scholarly journals Microvascular Guidance: A Challenge to Support the Development of Vascularised Tissue Engineering Construct

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Irza Sukmana
Keyword(s):  
Tissue Engineering ◽  
Three Dimensional ◽  
Artificial Organ ◽  
Vascular Networks ◽  
Tissue Constructs ◽  
Future Challenges ◽  
Engineered Tissue ◽  
And Function ◽  
Tissue Construct

The guidance of endothelial cell organization into a capillary network has been a long-standing challenge in tissue engineering. Some research efforts have been made to develop methods to promote capillary networks inside engineered tissue constructs. Capillary and vascular networks that would mimic blood microvessel function can be used to subsequently facilitate oxygen and nutrient transfer as well as waste removal. Vascularization of engineering tissue construct is one of the most favorable strategies to overpass nutrient and oxygen supply limitation, which is often the major hurdle in developing thick and complex tissue and artificial organ. This paper addresses recent advances and future challenges in developing three-dimensional culture systems to promote tissue construct vascularization allowing mimicking blood microvessel development and function encounteredin vivo. Bioreactors systems that have been used to create fully vascularized functional tissue constructs will also be outlined.

scholarly journals In vivo tissue engineering of a trilayered leaflet-shaped tissue construct

2020 ◽  
Vol 15 (1) ◽  
pp. 1177-1192
Author(s):  
Soumen Jana ◽  
Amir Lerman
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Heart Valve ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Tissue Constructs ◽  
In Vivo Tissue Engineering ◽  
Engineered Tissue ◽  
Tissue Construct

Aim: We aimed to develop a leaflet-shaped trilayered tissue construct mimicking the morphology of native heart valve leaflets. Materials & methods: Electrospinning and in vivo tissue engineering methods were employed. Results: We developed leaflet-shaped microfibrous scaffolds, each with circumferentially, randomly and radially oriented three layers mimicking the trilayered, oriented structure of native leaflets. After 3 months in vivo tissue engineering with the scaffolds, the generated leaflet-shaped tissue constructs had a trilayered structure mimicking the orientations of native heart valve leaflets. Presence of collagen, glycosaminoglycans and elastin seen in native leaflets was observed in the engineered tissue constructs. Conclusion: Trilayered, oriented fibrous scaffolds brought the orientations of the infiltrated cells and their produced extracellular matrix proteins into the constructs.

scholarly journals A Customizable, Low-Cost Perfusion System for Sustaining Tissue Constructs

2018 ◽  
Vol 23 (6) ◽  
pp. 592-598
Author(s):  
Brian J. O’Grady ◽  
Jason X. Wang ◽  
Shannon L. Faley ◽  
Daniel A. Balikov ◽  
Ethan S. Lippmann ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Viability ◽  
Large Scale ◽  
Low Cost ◽  
Three Dimensional ◽  
Tissue Scaffolds ◽  
Perfusion System ◽  
Pump System ◽  
Tissue Constructs ◽  
Engineered Tissue

The fabrication of engineered vascularized tissues and organs requiring sustained, controlled perfusion has been facilitated by the development of several pump systems. Currently, researchers in the field of tissue engineering require the use of pump systems that are in general large, expensive, and generically designed. Overall, these pumps often fail to meet the unique demands of perfusing clinically useful tissue constructs. Here, we describe a pumping platform that overcomes these limitations and enables scalable perfusion of large, three-dimensional hydrogels. We demonstrate the ability to perfuse multiple separate channels inside hydrogel slabs using a preprogrammed schedule that dictates pumping speed and time. The use of this pump system to perfuse channels in large-scale engineered tissue scaffolds sustained cell viability over several weeks.

scholarly journals Next Stage Approach to Tissue Engineering Skeletal Muscle

2020 ◽  
Vol 7 (4) ◽  
pp. 118
Author(s):  
Gregory Reid ◽  
Fabio Magarotto ◽  
Anna Marsano ◽  
Michela Pozzobon
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Large Scale ◽  
Regeneration Process ◽  
Promising Alternative ◽  
Alternative Treatment Strategy ◽  
Engineered Tissue ◽  
And Function ◽  
Natural Tissue

