Endothelial cell seeding of (heparinized) collagen matrices: effects of bFGF pre-loading on proliferation (after low density seeding) and pro-coagulant factors

Wissink, M.J.B.; Beernink, R.; Scharenborg, Nicole M.; Poot, Andreas A.; Engbers, G.H.M.; Beugeling, T.; Aken, W.G. van; Feijén, Jan

doi:10.1016/s0168-3659(00)00202-9

Cited by 85 publications

(83 citation statements)

References 60 publications

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“…148 Scaffolds were seeded with stem cells and/or endothelial cells or incorporated with angiogenic factors to promote angiogenesis. [148][149][150][151] The minimum porosity necessary for the regeneration of a blood vessel is approximately 30 to 40 mm to enable the exchange of metabolic components and to facilitate endothelial cell entrance. 152,153 Artel et al showed that larger pore sizes of approximately 160 to 270 mm facilitated angiogenesis throughout scaffold by using multilayered agent-based model simulation.…”

Section: Angiogenesismentioning

confidence: 99%

Three-Dimensional Scaffolds for Tissue Engineering Applications: Role of Porosity and Pore Size

Loh

Choong

2013

Tissue Engineering Part B: Reviews

2,143

1,446

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Tissue engineering applications commonly encompass the use of three-dimensional (3D) scaffolds to provide a suitable microenvironment for the incorporation of cells or growth factors to regenerate damaged tissues or organs. These scaffolds serve to mimic the actual in vivo microenvironment where cells interact and behave according to the mechanical cues obtained from the surrounding 3D environment. Hence, the material properties of the scaffolds are vital in determining cellular response and fate. These 3D scaffolds are generally highly porous with interconnected pore networks to facilitate nutrient and oxygen diffusion and waste removal. This review focuses on the various fabrication techniques (e.g., conventional and rapid prototyping methods) that have been employed to fabricate 3D scaffolds of different pore sizes and porosity. The different pore size and porosity measurement methods will also be discussed. Scaffolds with graded porosity have also been studied for their ability to better represent the actual in vivo situation where cells are exposed to layers of different tissues with varying properties. In addition, the ability of pore size and porosity of scaffolds to direct cellular responses and alter the mechanical properties of scaffolds will be reviewed, followed by a look at nature's own scaffold, the extracellular matrix. Overall, the limitations of current scaffold fabrication approaches for tissue engineering applications and some novel and promising alternatives will be highlighted.

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Section: Angiogenesismentioning

confidence: 99%

Three-Dimensional Scaffolds for Tissue Engineering Applications: Role of Porosity and Pore Size

Loh

Choong

2013

Tissue Engineering Part B: Reviews

2,143

1,446

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“…EC function has also been shown to depend on cell density and level of confluence [140]. A number of studies have noted significant differences in initial EC function dependent on the underlying substrate, which become insignificant when confluence is reached [140,144,164,165]. For example, bovine and porcine EC cultured sparsely on TCPS, coated with different concentrations of poly(HEMA) to vary adhesiveness, showed variations in F-actin and cell shape which correlated with levels of prostacyclin [166].…”

Section: Molecular Expression Studiesmentioning

confidence: 99%

The influence of biomaterials on endothelial cell thrombogenicity

2007

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Driven by tissue engineering and regenerative medicine, endothelial cells are being used in combination with biomaterials in a number of applications for the purpose of improving blood compatibility and host integration. Endothelialized vascular grafts are beginning to be used clinically with some success in some centers, while endothelial seeding is being explored as a means of creating a vasculature within engineered tissues. The underlying assumption of this strategy is that when cultured on artificial biomaterials, a confluent layer of endothelial cells maintain their nonthrombogenic phenotype. In this review the existing knowledge base of endothelial cell thrombogenicity cultured on a number of different biomaterials is summarized. The importance of selecting appropriate endpoint measures that are most reflective of overall surface thrombogenicity is the focus of this review. Endothelial cells inhibit thrombosis through three interconnected regulatory systems (1) the coagulation cascade (2) the cellular components of the blood such as leukocytes and platelets and (3) the complement cascade, and also through effects on fibrinolysis and vascular tone, the latter which influences blood flow. Thus, in order to demonstrate the thromobgenic benefit of seeding a biomaterial with EC, the conditions under which EC surfaces are more likely to exhibit lower thrombogenicity than unseeded biomaterial surfaces need to be consistent with the experimental context. The endpoints selected should be appropriate for the dominant thrombotic process that occurs under the given experimental conditions.

