. The issues range from unavailability of a healthy vein the patient can spare complexity of harvesting and longevity of the surgical procedure to the long time (4-6 months) required for healing of the fistula. The goal of the Phase II study is to assess in vivo the BioAccess grafts (6mm ID) as well as clinically utilized ePTFE grafts in a canine arteriovenous (carotid artery to jugular vein) shunt access model. BioAccess grafts will be evaluated for patency, infection-resistance, gross hematoma formation, surface thrombus formation and hyperplasia formation after being punctured various times for 30 and 60 days. With the increase in aging population of ESRD patients, higher occurrence of diabetes and obesity, the options for a patient arereduced to immediate hemodialysis. Thus, there is an increasing demand for hemodialysis grafts with immediate access and better healing properties.

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