Experimental Non-Inferiority Trial of Synthetic Small-calibre Biodegradable vs. Stable Vascular Grafts Departments of 1 Cardiovascular Surgery, 3 Pathology.

Slides:

Advertisements

Similar presentations

Biomaterials Science Part II: Materials in Medicine Synthetic Vascular Grafts March 6, 2010 assignment reading: Brett C. Isenberg, Chrysanthi Williams.

Advertisements

Remodelling Ability of living tissue to adapt to its environment by changing its shape and structure Modifies mechanical properties Driven by tendency.

Preliminary experience with tissue engineering of a venous vascular patch by using bone marrow–derived cells and a hybrid biodegradable polymer scaffold

Pathology Of Explanted Cryopreserved Allograft Heart Valves: Comparison With Aortic Valves From Orthotopic Heart Transplants Richard N. Mitchell, MD,

Porcine carotid artery replacement with biodegradable electrospun poly-e-caprolactone vascular prosthesis Wojciech Mrówczyński, MD, PhD, Damiano Mugnai,

Porcine carotid artery replacement with biodegradable electrospun poly-e-caprolactone vascular prosthesis Wojciech Mrówczyński, MD, PhD, Damiano Mugnai,

Bioengineered vascular access maintains structural integrity in response to arteriovenous flow and repeated needle puncture Bryan W. Tillman, MD, PhD,

Mesenchymal stem cells attenuate angiotensin II-induced aortic aneurysm growth in apolipoprotein E-deficient mice Ryotaro Hashizume, MD, Aika Yamawaki-Ogata,

The OrbusNeich EPC Capture Biodegradable Polymer Sirolimus-eluting Stent Program Michael JB Kutryk, MD, PhD St Michael’s Hospital, Toronto.

Biodegradable polymer with collagen microsponge serves as a new bioengineered cardiovascular prosthesis Shigemitsu Iwai, MD, Yoshiki Sawa, MD, Hajime.

Larisse K. Lee, MD, Peter L. Faries, MD Journal of Vascular Surgery

Reconstruction of pulmonary artery with porcine small intestinal submucosa in a lamb surgical model: Viability and growth potential Lorenzo Boni, MD,

Endograft technology: a delivery vehicle for intravascular gene therapy Darwin Eton, MD, Hong Yu, PhD, Yingcai Wang, PhD, Jeffrey Raines, PhD, Gary Striker,

David Stecher, MD, Frebus J. van Slochteren, MSc, Imo E

Biomatrix/Polymer Composite Material for Heart Valve Tissue Engineering Christof Stamm, MD, Amir Khosravi, MD, Niels Grabow, MS, Kathleen Schmohl, PhD,

Experimental generation of a tissue-engineered functional and vascularized trachea Thorsten Walles, MD, Bettina Giere, Michael Hofmann, PhD, Johanna Schanz,

Development of a “leak-proof,” knitted Dacron vascular prosthesis

Experimental noninferiority trial of synthetic small-caliber biodegradable versus stable vascular grafts Damiano Mugnai, MD, Jean-Christophe Tille, MD,

Histologic analysis of stent graft oversizing in the thoracic aorta

Elysse C. Filipe et al. BTS 2018;3:38-53

Novel Tissue-Engineered Biodegradable Material for Reconstruction of Vascular Wall Shigemitsu Iwai, MD, Yoshiki Sawa, MD, Satoshi Taketani, MD, Kei Torikai,

Tissue-engineered stent-graft integrates with aortic wall by recruiting host tissue into graft scaffold Mugiho Takeuchi, MD, Toru Kuratani, MD, PhD,

Preliminary experience with tissue engineering of a venous vascular patch by using bone marrow–derived cells and a hybrid biodegradable polymer scaffold

Lucas P. Neff, MD, Bryan W. Tillman, MD, PhD, Saami K

Boundary layer infusion of heparin prevents thrombosis and reduces neointimal hyperplasia in venous polytetrafluoroethylene grafts without systemic anticoagulation

Prevention of perioperative vascular prosthetic infection with a novel triple antimicrobial- bonded arterial graft Ibrahim Aboshady, MD, Issam Raad, MD,

A novel bioengineered small-caliber vascular graft incorporating heparin and sirolimus: Excellent 6-month patency Yosuke Ishii, MD, Shun-ichiro Sakamoto,

Engineered Living Blood Vessels: Functional Endothelia Generated From Human Umbilical Cord-Derived Progenitors Dörthe Schmidt, MD, Lars M. Asmis, MD,

Interleukin 18 binding protein (IL18-BP) inhibits neointimal hyperplasia after balloon injury in an atherosclerotic rabbit model Jian-Ming Li, MD, Mohammad.

Decellularized heart valve as a scaffold for in vivo recellularization: Deleterious effects of granulocyte colony-stimulating factor Francis Juthier,

Basic fibroblast growth factor slow release stent graft for endovascular aortic aneurysm repair: A canine model experiment Masaki Kajimoto, MD, Takatsugu.

