Saint Josephs Translational Research Institute

Atlanta, GA, United States

Saint Josephs Translational Research Institute

Atlanta, GA, United States
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Peck M.,Cytograft Tissue Engineering, Inc. | Dusserre N.,Cytograft Tissue Engineering, Inc. | McAllister T.N.,Cytograft Tissue Engineering, Inc. | McAllister T.N.,Saint Josephs Translational Research Institute | And 2 more authors.
Materials Today | Year: 2011

A long-standing limitation in tissue engineering has been the dogmatic reliance on synthetic scaffolds for building tissues with significant mechanical functions despite their deleterious effects (inflammation, scarring, infection, etc.). Tissue engineering by self-assembly (TESA) is a novel approach that relies on the cell's ability to produce natural extracellular matrix TESA can be used to produce structures that have physiological strength and are not recognized as foreign in vivo. We have developed a tissue-engineered blood vessel that has shown great promise as an arteriovenous shunt. Here, we review our journey from bench-top to bedside and discuss future applications of the TESA approach. © 2011 Elsevier Ltd.

Peck M.,Cytograft Tissue Engineering, Inc. | Gebhart D.,Cytograft Tissue Engineering, Inc. | Dusserre N.,Cytograft Tissue Engineering, Inc. | McAllister T.N.,Cytograft Tissue Engineering, Inc. | And 3 more authors.
Cells Tissues Organs | Year: 2012

Dacron® (polyethylene terephthalate) and Goretex® (expanded polytetrafluoroethylene) vascular grafts have been very successful in replacing obstructed blood vessels of large and medium diameters. However, as diameters decrease below 6 mm, these grafts are clearly outperformed by transposed autologous veins and, particularly, arteries. With approximately 8 million individuals with peripheral arterial disease, over 500,000 patients diagnosed with end-stage renal disease, and over 250,000 patients per year undergoing coronary bypass in the USA alone, there is a critical clinical need for a functional small-diameter conduit [Lloyd-Jones et al., Circulation 2010;121:e46-e215]. Over the last decade, we have witnessed a dramatic paradigm shift in cardiovascular tissue engineering that has driven the field away from biomaterial-focused approaches and towards more biology-driven strategies. In this article, we review the preclinical and clinical efforts in the quest for a tissue-engineered blood vessel that is free of permanent synthetic scaffolds but has the mechanical strength to become a successful arterial graft. Special emphasis is given to the tissue engineering by self-assembly (TESA) approach, which has been the only one to reach clinical trials for applications under arterial pressure. Copyright © 2011 S. Karger AG, Basel.

Superko H.R.,Mercer University | Superko H.R.,Celera | Superko H.R.,Heart Genetics | Pendyala L.,University of Louisville | And 6 more authors.
Journal of Clinical Lipidology | Year: 2012

Objective: To assess the clinical utility of measuring high-density lipoprotein (HDL) subfractions to assess coronary heart disease (CHD) risk. Methods: Literature review of 80 published investigations. Results: Measurements of HDL2b by gradient gel electrophoresis provided more consistent evidence of CHD risk than measurement of HDL2 cholesterol. Five of the seven studies that compared the extent or progression of atherosclerosis with gradient gel electrophoresis estimates of HDL subclasses (71%) assigned statistical significance to HDL2b. Ten of the 11 case-control comparisons (91%) reported lower HDL2b in cases. In contrast, of the 16 association studies relating HDL2 cholesterol and HDL3 cholesterol to extent of disease, five reported no significant relationships with either subfraction, two reported significant relationships with both HDL2 and HDL3 cholesterol, four reported significant relationships with HDL2 but not HDL3 cholesterol, and five reported relationships with HDL3 but not HDL2 cholesterol. Forty-five percent of the case-control comparisons reported that both HDL2 cholesterol and HDL3 cholesterol were significantly lower in cases than controls, 17% failed to find significance for either subfraction, and the remainder reported significantly lower values in cases for HDL2 cholesterol only (26%) or HDL3 cholesterol only (11%). On average, the case-control differences were similar for HDL2 (-0.12 ± 0.01 mmol/L) and HDL3 cholesterol (-0.10 ± 0.02 mmol/L), although relative to controls, the percent reduction was twice as great for HDL2 (-25.7 ± 2.9%) than HDL3 cholesterol (-12.1 ± 1.5%). Eight prospective studies were identified and four reported that both HDL2 and HDL3 predicted lower risk for CHD, one reported reductions in risk for HDL2 but not HDL3 cholesterol, and three reported reductions in risk for HDL3 but not HDL2 cholesterol. None of the prospective studies show that measurements of HDL cholesterol subfractions improve the identification of persons at risk. Conclusions: HDL2 and HDL3 cholesterol do not distinguish cardioprotective differences between HDL subclasses. More extensive characterization of HDL particles by one or two dimensional gel electrophoresis, ion mobility, or ultracentrifugation may provide more specific information about CHD risk than the measurement of HDL cholesterol, HDL3 cholesterol, or HDL2 cholesterol. © 2012 National Lipid Association. All rights reserved.

