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Journal ArticleDOI

Adult Stem Cells Spheroids to Optimize Cell Colonization in Scaffolds for Cartilage and Bone Tissue Engineering

TL;DR: An automated combinatorial approach that integrates spheroids into scaffolds is starting to be investigated for macro-scale tissue biofabrication.
Abstract: Top-down tissue engineering aims to produce functional tissues using biomaterials as scaffolds, thus providing cues for cell proliferation and differentiation. Conversely, the bottom-up approach aims to precondition cells to form modular tissues units (building-blocks) represented by spheroids. In spheroid culture, adult stem cells are responsible for their extracellular matrix synthesis, re-creating structures at the tissue level. Spheroids from adult stem cells can be considered as organoids, since stem cells recapitulate differentiation pathways and also represent a promising approach for identifying new molecular targets (biomarkers) for diagnosis and therapy. Currently, spheroids can be used for scaffold-free (developmental engineering) or scaffold-based approaches. The scaffold promotes better spatial organization of individual spheroids and provides a defined geometry for their 3D assembly in larger and complex tissues. Furthermore, spheroids exhibit potent angiogenic and vasculogenic capacity and serve as efficient vascularization units in porous scaffolds for bone tissue engineering. An automated combinatorial approach that integrates spheroids into scaffolds is starting to be investigated for macro-scale tissue biofabrication.
Citations
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01 Jan 2009
TL;DR: Organ printing can be defined as layer-by-layer additive robotic biofabrication of three-dimensional functional living macrotissues and organ constructs using tissue spheroids as building blocks.
Abstract: Organ printing can be defined as layer-by-layer additive robotic biofabrication of three-dimensional functional living macrotissues and organ constructs using tissue spheroids as building blocks. The microtissues and tissue spheroids are living materials with certain measurable, evolving and potentially controllable composition, material and biological properties. Closely placed tissue spheroids undergo tissue fusion - a process that represents a fundamental biological and biophysical principle of developmental biology-inspired directed tissue self-assembly. It is possible to engineer small segments of an intraorgan branched vascular tree by using solid and lumenized vascular tissue spheroids. Organ printing could dramatically enhance and transform the field of tissue engineering by enabling large-scale industrial robotic biofabrication of living human organ constructs with "built-in" perfusable intraorgan branched vascular tree. Thus, organ printing is a new emerging enabling technology paradigm which represents a developmental biology-inspired alternative to classic biodegradable solid scaffold-based approaches in tissue engineering.

942 citations

Journal ArticleDOI
TL;DR: This review, encompassing the fundamental concepts of regenerative medicine, is intended to provide a comprehensive portrait of important progress in stem cell research and development.
Abstract: Over the past 20 years, and particularly in the last decade, significant developmental milestones have driven basic, translational, and clinical advances in the field of stem cell and regenerative medicine. In this article, we provide a systemic overview of the major recent discoveries in this exciting and rapidly developing field. We begin by discussing experimental advances in the generation and differentiation of pluripotent stem cells (PSCs), next moving to the maintenance of stem cells in different culture types, and finishing with a discussion of three-dimensional (3D) cell technology and future stem cell applications. Specifically, we highlight the following crucial domains: 1) sources of pluripotent cells; 2) next-generation in vivo direct reprogramming technology; 3) cell types derived from PSCs and the influence of genetic memory; 4) induction of pluripotency with genomic modifications; 5) construction of vectors with reprogramming factor combinations; 6) enhancing pluripotency with small molecules and genetic signaling pathways; 7) induction of cell reprogramming by RNA signaling; 8) induction and enhancement of pluripotency with chemicals; 9) maintenance of pluripotency and genomic stability in induced pluripotent stem cells (iPSCs); 10) feeder-free and xenon-free culture environments; 11) biomaterial applications in stem cell biology; 12) three-dimensional (3D) cell technology; 13) 3D bioprinting; 14) downstream stem cell applications; and 15) current ethical issues in stem cell and regenerative medicine. This review, encompassing the fundamental concepts of regenerative medicine, is intended to provide a comprehensive portrait of important progress in stem cell research and development. Innovative technologies and real-world applications are emphasized for readers interested in the exciting, promising, and challenging field of stem cells and those seeking guidance in planning future research direction.

