Wystrychowski W.,Medical University of Silesia, Katowice |
McAllister T.N.,Cytograft Tissue Engineering, Inc. |
Zagalski K.,Medical University of Silesia, Katowice |
Dusserre N.,Cytograft Tissue Engineering, Inc. |
And 2 more authors.
Journal of Vascular Surgery | Year: 2014
An arteriovenous fistula is the current gold standard for chronic hemodialysis access. Tunneled catheters or synthetic grafts have poorer outcomes and much higher risks of infection. This report presents the first clinical use of a completely biological, allogeneic, nonliving, and human tissue-engineered vascular graft. Tissue-engineered vascular grafts built from allogeneic fibroblasts were implanted as shunts in three hemodialysis patients. The tissue-engineered vascular graft was stored for 9 months, without loss of mechanical strength. Implanted grafts showed no signs of degradation or dilation, with time points up to 11 months. Results of panel-reactive antibody and cross-reactivity tests showed no evidence of immune responses. © 2014 by the Society for Vascular Surgery.
Cytograft Tissue Engineering, Inc. | Date: 2013-03-25
A single-layer tissue sheet having a puncture strength of 2 kgf to 6 kgf. A valve, such as a heart valve, made of one or more leaflets formed from a single-layer tissue sheet. A method of making a tissue sheet having a puncture strength of 2 kgf to 5 kgf. The ultra-strong tissue sheets described herein have very long culture times, such as in excess of 20 weeks. Valves that comprise one or more leaflets made from the ultra-strong tissue sheets described herein may be delivered via trans-cathete aortic valve implantation.
Cytograft Tissue Engineering, Inc. | Date: 2010-03-17
The invention includes methods and apparatus to deploy a blood vessel conduit via a catheter-based, percutaneous approach. In particular, a prosthetic blood conduit can be introduced around or through an arterial obstruction without requiring open bypass surgery. The technology includes coupling devices for docking the tips of two catheters, one situated inside a blood vessel, the other situated outside the blood vessel wall.
Cytograft Tissue Engineering, Inc. | Date: 2012-04-23
The present technology provides for a cell-synthesized biological particle, the processes for making a cell-synthesized particle, and a process for assembling such cell-synthesized particles into tissues and organs. The particles are synthesized in culture in vitro by living cells that produce natural extracellular matrix. Multiple particles can be assembled into tissues that have significant void space. The particles or tissues can act as a substrate for additional cell types. The particles or tissues can be further cultured in vitro to achieve favorable cell or extracellular matrix growth, organization or other desired characteristics. The particles or tissues can be devitalized or decellularized. The particles or tissues can be injected or implanted in a human to repair, enhance, or create a secretory, mechanical, or aesthetic function.
Cytograft Tissue Engineering, Inc. | Date: 2013-11-18
The technology described herein generally relates to the field of tissue engineering and treatment of cardiovascular disease by endovascular repair. The technology more particularly relates to devices and methods to produce a tissue-based implant that can be used for abdominal aorta aneurysm, thoracic aorta aneurysm, or other cardiovascular repair.
Cytograft Tissue Engineering, Inc. | Date: 2011-01-19
This invention relates to a system for the manufacture of a tissue engineering blood vessels (TEBV) made from a cultured fibroblast sheet rolled into a multilayer vessel which has sufficient burst strength to withstand physiological blood pressure without the inclusion of smooth muscle cells or synthetic scaffolding. The TEBV is made in a bioreactor system comprising at least one module that contains a cultured tissue sheet, first mandrel onto which said tissue sheet is rolled, a motion control device into which said first mandrel is fitted and a clamping device for securing the tissue sheet onto the first mandrel.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 215.41K | Year: 2010
DESCRIPTION (provided by applicant): Previously, we have reported excellent clinical results with a tissue engineered vascular graft built using a self-assembly approach termed Sheet-Based Tissue Engineering (SBTE). The principal drawback of this approach, however, is the high manufacturing costs due to a long production time. In order to make this technology clinically available, we need to find a more commercially viable manufacturing approach. We hypothesized that we could build cell-synthesized threads that could be assembled into more complex constructs. This novel evolution of our technology builds upon the clinical successes demonstrated for SBTE (long-term strength and durability, remarkable biocompatibility, resistance to infection, and anti-thrombogenicity) but now introduces the possibility of a faster and less costly assembly strategy using existing medical textiles technologies. The overarching objective of this grant is to develop the foundation for this novel self-assembly platform technology, which we term Thread-Based Tissue Engineering (TBTE). In preliminary studies we have demonstrated that we can produce cell-synthesized threads and weave or braid tubular conduits. Importantly, this reduces the manufacturing time of the vascular graft from over 7 months to less than 3 months. While our first target is to produce a small diameter blood vessel for vascular reconstruction, TBTE will be a very versatile platform technology that can provide a scaffold for a variety of target tissues and organs. In order to develop the basic tools and initial prototypes for the in vivo studies planned for Phase II, this Phase I project will achieve the following specific aims: 1. Generate a library of human threads and determine their Mechanical properties. 