A 3-Layered Bioartificial Blood Vessel with Physiological Wall Architecture Generated by Mechanical Stimulation

Helms, Florian; Lau, Skadi; Aper, Thomas; Zippusch, Sarah; Klingenberg, Melanie; Haverich, Axel; Wilhelmi, Mathias; Böer, Ulrike

doi:10.1007/s10439-021-02728-9

Cited by 22 publications

(11 citation statements)

References 33 publications

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“…These free‐standing segments are needed to enable easy and quick vascular anastomoses in the potential target organism. Therefore, fibrin grafts have been shown to be of sufficient mechanical strength to withstand physiological and supraphysiological pressures even without structural support of surrounding tissue (Helms, Haverich, et al, 2021; Helms, Lau, et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…The effect of shear stress on endothelial cell alignment is long known and well-studied for luminal endothelial cells seeded in larger diameter vessels (Resnick et al, 2003). Also, the alignment of EC fibrin matrices with interstitial perfusion has been described before (Bachmann et al, 2018) and we previously showed that mechanical forces such as cyclic stretch can induce capillary-like tube alignment (Helms, Lau, et al, 2021). An alternative or additional factor may also be explained by a gradient in oxygen saturation between the area directly surrounding the microchannels and more peripheral areas.…”

Section: Perfusion Strategymentioning

confidence: 92%

“…The perfusion system used here (Figure 2) is a modified version of a hemodynamic simulator described in detail elsewhere (Helms, Lau, et al, 2021). Briefly, a peristaltic pump (P) was combined with a compliance chamber (C) to generate a continuous nonpulsatile F I G U R E 1 Flow-chamber design and construct generation.…”

Section: Perfusion System Setupmentioning

confidence: 99%

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An encapsulated fibrin‐based bioartificial tissue construct with integrated macrovessels, microchannels, and capillary tubes

Helms

Zippusch

Theilen

et al. 2022

Biotech & Bioengineering

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Facilitating sufficient nutrient and oxygen supply in large‐scale bioartificial constructs is a critical step in organ bioengineering. Immediate perfusion not only depends on a dense capillary network, but also requires integrated large‐diameter vessels that allow vascular anastomoses during implantation. These requirements set high demands for matrix generation as well as for in vitro cultivation techniques and remain mostly unsolved challenges up until today. Additionally, bioartificial constructs must have sufficient biomechanical stability to withstand mechanical stresses during and after implantation. We developed a bioartificial tissue construct with a fibrin matrix containing human umbilical vein endothelial cells and adipose tissue‐derived stem cells facilitating capillary‐like network formation. This core matrix was surrounded by a dense acellular fibrin capsule providing biomechanical stability. Two fibrin‐based macrovessels were integrated on each side of the construct and interconnected via four 1.2 mm thick microchannels penetrating the cellularized core matrix. After 4 days of perfusion in a custom‐built bioreactor, homogeneous capillary‐like network formation throughout the core matrix was observed. The fibrin capsule stabilized the core matrix and facilitated the generation of a self‐supporting construct. Thus, the encapsulated fibrin tissue construct could provide a universal prevascularized matrix for seeding with different cell types in various tissue engineering approaches.

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Section: Discussionmentioning

confidence: 99%

Section: Perfusion Strategymentioning

confidence: 92%

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An encapsulated fibrin‐based bioartificial tissue construct with integrated macrovessels, microchannels, and capillary tubes

Helms

Zippusch

Theilen

et al. 2022

Biotech & Bioengineering

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“…While in vitro tissue engineering is difficult to form a complete endothelial layer and mature elastic fibers in a short period of time [ 22 ]. Extracellular matrix (ECM) scaffolds preserve the three-dimensional architecture and the two most vital proteins collagen and elastin, which elastin is to confer compliance and collagen is responsible for the resistance to rupture [ 23 ]. Our previous experiments found that decellularized vessels after chemical cross-linking arrangement with mechanical properties matching those of the autologous vasculature.…”