Large-scale muscle injury in humans initiates a complex regeneration process, as not only the muscular, but also the vascular and neuro-muscular compartments have to be repaired. Conventional therapeutic strategies often fall short of reaching the desired functional outcome, due to the inherent complexity of natural skeletal muscle. Tissue engineering offers a promising alternative treatment strategy, aiming to achieve an engineered tissue close to natural tissue composition and function, able to induce long-term, functional regeneration after in vivo implantation. This review aims to summarize the latest approaches of tissue engineering skeletal muscle, with specific attention toward fabrication, neuro-angiogenesis, multicellularity and the biochemical cues that adjuvate the regeneration process.

scholarly journals Quantifying Vascular Density in Tissue Engineered Constructs Using Machine Learning

2021 ◽  
Vol 12 ◽  
Author(s):  
Hannah A. Strobel ◽  
Alex Schultz ◽  
Sarah M. Moss ◽  
Rob Eli ◽  
James B. Hoying
Keyword(s):  
Machine Learning ◽  
Three Dimensional ◽  
Vascular Density ◽  
Form And Function ◽  
Tissue Constructs ◽  
Automated Method ◽  
Frequent Monitoring ◽  
Ideal Tool ◽  
Engineered Tissue ◽  
And Function

Given the considerable research efforts in understanding and manipulating the vasculature in tissue health and function, making effective measurements of vascular density is critical for a variety of biomedical applications. However, because the vasculature is a heterogeneous collection of vessel segments, arranged in a complex three-dimensional architecture, which is dynamic in form and function, it is difficult to effectively measure. Here, we developed a semi-automated method that leverages machine learning to identify and quantify vascular metrics in an angiogenesis model imaged with different modalities. This software, BioSegment, is designed to make high throughput vascular density measurements of fluorescent or phase contrast images. Furthermore, the rapidity of assessments makes it an ideal tool for incorporation in tissue manufacturing workflows, where engineered tissue constructs may require frequent monitoring, to ensure that vascular growth benchmarks are met.

scholarly journals Coaxial Electrohydrodynamic Bioprinting of Pre-vascularized Cell-laden Constructs for Tissue Engineering

2021 ◽  
Vol 7 (3) ◽  
Author(s):  
Mao Mao ◽  
Hongtao Liang ◽  
Jiankang He ◽  
Ayiguli Kasimu ◽  
Yanning Zhang ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Feeding Rate ◽  
Three Dimensional ◽  
Vascular Networks ◽  
The Core ◽  
Collagen Hydrogel ◽  
Tissue Constructs ◽  
Vascular Structures ◽  
Living Tissues ◽  
Moving Speed

Recapitulating the vascular networks that maintain the delivery of nutrition, oxygen, and byproducts for the living cells within the three-dimensional (3D) tissue constructs is a challenging issue in the tissue-engineering area. Here, a novel coaxial electrohydrodynamic (EHD) bioprinting strategy is presented to fabricate thick pre-vascularized cell-laden constructs. The alginate and collagen/calcium chloride solution were utilized as the outer-layer and inner-layer bioink, respectively, in the coaxial printing nozzle to produce the core-sheath hydrogel filaments. The effect of process parameters (the feeding rate of alginate and collagen and the moving speed of the printing stage) on the size of core and sheath lines within the printed filaments was investigated. The core-sheath filaments were printed in the predefined pattern to fabricate lattice hydrogel with perfusable lumen structures. Endothelialized lumen structures were fabricated by culturing the core-sheath filaments with endothelial cells laden in the core collagen hydrogel. Multilayer core-sheath filaments were successfully printed into 3D porous hydrogel constructs with a thickness of more than 3 mm. Finally, 3D pre-vascularized cardiac constructs were successfully generated, indicating the efficacy of our strategy to engineer living tissues with complex vascular structures.

scholarly journals Microvascular fragment spheroids: Three-dimensional vascularization units for tissue engineering and regeneration

