scholarly journals Optimization of the Fluidic-Based Assembly for Three-Dimensional Construction of Multicellular Hydrogel Micro-Architecture in Mimicking Hepatic Lobule-like Tissues

Micromachines ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1129
Author(s):  
Qian Liang ◽  
Yaozhen Hou ◽  
Fei Meng ◽  
Huaping Wang
Keyword(s):  
Tissue Engineering ◽  
Simulation Model ◽  
Success Rate ◽  
Three Dimensional ◽  
Assembly Process ◽  
Liver Lobule ◽  
Cellular Models ◽  
Assembly Method ◽  
3D Assembly

Three-dimensional (3D) assembly of microstructures encapsulating co-cultured multiple cells can highly recapitulate the in vivo tissues, which has a great prospect in tissue engineering and regenerative medicine. In order to fully mimic the in vivo architecture, the hydrogel microstructure needs to be designed into a special shape and spatially organized without damage, which is very challenging because of its limited mechanical properties. Here, we propose a 3D assembly method for the construction of liver lobule-like microstructures (a mimetic gear-like microstructure of liver lobule) through the local fluidic interaction. Although the method has been proven and is known as the consensual means for constructing 3D cellular models, it is still challenging to improve the assembly efficiency and the assembly success rate by adjusting the fluidic force of non-contact lifting and stacking. To improve the assembly efficiency and the assembly success rate, a fluidic simulation model is proposed based on the mechanism of the interaction between the microstructures and the fluid. By computing the simulation model, we found three main parameters that affect the assembly process; they are the velocity of the microflow, the tilt angle of the manipulator and the spacing between the microstructures and the manipulator. Compared with our previous work, the assembly efficiency was significantly improved 63.8% by using the optimized parameters of the model for assembly process, and the assembly success rate was improved from 98% to 99.5%. With the assistance of the assembly simulation, the luminal 3D micromodels of liver tissue show suitable bioactivity and biocompatibility after long-term hepatocytes culture. We anticipate that our method will be capable of improving the efficiency of the microstructures assembly to regenerate more complex multicellular constructs with unprecedented possibilities for future tissue engineering applications.

scholarly journals Pulsed Microfluid Force-Based On-Chip Modular Fabrication for Liver Lobule-Like 3D Cellular Models

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
J. Cui ◽  
H. P. Wang ◽  
Q. Shi ◽  
T. Sun
Keyword(s):  
3D Structure ◽  
Perfusion Culture ◽  
Layer By Layer ◽  
Cell Distribution ◽  
Liver Lobule ◽  
Cellular Models ◽  
Assembly Method ◽  
On Chip

In vitro three-dimensional (3D) cellular models with native tissue-like architectures and functions have potential as alternatives to human tissues in regenerative medicine and drug discovery. However, it is difficult to replicate liver constructs that mimic in vivo microenvironments using current approaches in tissue engineering because of the vessel-embedded 3D structure and complex cell distribution of the liver. This paper reports a pulsed microflow-based on-chip 3D assembly method to construct 3D liver lobule-like models that replicate the spatial structure and functions of the liver lobule. The heterogeneous cell-laden assembly units with hierarchical cell distribution are fabricated through multistep photopatterning of different cell-laden hydrogels. Through fluid force interaction by pulsed microflow, the hierarchical assembly units are driven to a stack, layer by layer, and thus spatially assemble into 3D cellular models in the closed liquid chamber of the assembly chip. The 3D models with liver lobule-like hexagonal morphology and radial cell distribution allow the dynamic perfusion culture to maintain high cell viability and functional expression during long-term culture in vitro. These results demonstrate that the fabricated 3D liver lobule-like models are promising for drug testing and the study of individual diagnoses and treatments.

scholarly journals The Revolutionary Roads to Study Cell–Cell Interactions in 3D In Vitro Pancreatic Cancer Models

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 930
Author(s):  
Donatella Delle Cave ◽  
Riccardo Rizzo ◽  
Bruno Sainz ◽  
Giuseppe Gigli ◽  
Loretta L. del Mercato ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Response ◽  
Three Dimensional ◽  
Cellular Models ◽  
Common Cancer ◽  
Cancer Models ◽  
Anti Cancer ◽  
Tumor Environment

Pancreatic cancer, the fourth most common cancer worldwide, shows a highly unsuccessful therapeutic response. In the last 10 years, neither important advancements nor new therapeutic strategies have significantly impacted patient survival, highlighting the need to pursue new avenues for drug development discovery and design. Advanced cellular models, resembling as much as possible the original in vivo tumor environment, may be more successful in predicting the efficacy of future anti-cancer candidates in clinical trials. In this review, we discuss novel bioengineered platforms for anticancer drug discovery in pancreatic cancer, from traditional two-dimensional models to innovative three-dimensional ones.

