Automated Bioreactor System for the Cultivation of Autologous Tissue-Engineered Vascular Grafts

Stanislawski, Nils; Cholewa, Fabian; Heymann, Henrik; Kraus, Xenia; Heene, Sebastian; Witt, Martin; Thoms, Stefanie; Blume, Cornelia; Blume, Holger

doi:10.1109/embc44109.2020.9175340

Cited by 6 publications

(6 citation statements)

References 10 publications

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“…For this purpose, the repopulation of the decellularized SDVGs with host cellular populations may attenuate the aforementioned lethal consequences. The proper repopulation of the decellularized vascular grafts can be performed with the use of a suitable bioreactor system [ 61 ]. In this process, the optimum conditions for the repopulation of the grafts can be adjusted, ensuring the uniform distribution and proliferation of the cellular populations [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Improved Repopulation Efficacy of Decellularized Small Diameter Vascular Grafts Utilizing the Cord Blood Platelet Lysate

et al. 2021

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Background: The development of functional bioengineered small-diameter vascular grafts (SDVGs), represents a major challenge of tissue engineering. This study aimed to evaluate the repopulation efficacy of biological vessels, utilizing the cord blood platelet lysate (CBPL). Methods: Human umbilical arteries (hUAs, n = 10) were submitted to decellularization. Then, an evaluation of decellularized hUAs, involving histological, biochemical and biomechanical analysis, was performed. Wharton’s Jelly (WJ) Mesenchymal Stromal Cells (MSCs) were isolated and characterized for their properties. Then, WJ-MSCs (1.5 × 106 cells) were seeded on decellularized hUAs (n = 5) and cultivated with (Group A) or without the presence of the CBPL, (Group B) for 30 days. Histological analysis involving immunohistochemistry (against Ki67, for determination of cell proliferation) and indirect immunofluorescence (against activated MAP kinase, additional marker for cell growth and proliferation) was performed. Results: The decellularized hUAs retained their initial vessel’s properties, in terms of key-specific proteins, the biochemical and biomechanical characteristics were preserved. The evaluation of the repopulation process indicated a more uniform distribution of WJ-MSCs in group A compared to group B. The repopulated vascular grafts of group B were characterized by greater Ki67 and MAP kinase expression compared to group A. Conclusion: The results of this study indicated that the CBPL may improve the repopulation efficacy, thus bringing the biological SDVGs one step closer to clinical application.

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Section: Discussionmentioning

confidence: 99%

Improved Repopulation Efficacy of Decellularized Small Diameter Vascular Grafts Utilizing the Cord Blood Platelet Lysate

et al. 2021

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“…Bioreactors have been applied to create models for tissueengineered vascular grafts, with the eventual goal of using them as in vivo vascular grafts (215,216), or utilizing them to study vascular physiology and pathophysiology (191). For example, a study by Aper et al described the use of a pulsatile bioreactor to develop an autologous small-caliber vascular graft composed of a fibrin scaffold in combination with late outgrowth endothelial and smooth muscle cells isolated from peripheral blood progenitors (67).…”

Section: Dynamic Culture Conditionsmentioning

confidence: 99%

3D Tissue-Engineered Vascular Drug Screening Platforms: Promise and Considerations

Marei

Samaan

Al-Quradaghi

et al. 2022

Front. Cardiovasc. Med.

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Despite the efforts devoted to drug discovery and development, the number of new drug approvals have been decreasing. Specifically, cardiovascular developments have been showing amongst the lowest levels of approvals. In addition, concerns over the adverse effects of drugs to the cardiovascular system have been increasing and resulting in failure at the preclinical level as well as withdrawal of drugs post-marketing. Besides factors such as the increased cost of clinical trials and increases in the requirements and the complexity of the regulatory processes, there is also a gap between the currently existing pre-clinical screening methods and the clinical studies in humans. This gap is mainly caused by the lack of complexity in the currently used 2D cell culture-based screening systems, which do not accurately reflect human physiological conditions. Cell-based drug screening is widely accepted and extensively used and can provide an initial indication of the drugs' therapeutic efficacy and potential cytotoxicity. However, in vitro cell-based evaluation could in many instances provide contradictory findings to the in vivo testing in animal models and clinical trials. This drawback is related to the failure of these 2D cell culture systems to recapitulate the human physiological microenvironment in which the cells reside. In the body, cells reside within a complex physiological setting, where they interact with and respond to neighboring cells, extracellular matrix, mechanical stress, blood shear stress, and many other factors. These factors in sum affect the cellular response and the specific pathways that regulate variable vital functions such as proliferation, apoptosis, and differentiation. Although pre-clinical in vivo animal models provide this level of complexity, cross species differences can also cause contradictory results from that seen when the drug enters clinical trials. Thus, there is a need to better mimic human physiological conditions in pre-clinical studies to improve the efficiency of drug screening. A novel approach is to develop 3D tissue engineered miniaturized constructs in vitro that are based on human cells. In this review, we discuss the factors that should be considered to produce a successful vascular construct that is derived from human cells and is both reliable and reproducible.