The role of circulating cells in the healing of vascular prostheses

Long-term patency of small-diameter vascular graft made from fibroin, a silk-based biodegradable material Soichiro Enomoto, MD, PhD, Makoto Sumi, MD,

Targeted imaging of matrix metalloproteinase activity in the evaluation of remodeling tissue-engineered vascular grafts implanted in a growing lamb model

Influence of endothelial cell seeding on platelet deposition and patency in small- diameter Dacron arterial grafts Brent T. Allen, M.D., Julie A. Long,

Novel Bioresorbable Vascular Graft With Sponge-Type Scaffold as a Small-Diameter Arterial Graft Tadahisa Sugiura, MD, PhD, Shuhei Tara, MD, PhD, Hidetaka.

Compound polyglactin 910/polypropylene small vessel prostheses

A novel vascularized patch enhances cell survival and modifies ventricular remodeling in a rat myocardial infarction model Qi Zhou, MD, PhD, Jian-Ye.

Utilization of shape memory in external vein-graft meshes allows extreme diameter constriction for suppressing intimal hyperplasia: A non-human primate.

Chronic in vitro shear stress stimulates endothelial cell retention on prosthetic vascular grafts and reduces subsequent in vivo neointimal thickness

An “off the shelf” vascular allograft supports angiogenic growth in three-dimensional tissue engineering Johann M. Zdolsek, MD, Wayne A. Morrison, MB.

Michael A. Rosenbaum, MD, Keiko Miyazaki, MD, Scott M. Colles, Linda M

Paclitaxel coating of the luminal surface of hemodialysis grafts with effective suppression of neointimal hyperplasia Insu Baek, MS, Cheng Zhe Bai, PhD,

Mechanisms of arterial graft failure. II

Enhanced intimal thickening of expanded polytetrafluoroethylene grafts coated with fibrin or fibrin-releasing vascular endothelial growth factor in the.

Adventitial elastolysis is a primary event in aneurysm formation

Conformational stress and anastomotic hyperplasia

The pathology of fresh and cryopreserved homograft heart valves: An analysis of forty explanted homograft valves David R. Koolbergen, MD, Mark G. Hazekamp,

Differentiating transmural from transanastomotic prosthetic graft endothelialization through an isolation loop-graft model Timothy Pennel, MBChB, Peter.

Vein graft failure Journal of Vascular Surgery

Hiromichi Miwa, MD, Takehisa Matsuda, PhD Journal of Vascular Surgery

A self-renewing, tissue-engineered vascular graft for arterial reconstruction Kei Torikai, MD, Hajime Ichikawa, MD, PhD, Koichiro Hirakawa, MS, Goro Matsumiya,

The temporal relationship between the development of vein graft intimal hyperplasia and growth factor gene expression John R. Hoch, MD, Vida K. Stark,

Living, autologous pulmonary artery conduits tissue engineered from human umbilical cord cells Simon P Hoerstrup, MD, Alexander Kadner, MD, Christian.

In situ tissue regeneration using a novel tissue-engineered, small-caliber vascular graft without cell seeding Takenori Yokota, MD, Hajime Ichikawa,

Michael A. Ricci, MD, Gail Strindberg, MD, Jeffery M

Dacron inhibition of arterial regenerative activities

Impact of endothelial cell seeding on long-term patency and subendothelial proliferation in a small-caliber highly porous polytetrafluoroethylene graft

Robert A. McCready, M. D. , Margaret A. Price, B. S. , Richard J

Decellularization reduces calcification while improving both durability and 1-year functional results of pulmonary homograft valves in juvenile sheep

Mostafa N. El-Sanadiki, MB, MS, K. Simon Cross, MB, John J

Newly Developed Tissue-Engineered Material for Reconstruction of Vascular Wall Without Cell Seeding Hiroaki Takahashi, MD, PhD, Takenori Yokota, MD,

Neointimal hyperplasia on a cell-seeded polytetrafluoroethylene graft is promoted by transfer of tissue plasminogen activator gene and inhibited by transfer.

Polyurethane vascular prostheses decreases neointimal formation compared with expanded polytetrafluoroethylene Marc G. Jeschke, MD, Valentin Hermanutz,

Howard P. Greisler, M. D. , Eric D. Endean, M. D. , John J. Klosak, M

Small-caliber heparin-coated ePTFE grafts reduce platelet deposition and neointimal hyperplasia in a baboon model Peter H Lin, MD, Changyi Chen, MD,

Prevention of perioperative vascular prosthetic infection with a novel triple antimicrobial- bonded arterial graft Ibrahim Aboshady, MD, Issam Raad, MD,

Richard L. Binns, MD Journal of Vascular Surgery

Development of Decellularized Aortic Valvular Conduit Coated by Heparin–SDF-1α Multilayer Jingxin Zhou, PhD, Xiaofeng Ye, MD, PhD, Zhe Wang, MD, Jun.

Neointimal formation at the sites of anastomosis of the internal thoracic artery grafts after coronary artery bypass grafting in human subjects: An immunohistochemical.