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.

scholarly journals Encapsulation of Rat Bone Marrow Derived Mesenchymal Stem Cells in Alginate Dialdehyde/Gelatin Microbeads with and without Nanoscaled Bioactive Glass for In Vivo Bone Tissue Engineering

Materials ◽  
2018 ◽  
Vol 11 (10) ◽  
pp. 1880 ◽  
Author(s):  
Ulrike Rottensteiner-Brandl ◽  
Rainer Detsch ◽  
Bapi Sarker ◽  
Lara Lingens ◽  
Katrin Köhn ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Marrow ◽  
Cell Survival ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Immune Reaction ◽  
Three Dimensional ◽  
High Cell ◽  
Rat Bone

Alginate dialdehyde (ADA), gelatin, and nano-scaled bioactive glass (nBG) particles are being currently investigated for their potential use as three-dimensional scaffolding materials for bone tissue engineering. ADA and gelatin provide a three-dimensional scaffold with properties supporting cell adhesion and proliferation. Combined with nanocristalline BG, this composition closely mimics the mineral phase of bone. In the present study, rat bone marrow derived mesenchymal stem cells (MSCs), commonly used as an osteogenic cell source, were evaluated after encapsulation into ADA-gelatin hydrogel with and without nBG. High cell survival was found in vitro for up to 28 days with or without addition of nBG assessed by calcein staining, proving the cell-friendly encapsulation process. After subcutaneous implantation into rats, survival was assessed by DAPI/TUNEL fluorescence staining. Hematoxylin-eosin staining and immunohistochemical staining for the macrophage marker ED1 (CD68) and the endothelial cell marker lectin were used to evaluate immune reaction and vascularization. After in vivo implantation, high cell survival was found after 1 week, with a notable decrease after 4 weeks. Immune reaction was very mild, proving the biocompatibility of the material. Angiogenesis in implanted constructs was significantly improved by cell encapsulation, compared to cell-free beads, as the implanted MSCs were able to attract endothelial cells. Constructs with nBG showed higher numbers of vital MSCs and lectin positive endothelial cells, thus showing a higher degree of angiogenesis, although this difference was not significant. These results support the use of ADA/gelatin/nBG as a scaffold and of MSCs as a source of osteogenic cells for bone tissue engineering. Future studies should however improve long term cell survival and focus on differentiation potential of encapsulated cells in vivo.

Tough Double-Network Hydrogels as Scaffolds for Tissue Engineering

2012 ◽  
pp. 213-222
Author(s):  
Jing Jing Yang ◽  
Jian Fang Liu ◽  
Takayuki Kurokawa ◽  
Nobuto Kitamura ◽  
Kazunori Yasuda ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Three Dimensional ◽  
Cartilage Regeneration ◽  
Cell Types ◽  
Embryoid Bodies ◽  
Living Tissue ◽  
Double Network ◽  
Dimensional Network

Hydrogels are used as scaffolds for tissue engineering in vitro & in vivo because their three-dimensional network structure and viscoelasticity are similar to those of the macromolecular-based extracellular matrix (ECM) in living tissue. Especially, the synthetic hydrogels with controllable and reproducible properties were used as scaffolds to study the behaviors of cells in vitro and implanted test in vivo. In this review, two different structurally designed hydrogels, single-network (SN) hydrogels and double-network (DN) hydrogels, were used as scaffolds. The behavior of two cell types, anchorage-dependent cells and anchorage-independent cells, and the differentiation behaviors of embryoid bodies (EBs) were investigated on these hydrogels. Furthermore, the behavior of chondrocytes on DN hydrogels in vitro and the spontaneous cartilage regeneration induced by DN hydrogels in vivo was examined.

scholarly journals Tissue-engineered Oral Mucosa

2012 ◽  
Vol 91 (7) ◽  
pp. 642-650 ◽  
Author(s):  
K. Moharamzadeh ◽  
H. Colley ◽  
C. Murdoch ◽  
V. Hearnden ◽  
W.L. Chai ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Soft Tissue ◽  
Oral Mucosa ◽  
Dental Materials ◽  
Three Dimensional ◽  
Bacterial Invasion ◽  
Graft Material ◽  
Oral Diseases

Advances in tissue engineering have permitted the three-dimensional (3D) reconstruction of human oral mucosa for various in vivo and in vitro applications. Tissue-engineered oral mucosa have been further optimized in recent years for clinical applications as a suitable graft material for intra-oral and extra-oral repair and treatment of soft-tissue defects. Novel 3D in vitro models of oral diseases such as cancer, Candida, and bacterial invasion have been developed as alternatives to animal models for investigation of disease phenomena, their progression, and treatment, including evaluation of drug delivery systems. The introduction of 3D oral mucosal reconstructs has had a significant impact on the approaches to biocompatibility evaluation of dental materials and oral healthcare products as well as the study of implant-soft tissue interfaces. This review article discusses the recent advances in tissue engineering and applications of tissue-engineered human oral mucosa.