2. Generate a library of canine threads and determine their mechanical properties. 3. Build prototype blood vessels and mechanical milestones. DELIVERABLE AND GO/NO GO MILESTONE: In this proof-of-concept study, we will need to demonstrate an assembly protocol that produces blood vessels that meet the critical mechanical properties release criteria we have established for our previous clinical trials with the sheet-based tissue engineered vascular grafts (burst pressures gt1700 mmHg and suture pull-out strength gt 75 gf). PUBLIC HEALTH RELEVANCE: Over the last 10 years we have developed a completely biological tissue engineered vascular graft comprised exclusively of human cells, without the need for exogenous biomaterials or synthetic scaffolds. While initial clinical use of this engineered graft represented a landmark achievement in the field, the manufacturing process is time consuming and expensive and thus, we are exploring a new manufacturing process, termed thread based tissue engineering (TBTE), in which cell-synthesized, biological threads can be woven or braided into robust tissues, decreasing the total manufacturing time down from 6-9 months in previous studies to 3-8 weeks. In this grant, we plan to build and characterize a library of threads built from human and animal cells and this library of functional and mechanical characteristics will form the basis for manufacturing more complex tissues, including a vascular graft for in vivo use in Phase II of this SBIR funding mechanism.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 214.91K | Year: 2010
DESCRIPTION (provided by applicant): Abdominal aorta aneurysms (AAA) are diagnosed in more than 100,000 patients in the U.S. each year. About 70% of these patients require surgical intervention to prevent aneurysm progression. Nearly 20 years ago, Parodi revolutionized AAA treatment and repair by using an ePTFE stent graft that could be delivered via an endovascular approach. Today, more than 35,000 AAA stent grafts are placed annually, making AAA repair devices a 700 million industry in the U.S. alone. Despite the rapid adoption of endovascular repair, the devices are associated with a significant failure rate (more than 20% at one year). The majority of these failures are caused by leakage around or through the device. This type of endoleakage is caused by relative motion between the stent graft device and the native aorta. This relative motion is aggravated by the fact that the stent grafts are static devices that cannot remodel as the native aorta moves and remodels dynamically. Moreover, most stent grafts are wrapped in ePTFE (Teflon), which works well as a blood contacting surface, but does not adhere well to the surrounding tissue. We hypothesized that by replacing the ePTFE covering on a stent graft with a biological sheet, we might improve upon the fixation of the device into the native aorta. That is, by providing a natural collagen substrate which would support cell ingrowth and tissue adhesion, we would increase the bonding strength between the device and the native aorta. We termed this approach biological neck fixation. The objective of this Phase I grant is to demonstrate the initial feasibility of biological neck fixation such that we can more appropriately justify expanded efficacy studies in Phase II. Specifically, in Phase I, we will: develop a sheet built from canine cells that closely matches the mechanical properties of human sheets that we have developed previously (Specific Aim 1); implant the biological stent graft via a 10 French catheter in a canine model to evaluate durability, morphology, and histological properties (Specific Aim 2.1); and compare the adhesion and anchoring properties of biological stent grafts relative to the standard of care in a canine model (Specific Aim 2.2). Exclusion of the AAA without signs of migration or endoleakage at 3 months post-implant, and equal or greater anchoring strength relative to ePTFE stent grafts will be the key milestones to justify advancing to Phase II. The long-term objective of this project will be to commercialize a completely biological stent graft that can remodel with the host aorta, thereby reducing the overall failure rate relative to the current standard of care. PUBLIC HEALTH RELEVANCE: Abdominal aorta aneurysms (AAA) are diagnosed in more than 100,000 patients in the U.S. each year, and are the 13th leading cause of death. Today, more than 35,000 AAA endovascular stent grafts are placed annually, making AAA repair devices a 700 million industry in the U.S. alone. This Research Proposal describes a new repair device which may significantly reduce the relatively high failure rates associated with the standard of care in AAA repair.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.47M | Year: 2011
DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of death in industrialized nations. While interventional techniques such as angioplasty and/or stenting can often delay the need for coronary arterial bypass surgery (CABG),long-term efficacy still favors revascularization. Still today, 450,000 coronary bypasses are performed annually in the U.S. alone. Moreover, the number of revascularization procedures for peripheral arterial disease or hemodialysis access is increasingdramatically. Today, 400,000 hemodialysis patients in the U.S. need a patent vascular graft to survive. Creation and maintenance of hemodialysis access grafts takes up nearly 2% of Medicare's entire budget. In addition, population aging and increasing incidence of diabetes and obesity indicate that this is a major public health concern. A patient's own blood vessels clearly remain the best conduits for both coronary and peripheral bypass, as well as for hemodialysis access. Unfortunately, native veinor artery may not be available due to previous harvest or systemic disease progression. Indeed, the primary limitation to arterial revascularization is the availability of suitable native graft material. While synthetic blood vessels made from materialssuch as Dacron or expanded polytetraflouroethylene (ePTFE) perform well in large diameter applications, these synthetic conduits show unacceptably high failure rates in small diameter applications. We have recently reported excellent clinical trials results with a completely biological human vascular graft built in vitro using a self-assembly approach termed Sheet-Based Tissue Engineering (SBTE). However, a significant drawback of this self-assembly approach is the long production time. Here, we propose the development of a novel assembly strategy, called Thread-Based Tissue Engineering (TBTE). This novel approach offers the same advantages of a completely biological human product but will dramatically reduce the production time and cost. Combined with an allogeneic and/or devitalization approach, TBTE could finally make completely biological human vascular grafts available off-the-shelf and commercially much more competitive. In Phase I of this project, we demonstrated our ability to createthreads of various strengths and sizes from both clinically relevant human cells and from canine cells. These threads were then woven into tubes on a custom circular loom to create human and canine vascular grafts. These grafts displayed promising mechanical properties in vitro. Phase I culminated in a short-term in vivo study that demonstrated the very promising clinical potential of human and canine grafts. These results met and exceeded all milestones set forth in the Phase I proposal. In SpecificAim 1 of Phase II, we will finalize the graft design based on promising data obtained in Phase I. These efforts will lead to six designs that will be tested in vivo in Specific Aim 2. Groups of four canines will receive H7 cm x 4.2 mm unendothelialized,devitalized grafts as arteriovenous shunts (femoral-to-femoral). The six designs will be: 1) Autologous, 2) Allogeneic, 3) Allogeneic decellularized, 4) Allogeneic gamma- sterilized, 5) Allogeneic seeded with autologous bone marrow in the operating room,6) Allogeneic, punctured 3 times weekly with a 16Ga hemodialysis needle after a 3 month post-implantation maturation period. These groups cover the following cost-effectiveness range: 1lt lt 5lt lt 3lt 2lt 4. By comparing the performance of these groups, we can determine which design offers the best combination of efficacy and cost. Group 6 will give a first glimpse at the potential of this new type of graft to serve as a hemodialysis access graft. Finally, In Specific Aim 3, we will explore importantparameters for the long-term commercialization of these grafts. We will study the use of serum-free medium to produce threads, which would improve reproducibility, reduce cost and simplify regulatory acceptance of the grafts (compared to bovine serum-containing medium). We will also study the use of molecular crowding additives to the culture medium. These large molecules have the potential to double or triple collagen assembly and hence, reduce production time and cost. Finally, we will determine if we can seed an endothelium on the woven grafts. While endothelium is not critical in high-flow applications like hemodialysis access grafts, it will be for other important markets/indications like coronary or lower limb bypass. However, establishing anautologous endothelium (allogeneic endothelium are highly immunogenic) introduces significant additional costs. As a cost-effective alternative, we will explore the possibility of replacing it by a new type of heparin coating. This Phase II project will provide: 1) the most cost-effective yet efficacious graft design; 2) initial in vivo efficacy data to justify a more extensive in vivo study to support and IND-submission; 3) additional data to further improve the grafts commercial and regulatory prospects. PUBLIC HEALTH RELEVANCE: Over the last 10 years we have developed a completely biological tissue engineered vascular graft comprised exclusively of human cells, without the need for exogenous biomaterials or synthetic scaffolds. While initialclinical use of this engineered graft represented a landmark achievement in the field, the manufacturing process is time consuming and expensive and thus, we have developed and performed initial optimization work on a much faster manufacturing process,termed Thread-based Tissue Engineering (TBTE), in which cell- synthesized, biological threads are woven into robust tissues. In this grant, we propose to expand our initial work into developing a clinically relevant graft, investigate the in vivo performance of the grafts in a canine model, and research key parameters to facilitate the transition to commercialization.
