Mechanical Stimulation Induces Vasa Vasorum Capillary Alignment in a Fibrin-Based Tunica Adventitia

Research output: Contribution to journalArticleResearchpeer review

Authors

  • Florian Helms
  • Sarah Zippusch
  • Thomas Aper
  • Stefan Kalies
  • Alexander Heisterkamp
  • Axel Haverich
  • Ulrike Böer
  • Mathias Wilhelmi

Research Organisations

External Research Organisations

  • NIFE - Lower Saxony Centre for Biomedical Engineering, Implant Research and Development
  • Hannover Medical School (MHH)
  • St. Bernward Hospital
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Details

Original languageEnglish
Pages (from-to)818-832
Number of pages15
JournalTissue Engineering - Part A
Volume28
Issue number19-20
Early online date26 Jul 2022
Publication statusPublished - 13 Oct 2022

Abstract

Generation of bioartificial blood vessels with a physiological three-layered wall architecture is a long pursued goal in vascular tissue engineering. While considerable advances have been made to resemble the physiological tunica intima and media morphology and function in bioartificial vessels, only very few studies have targeted the generation of a tunica adventitia, including its characteristic vascular network known as the vasa vasorum, which are essential for graft nutrition and integration. In healthy native blood vessels, capillary vasa vasorum are aligned longitudinally to the vessel axis. Thus, inducing longitudinal alignment of capillary tubes to generate a physiological tunica adventitia morphology and function may be advantageous in bioengineered vessels as well. In this study, we investigated the effect of two biomechanical stimulation parameters, longitudinal tension and physiological cyclic stretch, on tube alignment in capillary networks formed by self-assembly of human umbilical vein endothelial cells in tunica adventitia-equivalents of fibrin-based bioartificial blood vessels. Moreover, the effect of changes of the biomechanical environment on network remodeling after initial tube formation was analyzed. Both, longitudinal tension and cyclic stretch by pulsatile perfusion induced physiological capillary tube alignment parallel to the longitudinal vessel axis. This effect was even more pronounced when both biomechanical factors were applied simultaneously, which resulted in an alignment of 57.2 ± 5.2% within 5° of the main vessel axis. Opposed to that, a random tube orientation was observed in vessels incubated statically. Scanning electron microscopy showed that longitudinal tension also resulted in longitudinal alignment of fibrin fibrils, which may function as a guidance structure for directed capillary tube formation. Moreover, existing microvascular networks showed distinct remodeling in response to addition or withdrawal of mechanical stimulation with corresponding increase or decrease of the degree of alignment. With longitudinal tension and cyclic stretch, we identified two mechanical stimuli that facilitate the generation of a prevascularized tunica adventitia-equivalent with physiological tube alignment in bioartificial vascular grafts. Fibrin-based bioartificial vessels represent a promising regenerative approach to generate vascular grafts with superior biocompatibility and hemocompatibility compared to currently available synthetic graft materials. Precapillarization of bioartificial vascular grafts may improve nutrition of the vessel wall and integration of the graft into the target organism's microvasculature. In native vessels, physiological vasa vasorum alignment is pivotal for proper function of the tunica adventitia. Thus, it is necessary to induce longitudinal capillary alignment in the tunica adventitia of bioengineered vessels as well to secure long-term graft patency and function. This alignment can be reliably achieved by controlled biomechanical stimulation in vitro.

Keywords

    bioartificial vessels, capillary networks, mechanical stimulation, vasa vasorum, vascular grafts, vascular tissue engineering

ASJC Scopus subject areas

Sustainable Development Goals

Cite this

Mechanical Stimulation Induces Vasa Vasorum Capillary Alignment in a Fibrin-Based Tunica Adventitia. / Helms, Florian; Zippusch, Sarah; Aper, Thomas et al.
In: Tissue Engineering - Part A, Vol. 28, No. 19-20, 13.10.2022, p. 818-832.