Comparison on the Osteogenesis Potential between Poly(lactide-Co-Glycolide) and Alginate as Bone Tissue Engineering Scaffold In Vivo

2007 ◽  
Vol 330-332 ◽  
pp. 1173-1176 ◽  
Author(s):  
Cai Li ◽  
Run Liang Chen ◽  
Lei Liu ◽  
Yun Feng Lin ◽  
Wei Dong Tian ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Three Dimensional ◽  
Tissue Engineering Scaffold ◽  
Autogenous Bone ◽  
Mechanical Characters

Poly(lactide-co-glycolide) (PLGA) and alginate(AG) are the most promising scaffolds in the bone tissue engineering for their stable mechanical characters and three-dimensional porous structure. This study aimed to assay the in vivo osteogenesis potentials by loading the autogenous bone marrow stromal cells (BMSCs) on PLGA or AG. The results suggested that PLGA and AG are both ideal bone tissue engineering scaffold. BMSCs/AG has stronger osteogenesis potentials in vivo than BMSCs/PLGA.

Requirements for the Manufacturing of Scaffold Biomaterial With Features at Multiple Scales

2005 ◽  
Author(s):  
I. M. Sebastine ◽  
D. J. Williams
Keyword(s):  
Tissue Engineering ◽  
Multiple Scales ◽  
Cell Attachment ◽  
Structural Parameters ◽  
Complex Function ◽  
Three Dimensional ◽  
Cell Orientation ◽  
Length Scales

Tissue engineering aims to restore the complex function of diseased tissue using cells and scaffold materials. Tissue engineering scaffolds are three-dimensional (3D) structures that assist in the tissue engineering process by providing a site for cells to attach, proliferate, differentiate and secrete an extra-cellular matrix, eventually leading cells to form a neo-tissue of predetermined, three-dimensional shape and size. For a scaffold to function effectively, it must possess the optimum structural parameters conducive to the cellular activities that lead to tissue formation; these include cell penetration and migration into the scaffold, cell attachment onto the scaffold substrate, cell spreading and proliferation and cell orientation. In vivo, cells are organized in functional tissue units that repeat on the order of 100 μm. Fine scaffold features have been shown to provide control over attachment, migration and differentiation of cells. In order to design such 3D featured constructs effectively understanding the biological response of cells across length scales from nanometer to millimeter range is crucial. Scaffold biomaterials may need to be tailored at three different length scales: nanostructure (<1μm), microstructure (<20–100μm), and macrostructure (>100μm) to produce biocompatible and biofunctional scaffolds that closely resemble the extracellular matrix (ECM) of the natural tissue environment and promote cell adhesion, attachment, spreading, orientation, rate of movement, and activation. Identification of suitable fabrication techniques for manufacturing scaffolds with the required features at multiple scales is a significant challenge. This review highlights the effect and importance of the features of scaffolds that can influence the behaviour of cells/tissue at different length scales in vitro to increase our understanding of the requirements for the manufacture of functional 3D tissue constructs.

Informatics Challenges in Tissue Engineering and Biomaterials

2003 ◽  
Vol 17 (1) ◽  
pp. 49-54 ◽  
Author(s):  
D. Rekow
Keyword(s):  
Tissue Engineering ◽  
Clinical Performance ◽  
Three Dimensional ◽  
Thin Layers ◽  
Material Surface ◽  
Dental Restorations ◽  
Scaffold Materials ◽  
Ceramic Crowns ◽  
Three Dimensional Configuration

Both tissue engineering and biomaterials have made tremendous strides recently, yet major questions remain unanswered. Tissue-engineered products have come to the market; others are in development. A fundamental issue that informatics could address for tissue engineering is to describe and to predict the cascade of biochemical and cellular reactions that occur as a function of time and implant material: surface texture, microporosity; pore size, density, and connectivity; and three-dimensional configuration. Behavior of ceramics, a subset of tissue-engineering scaffold materials and a mainstay of dental restorations, has been studied extensively for very thin layers and for thicknesses greater than 2 mm. Until recently, little has been known about dentally relevant thickness of 1–2 mm. Results have been surprising and are continuing to develop. Still, at least one fundamental question remains that could be addressed by informatics techniques: Where, along the spectrum of flat-polished material to 10-year clinical in vivo study, can we test to predict clinical performance of all-ceramic crowns accurately?

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