Towards a Clinically Applicable Tissue Engineered Vascular Graft

2013 ◽  
Author(s):  
W. S. Sheridan ◽  
O. Grant ◽  
A. Lopez-Noriega ◽  
G. P. Duffy ◽  
B. P. Murphy
Keyword(s):  
Shelf Life ◽  
Vascular Graft ◽  
Vascular Tissue ◽  
Limiting Factors ◽  
Tissue Replacement ◽  
Large Patient ◽  
Arterial Tissue ◽  
Long Term Preservation

Decellularized arterial tissue has shown promising use as a scaffold for vascular tissue replacement; similar structural and functional characteristics to the native tissue are maintained and these scaffolds are non-thrombogenic, non immunogenic with the ability to remodel and grow in vivo[1]. However, there still remains a number of limiting factors in clinically translating these scaffolds. Namely, producing a range of geometries to accommodate a large patient cohort within clinically feasible manufacturing times and costs. Furthermore, these scaffolds must be suitable for long term preservation to produce a reasonable shelf life and be capable of undergoing standard sterilization techniques.

scholarly journals Assessment of Electrospun Pellethane-Based Scaffolds for Vascular Tissue Engineering

Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3678
Author(s):  
Vera Chernonosova ◽  
Alexandr Gostev ◽  
Ivan Murashov ◽  
Boris Chelobanov ◽  
Andrey Karpenko ◽  
...  
Keyword(s):  
Vascular Tissue ◽  
Ex Vivo ◽  
Vascular Grafts ◽  
Wistar Rat ◽  
Graft Occlusion ◽  
Suitable Candidate ◽  
Large Animals ◽  
Cell Adhesion And Proliferation

We examined the physicochemical properties and the biocompatibility and hemocompatibility of electrospun 3D matrices produced using polyurethane Pellethane 2363-80A (Pel-80A) blends Pel-80A with gelatin or/and bivalirudin. Two layers of vascular grafts of 1.8 mm in diameter were manufactured and studied for hemocompatibility ex vivo and functioning in the infrarenal position of Wistar rat abdominal aorta in vivo (n = 18). Expanded polytetrafluoroethylene (ePTFE) vascular grafts of similar diameter were implanted as a control (n = 18). Scaffolds produced from Pel-80A with Gel showed high stiffness with a long proportional limit and limited influence of wetting on mechanical characteristics. The electrospun matrices with gelatin have moderate capacity to support cell adhesion and proliferation (~30–47%), whereas vascular grafts with bivalirudin in the inner layer have good hemocompatibility ex vivo. The introduction of bivalirudin into grafts inhibited platelet adhesion and does not lead to a change hemolysis and D-dimers concentration. Study in vivo indicates the advantages of Pel-80A grafts over ePTFE in terms of graft occlusion, calcification level, and blood velocity after 6 months of implantation. The thickness of neointima in Pel-80A–based grafts stabilizes after three months (41.84 ± 20.21 µm) and does not increase until six months, demonstrating potential for long-term functioning without stenosis and as a suitable candidate for subsequent preclinical studies in large animals.

scholarly journals Long-Term Hypoxic/Hypocapnic Storage of Red Blood Cells Results in Amelioration of Lesion Hallmarks and Increased In Vivorecovery at 24 Hours Post-Transfusion

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4995-4995
Author(s):  
Jose A Cancelas ◽  
F. Bernadette West ◽  
Matthew Karaffin ◽  
Tatsuro Yoshida ◽  
Neeta Rugg ◽  
...  
Keyword(s):  
Shelf Life ◽  
Research Funding ◽  
Storage System ◽  
Processing System ◽  
Test Group ◽  
Wilcoxon Test ◽  
And Control ◽  
2,3 Dpg

