Accelerating Vascularization in Polycaprolactone Scaffolds by Endothelial Progenitor Cells

Singh, Shivani; Wu, Benjamin M.; Dunn, James C.Y.

doi:10.1089/ten.tea.2010.0708

Cited by 51 publications

(39 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[2][3][4][5] Possible sources of autologous ECs include circulating endothelial progenitor cells and ECs derived from induced pluripotent stem cells single cell source of stem cells, ECs, and pericytes. 9,10 Our group has previously demonstrated that early passage ASCs are inherently heterogeneous, containing a residual subpopulation of endothelial progenitors that can proliferate extensively to grow into densely interconnected vascular networks.…”

mentioning

confidence: 99%

Hypoxia Inhibits De Novo Vascular Assembly of Adipose-Derived Stromal/Stem Cell Populations, but Promotes Growth of Preformed Vessels

Hutton

Grayson

2016

Tissue Engineering Part A

View full text Add to dashboard Cite

Vascularization is critical for cell survival within tissue-engineered grafts. Adipose-derived stromal/stem cells (ASCs) are widely used in tissue engineering applications as they are a clinically relevant source of stem cells and endothelial progenitor cells. ASCs have previously been shown to self-assemble into pericyte-stabilized vascular networks in normoxic (20% O 2 ) cultures. This capacity for de novo vascular assembly may accelerate graft vascularization in vivo rather than relying solely on angiogenic ingrowth. However, oxygen depletion within large cell-seeded grafts will be rapid, and it is unclear how this worsening hypoxic environment will impact the vascular assembly of the transplanted cells. The objectives of this study were to determine whether ASC-derived vessels could grow in hypoxia and to assess whether the vessel maturity (i.e., individual cells vs. preformed vessels) influenced this hypoxic response. Utilizing an in vitro vascularization model, ASCs were encapsulated within fibrin gels and cultured in vitro for up to 6 days in either normoxia (20% O 2 ) or hypoxia (0.2% or 2% O 2 ). In a subsequent experiment, vessels were allowed to preform in normoxia for 6 days before an additional 6 days of either normoxia or hypoxia. Viability, vessel growth, pericyte coverage, proliferation, metabolism, and angiogenic factor expression were assessed for each experimental approach. Vessel growth was dramatically inhibited in both moderate and severe hypoxia (47% and 11% total vessel length vs. normoxia, respectively), despite maintaining high cell viability and upregulating endogenous expression of vascular endothelial growth factor in hypoxia. Bromodeoxyuridine labeling indicated significantly reduced proliferation of endothelial cells in hypoxia. In contrast, when vascular networks were allowed to preform for 6 days in normoxia, vessels not only survived but also continued to grow more in hypoxia than those maintained in normoxia. These findings demonstrate that vascular assembly and growth are tightly regulated by oxygen tension and may be differentially affected by hypoxic conditions based on the maturity of the vessels. Understanding this relationship is critical to developing effective approaches to engineer viable tissue-engineered grafts in vivo.

show abstract

mentioning

confidence: 99%

Hypoxia Inhibits De Novo Vascular Assembly of Adipose-Derived Stromal/Stem Cell Populations, but Promotes Growth of Preformed Vessels

Hutton

Grayson

2016

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…Another study evaluated in vivo implantation of Nano-D400G and Nano-PCL revealed higher vascular density and less inflammation after 4 weeks in Nano PCL (Giavaresi et al, 2006). The PCL has some preference in the terms of recellularization, where Singh et al found an increase in angiogenesis and vasculogenesis in heparin-PCL scaffolds seeded by endothelial progenitor cells after 1 week (Singh et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

A novel surgical technique for a rat subcutaneous implantation of a tissue engineered scaffold