Presentation transcript:

Experimental Non-Inferiority Trial of Synthetic Small-calibre Biodegradable vs. Stable Vascular Grafts Departments of 1 Cardiovascular Surgery, 3 Pathology and 4 Radiology University Hospital of Geneva; Dept. of 2 Pharmaceutics & Biopharmaceutics EPGL, University of Geneva; Switzerland. 1 Beat H. WALPOTH, MD FAHA Damiano Mugnai 1, Sarra de Valence 2, Wojciech Mrowczynski 1, Jean-Christophe Tille 3, Xavier Montet 4, Robert Gurny 2, Michael Moeller 2, Afksendiyos Kalangos 1

OBJECTIVES: There is a big need for shelf- ready, synthetic, small calibre prostheses for cardiovascular revascularisation procedures. Biodegradable scaffolds resistant to degradation-induced aneurysm formation in the systemic arterial circulation have been developed for : “ in vivo vascular tissue-engineering” Our aim is to assess the long-term results of synthetic, biodegradable, electrospun, small- calibre vascular grafts compared to ePTFE for aortic replacement in the rat model.

Vascular Tissue Engineering: Manufacturing of scaffolds Biodegradable grafts (polycaprolactone = PCL) were produced by random nano-fibre electro-spinning (porosity 80%) Modern “BARBAPAPA” technique to create novel vascular grafts

METHODS - I : 14 anaesthetised Sprague Dawley rats (male, 275g), received an infrarenal aortic graft (8 biodegradable; 6 ePTFE) replacement (end-to- end; 2mm ID; 20mm long) and 6 rats (same age) served as sham (controls) PCL graft Quality and patency control after surgery with transit time flowmeter 2 mm ePTFE graft

METHODS - II: After 15 months survival in vivo high resolution ultra-sonography (Visualsonics) and angiography were performed to assess patency, stenosis, aneurysm formation, intimal hyperplasia and compliance. After explantation micro CT calcification quantification, histology, immuno-histology, scanning electron microscopy (SEM) and morphometry were carried out. Rat 24 3 weeks after operation Rat 24 3 weeks after operation

PCL ( n=8) ePTFE (n=6) P< Patency (%) 10067ns Endothelialization (%) 9893ns Compliance (%) Calcification (%) Intimal Hyperplasia (µm) Cellular Ingrowth (%) RESULTS: PCL vs. ePTFE grafts at 15 months

Angiography after 15 months implantation A & B = ePTFE C = PCL D = Native Aorta

Vascular Compliance

HISTOLOGIC ASSESSMENT AFTER 15 MO IMPLANTATION PCL Morphological analysis of PLC grafts. (A) SEM image of the lumen of the PCL graft after explantation showing complete endothelialization. (B) Longitudinal section of the graft wall showing homogenous cellular infiltration giant cells on the periphery (arrows; HE staining, 100x magnification). (C) Neo-intima with spindle shape cells above a calcified area, indicated by the arrow. An endothelium is present on the luminal side. (HE staining, 200x magnification). (D) Immunohistochemistry anti CD31 labeling endothelial cells on the luminal side (200x magnification) (E) Elastin deposition in the neo-intimal layers is revealed in blue and collagen deposition is revealed in green by a Miller-Masson staining (200x magnification). (F) Immunohistochemistry anti Smooth Mucle Actin demonstrating positivity in spindle shape cells forming the neo-intima (200x magnification).

HISTOLOGIC ASSESSMENT AFTER 15 MO IMPLANTATION ePTFE Morphological analysis of ePTFE grafts. (A) Longitudinal section of the graft wall with neointima formation, limited cellular infiltration in the graft body and no giant cell reaction (HE staining, 100x magnification). (B) Neointima formation under the endothelium (indicated by an arrow) with no signs of calcification (HE staining, 200x magnification). (C) Miller- Masson staining revealing elastin fibers in bleu in the neointima and collagen depositions in green in the inner part of the graft (200x magnification). (D) Von Kossa staining showing in black the calcifications in the graft body (100x magnification). (E) SEM image of the lumen of the graft showing incomplete endothelialization (see insert) and microthrombi.

SUMMARY PCL vs. ePTFE grafts at 15 months : 100% patency vs. 67% for ePTFE No aneurysms, no stenosis Rapid and complete endothelialisation Similar neo-intima formation to ePTFE Better compliance than ePTFE, but Worse compliance than native aorta Less micro-calcifications than ePTFE (PET) Better cellular ingrowth in PCL grafts Vascular remodelling with live cells and ECM formation (collagen and elastin) with PCL degradation (65% MW reduction)

CONCLUSIONS Synthetic biodegradable small calibre nano-fibre polycaprolactone grafts show excellent results after 15 months of aortic replacement and compare favourably with the clinically used ePTFE grafts. Thus, such novel in situ tissue engineered grafts could become a future option for clinical applications such as coronary artery bypass grafting or endografting. PCL vs. ePTFE grafts at 15 months :