The performance of heparin modified poly(ε‐caprolactone) small diameter tissue engineering vascular graft in canine—A long‐term pilot experiment in vivo

Small diameter (<6 mm) vessel grafts still pose a challenge for scientists worldwide. Decellularised umbilical artery (dUA) remains promising as small diameter tissue engineered vascular graft (TEVG), yet their immunogenicity remains unknown. Herein, we evaluated the host immune responses, with a focus on the innate part, towards human dUA implantation in mice, and confirmed our findings in an ex vivo allogeneic human setup. Overall, we did not observe any differences in the number of circulating white blood cells nor the number of monocytes among three groups of mice (1) dUA patch; (2) Sham; and (3) Mock throughout the study (day −7 to 28). Likewise, we found no difference in systemic inflammatory and anti-inflammatory cytokine levels between groups. However, a massive local remodelling response with M2 macrophages were observed in the dUA at day 28, whereas M1 macrophages were less frequent. Moreover, human monocytes from allogeneic individuals were differentiated into macrophages and exposed to lyophilised dUA to maximize an eventual M1 response. Yet, dUA did not elicit any immediate M1 response as determined by the absence of CCR7 and CXCL10. Together this suggests that human dUA elicits a minimal pro-inflammatory response further supporting its use as a TEVG in an allogeneic setup.

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Scaffolds in tissue engineering of blood vessels

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y10-073 ◽

2010 ◽

Vol 88 (9) ◽

pp. 855-873 ◽

Cited By ~ 60

Author(s):

Divya Pankajakshan ◽

Devendra K. Agrawal

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Blood Vessels ◽

Vascular Tissue ◽

Small Diameter ◽

Biological Scaffolds ◽

Hemodynamic Forces ◽

Biodegradable Scaffolds

Tissue engineering of small diameter (<5 mm) blood vessels is a promising approach for developing viable alternatives to autologous vascular grafts. It involves in vitro seeding of cells onto a scaffold on which the cells attach, proliferate, and differentiate while secreting the components of extracellular matrix that are required for creating the tissue. The scaffold should provide the initial requisite mechanical strength to withstand in vivo hemodynamic forces until vascular smooth muscle cells and fibroblasts reinforce the extracellular matrix of the vessel wall. Hence, the choice of scaffold is crucial for providing guidance cues to the cells to behave in the required manner to produce tissues and organs of the desired shape and size. Several types of scaffolds have been used for the reconstruction of blood vessels. They can be broadly classified as biological scaffolds, decellularized matrices, and polymeric biodegradable scaffolds. This review focuses on the different types of scaffolds that have been designed, developed, and tested for tissue engineering of blood vessels, including use of stem cells in vascular tissue engineering.

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Tissue ingrowth markedly reduces mechanical anisotropy and stiffness in fibre direction of highly aligned electrospun polyurethane scaffolds

10.1101/779942 ◽

2019 ◽

Cited By ~ 2

Author(s):

Hugo Krynauw ◽

Jannik Buescher ◽

Josepha Koehne ◽

Loes Verrijt ◽

Georges Limbert ◽

...

Keyword(s):

Elastic Modulus ◽

Vascular Graft ◽

Small Diameter ◽

Mechanical Anisotropy ◽

Fibre Direction ◽

Tissue Ingrowth ◽

Fibre Alignment ◽

Random Fibre ◽

Directed Research

AbstractPurposeThe lack of long-term patency of synthetic vascular grafts currently available on the market has directed research towards improving the performance of small diameter grafts. Improved radial compliance matching and tissue ingrowth into the graft scaffold are amongst the main goals for an ideal vascular graft.MethodsBiostable polyurethane scaffolds were manufactured by electrospinning and implanted in subcutaneous and circulatory positions in the rat for 7, 14 and 28 days. Scaffold morphology, tissue ingrowth, and mechanical properties of the scaffolds were assessed before implantation and after retrieval.ResultsTissue ingrowth after 24 days was 96.5 ± 2.3% in the subcutaneous implants and 77.8 ± 5.4% in the circulatory implants. Over the 24 days implantation, the elastic modulus at 12% strain decreased by 59% in direction of the fibre alignment whereas it increased by 1379% transverse to the fibre alignment of the highly aligned scaffold of the subcutaneous implants. The lesser aligned scaffold of the circulatory graft implants exhibited an increase of the elastic modulus at 12% strain by 77% in circumferential direction.ConclusionBased on the observations, it is proposed that the mechanism underlying the softening of the highly aligned scaffold in the predominant fibre direction is associated with scaffold compaction and local displacement of fibres by the newly formed tissue. The stiffening of the scaffold, observed transverse to highly aligned fibres and for more a random fibre distribution, represents the actual mechanical contribution of the tissue that developed in the scaffold.