Pendyala L.K.,Saint Josephs Translational Research Institute | Matsumoto D.,Saint Josephs Translational Research Institute | Shinke T.,Saint Josephs Translational Research Institute | Iwasaki T.,Terumo Corporation | And 10 more authors.
JACC: Cardiovascular Interventions | Year: 2012

Objectives: The current study sought to examine inflammation at the stented segments of Nobori (Terumo Corporation, Tokyo, Japan) and Cypher (Cordis, Miami, Florida) drug-eluting stents (DES), as well as free radical production and endothelial function of the adjacent nonstented segments in a pig coronary model. Background: Nobori is a novel DES, incorporating a biolimus A9-eluting biodegradable polymer coated only on the abluminal surface of the stent. These unique features may favorably affect inflammation and endothelial function, as compared to the currently marketed DES. Presently, pre-clinical data on direct comparison of the various generations of DES are not available. Methods: A total of 18 DES were implanted in pig coronary arteries and subsequently explanted at 1 month. Stented segments were assessed by angiography and histology. Ex vivo vasomotor function and superoxide production in segments proximal and distal to the stent were determined. The vasoconstriction, endothelial-dependent relaxation, and endothelial-independent relaxation of proximal and distal nonstented segments were measured. Results: Histological evaluation revealed lower inflammatory response with Nobori than with Cypher DES. There is trend for lower angiographic percentage diameter stenosis in Nobori versus Cypher groups (p = 0.054). There was increased endothelium-dependent relaxation, decreased endothelin-1-mediated contraction, and less superoxide production in the vessel segments proximal and distal to Nobori versus Cypher stents. Conclusions: Our data show significantly lower inflammatory response in the stented segments, and rapid recovery of endothelial function of peristent segments in the Nobori group compared with Cypher DES group at 1 month in porcine coronary artery model. © 2012 American College of Cardiology Foundation.

Fallon A.M.,CorMatrix Cardiovascular Inc. | Goodchild T.T.,Saint Josephs Translational Research Institute | Cox J.L.,Washington University in St. Louis | Matheny R.G.,CorMatrix Cardiovascular Inc.
Journal of Thoracic and Cardiovascular Surgery | Year: 2014

Objectives A novel bioprosthetic tricuspid valve was constructed from an acellular extracellular matrix (ECM) bioscaffold. The valve's mechanical functionality and potential for histologic regeneration was evaluated in an ovine model. Methods The native tricuspid valves of 4 domestic sheep were excised and replaced with bioprosthetic valves constructed from the ECM bioscaffold material shaped into the form of a tube. In vivo function was assessed over time by transthoracic echocardiography. Animals were euthanized at 3, 5, 8, and 12 months after valve implantation, and explanted valves were examined for gross morphology and by qualitative histopathologic analysis. Results All 4 sheep survived until the specified date. Forward flow by echocardiography was normal with trivial to mild regurgitation. Annular morphology and mobility of the leaflets appeared normal with excellent leaflet coaptation. Explanted valves were grossly normal at all time points and showed evidence of progressive tissue remodeling and integration at the host-tissue interface. Histopathologic analysis demonstrated massive host-cell infiltration, structural reorganization of the ECM bioscaffold, elastin generation at the annulus by 3 months, and increased collagen organization and glycosaminoglycan presence in the leaflets by 5 months, with no evidence of foreign body response. Conclusions When implanted in the form of a tubular valve, the acellular ECM bioscaffold demonstrates feasibility as a biomechanically sound bioprosthetic tricuspid valve replacement with evidence of progressive endothelialization and constructive tissue remodeling. © 2014 by The American Association for Thoracic Surgery.