Section: Discussionmentioning

confidence: 99%

The crescendo pulse frequency of shear stress stimulates the endothelialization of bone marrow mesenchymal stem cells on the luminal surface of decellularized scaffold in the bioreactor

et al. 2022

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A completely confluent endothelial cell (EC) monolayer is required to maintain proper vascular function in small diameter tissue-engineered vascular graft (TEVG). However, the most effective method for EC attachment to the luminal surface and formation of an entire endothelium layer that works in vitro remains a complicated challenge that requires urgent resolution. Although pulsatile flow has been shown to be better suited for the generation of functional endothelium, the optimal frequency setting is unknown. Several pulsatile flow frequencies were used to implant rat bone mesenchymal stem cells (MSC) into the lumen of decellularized porcine carotid arteries. The endothelium's integrity and cell activity were investigated in order to determine the best pulse frequency settings. The results showed that MSC were maximally preserved and exhibited maximal morphological changes with improved endothelialization performance in response to increased pulse stimulation frequency. Increased pulse frequency stimulation stimulates the expression of mechanoreceptor markers, cytoskeleton reorganization in the direction of blood flow, denser skeletal proteins fibronectin, and stronger intercellular connections when compared to constant pulse frequency stimulation. MSC eventually develops an intact endothelial layer with anti-thrombotic properties on the inner wall of the decellularized tubular lumen. Conclusion: The decellularized vessels retain the three-dimensional structure of the vasculature, have a surface topography suitable for MSC growth, and have good mechanical properties. By increasing the frequency of pulsed stimulation, MSC endothelialize the lumen of the decellularized vasculature. It is expected to have anti-thrombotic and anti-neointimal hyperplasia properties after implantation, ultimately improving the patency of TEVG.

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“…In their work, Florian Helms et al realized a trilayered blood vessel using the step by step casting technique ( Helms et al, 2021 ). In a first step, ASCs were differentiated into SMCs which were integrated into a tubular fibrin matrix compacted in a mold to create the media layer.…”

Section: Biofabrication Techniquesmentioning

confidence: 99%

Vascular Tissue Engineering: Challenges and Requirements for an Ideal Large Scale Blood Vessel

Devillard

Marquette

2021

Front. Bioeng. Biotechnol.

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Since the emergence of regenerative medicine and tissue engineering more than half a century ago, one obstacle has persisted: the in vitro creation of large-scale vascular tissue (>1 cm3) to meet the clinical needs of viable tissue grafts but also for biological research applications. Considerable advancements in biofabrication have been made since Weinberg and Bell, in 1986, created the first blood vessel from collagen, endothelial cells, smooth muscle cells and fibroblasts. The synergistic combination of advances in fabrication methods, availability of cell source, biomaterials formulation and vascular tissue development, promises new strategies for the creation of autologous blood vessels, recapitulating biological functions, structural functions, but also the mechanical functions of a native blood vessel. In this review, the main technological advancements in bio-fabrication are discussed with a particular highlights on 3D bioprinting technologies. The choice of the main biomaterials and cell sources, the use of dynamic maturation systems such as bioreactors and the associated clinical trials will be detailed. The remaining challenges in this complex engineering field will finally be discussed.

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A 3-Layered Bioartificial Blood Vessel with Physiological Wall Architecture Generated by Mechanical Stimulation

Cited by 22 publications

References 33 publications

An encapsulated fibrin‐based bioartificial tissue construct with integrated macrovessels, microchannels, and capillary tubes

An encapsulated fibrin‐based bioartificial tissue construct with integrated macrovessels, microchannels, and capillary tubes

The crescendo pulse frequency of shear stress stimulates the endothelialization of bone marrow mesenchymal stem cells on the luminal surface of decellularized scaffold in the bioreactor

Vascular Tissue Engineering: Challenges and Requirements for an Ideal Large Scale Blood Vessel

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