Development of Decellularized Human Umbilical Arteries as Small-Diameter Vascular Grafts

Gui, Liqiong; Muto, Akihito; Chan, Stephen A.; Breuer, Christopher K.; Niklason, Laura E.

doi:10.1089/ten.tea.2008.0526

Cited by 211 publications

(201 citation statements)

References 52 publications

(73 reference statements)

Supporting

Mentioning

186

Contrasting

Unclassified

Order By: Relevance

“…28,29 Briefly, samples were fixed with 1% glutaraldehyde solution in 0.1 M sodium cacodylate buffer (pH 7.4; Polysciences) for 5 min, washed with distilled water for 5 min, and dehydrated with 5-min exchanges in each of 70%, 85%, and 95% aqueous ethanol and absolute ethanol. Samples were further immersed in hexamethyldisilazane (Polysciences) for 10 min and air-dried overnight.…”

Section: Scanning Electron Microscopymentioning

confidence: 99%

Development of Novel Biodegradable Polymer Scaffolds for Vascular Tissue Engineering

Gui

Zhao

Spencer³

et al. 2011

Tissue Engineering Part A

Self Cite

View full text Add to dashboard Cite

Functional connective tissues have been developed using tissue engineering approach by seeding cells on biodegradable scaffolds such as polyglycolic acid (PGA). However, a major drawback of tissue engineering approaches that utilize synthetic polymers is the persistence of polymer remnants in engineered tissues at the end of culture. Such polymer fragments may significantly degrade tissue mechanics and stimulate local inflammatory responses in vivo. In this study, several polymeric materials with a range of degradation profiles were developed and evaluated for their potential applications in construction of collagen matrix-rich tissues, particularly tissue-engineered blood vessels. The degradation characteristics of these polymers were compared as were their characteristics vis-à -vis cell adhesion and proliferation, collagen synthesis, and ability to support growth of engineered vessels. Under aqueous conditions at 378C, Polymer I (comprising 84% glycolide and 16% trimethylene carbonate [TMC]) had a similar degradation profile to PGA, Polymer II (comprising 84% glycolide, 14% TMC, and 2% polyethylene succinate) degradedly more slowly, but Polymer III (comprising 87% glycolide, 7% TMC, and 6% polyethylene glycol) had a more extensive degradation as compared to PGA. All polymers supported cell proliferation, but Polymer III improved collagen production and engineered vessel mechanics as compared with PGA. In addition, more slowly degrading polymers were associated with poorer final vessel mechanics. These results suggest that polymers that degrade more quickly during tissue culture actually result in improved engineered tissue mechanics, by virtue of decreased disruption of collagenous extracellular matrix.

show abstract

Section: Scanning Electron Microscopymentioning

confidence: 99%

Development of Novel Biodegradable Polymer Scaffolds for Vascular Tissue Engineering

Gui

Zhao

Spencer³

et al. 2011

Tissue Engineering Part A

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our results show that S1P-treated EC attached better to the DHUV treated under both static and dynamic cell seeding conditions. An in vivo test of using the decellularized small caliber blood vessel for implantation showed that acute thrombosis in the first 24 h cause is the primary blood vessel failure [59]. Thus, a confluent endothelial layer is important for graft patency.…”

Section: Discussionmentioning

confidence: 99%

“…The change in the optical density of the solution versus time was plotted. Clotting times were estimated for all test materials, including the tubes, non-seeded HUV, cell-seeded HUV and cellseeded HUV with S1P treatment as previously described [38,39].…”

Section: Coagulation and Kinetic Clotting Testsmentioning

confidence: 99%

Sphingosine-1-phosphate improves endothelialization with reduction of thrombosis in recellularized human umbilical vein graft by inhibiting syndecan-1 shedding in vitro