Fallon A.,CorMatrix Cardiovascular Inc. | Goodchild T.,Saint Josephs Translational Research Institute | Wang R.,Georgia Institute of Technology | Matheny R.G.,CorMatrix Cardiovascular Inc.
Journal of Surgical Research | Year: 2012

Background: We evaluated the in vitro strength and in vivo arterial-wall response to an extracellular-matrix-based patch material in a sheep model of carotid artery repair. Materials and Methods: A six-ply sheet of acellular, porcine extracellular matrix (ECM) was subjected to in vitro material strength testing and implanted in 15 sheep for 30, 90, and 180 d. Bovine pericardium was used as a control in some animals. In vivo graft patency was assessed by angiography. Explanted grafts were evaluated by histopathology and burst-strength testing. Results: Mean (SD) in vitro suture retention force of the ECM sheet was 14.5 (3.06) N; tensile strength was 29.7 (6.11) N; and probe burst strength was 185 (22.6) N. In vivo, mild stenosis was observed at 30 d for all patches; stenosis was absent at 90 d in the ECM-repaired arteries but not bovine pericardium controls. Pseudoaneurysm was not observed in any animal. Histopathology showed progressive graft degradation, collagen deposition, formation of neocapillaries and fibrocellular neointima, and endothelialization, but no calcification. Mean (SD) burst pressure for unrepaired arteries was 2608 (858) mmHg and 1473 (694) mmHg for ECM-repaired vessels. Mean change in diameter from unloaded state to burst pressure was 29% (9.7) for unrepaired vessels and 24% (13.4) for ECM-repaired vessels. Conclusions: The six-ply ECM sheet can withstand the forces encountered after carotid artery repair. In sheep, it shows evidence of progressive, constructive remodeling as early as 30 d post-implantation with rapid deposition of endothelium. ECM shows promise as a patch material for CEA repair. © 2012 Elsevier Inc. All rights reserved.

Rigatelli G.,Rovigo General Hospital | Dell'Avvocata F.,Rovigo General Hospital | Ronco F.,Rovigo General Hospital | Cardaioli P.,Rovigo General Hospital | And 6 more authors.
JACC: Cardiovascular Interventions | Year: 2010

Objectives: In the present study, we sought to assess the effectiveness of migraine treatment by means of primary patent foramen ovale (PFO) transcatheter closure in patients with anatomical and functional characteristics predisposing to paradoxical embolism without previous cerebral ischemia. Background: The exact role for transcatheter closure of PFO in migraine therapy has yet to be elucidated. Methods: We enrolled 86 patients (68 female, mean age 40.0 ± 3.7 years) referred to our center over a 48-month period for a prospective study to evaluate severe, disabling, medication-refractory migraine and documented PFO. The Migraine Disability Assessment Score (MIDAS) was used to assess the incidence and severity of migraine. Criteria for intervention included all of the following: basal shunt and shower/curtain shunt pattern on transcranial Doppler and echocardiography, presence of interatrial septal aneurysm and Eustachian valve, 3 to 4 class MIDAS score, coagulation abnormalities, and medication-refractory migraine with or without aura. Results: On the basis of our inclusion criteria, we enrolled 40 patients (34 females, mean age 35.0 ± 6.7 years, mean MIDAS 35.8 ± 4.7) for transcatheter PFO closure; the remainder continued on previous medical therapy. Percutaneous closure was successful in all cases, with no peri-procedural or in-hospital complications. After a mean follow-up of 29.2 ± 14.8 months (range 6 to 48 months), PFO closure was complete in 95%; all patients (100%) reported improved migraine symptomatology (mean MIDAS score 8.3 ± 7.8, p < 0.03). Specifically, auras were eliminated in 100% of patients after closure. Conclusions: Primary transcatheter PFO closure resulted in a very significant reduction in migraine in patients satisfying our criteria. © 2010 American College of Cardiology Foundation.