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Elastin-Sprayed Tubular Scaffolds With Microstructures and Nanotextures for Vascular Tissue Engineering

Volume 1A: Abdominal Aortic Aneurysms; Active and Reactive Soft Matter; Atherosclerosis; BioFluid Mechanics; Education; Biotransport Phenomena; Bone, Joint and Spine Mechanics; Brain Injury; Cardiac Mechanics; Cardiovascular Devices, Fluids and Imaging; Cartilage and Disc Mechanics; Cell and Tissue Engineering; Cerebral Aneurysms; Computational Biofluid Dynamics; Device Design, Human Dynamics, and Rehabilitation; Drug Delivery and Disease Treatment; Engineered Cellular Environments ◽

10.1115/sbc2013-14448 ◽

2013 ◽

Author(s):

Jinah Jang ◽

Junghyuk Ko ◽

Dong-Woo Cho ◽

Martin B. G. Jun ◽

Deok-Ho Kim

Keyword(s):

Tissue Engineering ◽

Vascular Graft ◽

Vascular Tissue ◽

High Surface ◽

Small Diameter ◽

Vascular Tissue Engineering ◽

Biophysical Properties ◽

Fibrous Scaffold ◽

Cardiovascular Tissue ◽

Highly Porous

Development of a small-diameter vascular graft (<6 mm) have been challenging due to thrombosis and intimal hyperplasia [1]. To overcome this problem, cardiovascular tissue engineers have attempted to construct a highly porous and biocompatible fibrous scaffold providing a sufficient mechanical strength for the regeneration of a functional tissue [2–5]. Herein, we present a 3D tubular-shaped micro/nanofibrous composite-layered scaffold for vascular tissue engineering. The surface of scaffold has high surface roughness by introducing nanofibrous layer and the biophysical properties have been fulfilled by using microfibrous layer. Moreover, the atomized spraying technique is applied to spray elastin proteins, which is well known as an antithrombogenic material, on the surface of micro/nanofibrous composite-layered scaffold to introduce an appropriate antithrombogenic surface.

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Establishment of Collagen: Hydroxyapatite/BMP-2 Mimetic Peptide Composites

Materials ◽

10.3390/ma13051203 ◽

2020 ◽

Vol 13 (5) ◽

pp. 1203

Author(s):

Liane Schuster ◽

Nina Ardjomandi ◽

Marita Munz ◽

Felix Umrath ◽

Christian Klein ◽

...

Keyword(s):

Tissue Engineering ◽

Cost Effective ◽

Quartz Crystals ◽

Mimetic Peptide ◽

Glutamic Acid Residue ◽

Hydroxyapatite Composite ◽

Mimetic Peptides ◽

Periosteal Cells

Extensive efforts were undertaken to develop suitable biomaterials for tissue engineering (TE) applications. To facilitate clinical approval processes and ensure the success of TE applications, bioinspired concepts are currently focused on. Working on bone tissue engineering, we describe in the present study a method for biofunctionalization of collagen/hydroxyapatite composites with BMP-2 mimetic peptides. This approach is expected to be fundamentally transferable to other tissue engineering fields. A modified BMP-2 mimetic peptide containing a negatively charged poly-glutamic acid residue (E7 BMP-2 peptide) was used to bind positively charged hydroxyapatite (HA) particles by electrostatic attraction. Binding efficiency was biochemically detected to be on average 85% compared to 30% of BMP-2 peptide without E7 residue. By quartz crystal microbalance (QCM) analysis, we could demonstrate the time-dependent dissociation of the BMP-2 mimetic peptides and the stable binding of the E7 BMP-2 peptides on HA-coated quartz crystals. As shown by immunofluorescence staining, alkaline phosphatase expression is similar to that detected in jaw periosteal cells (JPCs) stimulated with the whole BMP-2 protein. Mineralization potential of JPCs in the presence of BMP-2 mimetic peptides was also shown to be at least similar or significantly higher when low peptide concentrations were used, as compared to JPCs cultured in the presence of recombinant BMP-2 controls. In the following, collagen/hydroxyapatite composite materials were prepared. By proliferation analysis, we detected a decrease in cell viability with increasing HA ratios. Therefore, we chose a collagen/hydroxyapatite ratio of 1:2, similar to the natural composition of bone. The following inclusion of E7 BMP-2 peptides within the composite material resulted in significantly elevated long-term JPC proliferation under osteogenic conditions. We conclude that our advanced approach for fast and cost-effective scaffold preparation and biofunctionalization is suitable for improved and prolonged JPC proliferation. Further studies should prove the functionality of composite scaffolds in vivo.

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

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.629.60 ◽

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.

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Applying elastic fibre biology in vascular tissue engineering

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2007.2134 ◽

2007 ◽

Vol 362 (1484) ◽

pp. 1293-1312 ◽

Cited By ~ 49

Author(s):

Cay M Kielty ◽

Simon Stephan ◽

Michael J Sherratt ◽

Matthew Williamson ◽

C. Adrian Shuttleworth

Keyword(s):

Tissue Engineering ◽

Vascular Graft ◽

Vascular Tissue ◽

Small Diameter ◽

Elastic Fibre ◽

Vascular Tissue Engineering ◽

Western Society ◽

Elastic Recoil ◽

Vessel Structure ◽

Biomaterial Scaffolds

For the treatment of vascular disease, the major cause of death in Western society, there is an urgent need for tissue-engineered, biocompatible, small calibre artery substitutes that restore biological function. Vascular tissue engineering of such grafts involves the development of compliant synthetic or biomaterial scaffolds that incorporate vascular cells and extracellular matrix. Elastic fibres are major structural elements of arterial walls that can enhance vascular graft design and patency. In blood vessels, they endow vessels with the critical property of elastic recoil. They also influence vascular cell behaviour through direct interactions and by regulating growth factor activation. This review addresses physiological elastic fibre assembly and contributions to vessel structure and function, and how elastic fibre biology is now being exploited in small diameter vascular graft design.

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