2021 ◽  
Vol 12 ◽  
pp. 204173142110355
Author(s):  
Lisa Nalbach ◽  
Danièle Müller ◽  
Selina Wrublewsky ◽  
Wolfgang Metzger ◽  
Michael D Menger ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Function ◽  
Smooth Muscle Actin ◽  
Three Dimensional ◽  
Stromal Vascular Fraction ◽  
Muscle Actin ◽  
Tissue Constructs ◽  
First Time ◽  
Tissue Defects

Adipose tissue-derived microvascular fragments (MVF) serve as vascularization units in tissue engineering and regenerative medicine. Because a three-dimensional cellular arrangement has been shown to improve cell function, we herein generated for the first time MVF spheroids to investigate whether this further increases their vascularization potential. These spheroids exhibited a morphology, size, and viability comparable to that of previously introduced stromal vascular fraction (SVF) spheroids. However, MVF spheroids contained a significantly higher number of CD31-positive endothelial cells and α-smooth muscle actin (SMA)-positive perivascular cells, resulting in an enhanced angiogenic sprouting activity. Accordingly, they also exhibited an improved in vivo vascularization and engraftment after transplantation into mouse dorsal skinfold chambers. These findings indicate that MVF spheroids are superior to SVF spheroids and, thus, may be highly suitable to improve the vascularization of tissue defects and implanted tissue constructs.

scholarly journals 3D Bioprinting of Vascularized Tissues for in vitro and in vivo Applications

2021 ◽  
Vol 9 ◽  
Author(s):  
Earnest P. Chen ◽  
Zeren Toksoy ◽  
Bruce A. Davis ◽  
John P. Geibel
Keyword(s):  
Tissue Engineering ◽  
Drug Testing ◽  
Rapid Development ◽  
Three Dimensional ◽  
3D Bioprinting ◽  
Vascular Networks ◽  
Main Challenge ◽  
3D Printed

With a limited supply of organ donors and available organs for transplantation, the aim of tissue engineering with three-dimensional (3D) bioprinting technology is to construct fully functional and viable tissue and organ replacements for various clinical applications. 3D bioprinting allows for the customization of complex tissue architecture with numerous combinations of materials and printing methods to build different tissue types, and eventually fully functional replacement organs. The main challenge of maintaining 3D printed tissue viability is the inclusion of complex vascular networks for nutrient transport and waste disposal. Rapid development and discoveries in recent years have taken huge strides toward perfecting the incorporation of vascular networks in 3D printed tissue and organs. In this review, we will discuss the latest advancements in fabricating vascularized tissue and organs including novel strategies and materials, and their applications. Our discussion will begin with the exploration of printing vasculature, progress through the current statuses of bioprinting tissue/organoids from bone to muscles to organs, and conclude with relevant applications for in vitro models and drug testing. We will also explore and discuss the current limitations of vascularized tissue engineering and some of the promising future directions this technology may bring.

scholarly journals Biopolymer-Based Microcarriers for Three-Dimensional Cell Culture and Engineered Tissue Formation

2020 ◽  
Vol 21 (5) ◽  
pp. 1895 ◽  
Author(s):  
Lixia Huang ◽  
Ahmed M.E. Abdalla ◽  
Lin Xiao ◽  
Guang Yang
Keyword(s):  
Cell Culture ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Cellular Interactions ◽  
Regeneration Medicine ◽  
Promising Tool ◽  
Engineered Tissues ◽  
Engineered Tissue ◽  
And Function

The concept of three-dimensional (3D) cell culture has been proposed to maintain cellular morphology and function as in vivo. Among different approaches for 3D cell culture, microcarrier technology provides a promising tool for cell adhesion, proliferation, and cellular interactions in 3D space mimicking the in vivo microenvironment. In particular, microcarriers based on biopolymers have been widely investigated because of their superior biocompatibility and biodegradability. Moreover, through bottom-up assembly, microcarriers have opened a bright door for fabricating engineered tissues, which is one of the cutting-edge topics in tissue engineering and regeneration medicine. This review takes an in-depth look into the recent advancements of microcarriers based on biopolymers—especially polysaccharides such as chitosan, chitin, cellulose, hyaluronic acid, alginate, and laminarin—for 3D cell culture and the fabrication of engineered tissues based on them. The current limitations and potential strategies were also discussed to shed some light on future directions.

