scholarly journals 3D Bioprinting for Vascularized Tissue-Engineered Bone Fabrication

Materials ◽  
2020 ◽  
Vol 13 (10) ◽  
pp. 2278 ◽  
Author(s):  
Fei Xing ◽  
Zhou Xiang ◽  
Pol Maria Rommens ◽  
Ulrike Ritz
Keyword(s):  
Three Dimensional ◽  
Current Status ◽  
Layer By Layer ◽  
3D Bioprinting ◽  
Vascular Networks ◽  
Waste Products ◽  
Tissue Microenvironment ◽  
Spatial Architecture

Vascularization in bone tissues is essential for the distribution of nutrients and oxygen, as well as the removal of waste products. Fabrication of tissue-engineered bone constructs with functional vascular networks has great potential for biomimicking nature bone tissue in vitro and enhancing bone regeneration in vivo. Over the past decades, many approaches have been applied to fabricate biomimetic vascularized tissue-engineered bone constructs. However, traditional tissue-engineered methods based on seeding cells into scaffolds are unable to control the spatial architecture and the encapsulated cell distribution precisely, which posed a significant challenge in constructing complex vascularized bone tissues with precise biomimetic properties. In recent years, as a pioneering technology, three-dimensional (3D) bioprinting technology has been applied to fabricate multiscale, biomimetic, multi-cellular tissues with a highly complex tissue microenvironment through layer-by-layer printing. This review discussed the application of 3D bioprinting technology in the vascularized tissue-engineered bone fabrication, where the current status and unique challenges were critically reviewed. Furthermore, the mechanisms of vascular formation, the process of 3D bioprinting, and the current development of bioink properties were also discussed.

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 Soft robotic constrictor for in vitro modeling of dynamic tissue compression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jungwook Paek ◽  
Joseph W. Song ◽  
Ehsan Ban ◽  
Yuma Morimitsu ◽  
Chinedum O. Osuji ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Physiological Changes ◽  
Vascular Networks ◽  
Human Endothelial Cells ◽  
In Vitro Modeling ◽  
Tissue Microenvironment ◽  
Cyclic Compression ◽  
Applied Forces ◽  
New Research

AbstractHere we present a microengineered soft-robotic in vitro platform developed by integrating a pneumatically regulated novel elastomeric actuator with primary culture of human cells. This system is capable of generating dynamic bending motion akin to the constriction of tubular organs that can exert controlled compressive forces on cultured living cells. Using this platform, we demonstrate cyclic compression of primary human endothelial cells, fibroblasts, and smooth muscle cells to show physiological changes in their morphology due to applied forces. Moreover, we present mechanically actuatable organotypic models to examine the effects of compressive forces on three-dimensional multicellular constructs designed to emulate complex tissues such as solid tumors and vascular networks. Our work provides a preliminary demonstration of how soft-robotics technology can be leveraged for in vitro modeling of complex physiological tissue microenvironment, and may enable the development of new research tools for mechanobiology and related areas.

scholarly journals Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure

Gut ◽  
2020 ◽  
pp. gutjnl-2019-319960 ◽  
Author(s):  
Huayu Yang ◽  
Lejia Sun ◽  
Yuan Pang ◽  
Dandan Hu ◽  
Haifeng Xu ◽  
...  
Keyword(s):  
Drug Metabolism ◽  
Liver Failure ◽  
Human Liver ◽  
Three Dimensional ◽  
3D Bioprinting ◽  
Heparg Cells ◽  
Liver Functions ◽  
Human Specific

ObjectiveShortage of organ donors, a critical challenge for treatment of end-stage organ failure, has motivated the development of alternative strategies to generate organs in vitro. Here, we aim to describe the hepatorganoids, which is a liver tissue model generated by three-dimensional (3D) bioprinting of HepaRG cells and investigate its liver functions in vitro and in vivo.Design3D bioprinted hepatorganoids (3DP-HOs) were constructed using HepaRG cells and bioink, according to specific 3D printing procedures. Liver functions of 3DP-HOs were detected after 7 days of differentiation in vitro, which were later transplanted into Fah-deficient mice. The in vivo liver functions of 3DP-HOs were evaluated by survival time and liver damage of mice, human liver function markers and human-specific debrisoquine metabolite production.Results3DP-HOs broadly acquired liver functions, such as ALBUMIN secretion, drug metabolism and glycogen storage after 7 days of differentiation. After transplantation into abdominal cavity of Fah-/-Rag2-/- mouse model of liver injury, 3DP-HOs further matured and displayed increased synthesis of liver-specific proteins. Particularly, the mice acquired human-specific drug metabolism activities. Functional vascular systems were also formed in transplanted 3DP-HOs, further enhancing the material transport and liver functions of 3DP-HOs. Most importantly, transplantation of 3DP-HOs significantly improved the survival of mice.ConclusionsOur results demonstrated a comprehensive proof of principle, which indicated that 3DP-HO model of liver tissues possessed in vivo hepatic functions and alleviated liver failure after transplantation, suggesting that 3D bioprinting could be used to generate human liver tissues as the alternative transplantation donors for treatment of liver diseases.