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“…F I G U R E 1 Bioreactor setup. (A) Schematic of a bioreactor setup for in vitro cultivation of a TEVG with external control unit for parallelization of cultivation processes; (B) Demonstration of assembled Bioreactor Setup [24] Pressure here was applied intermittently or uniformly to support the maturation of differentiated endothelial cells (e.g., indicated by vascular endothelial growth factor receptor-2, von-Willebrand-factor or vascular endothelialcadherin), or SMCs (e.g., α-smooth muscle actin or smooth muscle myosin heavy chain) [26,27]. In addition, cells developed an anti-thrombogenic gene profile [8].…”

Section: Monitoring and Control Of Physical Conditionsmentioning

confidence: 99%

“…To realize a close cultivation control, the exemplarily presented bioreactor system includes enzyme‐based electrochemical biosensors to monitor the glucose and lactate concentration of the media [ 24 ]. These disposable sensors must be periodically calibrated and intermittently flushed with saline buffer solutions to prolong the sensors’ lifetime.…”

Section: Technical Trends In Bioreactor Designmentioning

confidence: 99%

“…Another comprehensive cultivation process for TEVGs (featuring, e.g., automated concentration measurement of glucose or lactate, online 3D visualization, shear stress analysis, etc.) has been elaborated and improved over several years at the Leibniz University of Hannover in [ 22 , 23 , 24 ]. This rotational‐perfusion bioreactor system comprises an automated monitoring and control of physiological conditions, and an online 3D visualization and geometrical analysis system.…”

Section: Technical Trends In Bioreactor Designmentioning

confidence: 99%

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Vascular implants – new aspects for in situ tissue engineering

Blume

Kraus

Heene

et al. 2022

Engineering in Life Sciences

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Conventional synthetic vascular grafts require ongoing anticoagulation, and autologous venous grafts are often not available in elderly patients. This review highlights the development of bioartificial vessels replacing brain-dead donoror animal-deriving vessels with ongoing immune reactivity. The vision for such bio-hybrids exists in a combination of biodegradable scaffolds and seeding with immune-neutral cells, and here different cells sources such as autologous progenitor cells or stem cells are relevant. This kind of in situ tissue engineering depends on a suitable bioreactor system with elaborate monitoring systems, three-dimensional (3D) visualization and a potential of cell conditioning into the direction of the targeted vascular cell phenotype. Necessary bioreactor tools for dynamic and pulsatile cultivation are described. In addition, a concept for design of vasa vasorum is outlined, that is needed for sustainable nutrition of the wall structure in large caliber vessels. For scaffold design and cell adhesion additives, different materials and technologies are discussed. 3D printing is introduced as a relatively new field with promising prospects, for example, to create complex geometries or micro-structured surfaces for optimal cell adhesion and ingrowth in a standardized and custom designed procedure. Summarizing, a bio-hybrid vascular prosthesis from a controlled biotechnological process is thus coming more and more into view. It has the potential to withstand strict approval requirements applied for advanced therapy medicinal products.

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Automated Bioreactor System for the Cultivation of Autologous Tissue-Engineered Vascular Grafts

Cited by 6 publications

References 10 publications

Improved Repopulation Efficacy of Decellularized Small Diameter Vascular Grafts Utilizing the Cord Blood Platelet Lysate

Improved Repopulation Efficacy of Decellularized Small Diameter Vascular Grafts Utilizing the Cord Blood Platelet Lysate

3D Tissue-Engineered Vascular Drug Screening Platforms: Promise and Considerations

Vascular implants – new aspects for in situ tissue engineering

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