et al. 2017

View full text Add to dashboard Cite

a b s t r a c tSphingosine-1-phosphate (S1P) has been known to promote endothelial cell (EC) proliferation and protect Syndecan-1 (SDC1) from shedding, thereby maintaining this antithrombotic signal. In the present study, we investigated the effect of S1P in the construction of a functional tissue-engineered blood vessel by using human endothelial cells and decellularized human umbilical vein (DHUV) scaffolds. Both human umbilical vein endothelial cells (HUVEC) and human cord blood derived endothelial progenitor cells (EPC) were seeded onto the scaffold with or without the S1P treatment. The efficacy of recellularization was determined by using the fluorescent marker CellTracker CMFDA and anti-CD31 immunostaining. The antithrombotic effect of S1P was examined by the anti-aggregation tests measuring platelet adherence and clotting time. Finally, we altered the expression of SDC1, a major glycocalyx protein on the endothelial cell surface, using MMP-7 digestion to explore its role using platelet adhesion tests in vitro. The result showed that S1P enhanced the attachment of HUVEC and EPC. Based on the anti-aggregation tests, S1P-treated HUVEC recellularized vessels when grafted showed reduced thrombus formation compared to controls. Our results also identified reduced SDC1 shedding from HUVEC responsible for inhibition of platelet adherence. However, no significant antithrombogenic effect of S1P was observed on EPC. In conclusion, S1P is an effective agent capable of decreasing thrombotic risk in engineered blood vessel grafts. Statement of SignificanceSphingosine-1phosphate (S1P) is a low molecular-weight phospholipid mediator that regulates diverse biological activities of endothelial cell, including survival, proliferation, cell barrier integrity, and also influences the development of the vascular system. Based on these characters, we the first time to use it as an additive during the process of a small caliber blood vessel construction by decellularized human umbilical vein and endothelial cell/endothelial progenitor. We further explored the function and Contents lists available at ScienceDirect Acta Biomaterialia j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l oc a t e / a c t a b i o m a t mechanism of S1P in promoting revascularization and protection against thrombosis in this tissue engineered vascular grafts. The results showed that S1P could not only accelerate the generation but also reduce thrombus formation of small caliber blood vessel.

show abstract

“…2, 14 The vessel growth medium is optimized specially to support ECM synthesis and consists of high-glucose DMEM supplemented with 10% FBS, penicillin G (100 U/mL; Sigma), ascorbic acid (50 ng/mL; Sigma), CuSO 4 (3 ng/mL; Sigma), HEPES (5 mM; Sigma), proline (50 ng/mL; Sigma), glycine (50 ng/mL; Sigma), and alanine (20 ng/mL; Sigma). The culture medium was refreshed weekly and ascorbic acid was refreshed every 2 days.…”

Section: Figmentioning

confidence: 99%

Design and Use of a Novel Bioreactor for Regeneration of Biaxially Stretched Tissue-Engineered Vessels

Huang

Lee

Calle

et al. 2015

Tissue Engineering Part C: Methods

Self Cite

View full text Add to dashboard Cite

Conventional bioreactors are used to enhance extracellular matrix (ECM) production and mechanical strength of tissue-engineered vessels (TEVs) by applying circumferential strain, which is uniaxial stretching. However, the resulting TEVs still suffer from inadequate mechanical properties, where rupture strengths and compliance values are still very different from native arteries. The biomechanical milieu of native arteries consists of both circumferential and axial loading. Therefore, to better simulate the physiological stresses acting on native arteries, we built a novel bioreactor system to enable biaxial stretching of engineered arteries during culture. This new bioreactor system allows for independent control of circumferential and axial stretching parameters, such as displacement and beat rate. The assembly and setup processes for this biaxial bioreactor system are reliable with a success rate greater than 75% for completion of long-term sterile culture. This bioreactor also supports side-by-side assessments of TEVs that are cultured under three types of mechanical conditions (static, uniaxial, and biaxial), all within the same biochemical environment. Using this bioreactor, we examined the impact of biaxial stretching on arterial wall remodeling of TEVs. Biaxial TEVs developed the greatest wall thickness compared with static and uniaxial TEVs. Unlike uniaxial loading, biaxial loading led to undulated collagen fibers that are commonly found in native arteries. More importantly, the biaxial TEVs developed the most mature elastin in the ECM, both qualitatively and quantitatively. The presence of mature extracellular elastin along with the undulated collagen fibers may contribute to the observed vascular compliance in the biaxial TEVs. The current work shows that biaxial stretching is a novel and promising means to improve TEV generation. Furthermore, this novel system allows us to optimize biomechanical conditioning by unraveling the interrelationships among the applied mechanical stress, the resulting ECM properties, and the mechanics of TEVs.

show abstract

Development of Decellularized Human Umbilical Arteries as Small-Diameter Vascular Grafts

Cited by 211 publications

References 52 publications

Development of Novel Biodegradable Polymer Scaffolds for Vascular Tissue Engineering

Development of Novel Biodegradable Polymer Scaffolds for Vascular Tissue Engineering

Sphingosine-1-phosphate improves endothelialization with reduction of thrombosis in recellularized human umbilical vein graft by inhibiting syndecan-1 shedding in vitro

Design and Use of a Novel Bioreactor for Regeneration of Biaxially Stretched Tissue-Engineered Vessels

Contact Info

Product

Resources

About