Khorramirouz

Noble

et al. 2018

Acta Histochemica

View full text Add to dashboard Cite

Objectives Subcutaneous implantations in small animal models are currently required for preclinical studies of acellular tissue to evaluate biocompatibility, including host recellularization and immunogenic reactivity. Methods Three rat subcutaneous implantation methods were evaluated in six Sprague Dawley rats. An acellular xenograft made from porcine pericardium was used as the tissue-scaffold. Three implantation methods were performed; 1) Suture method is where a tissue-scaffold was implanted by suturing its border to the external oblique muscle, 2) Control method is where a tissue-scaffold was implanted without any suturing or support, 3) Frame method is where a tissue-scaffold was attached to a circular frame composed of polycaprolactone (PCL) biomaterial and placed subcutaneously. After 1 and 4 weeks, tissue-scaffolds were explanted and evaluated by hematoxylin and eosin (H&E), Masson’s trichrome, Picrosirius Red, transmission electron microscopy (TEM), immunohistochemistry, and mechanical testing. Results Macroscopically, tissue-scaffold degradation with the suture method and tissue-scaffold folding with the control method were observed after 4 weeks. In comparison, the frame method demonstrated intact tissue scaffolds after 4 weeks. H&E staining showed progressive cell repopulation over the course of the experiment in all groups with acute and chronic inflammation observed in suture and control methods throughout the duration of the study. Immunohistochemistry quantification of CD3, CD 31, CD 34, CD 163, and αSMA showed a statistically significant differences between the suture, control and frame methods (P < 0.05) at both time points. The average tensile strength was 4.03 ± 0.49, 7.45 ± 0.49 and 5.72 ± 1.34 (MPa) after 1 week and 0.55 ± 0.26, 0.12 ± 0.03 and 0.41 ± 0.32 (MPa) after 4 weeks in the suture, control, and frame methods; respectively. TEM analysis showed an increase in inflammatory cells in both suture and control methods following implantation. Conclusion Rat subcutaneous implantation with the frame method was performed with success and ease. The surgical approach used for the frame technique was found to be the best methodology for in vivo evaluation of tissue engineered acellular scaffolds, where the frame method did not compromise mechanical strength, but it reduced inflammation significantly.

show abstract

“…This is typically associated with the intracellular upregulation of hypoxia-inducible factor (HIF)-1α and HIF-1α-mediated expression of VEGF [47]. On the other hand, in contrast to tissue-specific cells, stem cells exhibit the capacity to differentiate into vascular cells and to self-assemble into novel microvessels [48]. Schumann et al [11] recently seeded both cell types, i.e.…”

Section: Stimulating Angiogenesis In Tissue Constructsmentioning

confidence: 99%

Vascularization in Tissue Engineering: Angiogenesis versus Inosculation

Laschke

Menger²

2012

Eur Surg Res

168

127

View full text Add to dashboard Cite

Background/Purpose: The key challenge in tissue engineering is the establishment of an efficient vascularization for tissue constructs guaranteeing long-term survival and function. Vascularization may be achieved by the stimulation of angiogenesis or the inosculation of preformed microvascular networks within the implants to the host microvasculature. The present review provides an overview of these two concepts applied in tissue engineering. Methods: A literature search was performed in PubMed for publications focusing on vascularization, angiogenesis and inosculation in tissue engineering. Results: Several strategies have been proposed to stimulate the ingrowth of new blood vessels into tissue constructs. These include the modification of the chemical composition and architecture of scaffolds, their bioactivation by incorporation of growth factor delivery systems or by cell seeding as well as the stimulation of stem cell recruitment. However, because angiogenesis is a time-consuming process, all of these approaches cannot prevent ischemic cell death within larger 3-dimensional tissue constructs during the initial phase after implantation. To overcome this problem, in vitro or in situ prevascularization has emerged as a novel concept in tissue engineering. This bears the advantage that preformed microvascular networks within tissue constructs simply have to inosculate with the host microvasculature at the implantation site to get completely blood-perfused within a short period of time. Conclusions: During the last years, considerable progress has been made in the development of promising vascularization strategies in tissue engineering. Particularly the inosculation of preformed microvascular networks has the great potential to markedly improve the survival of tissue constructs after implantation. The optimization of this vascularization strategy may pave the way for a broad clinical use of tissue engineering applications in the future.

show abstract

Accelerating Vascularization in Polycaprolactone Scaffolds by Endothelial Progenitor Cells

Cited by 51 publications

References 24 publications

Hypoxia Inhibits De Novo Vascular Assembly of Adipose-Derived Stromal/Stem Cell Populations, but Promotes Growth of Preformed Vessels

Hypoxia Inhibits De Novo Vascular Assembly of Adipose-Derived Stromal/Stem Cell Populations, but Promotes Growth of Preformed Vessels

A novel surgical technique for a rat subcutaneous implantation of a tissue engineered scaffold

Vascularization in Tissue Engineering: Angiogenesis versus Inosculation

Contact Info

Product

Resources

About