scholarly journals 3D Bioprinting of Human Tissues: Biofabrication, Bioinks and Bioreactors

2021 ◽  
Vol 22 (8) ◽  
pp. 3971
Author(s):  
Jianhua Zhang ◽  
Esther Wehrle ◽  
Marina Rubert ◽  
Ralph Müller
Keyword(s):  
Tissue Engineering ◽  
Human Tissue ◽  
Fluid Shear Stress ◽  
Pharmaceutical Research ◽  
Three Dimensional ◽  
Biological Tissues ◽  
Layer By Layer ◽  
Human Tissues ◽  
3D Bioprinting

The field of tissue engineering has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes for regenerative medicine and pharmaceutical research. Conventional scaffold-based approaches are limited in their capacity to produce constructs with the functionality and complexity of native tissue. Three-dimensional (3D) bioprinting offers exciting prospects for scaffolds fabrication, as it allows precise placement of cells, biochemical factors, and biomaterials in a layer-by-layer process. Compared with traditional scaffold fabrication approaches, 3D bioprinting is better to mimic the complex microstructures of biological tissues and accurately control the distribution of cells. Here, we describe recent technological advances in bio-fabrication focusing on 3D bioprinting processes for tissue engineering from data processing to bioprinting, mainly inkjet, laser, and extrusion-based technique. We then review the associated bioink formulation for 3D bioprinting of human tissues, including biomaterials, cells, and growth factors selection. The key bioink properties for successful bioprinting of human tissue were summarized. After bioprinting, the cells are generally devoid of any exposure to fluid mechanical cues, such as fluid shear stress, tension, and compression, which are crucial for tissue development and function in health and disease. The bioreactor can serve as a simulator to aid in the development of engineering human tissues from in vitro maturation of 3D cell-laden scaffolds. We then describe some of the most common bioreactors found in the engineering of several functional tissues, such as bone, cartilage, and cardiovascular applications. In the end, we conclude with a brief insight into present limitations and future developments on the application of 3D bioprinting and bioreactor systems for engineering human tissue.

scholarly journals Development and Application of 3D Bioprinted Scaffolds Supporting Induced Pluripotent Stem Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Dezhi Lu ◽  
Yang Liu ◽  
Wentao Li ◽  
Hongshi Ma ◽  
Tao Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Three Dimensional ◽  
Layer By Layer ◽  
3D Bioprinting ◽  
Differentiation Potential ◽  
Human Ipscs ◽  
Induced Pluripotent

Three-dimensional (3D) bioprinting is a revolutionary technology that replicates 3D functional living tissue scaffolds in vitro by controlling the layer-by-layer deposition of biomaterials and enables highly precise positioning of cells. With the development of this technology, more advanced research on the mechanisms of tissue morphogenesis, clinical drug screening, and organ regeneration may be pursued. Because of their self-renewal characteristics and multidirectional differentiation potential, induced pluripotent stem cells (iPSCs) have outstanding advantages in stem cell research and applications. In this review, we discuss the advantages of different bioinks containing human iPSCs that are fabricated by using 3D bioprinting. In particular, we focus on the ability of these bioinks to support iPSCs and promote their proliferation and differentiation. In addition, we summarize the applications of 3D bioprinting with iPSC-containing bioinks and put forward new views on the current research status.

Potential of fibroblasts to regulate the formation of three-dimensional vessel-like structures from endothelial cells in vitro

2006 ◽  
Vol 290 (5) ◽  
pp. C1385-C1398 ◽  
Author(s):  
Leoni A. Kunz-Schughart ◽  
Josef A. Schroeder ◽  
Marit Wondrak ◽  
Frank van Rey ◽  
Karla Lehle ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Network Formation ◽  
Umbilical Vein ◽  
Three Dimensional ◽  
Artificial Substrates ◽  
Vascular Networks ◽  
Electron Microscopic ◽  
Tubule Formation