Setia N.,Sir Ganga Ram Hospital | Verma I.C.,Sir Ganga Ram Hospital | Khan B.,Saint Josephs Translational Research Institute | Arora A.,Sir Ganga Ram Hospital
Cardiology Research and Practice | Year: 2012

Cardiovascular disease (CVD) is the leading cause of death in India, accounting for 28% of mortality. The average age of onset of CVD is younger (below 55 years) among Indians than in other populations. This may be due to bad lifestyle, genetic factors, or both. Hypertension, smoking, diabetes, and physical inactivity have been identified as modifiable risk factors for heart disease. Hypercholesterolemia is the most common and treatable cause of heart disease. Genetic factors that lead to hypercholesterolemia have not been fully studied in India. Familial Hypercholesterolemia results from mutations in the LDL receptor, ApoB, PCSK9, and ApoE genes. There is an urgent need to screen subjects with premature CAD and their relatives in India for the presence of FH, identify the mutations that lead to high cholesterol, and carry out cascade screening in the at-risk relatives. Those harbouring mutations in the above genes can be treated to lower the cholesterol levels, prevent early CVD, and avoid death. A programme based on these lines has been initiated in Delhi. Copyright © 2012 N. Setia et al.

Saint Josephs Translational Research Institute | Date: 2011-04-19

The present invention provides an access device for surgery. The access device includes a guide member and a head member. The guide member and head member define a channel configured to receive and guide a sterile flexible scope with a working channel. The guide member and head member cooperate to extend through a small opening of 2 cm or less to access tissue structures. The head member may include surfaces to separate a pericardium from a surface of the heart, stabilize a beating heart and, with the endoscope, provide visibility for the implantation of a therapeutic such as stem cells to the surface of the heart with improved safety and accuracy. Ranges of other diagnostic, application of therapeutics or biologics, and observational applications may be facilitated by the access device, such as TMR, ablation, echo-probe diagnostics, LAA isolation, observation of the same procedures, etc.

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 182.97K | Year: 2011

DESCRIPTION (provided by applicant): Percutaneous coronary intervention (PCI) is the most frequently employed strategy to revascularize atherosclerotic stenosis of native coronary arteries and saphenous vein grafts. Tissue perfusion is frequently impairedfollowing PCI, particularly in patients with ST segment elevation myocardial infarction (STEMI). This results in the no-reflow phenomenon which is an important predictor of mortality. Adenosine is an endogenous nucleoside that attenuates many of the mechanisms responsible for the no-reflow phenomenon. Experimental and clinical studies have confirmed adenosine's efficacy in enhancing myocardial salvage and improving microvascular blood flow. Adensoine's full therapeutic potential is compromised due to its ultra short half life requiring large doses to obtain adequate blood levels at the target organ. Since the guidewire is the first PCI device that perturbs the vascular bed, we have developed the concept of elution of adenosine continuously via an adenosine-polymer-coated guidewire. We have developed a number of unique physiologic polymers in which adenosine can be covalently incorporated and placed on a guidewire. We tested out first generation polymers (LDI-glycerol and LDI-adenosine) in a small animal model and verified that it resulted in a substantial increase in blood flow. However in a large animal model the kinetic profile was too rapid for a typical interventional procedure (~45 mins). We have subsequently developed two new polymers, LDI- cysteineand LDI-PEG. Prior to initiating large animal studies in a Phase 2 study it is imperative we optimize the polymer structure, guidewire-coating methodology and kinetic release profile. We therefore propose the following studies with the new polymers to identify an ideal product. First we will develop and characterize the structure of the polymers and permutations thereof and evaluate numerous coating methodologies to optimize release kinetic profile. Second we will evaluate adenosine elution utilizing a temperature controlled recirculating water bath system and measure adenosine release serially with HPLC. Third we will determine if the selected polymer is safe for clinical use by employing NAMSA- based screening tests for cytotoxicity, pyrogenicity, hemolysis, and sensitization. Finally we will evaluate the stability and durability of the polymer with glass transition temperature experiments and by passing coated wires through simulated lesions. If the anti-no-reflow wire is shown to be effective in improving outcomes after interventional procedures it will represent a major advance in the treatment of patients with coronary artery disease undergoing PCI. This will have important societal benefits due to the large number of interventional procedures performed in the US each year for coronary artery disease. PUBLIC HEALTH RELEVANCE: The improved outcomes that may potentially occur with the device would have important societal benefits due to the large number of interventional procedures performed inthe US each year for atherosclerotic disease.

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