Soft-Tissue Analogue Design and Tissue Engineering of Liver

MRS Bulletin ◽  
1996 ◽  
Vol 21 (11) ◽  
pp. 52-54 ◽  
Author(s):  
Prabhas V. Moghe

Tissue engineering involves the application of physical and life sciences to develop functional substitutes for dysfunctional organs or tissue structures. From an engineering standpoint, tissues contain two basic components—the cells that are organized into proper units, and the material surrounding the cells, called the extracellular matrix (ECM). A third, frequently overlooked feature essential to the maintenance of the activity of the engineered tissue is the three-dimensional architecture of the cell-matrix composite.A comprehensive review of the scope and impact of tissue engineering has previously appeared. Tissue-engineered devices have the potential to reduce the annual health-care cost related to tissue loss and end-stage organ failure to the order of $400 billion, eight million invasive surgical procedures, and 65 million hospital days. A common approach to engineer a functional tissue is to place cells derived from a healthy organ or tissue type (identical or similar to the dysfunctional tissue/organ) on or within matrices analogous to host-tissue ECM. These systems can then be enclosed in appropriate membranes that isolate cells from immune rejection following implantation or can be transplanted directly with the administration of drugs that prevent the immune rejection. Another application of these systems is for extracorporeal (outside the patient's body) device support of a dysfunctional organ. In either instance, the success of the engineered tissue depends critically on the interactions of cells with the tissue analogues. The objective of this article is to outline the simplest matrix-design parameters to control these interactions. While organs are comprised of very different tissue types, for the sake of simplicity, this article is primarily pertinent to the tissue engineering of one major organ, the liver. The choice of this tissue type is intended to serve as a comprehensive generalization of many different cell types since in the diversity and complexity of its activities, the liver has few parallels. The development of an artificial liver is also critically awaited, as in the United States alone, 35,000 people, including the many wait listed for the exorbitant liver organ transplants ($300,000), die each year of chronic liver disorders. In many other countries, liver disease is the second leading cause of death.

Author(s):  
Jing Jing Yang ◽  
Jian Fang Liu ◽  
Takayuki Kurokawa ◽  
Nobuto Kitamura ◽  
Kazunori Yasuda ◽  
...  

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.


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 ◽  
...  

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.


Author(s):  
Soham Ghosh ◽  
J. Craig Dutton ◽  
Bumsoo Han

Freezing of biomaterials is emerging as one of the key biotechnologies in cell/tissue engineering, medicine and biology. Its applications include — 1) preservation of cell/tissue engineering products, 2) quality control of biospecimens cryopreserved in tissue banks and repositories, and 3) synthesis procedures of biomaterials such as decellularization of native tissues to create acellular (i.e., cell-free) complex three-dimensional extracellular matrices (ECMs). Traditionally, research efforts have focused on determining optimal freeze/thaw (F/T) protocols with chemical additives, so called cryoprotective agents, for a given cell/tissue-type by comparing the outcomes of F/T protocols, which are mainly gauged by cell viability. Although cell viability is the major constituent, it has recently been recognized that other features beyond viability are also critical to the functionality of biomaterials, including the microstructure of the ECM, the status of cell-matrix adhesion, and the cytoskeletal structure and organization [1, 2, 3].


2018 ◽  
Vol 9 ◽  
pp. 204173141878169 ◽  
Author(s):  
Alexandra Levin ◽  
Vaibhav Sharma ◽  
Lilian Hook ◽  
Elena García-Gareta

This article presents a case study to show the usefulness and importance of using factorial design in tissue engineering and biomaterials science. We used a full factorial experimental design (2 × 2 × 2 × 3) to solve a routine query in every biomaterial research project: the optimisation of cell seeding efficiency for pre-clinical in vitro cell studies, the importance of which is often overlooked. In addition, tissue-engineered scaffolds can be cellularised with relevant cell type(s) to form implantable tissue constructs, where the cell seeding method must be reliable and robust. Our results show the complex relationship between cells and scaffolds and suggest that the optimum seeding conditions for each material may be different due to different material properties, and therefore, should be investigated for individual scaffolds. Our factorial experimental design can be easily translated to other cell types and three-dimensional biomaterials, where multiple interacting variables can be thoroughly investigated for better understanding of cell–biomaterial interactions.


2019 ◽  
Vol 5 (2.2) ◽  
pp. 3 ◽  
Author(s):  
Krishna C. R. Kolan ◽  
Julie A. Semon ◽  
Bradley Bromet ◽  
Delbert E. Day ◽  
Ming C. Leu

Three-dimensional (3D) bioprinting technologies have shown great potential in the fabrication of 3D models for different human tissues. Stem cells are an attractive cell source in tissue engineering as they can be directed by material and environmental cues to differentiate into multiple cell types for tissue repair and regeneration. In this study, we investigate the viability of human adipose-derived mesenchymal stem cells (ASCs) in alginate-gelatin (Alg-Gel) hydrogel bioprinted with or without bioactive glass. Highly angiogenic borate bioactive glass (13-93B3) in 50 wt% is added to polycaprolactone (PCL) to fabricate scaffolds using a solvent-based extrusion 3D bioprinting technique. The fabricated scaffolds with 12 × 12 × 1 mm3 in overall dimensions are physically characterized, and the glass dissolution from PCL/glass composite over a period of 28 days is studied. Alg-Gel composite hydrogel is used as a bioink to suspend ASCs, and scaffolds are then bioprinted in different configurations: Bioink only, PCL+bioink, and PCL/glass+bioink, to investigate ASC viability. The results indicate the feasibility of the solvent-based bioprinting process to fabricate 3D cellularized scaffolds with more than 80% viability on day 0. The decrease in viability after 7 days due to glass concentration and static culture conditions is discussed. The feasibility of modifying Alg-Gel with 13-93B3 glass for bioprinting is also investigated, and the results are discussed.


Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1472 ◽  
Author(s):  
Luba Perry ◽  
Uri Merdler ◽  
Maria Elishaev ◽  
Shulamit Levenberg

Engineering of functional tissue, by combining either autologous or allogeneic cells with biomaterials, holds promise for the treatment of various diseases and injuries. Prevascularization of the engineered tissue was shown to enhance and improve graft integration and neovascularization post-implantation in immunocompromised mice. However, the neovascularization and integration processes of transplanted engineered tissues have not been widely studied in immunocompetent models. Here, we fabricated a three-dimensional (3D) vascularized murine muscle construct that was transplanted into immunocompetent and immunocompromised mice. Intravital imaging demonstrated enhanced neovascularization in immunocompetent mice compared to immunocompromised mice, 18 days post-implantation, indicating the advantageous effect of an intact immune system on neovascularization. Moreover, construct prevascularization enhanced neovascularization, integration, and myogenesis in both animal models. These findings demonstrate the superiority of implantation into immunocompetent over immunocompromised mice and, therefore, suggest that using autologous cells might be beneficial compared to allogeneic cells and subsequent immunosuppression. Taken together, these observations have the potential to advance the field of regenerative medicine and tissue engineering, ultimately reducing the need for donor organs and tissues.


2015 ◽  
Vol 40 (9) ◽  
pp. 973-985 ◽  
Author(s):  
E. Kloczko ◽  
D. Nikkhah ◽  
L. Yildirimer

Tissue engineering is believed to have great potential for the reconstruction of the hand after trauma, congenital absence and tumours. Due to the presence of multiple distinct tissue types, which together function in a precisely orchestrated fashion, the hand counts among the most complex structures to regenerate. As yet the achievements have been limited. More recently, the focus has shifted towards scaffolds, which provide a three-dimensional framework to mimic the natural extracellular environment for specific cell types. In particular their surface structures (or topographies) have become a key research focus to enhance tissue-specific cell attachment and growth into fully functioning units. This article reviews the current understanding in hand tissue engineering before focusing on the potential for scaffold topographical features on micro- and nanometre scales to achieve better functional regeneration of individual and composite tissues.


Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1762 ◽  
Author(s):  
Juan Cui ◽  
Huaping Wang ◽  
Qing Shi ◽  
Tao Sun ◽  
Qiang Huang ◽  
...  

Three-dimensional (3D) tissue models replicating liver architectures and functions are increasingly being needed for regenerative medicine. However, traditional studies are focused on establishing 2D environments for hepatocytes culture since it is challenging to recreate biodegradable 3D tissue-like architecture at a micro scale by using hydrogels. In this paper, we utilized a gelatin methacryloyl (GelMA) hydrogel as a matrix to construct 3D lobule-like microtissues for co-culture of hepatocytes and fibroblasts. GelMA hydrogel with high cytocompatibility and high structural fidelity was determined to fabricate hepatocytes encapsulated micromodules with central radial-type hole by photo-crosslinking through a digital micromirror device (DMD)-based microfluidic channel. The cellular micromodules were assembled through non-contact pick-up strategy relying on local fluid-based micromanipulation. Then the assembled micromodules were coated with fibroblast-laden GelMA, subsequently irradiated by ultraviolet for integration of the 3D lobule-like microtissues encapsulating multiple cell types. With long-term co-culture, the 3D lobule-like microtissues encapsulating hepatocytes and fibroblasts maintained over 90% cell viability. The liver function of albumin secretion was enhanced for the co-cultured 3D microtissues compared to the 3D microtissues encapsulating only hepatocytes. Experimental results demonstrated that 3D lobule-like microtissues fabricated by GelMA hydrogels capable of multicellular co-culture with high cell viability and liver function, which have huge potential for liver tissue engineering and regenerative medicine applications.


Author(s):  
W. Mark Saltzman

Tissue or organ transplantation are among the few options available for patients with excessive skin loss, heart or liver failure, and many common ailments, and the demand for replacement tissue greatly exceeds the supply, even before one considers the serious constraints of immunological tissue type matching to avoid immune rejection. Tissue engineering promises to help sidestep constraints on availability and overcome the scientific challenges, with huge medical benefits. This book lays out the principles of tissue engineering. It will be a useful reference work for those associated with this field and as a textbook for specialized courses in the subject. It is a companion volume to Saltzman's OUP book on drug delivery.


Materials ◽  
2018 ◽  
Vol 11 (11) ◽  
pp. 2199 ◽  
Author(s):  
Željka Kačarević ◽  
Patrick Rider ◽  
Said Alkildani ◽  
Sujith Retnasingh ◽  
Ralf Smeets ◽  
...  

Bioprinting is an emerging field in regenerative medicine. Producing cell-laden, three-dimensional structures to mimic bodily tissues has an important role not only in tissue engineering, but also in drug delivery and cancer studies. Bioprinting can provide patient-specific spatial geometry, controlled microstructures and the positioning of different cell types for the fabrication of tissue engineering scaffolds. In this brief review, the different fabrication techniques: laser-based, extrusion-based and inkjet-based bioprinting, are defined, elaborated and compared. Advantages and challenges of each technique are addressed as well as the current research status of each technique towards various tissue types. Nozzle-based techniques, like inkjet and extrusion printing, and laser-based techniques, like stereolithography and laser-assisted bioprinting, are all capable of producing successful bioprinted scaffolds. These four techniques were found to have diverse effects on cell viability, resolution and print fidelity. Additionally, the choice of materials and their concentrations were also found to impact the printing characteristics. Each technique has demonstrated individual advantages and disadvantages with more recent research conduct involving multiple techniques to combine the advantages of each technique.


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