Application areas of 3D bioprinting Ozbolat, Ibrahim T.; Peng, Weijie; Ozbolat, Veli
Drug discovery today,
August 2016, 2016-Aug, 2016-08-00, 20160801, Volume:
21, Issue:
8
Journal Article
Peer reviewed
Open access
•Bioprinting is a powerful technology in tissue and organ fabrication.•Bioprinting has gained significant interest in medicine and pharmaceutics.•Bioprinting has been widely used in various ...application areas.•Bioprinting technology is transiting to pharmaceutics and high-throughput screening.•Bioprinting for cancer research is an emerging direction.
Three dimensional (3D) bioprinting has been a powerful tool in patterning and precisely placing biologics, including living cells, nucleic acids, drug particles, proteins and growth factors, to recapitulate tissue anatomy, biology and physiology. Since the first time of cytoscribing cells demonstrated in 1986, bioprinting has made a substantial leap forward, particularly in the past 10 years, and it has been widely used in fabrication of living tissues for various application areas. The technology has been recently commercialized by several emerging businesses, and bioprinters and bioprinted tissues have gained significant interest in medicine and pharmaceutics. This Keynote review presents the bioprinting technology and covers a first-time comprehensive overview of its application areas from tissue engineering and regenerative medicine to pharmaceutics and cancer research.
Bioprinting is a powerful technology in the fabrication of living tissues and organs for tissue engineering and regenerative medicine, transplantation and clinics, pharmaceutics and high-throughput screening, as well as cancer research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Extrusion-based bioprinting (EBB) is a rapidly growing technology that has made substantial progress during the last decade. It has great versatility in printing various biologics, including ...cells, tissues, tissue constructs, organ modules and microfluidic devices, in applications from basic research and pharmaceutics to clinics. Despite the great benefits and flexibility in printing a wide range of bioinks, including tissue spheroids, tissue strands, cell pellets, decellularized matrix components, micro-carriers and cell-laden hydrogels, the technology currently faces several limitations and challenges. These include impediments to organ fabrication, the limited resolution of printed features, the need for advanced bioprinting solutions to transition the technology bench to bedside, the necessity of new bioink development for rapid, safe and sustainable delivery of cells in a biomimetically organized microenvironment, and regulatory concerns to transform the technology into a product. This paper, presenting a first-time comprehensive review of EBB, discusses the current advancements in EBB technology and highlights future directions to transform the technology to generate viable end products for tissue engineering and regenerative medicine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
3D bioprinting has emerged as a promising new approach for fabricating complex biological constructs in the field of tissue engineering and regenerative medicine. It aims to alleviate the hurdles of ...conventional tissue engineering methods by precise and controlled layer-by-layer assembly of biomaterials in a desired 3D pattern. The 3D bioprinting of cells, tissues, and organs Collection at Scientific Reports brings together a myriad of studies portraying the capabilities of different bioprinting modalities. This Collection amalgamates research aimed at 3D bioprinting organs for fulfilling demands of organ shortage, cell patterning for better tissue fabrication, and building better disease models.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Tissue engineering has been a promising field of research, offering hope for bridging the gap between organ shortage and transplantation needs. However, building three-dimensional (3-D) vascularized ...organs remains the main technological barrier to be overcome. Organ printing, which is defined as computer-aided additive biofabrication of 3-D cellular tissue constructs, has shed light on advancing this field into a new era. Organ printing takes advantage of rapid prototyping (RP) technology to print cells, biomaterials, and cell-laden biomaterials individually or in tandem, layer by layer, directly creating 3-D tissue-like structures. Here, we overview RP-based bioprinting approaches and discuss the current challenges and trends toward fabricating living organs for transplant in the near future.
