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

Author(s):  
Earnest P. Chen ◽  
Zeren Toksoy ◽  
Bruce A. Davis ◽  
John P. Geibel

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.

Materials ◽  
2020 ◽  
Vol 13 (10) ◽  
pp. 2278 ◽  
Author(s):  
Fei Xing ◽  
Zhou Xiang ◽  
Pol Maria Rommens ◽  
Ulrike Ritz

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.


Author(s):  
Dhakshinamoorthy Sundaramurthi ◽  
Sakandar Rauf ◽  
Charlotte Hauser

Alternative strategies that overcome existing organ transplantation methods are of increasing importance be-cause of ongoing demands and lack of adequate organ donors. Recent improvements in tissue engineering techniques offer improved solutions to this problem and will influence engineering and medicinal applications. Tissue engineering employs the synergy of cells, growth factors and scaffolds besides others with the aim to mimic the native extracellular matrix for tissue regeneration. Three-dimensional (3D) bioprinting has been explored to create organs for transplanta-tion, medical implants, prosthetics, in vitro models and 3D tissue models for drug testing. In addition, it is emerging as a powerful technology to provide patients with severe disease conditions with personalized treatments. Challenges in tis-sue engineering include the development of 3D scaffolds that closely resemble native tissues. In this review, existing printing methods such as extrusion-based, robotic dispensing, cellular inkjet, laser-assisted printing and integrated tissue organ printing (ITOP) are examined. Also, natural and synthetic polymers and their blends as well as peptides that are exploited as bioinks are discussed with emphasis on regenerative medicine applications. Furthermore, applications of 3D bioprinting in regenerative medicine, evolving strategies and future perspectives are summarized.


2021 ◽  
Vol 12 (4) ◽  
pp. 69
Author(s):  
Angelo V. Vasiliadis ◽  
Nikolaos Koukoulias ◽  
Konstantinos Katakalos

The meniscus is a critical component of a healthy knee joint. It is a complex and vital fibrocartilaginous tissue that maintains appropriate biomechanics. Injuries of the meniscus, particularly in the inner region, rarely heal and usually progress into structural breakdown, followed by meniscus deterioration and initiation of osteoarthritis. Conventional therapies range from conservative treatment, to partial meniscectomy and even meniscus transplantation. All the above have high long-term failure rates, with recurrence of symptoms. This communication presents a brief account of in vitro and in vivo studies and describes recent developments in the field of 3D-printed scaffolds for meniscus tissue engineering. Current research in meniscal tissue engineering tries to combine polymeric biomaterials, cell-based therapy, growth factors, and 3D-printed scaffolds to promote the healing of meniscal defects. Today, 3D-printing technology represents a big opportunity in the orthopaedic world to create more specific implants, enabling the rapid production of meniscal scaffolds and changing the way that orthopaedic surgeons plan procedures. In the future, 3D-printed meniscal scaffolds are likely to be available and will also be suitable substitutes in clinical applications, in an attempt to imitate the complexity of the native meniscus.


Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2146
Author(s):  
Jian Guan ◽  
Fu-zhen Yuan ◽  
Zi-mu Mao ◽  
Hai-lin Zhu ◽  
Lin Lin ◽  
...  

The limited self-healing ability of cartilage necessitates the application of alternative tissue engineering strategies for repairing the damaged tissue and restoring its normal function. Compared to conventional tissue engineering strategies, three-dimensional (3D) printing offers a greater potential for developing tissue-engineered scaffolds. Herein, we prepared a novel photocrosslinked printable cartilage ink comprising of polyethylene glycol diacrylate (PEGDA), gelatin methacryloyl (GelMA), and chondroitin sulfate methacrylate (CSMA). The PEGDA-GelMA-CSMA scaffolds possessed favorable compressive elastic modulus and degradation rate. In vitro experiments showed good adhesion, proliferation, and F-actin and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the scaffolds. When the CSMA concentration was increased, the compressive elastic modulus, GAG production, and expression of F-actin and cartilage-specific genes (COL2, ACAN, SOX9, PRG4) were significantly improved while the osteogenic marker genes of COL1 and ALP were decreased. The findings of the study indicate that the 3D-printed PEGDA-GelMA-CSMA scaffolds possessed not only adequate mechanical strength but also maintained a suitable 3D microenvironment for differentiation, proliferation, and extracellular matrix production of BMSCs, which suggested this customizable 3D-printed PEGDA-GelMA-CSMA scaffold may have great potential for cartilage repair and regeneration in vivo.


2020 ◽  
Vol 6 (1) ◽  
pp. 57-69
Author(s):  
Amirhosein Fathi ◽  
Farzad Kermani ◽  
Aliasghar Behnamghader ◽  
Sara Banijamali ◽  
Masoud Mozafari ◽  
...  

