Short-term cultivation of in situ prevascularized tissue constructs accelerates inosculation of their preformed microvascular networks after implantation into the host tissue

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Short-term cultivation of in situ prevascularized tissue constructs accelerates inosculation of their preformed microvascular networks after implantation into the host tissue. / Laschke, Matthias W; Mussawy, Haider; Schuler, Sandra; Kazakov, Andrey; Rücker, Martin; Eglin, David; Alini, Mauro; Menger, Michael D.

In: TISSUE ENG PT A, Vol. 17, No. 5-6, 03.2011, p. 841-53.

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@article{d8694c14da3d42808309389d6a2971ba,
title = "Short-term cultivation of in situ prevascularized tissue constructs accelerates inosculation of their preformed microvascular networks after implantation into the host tissue",
abstract = "Inosculation of preformed microvessels with the host microvasculature represents a promising approach to accelerate vascularization of tissue constructs. Herein, we analyzed whether cultivation of prevascularized tissue constructs promotes inosculation by reducing the perivascular cell coverage of the preformed microvessels. Poly(ester-urethane) scaffolds were implanted into FVB/N-TgN (Tie2/green fluorescent protein [GFP]) 287 Sato mice to generate prevascularized tissue constructs with GFP-positive microvessels. These constructs were then cultivated for 3 or 10 days before implantation into dorsal skinfold chambers of FVB/N mice to analyze inosculation and vascularization by intravital fluorescence microscopy and immunohistochemistry. Noncultivated tissue constructs served as controls. Cultivation reduced the number of α-smooth muscle actin-positive preformed microvessels within the constructs and increased the production of vascular endothelial growth factor. After 3 days of cultivation, tissue constructs still exhibited good cell viability, whereas apoptotic cell death was massively increased in the 10-day-cultivated group. After implantation, inosculation of preformed microvessels was accelerated in the 3-day-cultivated constructs. This resulted in an improved vascularization, as indicated by an increased functional microvessel density and blood perfusion. Immunohistochemical detection of GFP-positive microvessels revealed that internal and external inosculation occurs in parallel. In conclusion, this study demonstrates that inosculation of in situ prevascularized tissue constructs can be easily accelerated by destabilization of preformed microvessels and angiogenic activation during short-term cultivation.",
keywords = "Animals, Apoptosis, Cells, Cultured, Green Fluorescent Proteins, Hemodynamics, Immunohistochemistry, Implants, Experimental, Inflammation, Mice, Microscopy, Fluorescence, Microvessels, Nanostructures, Neovascularization, Physiologic, Particle Size, Prosthesis Implantation, Time Factors, Tissue Engineering, Tissue Scaffolds, Tumor Necrosis Factor-alpha, Vascular Endothelial Growth Factor A, X-Ray Microtomography, Journal Article, Research Support, Non-U.S. Gov't",
author = "Laschke, {Matthias W} and Haider Mussawy and Sandra Schuler and Andrey Kazakov and Martin R{\"u}cker and David Eglin and Mauro Alini and Menger, {Michael D}",
year = "2011",
month = mar,
doi = "10.1089/ten.TEA.2010.0329",
language = "English",
volume = "17",
pages = "841--53",
journal = "TISSUE ENG PT A",
issn = "1937-3341",
publisher = "Mary Ann Liebert Inc.",
number = "5-6",

}

RIS

TY - JOUR

T1 - Short-term cultivation of in situ prevascularized tissue constructs accelerates inosculation of their preformed microvascular networks after implantation into the host tissue

AU - Laschke, Matthias W

AU - Mussawy, Haider

AU - Schuler, Sandra

AU - Kazakov, Andrey

AU - Rücker, Martin

AU - Eglin, David

AU - Alini, Mauro

AU - Menger, Michael D

PY - 2011/3

Y1 - 2011/3

N2 - Inosculation of preformed microvessels with the host microvasculature represents a promising approach to accelerate vascularization of tissue constructs. Herein, we analyzed whether cultivation of prevascularized tissue constructs promotes inosculation by reducing the perivascular cell coverage of the preformed microvessels. Poly(ester-urethane) scaffolds were implanted into FVB/N-TgN (Tie2/green fluorescent protein [GFP]) 287 Sato mice to generate prevascularized tissue constructs with GFP-positive microvessels. These constructs were then cultivated for 3 or 10 days before implantation into dorsal skinfold chambers of FVB/N mice to analyze inosculation and vascularization by intravital fluorescence microscopy and immunohistochemistry. Noncultivated tissue constructs served as controls. Cultivation reduced the number of α-smooth muscle actin-positive preformed microvessels within the constructs and increased the production of vascular endothelial growth factor. After 3 days of cultivation, tissue constructs still exhibited good cell viability, whereas apoptotic cell death was massively increased in the 10-day-cultivated group. After implantation, inosculation of preformed microvessels was accelerated in the 3-day-cultivated constructs. This resulted in an improved vascularization, as indicated by an increased functional microvessel density and blood perfusion. Immunohistochemical detection of GFP-positive microvessels revealed that internal and external inosculation occurs in parallel. In conclusion, this study demonstrates that inosculation of in situ prevascularized tissue constructs can be easily accelerated by destabilization of preformed microvessels and angiogenic activation during short-term cultivation.

AB - Inosculation of preformed microvessels with the host microvasculature represents a promising approach to accelerate vascularization of tissue constructs. Herein, we analyzed whether cultivation of prevascularized tissue constructs promotes inosculation by reducing the perivascular cell coverage of the preformed microvessels. Poly(ester-urethane) scaffolds were implanted into FVB/N-TgN (Tie2/green fluorescent protein [GFP]) 287 Sato mice to generate prevascularized tissue constructs with GFP-positive microvessels. These constructs were then cultivated for 3 or 10 days before implantation into dorsal skinfold chambers of FVB/N mice to analyze inosculation and vascularization by intravital fluorescence microscopy and immunohistochemistry. Noncultivated tissue constructs served as controls. Cultivation reduced the number of α-smooth muscle actin-positive preformed microvessels within the constructs and increased the production of vascular endothelial growth factor. After 3 days of cultivation, tissue constructs still exhibited good cell viability, whereas apoptotic cell death was massively increased in the 10-day-cultivated group. After implantation, inosculation of preformed microvessels was accelerated in the 3-day-cultivated constructs. This resulted in an improved vascularization, as indicated by an increased functional microvessel density and blood perfusion. Immunohistochemical detection of GFP-positive microvessels revealed that internal and external inosculation occurs in parallel. In conclusion, this study demonstrates that inosculation of in situ prevascularized tissue constructs can be easily accelerated by destabilization of preformed microvessels and angiogenic activation during short-term cultivation.

KW - Animals

KW - Apoptosis

KW - Cells, Cultured

KW - Green Fluorescent Proteins

KW - Hemodynamics

KW - Immunohistochemistry

KW - Implants, Experimental

KW - Inflammation

KW - Mice

KW - Microscopy, Fluorescence

KW - Microvessels

KW - Nanostructures

KW - Neovascularization, Physiologic

KW - Particle Size

KW - Prosthesis Implantation

KW - Time Factors

KW - Tissue Engineering

KW - Tissue Scaffolds

KW - Tumor Necrosis Factor-alpha

KW - Vascular Endothelial Growth Factor A

KW - X-Ray Microtomography

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1089/ten.TEA.2010.0329

DO - 10.1089/ten.TEA.2010.0329

M3 - SCORING: Journal article

C2 - 20973748

VL - 17

SP - 841

EP - 853

JO - TISSUE ENG PT A

JF - TISSUE ENG PT A

SN - 1937-3341

IS - 5-6

ER -