The development of vessel-like structures in vitro to mimic as well as to realize the possibility of tissue-engineered small vascular networks presents a major challenge to cell biologists and biotechnologists. We aimed to establish a three-dimensional (3-D) culture system with an endothelial network that does not require artificial substrates or ECM compounds. By using human skin fibroblasts and endothelial cells (ECs) from the human umbilical vein (HUVECs) in diverse spheroid coculture strategies, we verified that fibroblast support and modulate EC migration, viability, and network formation in a 3-D tissue-like stromal environment. In mixed spheroid cultures consisting of human ECs and fibroblasts, a complex 3-D network with EC tubular structures, lumen formation, pinocytotic activity, and tight junction complexes has been identified on the basis of immunohistochemical and transmission electron microscopic imaging. Tubular networks with extensions up to 400 μm were achieved. When EC suspensions were used, EC migration and network formation were critically affected by the status of the fibroblast. However, the absence of EC migration into the center of 14-day, but not 3-day, precultured fibroblast spheroids could not be attributed to loss of F viability. In parallel, it was also confirmed that migrated ECs that entered cluster-like formations became apoptotic, whereas the majority of those forming vessel-like structures remained viable for >8 days. Our protocols allow us to study the nature of tubule formation in a manner more closely related to the in vivo situation as well as to understand the basis for the integration of capillary networks in tissue grafts and develop methods of quantifying the amount of angiogenesis in spheroids using fibroblast and other cells isolated from the same patient, along with ECs.

scholarly journals Development and Application of an Additively Manufactured Calcium Chloride Nebulizer for Alginate 3D-Bioprinting Purposes

2018 ◽  
Vol 9 (4) ◽  
pp. 63 ◽  
Author(s):  
Lukas Raddatz ◽  
Antonina Lavrentieva ◽  
Iliyana Pepelanova ◽  
Janina Bahnemann ◽  
Dominik Geier ◽  
...  
Keyword(s):  
Cell Culture ◽  
Culture Media ◽  
Single Cells ◽  
Matrix Material ◽  
Three Dimensional ◽  
Culture Cell ◽  
3D Bioprinting ◽  
Cacl2 Solution

Three-dimensional (3D)-bioprinting enables scientists to mimic in vivo micro-environments and to perform in vitro cell experiments under more physiological conditions than is possible with conventional two-dimensional (2D) cell culture. Cell-laden biomaterials (bioinks) are precisely processed to bioengineer tissue three-dimensionally. One primarily used matrix material is sodium alginate. This natural biopolymer provides both fine mechanical properties when gelated and high biocompatibility. Commonly, alginate is 3D bioprinted using extrusion based devices. The gelation reaction is hereby induced by a CaCl2 solution in the building chamber after material extrusion. This established technique has two main disadvantages: (1) CaCl2 can have toxic effects on the cell-laden hydrogels by oxygen diffusion limitation and (2) good printing resolution in the CaCl2 solution is hard to achieve, since the solution needs to be removed afterwards and substituted by cell culture media. Here, we show an innovative approach of alginate bioprinting based on a CaCl2 nebulizer. The device provides CaCl2 mist to the building platform inducing the gelation. The necessary amount of CaCl2 could be decreased as compared to previous gelation strategies and limitation of oxygen transfer during bioprinting can be reduced. The device was manufactured using the MJP-3D printing technique. Subsequently, its digital blueprint (CAD file) can be modified and additive manufactured easily and mounted in various extrusion bioprinters. With our approach, a concept for a more gentle 3D Bioprinting method could be shown. We demonstrated that the concept of an ultrasound-based nebulizer for CaCl2 mist generation can be used for 3D bioprinting and that the mist-induced polymerization of alginate hydrogels of different concentrations is feasible. Furthermore, different cell-laden alginate concentrations could be used: Cell spheroids (mesenchymal stem cells) and single cells (mouse fibroblasts) were successfully 3D printed yielding viable cells and stable hydrogels after 24 h cultivation. We suggest our work to show a different and novel approach on alginate bioprinting, which could be useful in generating cell-laden hydrogel constructs for e.g., drug screening or (soft) tissue engineering applications.

scholarly journals Regenerative medicine for skeletal muscle loss: a review of current tissue engineering approaches

2021 ◽  
Vol 32 (1) ◽  
Author(s):  
Benjamin Langridge ◽  
Michelle Griffin ◽  
Peter E. Butler
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Three Dimensional ◽  
In Vivo Studies ◽  
Current Status ◽  
Surgical Approaches ◽  
Muscle Loss ◽  
Functional Maturation