scholarly journals Mice with cleavage-resistant N-cadherin exhibit synapse anomaly in the hippocampus and outperformance in spatial learning tasks

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
M. Asada-Utsugi ◽  
K. Uemura ◽  
M. Kubota ◽  
Y. Noda ◽  
Y. Tashiro ◽  
...  
Keyword(s):  
Memory Function ◽  
Three Dimensional ◽  
Excitatory Synapses ◽  
Missense Mutations ◽  
Glutamatergic Synapses ◽  
Learning Tasks ◽  
Transmission Electron ◽  
Nmdar Activation ◽  
And Function

AbstractN-cadherin is a homophilic cell adhesion molecule that stabilizes excitatory synapses, by connecting pre- and post-synaptic termini. Upon NMDA receptor (NMDAR) activation by glutamate, membrane-proximal domains of N-cadherin are cleaved serially by a-disintegrin-and-metalloprotease 10 (ADAM10) and then presenilin 1(PS1, catalytic subunit of the γ-secretase complex). To assess the physiological significance of the initial N-cadherin cleavage, we engineer the mouse genome to create a knock-in allele with tandem missense mutations in the mouse N-cadherin/Cadherin-2 gene (Cdh2R714G, I715D, or GD) that confers resistance on proteolysis by ADAM10 (GD mice). GD mice showed a better performance in the radial maze test, with significantly less revisiting errors after intervals of 30 and 300 s than WT, and a tendency for enhanced freezing in fear conditioning. Interestingly, GD mice reveal higher complexity in the tufts of thorny excrescence in the CA3 region of the hippocampus. Fine morphometry with serial section transmission electron microscopy (ssTEM) and three-dimensional (3D) reconstruction reveals significantly higher synaptic density, significantly smaller PSD area, and normal dendritic spine volume in GD mice. This knock-in mouse has provided in vivo evidence that ADAM10-mediated cleavage is a critical step in N-cadherin shedding and degradation and involved in the structure and function of glutamatergic synapses, which affect the memory function.

scholarly journals Heidelberg-mCT-Analyzer: a novel method for standardized microcomputed-tomography-guided evaluation of scaffold properties in bone and tissue research

2015 ◽  
Vol 2 (11) ◽  
pp. 150496 ◽  
Author(s):  
Fabian Westhauser ◽  
Christian Weis ◽  
Melanie Hoellig ◽  
Tyler Swing ◽  
Gerhard Schmidmaier ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Three Dimensional ◽  
Characteristic Parameter ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Independent Analysis ◽  
Scaffold Properties

Bone tissue engineering and bone scaffold development represent two challenging fields in orthopaedic research. Micro-computed tomography (mCT) allows non-invasive measurement of these scaffolds’ properties in vivo . However, the lack of standardized mCT analysis protocols and, therefore, the protocols’ user-dependency make interpretation of the reported results difficult. To overcome these issues in scaffold research, we introduce the Heidelberg-mCT-Analyzer. For evaluation of our technique, we built 10 bone-inducing scaffolds, which underwent mCT acquisition before ectopic implantation (T0) in mice, and at explantation eight weeks thereafter (T1). The scaffolds’ three-dimensional reconstructions were automatically segmented using fuzzy clustering with fully automatic level-setting. The scaffold itself and its pores were then evaluated for T0 and T1. Analysing the scaffolds’ characteristic parameter set with our quantification method showed bone formation over time. We were able to demonstrate that our algorithm obtained the same results for basic scaffold parameters (e.g. scaffold volume, pore number and pore volume) as other established analysis methods. Furthermore, our algorithm was able to analyse more complex parameters, such as pore size range, tissue mineral density and scaffold surface. Our imaging and post-processing strategy enables standardized and user-independent analysis of scaffold properties, and therefore is able to improve the quantitative evaluations of scaffold-associated bone tissue-engineering projects.

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