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“…In addition, this group demonstrated that crosslinking of collagen had an adverse effect on the antigenicity and degradation rate of collagen, but stimulated endothelial cell adhesion and proliferation. 11,12 The suitability of collagen as a vascular graft material was also emphasized in a rabbit study, which established that collagengrafts were completely endothelialized after one month of implantation. 10 This study was undertaken to get a better understanding of the precise antithrombotic functions of immobilized heparin.…”

mentioning

confidence: 99%

“…9 -12 Potential advantages of the natural biological polymer collagen are its weak antigenicity and high tensile strength, which can resist high arterial blood pressures. Furthermore, collagen is a suitable substrate for endothelial cell growth in vitro, 11 which makes its application as an artificial vessel even more attractive. Nevertheless, the prothrombotic properties of collagen 13 are a major drawback in its applicability in blood contacting devices.…”

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confidence: 99%

Covalently-Bound Heparin Makes Collagen Thromboresistant

Keuren

Wielders

Driessen

et al. 2004

ATVB

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Objective-Blood compatibility of artificial surfaces depends on their immunogenic and thrombogenic properties.Collagen's weak antigenicity makes it an attractive candidate for stent coatings or fabrication of vascular grafts. However, the thrombogenic nature of collagen limits its application. We examined whether heparinization can make collagen more thromboresistant. Methods and Results-Collagen was heparinized by crosslinking collagen with extensively periodate oxidized heparin and/or by covalently bonding of mildly periodate oxidized heparin. Both ways of heparinization have no effect on platelet adhesion and could not abolish induction of platelet procoagulant activity. However, thrombin generation was completely prevented under static and flow conditions. The functionality of immobilized heparin was confirmed by specific uptake of antithrombin, 13.5Ϯ4.7 pmol/cm 2 and 1.95Ϯ0.21 pmol/cm 2 for mildly and heavily periodated heparin, respectively. Conclusions-These results indicate that immobilization of heparin on collagen, even as a crosslinker, is a very effective way to prevent surface thrombus formation. These data encourage the application of heparinized collagen as stent-graft material in animal and eventually human studies. Key Words: collagen Ⅲ heparin Ⅲ thrombogenicity Ⅲ thrombosis Ⅲ blood flow C ardiovascular disease, including vascular stenosis, is still the leading cause of death in Western society. Obstructive atherosclerotic disease, causing angina pectoris or even myocardial infarction, is currently treated by the implantation of a stent or through bypass surgery. Unfortunately, attempts to implant vascular grafts with a small diameter are not successful because of thrombotic and inflammatory reactions. 1-6 Thus, to enhance blood compatibility, a surface has to be designed that is both anti-immunogenic and thromboresistant. Collagen has been widely used in medical applications, including skin replacement, bone substitutes, and artificial valves. 7,8 Recently, a number of investigators attempted to use modified collagen as a vascular graft material. 9 -12 Potential advantages of the natural biological polymer collagen are its weak antigenicity and high tensile strength, which can resist high arterial blood pressures. Furthermore, collagen is a suitable substrate for endothelial cell growth in vitro, 11 which makes its application as an artificial vessel even more attractive. Nevertheless, the prothrombotic properties of collagen 13 are a major drawback in its applicability in blood contacting devices.To make collagen more thromboresistant, Wissink et al 14 coupled the sulfated polysaccharide, heparin, to collagen. An in vitro assay showed that the immobilized heparin was functionally active as it accelerated the thrombinantithrombin (AT) reaction. In addition, this group demonstrated that crosslinking of collagen had an adverse effect on the antigenicity and degradation rate of collagen, but stimulated endothelial cell adhesion and proliferation. 11,12 The suitability of collagen as a vascular g...

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Endothelial cell seeding of (heparinized) collagen matrices: effects of bFGF pre-loading on proliferation (after low density seeding) and pro-coagulant factors

Cited by 85 publications

References 60 publications

Three-Dimensional Scaffolds for Tissue Engineering Applications: Role of Porosity and Pore Size

Three-Dimensional Scaffolds for Tissue Engineering Applications: Role of Porosity and Pore Size

The influence of biomaterials on endothelial cell thrombogenicity

Covalently-Bound Heparin Makes Collagen Thromboresistant

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