Research output: Contribution to journalArticleResearchpeer review

Helms, F, Zippusch, S, Aper, T, Kalies, S, Heisterkamp, A, Haverich, A, Böer, U & Wilhelmi, M 2022, 'Mechanical Stimulation Induces Vasa Vasorum Capillary Alignment in a Fibrin-Based Tunica Adventitia', Tissue Engineering - Part A, vol. 28, no. 19-20, pp. 818-832. https://doi.org/10.1089/ten.tea.2022.0042
Helms, F., Zippusch, S., Aper, T., Kalies, S., Heisterkamp, A., Haverich, A., Böer, U., & Wilhelmi, M. (2022). Mechanical Stimulation Induces Vasa Vasorum Capillary Alignment in a Fibrin-Based Tunica Adventitia. Tissue Engineering - Part A, 28(19-20), 818-832. https://doi.org/10.1089/ten.tea.2022.0042
Helms F, Zippusch S, Aper T, Kalies S, Heisterkamp A, Haverich A et al. Mechanical Stimulation Induces Vasa Vasorum Capillary Alignment in a Fibrin-Based Tunica Adventitia. Tissue Engineering - Part A. 2022 Oct 13;28(19-20):818-832. Epub 2022 Jul 26. doi: 10.1089/ten.tea.2022.0042
Helms, Florian ; Zippusch, Sarah ; Aper, Thomas et al. / Mechanical Stimulation Induces Vasa Vasorum Capillary Alignment in a Fibrin-Based Tunica Adventitia. In: Tissue Engineering - Part A. 2022 ; Vol. 28, No. 19-20. pp. 818-832.
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title = "Mechanical Stimulation Induces Vasa Vasorum Capillary Alignment in a Fibrin-Based Tunica Adventitia",
abstract = "Generation of bioartificial blood vessels with a physiological three-layered wall architecture is a long pursued goal in vascular tissue engineering. While considerable advances have been made to resemble the physiological tunica intima and media morphology and function in bioartificial vessels, only very few studies have targeted the generation of a tunica adventitia, including its characteristic vascular network known as the vasa vasorum, which are essential for graft nutrition and integration. In healthy native blood vessels, capillary vasa vasorum are aligned longitudinally to the vessel axis. Thus, inducing longitudinal alignment of capillary tubes to generate a physiological tunica adventitia morphology and function may be advantageous in bioengineered vessels as well. In this study, we investigated the effect of two biomechanical stimulation parameters, longitudinal tension and physiological cyclic stretch, on tube alignment in capillary networks formed by self-assembly of human umbilical vein endothelial cells in tunica adventitia-equivalents of fibrin-based bioartificial blood vessels. Moreover, the effect of changes of the biomechanical environment on network remodeling after initial tube formation was analyzed. Both, longitudinal tension and cyclic stretch by pulsatile perfusion induced physiological capillary tube alignment parallel to the longitudinal vessel axis. This effect was even more pronounced when both biomechanical factors were applied simultaneously, which resulted in an alignment of 57.2 ± 5.2% within 5° of the main vessel axis. Opposed to that, a random tube orientation was observed in vessels incubated statically. Scanning electron microscopy showed that longitudinal tension also resulted in longitudinal alignment of fibrin fibrils, which may function as a guidance structure for directed capillary tube formation. Moreover, existing microvascular networks showed distinct remodeling in response to addition or withdrawal of mechanical stimulation with corresponding increase or decrease of the degree of alignment. With longitudinal tension and cyclic stretch, we identified two mechanical stimuli that facilitate the generation of a prevascularized tunica adventitia-equivalent with physiological tube alignment in bioartificial vascular grafts. Fibrin-based bioartificial vessels represent a promising regenerative approach to generate vascular grafts with superior biocompatibility and hemocompatibility compared to currently available synthetic graft materials. Precapillarization of bioartificial vascular grafts may improve nutrition of the vessel wall and integration of the graft into the target organism's microvasculature. In native vessels, physiological vasa vasorum alignment is pivotal for proper function of the tunica adventitia. Thus, it is necessary to induce longitudinal capillary alignment in the tunica adventitia of bioengineered vessels as well to secure long-term graft patency and function. This alignment can be reliably achieved by controlled biomechanical stimulation in vitro.",
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T1 - Mechanical Stimulation Induces Vasa Vasorum Capillary Alignment in a Fibrin-Based Tunica Adventitia

AU - Helms, Florian

AU - Zippusch, Sarah

AU - Aper, Thomas

AU - Kalies, Stefan

AU - Heisterkamp, Alexander

AU - Haverich, Axel

AU - Böer, Ulrike

AU - Wilhelmi, Mathias

N1 - Funding Information: This work was funded by the German Society for Implant Research and Development (funding title: ‘‘Vascularization of bioartificial implants 2017–2020’’) and the VHV-Foundation Hannover, Germany.