Oxidative damage, dysmetabolism and decreased levels of 2, 3-diphosphoglycerate (2,3-DPG) affect red blood cell (RBC) survival and the affinity of Hemoglobin for oxygen are relevant hallmarks of RBC storage lesion, especially in specific clinical contexts. We hypothesized that oxygen and carbon dioxide reduction followed by hypoxic/hypocapnic storage would result in amelioration of RBC lesion assessed at the end of their shelf-life and at the shelf-life mode (21 days).To determine the relevance of hypoxic/hypocapnic storage in humans, a pivotal, prospective, randomized, two‐arm, crossover, three‐center trial was conducted to evaluate [Hemanext®] hypoxic/hypocapnic processing system and was used to assess whether this process and storage method met standard FDA acceptability criteria for long-term RBC storage. The Test arm consisted of whole blood (WB)‐derived, leukoreduced RBC in AS-3 additive processed at room temperature with the Hemanext system for 3 hours to achieve hypoxic/hypocapnic state within 12 hours of phlebotomy which was maintained hypoxic during storage for up to 43 days at 1‐6°C (Test).Unprocessed units (Control) were stored within 8 hours under conventional storage conditions. Subjects (N=100) donated CP2D WB (500 ± 50 mL) and a minimum of 93 pairs of RBC units per arm were analyzed for in vitroquality parameters. For in vivo analysis at end of storage, RBCs from 19 test subjects and 21 control subjects (14 paired) from two sites were radiolabeled with 51‐Cr/99‐Tc(m), autologously transfused, and analyzed for 24-hour recovery. Differences between the Test and Control groups were analyzed using the paired t-test (Wilcoxon test where necessary). Paired analyses of 24-hour in vivorecoveries on day 43 was 89.3±4.5% and 84.8±6.2% for the test and control, respectively; p<0.01). Significantly higher levels of 2,3-DPG and adenosine 5'-triphosphate (ATP) were maintained for the Test group by days 21 and 42/43 of storage (Table 1). Percentage of hemolysis was similar in both groups. In summary, these data demonstrate that RBCs preserved in a user-friendly, self-contained hypoxic storage system are superior than the conventionally stored RBCs and may provide more viable RBCs for transfusion at 6 weeks of storage. Disclaimer: The51‐Cr/99‐Tc(m)labeling at one of the three sites occurred without prior RDRC approval and did not meet GMP standards. Disclosures Cancelas: Fresenius-Kabi: Research Funding; Cerus Co.: Research Funding; TerumoBCT: Consultancy, Research Funding; Hemanext: Consultancy, Research Funding; Macopharma Inc: Research Funding; Cytosorbents: Research Funding; Cellphire: Research Funding; Velico: Consultancy, Research Funding. Yoshida:New Health Sciences Inc.: Employment, Equity Ownership. Dioguardi:Hemanext: Employment. Iselin:Hemanext: Employment. Dunham:Hemanext: Employment.

Preparation of Electrospun Poly(ε-caprolactone)/Poly(trimethylene carbonate) Blend Scaffold for In Situ Vascular Tissue Engineering

2012 ◽  
Vol 629 ◽  
pp. 60-63
Author(s):  
Tao Jiang ◽  
Guo Quan Zhang ◽  
Hui Li ◽  
Ji Na Xun
Keyword(s):  
Tissue Engineering ◽  
Vascular Graft ◽  
Vascular Tissue ◽  
Electrospinning Process ◽  
Vascular Tissue Engineering ◽  
Trimethylene Carbonate ◽  
Scaffold Materials ◽  
Degradation Time

In the active field of vascular graft research, in situ vascular tissue engineering is a novel concept. This approach aims to use biodegradable synthetic materials. After implantation, the synthetic material progressively degrades and should be replaced by autologous cells. Poly (ε-caprolactone) (PCL) is often used for vascular graft because of its good mechanical strength and its biocompatibility. It is easily processed into micro and nano-fibers by electrospinning to form a porous, cell-friendly scaffold. However, the degradation time of polycaprolactone is too long to match the tissue regeneration time. In this study, poly (ε-caprolactone) /poly (trimethylene carbonate) (PTMC) blend scaffold materials have been prepared for biodegradable vascular graft using an electrospinning process. Because the degradation time of PTMC is shorter than PCL in vivo. The morphological characters of PCL/PTMC blend scaffold materials were investigated by scanning electron microscope (SEM). The molecular components and some physical characteristics of the blend scaffold materials were tested by FT-IR and DSC analysis.

scholarly journals Cell Tracking Technologies for Acute Ischemic Brain Injury

2015 ◽  
Vol 35 (7) ◽  
pp. 1090-1099 ◽  
Author(s):  
Felicity NE Gavins ◽  
Helen K Smith
Keyword(s):  
Cell Therapy ◽  
Cell Tracking ◽  
Imaging Techniques ◽  
Direct Analysis ◽  
Image Resolution ◽  
Tissue Replacement ◽  
Cell Monitoring ◽  
Growth Factor Release

Stem cell therapy has showed considerable potential in the treatment of stroke over the last decade. In order that these therapies may be optimized, the relative benefits of growth factor release, immunomodulation, and direct tissue replacement by therapeutic stem cells are widely under investigation. Fundamental to the progress of this research are effective imaging techniques that enable cell tracking in vivo. Direct analysis of the benefit of cell therapy includes the study of cell migration, localization, division and/or differentiation, and survival. This review explores the various imaging tools currently used in clinics and laboratories, addressing image resolution, long-term cell monitoring, imaging agents/isotopes, as well as safety and costs associated with each technique. Finally, burgeoning tracking techniques are discussed, with emphasis on multimodal imaging.