AbstractOver the last years, three-dimensional (3D) printing has been successfully applied to produce suitable substitutes for treating bone defects. In this work, 3D printed composite scaffolds of polycaprolactone (PCL) and strontium (Sr)- and cobalt (Co)-doped multi-component melt-derived bioactive glasses (BGs) were prepared for bone tissue engineering strategies. For this purpose, 30% of as-prepared BG particles (size <38 μm) were incorporated into PCL, and then the obtained composite mix was introduced into a 3D printing machine to fabricate layer-by-layer porous structures with the size of 12 × 12 × 2 mm3.The scaffolds were fully characterized through a series of physico-chemical and biological assays. Adding the BGs to PCL led to an improvement in the compressive strength of the fabricated scaffolds and increased their hydrophilicity. Furthermore, the PCL/BG scaffolds showed apatite-forming ability (i.e., bioactivity behavior) after being immersed in simulated body fluid (SBF). The in vitro cellular examinations revealed the cytocompatibility of the scaffolds and confirmed them as suitable substrates for the adhesion and proliferation of MG-63 osteosarcoma cells. In conclusion, 3D printed composite scaffolds made of PCL and Sr- and Co-doped BGs might be potentially-beneficial bone replacements, and the achieved results motivate further research on these materials.


2021 ◽  
Vol 7 (4) ◽  
pp. 444
Author(s):  
Pei Zhuang ◽  
Yi-Hua Chiang ◽  
Maria Serafim Fernanda ◽  
Mei He

Cancer still ranks as a leading cause of mortality worldwide. Although considerable efforts have been dedicated to anticancer therapeutics, progress is still slow, partially due to the absence of robust prediction models. Multicellular tumor spheroids, as a major three-dimensional (3D) culture model exhibiting features of avascular tumors, gained great popularity in pathophysiological studies and high throughput drug screening. However, limited control over cellular and structural organization is still the key challenge in achieving in vivo like tissue microenvironment. 3D bioprinting has made great strides toward tissue/organ mimicry, due to its outstanding spatial control through combining both cells and materials, scalability, and reproducibility. Prospectively, harnessing the power from both 3D bioprinting and multicellular spheroids would likely generate more faithful tumor models and advance our understanding on the mechanism of tumor progression. In this review, the emerging concept on using spheroids as a building block in 3D bioprinting for tumor modeling is illustrated. We begin by describing the context of the tumor microenvironment, followed by an introduction of various methodologies for tumor spheroid formation, with their specific merits and drawbacks. Thereafter, we present an overview of existing 3D printed tumor models using spheroids as a focus. We provide a compilation of the contemporary literature sources and summarize the overall advancements in technology and possibilities of using spheroids as building blocks in 3D printed tissue modeling, with a particular emphasis on tumor models. Future outlooks about the wonderous advancements of integrated 3D spheroidal printing conclude this review.


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.


2019 ◽  
Vol 6 (3) ◽  
pp. 59 ◽  
Author(s):  
Shicheng Ye ◽  
Jochem W.B. Boeter ◽  
Louis C. Penning ◽  
Bart Spee ◽  
Kerstin Schneeberger

Bioengineered livers are promising in vitro models for drug testing, toxicological studies, and as disease models, and might in the future be an alternative for donor organs to treat end-stage liver diseases. Liver tissue engineering (LTE) aims to construct liver models that are physiologically relevant. To make bioengineered livers, the two most important ingredients are hepatic cells and supportive materials such as hydrogels. In the past decades, dozens of hydrogels have been developed to act as supportive materials, and some have been used for in vitro models and formed functional liver constructs. However, currently none of the used hydrogels are suitable for in vivo transplantation. Here, the histology of the human liver and its relationship with LTE is introduced. After that, significant characteristics of hydrogels are described focusing on LTE. Then, both natural and synthetic materials utilized in hydrogels for LTE are reviewed individually. Finally, a conclusion is drawn on a comparison of the different hydrogels and their characteristics and ideal hydrogels are proposed to promote LTE.


2012 ◽  
Vol 91 (7) ◽  
pp. 642-650 ◽  
Author(s):  
K. Moharamzadeh ◽  
H. Colley ◽  
C. Murdoch ◽  
V. Hearnden ◽  
W.L. Chai ◽  
...  

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.


2018 ◽  
Vol 934 ◽  
pp. 129-133 ◽  
Author(s):  
Chao Fan Lv ◽  
Li Ya Zhu ◽  
Jian Ping Shi ◽  
Zong An Li ◽  
Wen Lai Tang ◽  
...  

Three-dimensional (3D) printing has been playing an important role in diverse areas in medicine. In order to promote the development of tissue engineering, this study attempts to fabricate tissue engineering scaffolds using the inkjet printing technology. Sodium alginate, exhibiting similar properties to the native human extracellular matrix (ECM), was used as bioink. The jetted fluid of sodium alginate would be gelatinized when printed into the calcium chloride solution. The characteristics of the 3D-printed sodium alginate scaffold were systematically measured and analyzed. The results show that, the pore size, porosity and degradation property of these scaffolds could be well controlled. This study indicates the capability of 3D bioprinting technology for preparing tissue engineering scaffolds.


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