Tissue engineering of perfused microvessels

Neumann, Thomas; Nicholson, Brian S.; Sanders, Joan E.

doi:10.1016/s0026-2862(03)00040-2

Cited by 75 publications

(41 citation statements)

References 29 publications

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“…Without the generation of a functional vascular network, the implanted cells will undergo apoptosis due to limitations in oxygen and nutrient supply. Strategies to generate perfused microvessels in tissue engineering applications are multifarious and comprise the use of in vitro fabricated perfused microvessels [Neumann et al, 2003], the induction of host blood vessel formation by various angiogenic growth factors such as VEGF and bFGF [Pieper et al, 2002;Perets et al, 2003;Zisch et al, 2003] or gene therapeutic approaches to induce neoangiogenesis [Rebar et al, 2002;Bouis et al, 2003; for a review, see Dor et al, 2003]. In this study, we have employed a cell-based approach to improve angiogenesis in tissue-engineered constructs, using endothelial cells grown in form of three-dimensional spheroids.…”

Section: Discussionmentioning

confidence: 99%

Development and Characterization of a Spheroidal Coculture Model of Endothelial Cells and Fibroblasts for Improving Angiogenesis in Tissue Engineering

Wenger

Kowalewski

Stahl

et al. 2005

Cells Tissues Organs

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Neovascularization is a critical step in tissue engineering applications since implantation of voluminous grafts without sufficient vascularity results in hypoxic cell death of central tissues. We have developed a three-dimensional spheroidal coculture system consisting of human umbilical vein endothelial cells (HUVECs) and human primary fibroblasts (hFBs) to improve angiogenesis in tissue engineering applications. Morphological analysis of cryosections from HUVEC/hFB cospheroids revealed a characteristic temporal and spatial organization with HUVECs located in the center of the cospheroid and a peripheral localization of fibroblasts. In coculture spheroids, the level of apoptosis of endothelial cells was strongly decreased upon cocultivation with fibroblasts. Collagen-embedded HUVEC spheroids develop numerous lumenized capillary-like sprouts. This was also apparent for HUVEC/hFB cospheroids, albeit to a lesser extent. Quantification of cumulative sprout length revealed an approximately 35% reduction in endothelial cell sprouting upon cocultivation with fibroblasts in cospheroids. The slight reduction in endothelial cell sprouting was not mediated by a paracrine mechanism but is most likely due to the formation of heterogenic cell contacts between HUVECs and hFBs within the cospheroid. The model system introduced in this study is suitable for the development of a preformed lumenized capillary-like network ex vivo and may therefore be useful for improving angiogenesis in in vivo tissue engineering applications.

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Section: Discussionmentioning

confidence: 99%

Development and Characterization of a Spheroidal Coculture Model of Endothelial Cells and Fibroblasts for Improving Angiogenesis in Tissue Engineering

Wenger

Kowalewski

Stahl

et al. 2005

Cells Tissues Organs

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“…By seeding SMCs onto strands of nylon line within a perfusion chamber, a parallel array of microvessels was formed that could be connected to a perfusion system. 106 The SMCs on the lines proliferated over a 21-day culture, at which time the perfusion chamber was filled with agar, the nylon was removed, and the microvessels were perfused. The ability of multiple microvessels to be perfused using one inlet and outlet suggests that functional anastomosis may be achieved in vivo with slight modification of the system.…”

Section: Vessel-embedded Hydrogelsmentioning

confidence: 99%

Vascularization Strategies for Tissue Engineering

Lovett

Lee

Edwards

et al. 2009

Tissue Engineering Part B: Reviews

815

685

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Tissue engineering is currently limited by the inability to adequately vascularize tissues in vitro or in vivo. Issues of nutrient perfusion and mass transport limitations, especially oxygen diffusion, restrict construct development to smaller than clinically relevant dimensions and limit the ability for in vivo integration. There is much interest in the field as researchers have undertaken a variety of approaches to vascularization, including material functionalization, scaffold design, microfabrication, bioreactor development, endothelial cell seeding, modular assembly, and in vivo systems. Efforts to model and measure oxygen diffusion and consumption within these engineered tissues have sought to quantitatively assess and improve these design strategies. This review assesses the current state of the field by outlining the prevailing approaches taken toward producing vascularized tissues and highlighting their strengths and weaknesses.

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“…Over the past decade, several investigators have pursued this target from a variety of avenues. However, while these studies have claimed the generation of 3D vascular network templates 2,[4][5][6][7][8][9] and endothelialized vessels, 3,[6][7][8]10,11 no study to date has shown a completely patent, contiguous endothelial cell layer throughout a 3D "vascular" network, created under fluid flow equivalent to natural vasculature and having a single inlet and outlet, even for short term.…”

Section: Introductionmentioning

confidence: 99%

A microdevice for the creation of patent, three-dimensional endothelial cell-based microcirculatory networks

2011

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Microvascular network formation is a significant and challenging goal in the engineering of large three-dimensional artificial tissue structures. We show here the development of a fully patent, 3D endothelial cell (microvascular) microfluidic network that has a single inlet and outlet, created in only 28 h in a microdevice involving fluid flow equivalent to natural vasculature. Our microdevice features a tailored “multi-rung ladder” network, a stylized mimic of an arterial-to-venous pedicle, designed to also allow for systematic and reproducible cell seeding. Immunofluorescence staining revealed a highly contiguous endothelial monolayer (human umbilical vein endothelial cells) throughout the whole network after 24 h of continuous perfusion. This network persisted for up to 72 h of culture, providing a useful template from which the effects of surface chemistry, fluid flow, and environmental conditions on the development of artificial vascular networks ex vivo may be rapidly and robustly evaluated.

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Tissue engineering of perfused microvessels

Cited by 75 publications

References 29 publications

Development and Characterization of a Spheroidal Coculture Model of Endothelial Cells and Fibroblasts for Improving Angiogenesis in Tissue Engineering

Development and Characterization of a Spheroidal Coculture Model of Endothelial Cells and Fibroblasts for Improving Angiogenesis in Tissue Engineering

Vascularization Strategies for Tissue Engineering

A microdevice for the creation of patent, three-dimensional endothelial cell-based microcirculatory networks

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