PY - 2022/10/13

Y1 - 2022/10/13

N2 - Generation of bioartificial blood vessels with a physiological three-layered wall architecture is a long pursued goal in vascular tissue engineering. While considerable advances have been made to resemble the physiological tunica intima and media morphology and function in bioartificial vessels, only very few studies have targeted the generation of a tunica adventitia, including its characteristic vascular network known as the vasa vasorum, which are essential for graft nutrition and integration. In healthy native blood vessels, capillary vasa vasorum are aligned longitudinally to the vessel axis. Thus, inducing longitudinal alignment of capillary tubes to generate a physiological tunica adventitia morphology and function may be advantageous in bioengineered vessels as well. In this study, we investigated the effect of two biomechanical stimulation parameters, longitudinal tension and physiological cyclic stretch, on tube alignment in capillary networks formed by self-assembly of human umbilical vein endothelial cells in tunica adventitia-equivalents of fibrin-based bioartificial blood vessels. Moreover, the effect of changes of the biomechanical environment on network remodeling after initial tube formation was analyzed. Both, longitudinal tension and cyclic stretch by pulsatile perfusion induced physiological capillary tube alignment parallel to the longitudinal vessel axis. This effect was even more pronounced when both biomechanical factors were applied simultaneously, which resulted in an alignment of 57.2 ± 5.2% within 5° of the main vessel axis. Opposed to that, a random tube orientation was observed in vessels incubated statically. Scanning electron microscopy showed that longitudinal tension also resulted in longitudinal alignment of fibrin fibrils, which may function as a guidance structure for directed capillary tube formation. Moreover, existing microvascular networks showed distinct remodeling in response to addition or withdrawal of mechanical stimulation with corresponding increase or decrease of the degree of alignment. With longitudinal tension and cyclic stretch, we identified two mechanical stimuli that facilitate the generation of a prevascularized tunica adventitia-equivalent with physiological tube alignment in bioartificial vascular grafts. Fibrin-based bioartificial vessels represent a promising regenerative approach to generate vascular grafts with superior biocompatibility and hemocompatibility compared to currently available synthetic graft materials. Precapillarization of bioartificial vascular grafts may improve nutrition of the vessel wall and integration of the graft into the target organism's microvasculature. In native vessels, physiological vasa vasorum alignment is pivotal for proper function of the tunica adventitia. Thus, it is necessary to induce longitudinal capillary alignment in the tunica adventitia of bioengineered vessels as well to secure long-term graft patency and function. This alignment can be reliably achieved by controlled biomechanical stimulation in vitro.

AB - Generation of bioartificial blood vessels with a physiological three-layered wall architecture is a long pursued goal in vascular tissue engineering. While considerable advances have been made to resemble the physiological tunica intima and media morphology and function in bioartificial vessels, only very few studies have targeted the generation of a tunica adventitia, including its characteristic vascular network known as the vasa vasorum, which are essential for graft nutrition and integration. In healthy native blood vessels, capillary vasa vasorum are aligned longitudinally to the vessel axis. Thus, inducing longitudinal alignment of capillary tubes to generate a physiological tunica adventitia morphology and function may be advantageous in bioengineered vessels as well. In this study, we investigated the effect of two biomechanical stimulation parameters, longitudinal tension and physiological cyclic stretch, on tube alignment in capillary networks formed by self-assembly of human umbilical vein endothelial cells in tunica adventitia-equivalents of fibrin-based bioartificial blood vessels. Moreover, the effect of changes of the biomechanical environment on network remodeling after initial tube formation was analyzed. Both, longitudinal tension and cyclic stretch by pulsatile perfusion induced physiological capillary tube alignment parallel to the longitudinal vessel axis. This effect was even more pronounced when both biomechanical factors were applied simultaneously, which resulted in an alignment of 57.2 ± 5.2% within 5° of the main vessel axis. Opposed to that, a random tube orientation was observed in vessels incubated statically. Scanning electron microscopy showed that longitudinal tension also resulted in longitudinal alignment of fibrin fibrils, which may function as a guidance structure for directed capillary tube formation. Moreover, existing microvascular networks showed distinct remodeling in response to addition or withdrawal of mechanical stimulation with corresponding increase or decrease of the degree of alignment. With longitudinal tension and cyclic stretch, we identified two mechanical stimuli that facilitate the generation of a prevascularized tunica adventitia-equivalent with physiological tube alignment in bioartificial vascular grafts. Fibrin-based bioartificial vessels represent a promising regenerative approach to generate vascular grafts with superior biocompatibility and hemocompatibility compared to currently available synthetic graft materials. Precapillarization of bioartificial vascular grafts may improve nutrition of the vessel wall and integration of the graft into the target organism's microvasculature. In native vessels, physiological vasa vasorum alignment is pivotal for proper function of the tunica adventitia. Thus, it is necessary to induce longitudinal capillary alignment in the tunica adventitia of bioengineered vessels as well to secure long-term graft patency and function. This alignment can be reliably achieved by controlled biomechanical stimulation in vitro.

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KW - capillary networks

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