AbstractSkeletal muscle is capable of regeneration following minor damage, more significant volumetric muscle loss (VML) however results in permanent functional impairment. Current multimodal treatment methodologies yield variable functional recovery, with reconstructive surgical approaches restricted by limited donor tissue and significant donor morbidity. Tissue-engineered skeletal muscle constructs promise the potential to revolutionise the treatment of VML through the regeneration of functional skeletal muscle. Herein, we review the current status of tissue engineering approaches to VML; firstly the design of biocompatible tissue scaffolds, including recent developments with electroconductive materials. Secondly, we review the progenitor cell populations used to seed scaffolds and their relative merits. Thirdly we review in vitro methods of scaffold functional maturation including the use of three-dimensional bioprinting and bioreactors. Finally, we discuss the technical, regulatory and ethical barriers to clinical translation of this technology. Despite significant advances in areas, such as electroactive scaffolds and three-dimensional bioprinting, along with several promising in vivo studies, there remain multiple technical hurdles before translation into clinically impactful therapies can be achieved. Novel strategies for graft vascularisation, and in vitro functional maturation will be of particular importance in order to develop tissue-engineered constructs capable of significant clinical impact.

scholarly journals 3D bioprinting dual-factor releasing and gradient-structured constructs ready to implant for anisotropic cartilage regeneration

2020 ◽  
Vol 6 (37) ◽  
pp. eaay1422 ◽  
Author(s):  
Ye Sun ◽  
Yongqing You ◽  
Wenbo Jiang ◽  
Bo Wang ◽  
Qiang Wu ◽  
...  
Keyword(s):  
Large Scale ◽  
Structural Integrity ◽  
Three Dimensional ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
3D Bioprinting ◽  
Deep Layers ◽  
Joint Prostheses

Cartilage injury is extremely common and leads to joint dysfunction. Existing joint prostheses do not remodel with host joint tissue. However, developing large-scale biomimetic anisotropic constructs mimicking native cartilage with structural integrity is challenging. In the present study, we describe anisotropic cartilage regeneration by three-dimensional (3D) bioprinting dual-factor releasing and gradient-structured constructs. Dual-factor releasing mesenchymal stem cell (MSC)–laden hydrogels were used for anisotropic chondrogenic differentiation. Together with physically gradient synthetic biodegradable polymers that impart mechanical strength, the 3D bioprinted anisotropic cartilage constructs demonstrated whole-layer integrity, lubrication of superficial layers, and nutrient supply in deep layers. Evaluation of the cartilage tissue in vitro and in vivo showed tissue maturation and organization that may be sufficient for translation to patients. In conclusion, one-step 3D bioprinted dual-factor releasing and gradient-structured constructs were generated for anisotropic cartilage regeneration, integrating the feasibility of MSC- and 3D bioprinting–based therapy for injured or degenerative joints.

scholarly journals A Novel Microplate 3D Bioprinting Platform for the Engineering of Muscle and Tendon Tissues

2018 ◽  
Vol 23 (6) ◽  
pp. 599-613 ◽  
Author(s):  
Sandra Laternser ◽  
Hansjoerg Keller ◽  
Olivier Leupin ◽  
Martin Rausch ◽  
Ursula Graf-Hausner ◽  
...  
Keyword(s):  
Drug Screening ◽  
Musculoskeletal Diseases ◽  
Marker Gene ◽  
Three Dimensional ◽  
In Vitro Models ◽  
3D Bioprinting ◽  
Promising Tool ◽  
Screening Platform

Two-dimensional (2D) cell cultures do not reflect the in vivo situation, and thus it is important to develop predictive three-dimensional (3D) in vitro models with enhanced reliability and robustness for drug screening applications. Treatments against muscle-related diseases are becoming more prominent due to the growth of the aging population worldwide. In this study, we describe a novel drug screening platform with automated production of 3D musculoskeletal-tendon-like tissues. With 3D bioprinting, alternating layers of photo-polymerized gelatin-methacryloyl-based bioink and cell suspension tissue models were produced in a dumbbell shape onto novel postholder cell culture inserts in 24-well plates. Monocultures of human primary skeletal muscle cells and rat tenocytes were printed around and between the posts. The cells showed high viability in culture and good tissue differentiation, based on marker gene and protein expressions. Different printing patterns of bioink and cells were explored and calcium signaling with Fluo4-loaded cells while electrically stimulated was shown. Finally, controlled co-printing of tenocytes and myoblasts around and between the posts, respectively, was demonstrated followed by co-culture and co-differentiation. This screening platform combining 3D bioprinting with a novel microplate represents a promising tool to address musculoskeletal diseases.

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