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Successful launch of a commercial drug requires significant investment of time and financial resources wherein late-stage failures become a reason for catastrophic failures in drug ...discovery. This calls for infusing constant innovations in technologies, which can give reliable prediction of efficacy, and more importantly, toxicology of the compound early in the drug discovery process before clinical trials. Though computational advances have resulted in more rationale in silico designing, in vitro experimental studies still require gaining industry confidence and improving in vitro-in vivo correlations. In this quest, due to their ability to mimic the spatial and chemical attributes of native tissues, three-dimensional (3D) tissue models have now proven to provide better results for drug screening compared to traditional two-dimensional (2D) models. However, in vitro fabrication of living tissues has remained a bottleneck in realizing the full potential of 3D models. Recent advances in bioprinting provide a valuable tool to fabricate biomimetic constructs, which can be applied in different stages of drug discovery research. This paper presents the first comprehensive review of bioprinting techniques applied for fabrication of 3D tissue models for pharmaceutical studies. A comparative evaluation of different bioprinting modalities is performed to assess the performance and ability of fabricating 3D tissue models for pharmaceutical use as the critical selection of bioprinting modalities indeed plays a crucial role in efficacy and toxicology testing of drugs and accelerates the drug development cycle. In addition, limitations with current tissue models are discussed thoroughly and future prospects of the role of bioprinting in pharmaceutics are provided to the reader.
Present advances in tissue biofabrication have crucial role to play in aiding the pharmaceutical development process achieve its objectives. Advent of three-dimensional (3D) models, in particular, is viewed with immense interest by the community due to their ability to mimic in vivo hierarchical tissue architecture and heterogeneous composition. Successful realization of 3D models will not only provide greater in vitro-in vivo correlation compared to the two-dimensional (2D) models, but also eventually replace pre-clinical animal testing, which has their own shortcomings. Amongst all fabrication techniques, bioprinting- comprising all the different modalities (extrusion-, droplet- and laser-based bioprinting), is emerging as the most viable fabrication technique to create the biomimetic tissue constructs. Notwithstanding the interest in bioprinting by the pharmaceutical development researchers, it can be seen that there is a limited availability of comparative literature which can guide the proper selection of bioprinting processes and associated considerations, such as the bioink selection for a particular pharmaceutical study. Thus, this work emphasizes these aspects of bioprinting and presents them in perspective of differential requirements of different pharmaceutical studies like in vitro predictive toxicology, high-throughput screening, drug delivery and tissue-specific efficacies. Moreover, since bioprinting techniques are mostly applied in regenerative medicine and tissue engineering, a comparative analysis of similarities and differences are also expounded to help researchers make informed decisions based on contemporary literature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. ...Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader.
Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision, which holds a great promise in fabrication of vascular or vascularized tissues for transplantation use. Although a great progress has recently been made on building perfusable tissues and branched vascular network, a comprehensive review on the state-of-the-art in vascular and vascularized tissue bioprinting has not reported so far. This contribution is thus significant because it discusses the use of three major bioprinting modalities in vascular tissue biofabrication for the first time in the literature and compares their strengths and limitations in details. Moreover, the use of scaffold-based and scaffold-free bioprinting is expounded within the domain of vascular tissue fabrication.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This paper discusses "bioink", bioprintable materials used in three dimensional (3D) bioprinting processes, where cells and other biologics are deposited in a spatially controlled pattern to ...fabricate living tissues and organs. It presents the first comprehensive review of existing bioink types including hydrogels, cell aggregates, microcarriers and decellularized matrix components used in extrusion-, droplet- and laser-based bioprinting processes. A detailed comparison of these bioink materials is conducted in terms of supporting bioprinting modalities and bioprintability, cell viability and proliferation, biomimicry, resolution, affordability, scalability, practicality, mechanical and structural integrity, bioprinting and post-bioprinting maturation times, tissue fusion and formation post-implantation, degradation characteristics, commercial availability, immune-compatibility, and application areas. The paper then discusses current limitations of bioink materials and presents the future prospects to the reader.