News Article | March 1, 2017
Research and Markets has announced the addition of the "Aortic Aneurysm Repair Devices Global Market - Forecast to 2023" report to their offering. The Aortic Aneurysm Repair Devices market is classified based on site, product, repair type and geography. The Aortic Aneurysm Repair Devices products market is divided into Stent grafts, Catheters, and Others. The Aortic Aneurysm Repair Devices by site market is segmented into Abdominal Aortic Aneurysm (AAA) and Thoracic Aortic Aneurysm (TAA). Abdominal aortic aneurysm market is further segmented into Infrarenal and Perarenal. The perarenal market is further sub-segmented into Juxtrarenal and Suprarenal. Thoracic Aortic Aneurysm market is divided into Ascending an aortic aneurysm, Descending aortic aneurysm, Thoracoabdominal Aortic Aneurysm (TAAA) and Thoracic Arch Aneurysm. The Aortic Aneurysm market by repair type is divided into Abdominal Aortic Aneurysm (AAA) and Thoracic Aortic Aneurysm (TAA). Abdominal aortic aneurysm is divided into open surgery and Endovascular aneurysm repair (EVAR). Thoracic aortic aneurysm repair is divided into open surgery and Thoracic endovascular aneurysm repair (TEVAR). Further, the Aortic Aneurysm Repair Devices market is separated by geographical regions into North America, Europe, Asia-pacific and Rest of the World. 2 Introduction 2.1 Key Take Aways 2.2 Report Description 2.3 Markets Covered 2.4 Stakeholders 2.5 Research Methodology 2.5.1 Market Size Estimation 2.5.2 Market Crackdown and Data Triangulation 2.5.3 Secondary Sources 2.5.4 Primary Sources 2.5.5 Key Data Points from Secondary Sources 2.5.6 Key Data Points from Primary Sources 2.5.7 Assumptions 3 Market Analysis 3.1 Introduction 3.2 Market Segmentation 3.3 Factors Influencing Market 3.3.1 Drivers and Opportunities 188.8.131.52 Rising Geriatric Population 184.108.40.206 Increasing Prevalence of Lifestyle Diseases 220.127.116.11 Growing Acceptance for Minimally Invasive Endovascular Surgeries 18.104.22.168 Technological Advancements in Evar 22.214.171.124 Mergers and Acquisitions 126.96.36.199 Market Expansion Opportunities in Emerging Nations 3.3.2 Restraints and Threats 188.8.131.52 Risks Associated With Endovascular Procedures Such as Endoleaks and Radiation Exposure 184.108.40.206 High Costs of an Endovascular Aneurysm Repair Procedures 220.127.116.11 Stringent Regulatory Approval Requirement for an Aortic Aneurysm Repair Product 18.104.22.168 Lack of Skilled Professionals 22.214.171.124 Challenges Associated With Repair of Complex Anatomies 126.96.36.199 Off-The-Shelf Stent Grafts in Treating Complex Anatomies 3.4 Regulatory Affairs 3.4.1 U.S. 3.4.2 Europe 3.4.3 India 3.4.4 China 3.4.5 Japan 3.5 Reimbursement Scenario 3.5.1 Reimbursement Table 3.6 Porter's Five Force Analysis 3.6.1 Threat of New Entrants 3.6.2 Threat of Substitutes 3.6.3 Bargaining Power of Suppliers 3.6.4 Bargaining Power of Buyers 3.6.5 Competitive Rivalry 3.7 Market Share Analysis 3.7.1 Aortic Aneurysm Repair Devices Global Market Share Analysis, by Major Players 3.7.2 Evar Global Market Share Analysis, by Major Players 3.7.3 Tevar Global Market Share Analysis, by Major Players 3.7.4 U.S. Evar Market Share Analysis, by Major Players 3.7.5 Europe Evar Market Share Analysis, by Major Players 3.7.6 Japan Evar Market Share Analysis, by Major Players 3.8 Patent Trends 8 Company Developments 8.1 Introduction 8.1.1 Product Approval as a Major Growth Strategy of Market Players 8.2 Product Approval 8.3 Agreements and Acquisitions 8.4 New Product Launch 8.5 Other Developments - Abiomed (U.S.) - B.Braun GmbH (Germany) - BiFlow medical (Israel) - Bolton Medical (U.S.) - Boston Scientific corporation (U.S.) - Braile Biomedica (Brazil) - Cardiatis (Belgium) - Cardinal Health, Inc. (U.S.) - Cook Medical, Inc. (U.S.) - Cytograft Tissue Engineering, Inc. (U.S.) - Endologix, Inc. (U.S.) - Endospan (Israel) - Fuji Systems Corporation (Japan) - Getinge Groups (Maquet) (Sweden) - GRIKIN Advanced Materials (China) - HDH Medical Ltd (Israel) - JOTEC GmbH (Germany) - Le Maitre Vascular, Inc. (U.S.) - LifeTech Scientific Corporation (China) - Lombard Medical Technologies (U.K.) - Medtronic PLC (Ireland) - MicroPort Scientific Corporation China) - Nano Endoluminal S.A. (Brazil) - S & G Biotech, Inc. (South Korea) - St. George Medical (France) - Terumo Medical Corporation (Japan) - Transcatheter Technologies GmbH (Germany) - Vivasure Medical (Ireland) - W. L. Gore and Associates (U.S.) For more information about this report visit http://www.researchandmarkets.com/research/4tpcxn/aortic_aneurysm Research and Markets is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.