Novel Electrospun Nanocomposites With Controllable Compositional Gradient and Degradation Kinetics for Vascular Tissue Engineering

2009 ◽  
Author(s):  
Walter Bonani ◽  
Antonella Motta ◽  
Claudio Migliaresi ◽  
Wei Tan
Keyword(s):  
Tissue Engineering ◽  
Vascular Tissue ◽  
Degradation Kinetics ◽  
Interpenetrating Networks ◽  
Compositional Gradient ◽  
Small Vessels ◽  
Synthetic Materials ◽  
Fiber Materials

Vascular graft materials currently used in the medical field are often made from bioinert synthetic materials such as polytetrafluoroethylene (PTFE). The high long-term failure rate of these materials in the replacement of small vessels is known to be associated with the lack of proper signaling events by PTFE to vascular cells causing adverse hemodynamic, inflammatory or coagulatory conditions. Tissue engineering approaches emerge as a promising method to obtain replacement vessels. These approaches are often based on homogeneous constructs or multilayer of homogeneous constructs are yet to demonstrate capability of controlling the integration of tissue engineering construct in vivo better for long-term patency. Therefore, constant and pressing is the demand for scaffold constructs which can provide not only proper mechanical support, but also precise molecular cues and degradation kinetics to facilitate the proper remodeling and integration process in vivo over the time for long-term patency. To this end, we have developed and demonstrated a novel double-electrospinning apparatus to obtain interpenetrating networks of nanofibers made from different polymers in a tailored proportion with heterogeneous gradient patterns of fiber materials and functional biomolecules.

scholarly journals Prevention of restenosis by a herpes simplex virus mutant capable of controlled long-term expression in vascular tissue in vivo

Gene Therapy ◽  
2001 ◽  
Vol 8 (24) ◽  
pp. 1840-1846 ◽  
Author(s):  
CL Skelly ◽  
MA Curi ◽  
SL Meyerson ◽  
DH Woo ◽  
D Hari ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Vascular Tissue ◽  
Virus Mutant ◽  
Simplex Virus

scholarly journals Nitrate-Functionalized poly(ε-Caprolactone) Small-Diameter Vascular Grafts Enhance Vascular Regeneration via Sustained Release of Nitric Oxide

2021 ◽  
Vol 9 ◽  
Author(s):  
Sen Yang ◽  
Xueni Zheng ◽  
Meng Qian ◽  
He Wang ◽  
Fei Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Tissue ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Post Transplantation ◽  
Vascular Regeneration ◽  
Vascular Progenitor Cells ◽  
Small Diameter Vascular Grafts

Artificial small-diameter vascular grafts (SDVG) fabricated from synthetic biodegradable polymers, such as poly(ε-caprolactone) (PCL), exhibit beneficial mechanical properties but are often faced with issues impacting their long-term graft success. Nitric oxide (NO) is an important physiological gasotransmitter with multiple roles in orchestrating vascular tissue function and regeneration. We fabricated a functional vascular graft by electrospinning of nitrate-functionalized poly(ε-caprolactone) that could release NO in a sustained manner via stepwise biotransformation in vivo. Nitrate-functionalized SDVG (PCL/NO) maintained patency following abdominal arterial replacement in rats. PCL/NO promoted cell infiltration at 3-months post-transplantation. In contrast, unmodified PCL SDVG showed slow cell in-growth and increased incidence of neointima formation. PCL/NO demonstrated improved endothelial cell (EC) alignment and luminal coverage, and more defined vascular smooth muscle cell (VSMC) layer, compared to unmodified PCL SDVG. In addition, release of NO stimulated Sca-1+ vascular progenitor cells (VPCs) to differentiate and contribute to rapid luminal endothelialization. Furthermore, PCL/NO inhibited the differentiation of VPCs into osteopontin-positive cells, thereby preventing vascular calcification. Overall, PCL/NO demonstrated enhanced cell ingrowth, EC monolayer formation and VSMC layer regeneration; whilst inhibiting calcified plaque formation. Our results suggested that PCL/NO could serve as promising candidates for improved and long-term success of SDVG implants.

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