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Improving the ability to predict the efficacy and toxicity of drug candidates earlier in the drug discovery process will speed up the introduction of new drugs into clinics. 3D in vitro systems have ...significantly advanced the drug screening process as 3D tissue models can closely mimic native tissues and, in some cases, the physiological response to drugs. Among various in vitro systems, bioprinting is a highly promising technology possessing several advantages such as tailored microarchitecture, high-throughput capability, coculture ability, and low risk of cross-contamination. In this opinion article, we discuss the currently available tissue models in pharmaceutics along with their limitations and highlight the possibilities of bioprinting physiologically relevant tissue models, which hold great potential in drug testing, high-throughput screening, and disease modeling.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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Stem cell encapsulation in hydrogels has been widely employed in tissue engineering, regenerative medicine, organ-on-a-chip devices and gene delivery; however, fabrication of ...native-like bone tissue using such a strategy has been a challenge, particularly in vitro, due to the limited cell loading densities resulting in weaker cell-cell interactions and lesser extra-cellular matrix deposition. In particular, scalable bone tissue constructs require vascular network to provide enough oxygen and nutrient supplies to encapsulated cells. To enhance stem cell function and generate pre-vascularized network, we here employed collagen/fibrin hydrogel as an encapsulation matrix for the incorporation of human mesenchymal stem cell/human umbilical vein endothelial cell (MSC/HUVEC) spheroids, and investigated their cellular behavior (including cell viability, morphology, proliferation, and gene expression profile) and compared to that of cell suspension- or MSC spheroids-laden hydrogels. MSC/HUVEC spheroids encapsulated in collagen/fibrin hydrogel showed better cell spreading and proliferation, and up-regulated osteogenic differentiation, and demonstrated pre-vascular network formation. Overall, MSC/HUVEC spheroids-laden hydrogels provided a highly suitable 3D microenvironment for bone tissue formation, which can be utilized in various applications, such as but not limited to tissue engineering, disease modeling and drug screening.
Stem cell encapsulation in hydrogels has been widely used in various areas such as tissue engineering, regenerative medicine, organ-on-a-chip devices and gene delivery; however, fabrication of native-like bone tissue using such an approach has been a challenge, particularly in vitro, due to the limited cell loading densities resulting in weaker cell-cell interactions and lesser extra-cellular matrix deposition. Here in this work, we have encapsulated spheroids of human mesenchymal stems cells (MSCs) in collagen/fibrin hydrogel and evaluated their viability, proliferation, osteogenic differentiation, and bone formation potential in vitro with respect to cell suspension-laden hydrogel samples. We have further incorporated human umbilical vein endothelial cells (HUVECs) into MSC spheroids and demonstrated that the presence of HUVECs in 3D spheroid culture in collagen/fibrin gel induced the formation of pre-vascular network, improved cell viability and proliferation, enhanced the osteogenic differentiation of spheroids, and increased their bone mineral deposition. In sum, MSC/HUVEC spheroids laden hydrogels provided a highly suitable 3D microenvironment for bone tissue formation, which can be utilized in various applications, such as but not limited to tissue engineering and regenerative medicine, disease modeling and drug screening.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Biofabricated tissues have found numerous applications in tissue engineering and regenerative medicine in addition to the promotion of disease modeling and drug development and screening. Although ...three-dimensional (3D) printing strategies for designing and developing customized tissue constructs have made significant progress, the complexity of innate multicellular tissues hinders the accurate evaluation of physiological responses in vitro. Cellular aggregates, such as spheroids, are 3D structures where multiple types of cells are co-cultured and organized with endogenously secreted extracellular matrix and are designed to recapitulate the key features of native tissues more realistically. 3D Bioprinting has emerged as a crucial tool for positioning of these spheroids to assemble and organize them into physiologically- and histologically-relevant tissues, mimicking their native counterparts. This has triggered the convergence of spheroid fabrication and bioprinting, leading to the investigation of novel engineering methods for successful assembly of spheroids while simultaneously enhancing tissue repair. This review provides an overview of the current state-of-the-art in spheroid bioprinting methods and elucidates the involved technologies, intensively discusses the recent tissue fabrication applications, outlines the crucial properties that influence the bioprinting of these spheroids and bioprinted tissue characteristics, and finally details the current challenges and future perspectives of spheroid bioprinting efforts in the growing field of biofabrication.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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