257 citations

Journal Article
TL;DR: In this article, the authors provide an overview of the recent trends in the preparation of injectable hydrogels, along with key factors to be kept in balance for designing an effective injectable hyrogel system.

229 citations

Journal ArticleDOI
TL;DR: This hybrid approach allows more complex mechanics and discrete biomimetic structures to address mechanotransduction and chemotactic/haptotactic cues and recent trends toward future manufacturing platforms are analyzed.
Abstract: The diversity of manufacturing processes used to fabricate 3D implants, scaffolds, and tissue constructs is continuously increasing. This growing number of different applicable fabrication technologies include electrospinning, melt electrowriting, volumetric-, extrusion-, and laser-based bioprinting, the Kenzan method, and magnetic and acoustic levitational bioassembly, to name a few. Each of these fabrication technologies feature specific advantages and limitations, so that a combination of different approaches opens new and otherwise unreachable opportunities for the fabrication of hierarchical cell-material constructs. Ongoing challenges such as vascularization, limited volume, and repeatability of tissue constructs at the resolution required to mimic natural tissue is most likely greater than what one manufacturing technology can overcome. Therefore, the combination of at least two different manufacturing technologies is seen as a clear and necessary emerging trend, especially within biofabrication. This hybrid approach allows more complex mechanics and discrete biomimetic structures to address mechanotransduction and chemotactic/haptotactic cues. Pioneering milestone papers in hybrid fabrication for biomedical purposes are presented and recent trends toward future manufacturing platforms are analyzed.

81 citations

Journal ArticleDOI
TL;DR: A new system for engineering cell spheroids by self-assembly of micro-scale monolayer of stem cells, which may have versatile applications in regenerative medicine for functionally improved 3D culture and therapeutic cell delivery.

79 citations

References
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Journal ArticleDOI
TL;DR: It is believed that 3D cultures will have a strong impact on drug screening and will also decrease the use of laboratory animals, for example, in the context of toxicity assays.
Abstract: Cell monolayers have serious limitations for cell biological investigations and for cell-based assays in drug screening and toxicity studies. However, the establishment of three-dimensional cultures as a mainstream approach requires the development of reliable protocols, new cell lines and suitable imaging techniques.

2,413 citations

Journal ArticleDOI
TL;DR: The state-of-the-art of topological design and manufacturing processes of various types of porous metals, in particular for titanium alloys, biodegradable metals and shape memory alloys are reviewed.

1,393 citations


"Adult Stem Cells Spheroids to Optim..." refers background in this paper

  • ...However, implanted scaffolds produced from metal materials are generally stiffer compared to live bones, leading to eventual failure of implants [34]....

    [...]

Journal ArticleDOI
TL;DR: Combined with recent advances in human pluripotent stem cell technologies, 3D-bioprinted tissue models could serve as an enabling platform for high-throughput predictive drug screening and more effective regenerative therapies.

1,130 citations


"Adult Stem Cells Spheroids to Optim..." refers background or methods in this paper

  • ...Scaffolds must recreate extracellular matrix in which cells in spheroids can adhere, proliferate, and differentiate [15]....

    [...]

  • ...Recently, spheroids have been used in the following ways (1) in tissue engineering, as a model of organogenesis, better known as developmental engineering [12–14]; (2) they have been seeded into biomaterials to improve tissue regeneration in vivo [15]; and (3) they have been used as building blocks for bioprinting and bioassembly approaches [16]....

    [...]

Journal ArticleDOI
TL;DR: Organ printing is a new emerging enabling technology paradigm which represents a developmental biology-inspired alternative to classic biodegradable solid scaffold-based approaches in tissue engineering.

1,043 citations


"Adult Stem Cells Spheroids to Optim..." refers methods in this paper

  • ...Recently, spheroids have been used in the following ways (1) in tissue engineering, as a model of organogenesis, better known as developmental engineering [12–14]; (2) they have been seeded into biomaterials to improve tissue regeneration in vivo [15]; and (3) they have been used as building blocks for bioprinting and bioassembly approaches [16]....

    [...]

01 Jan 2009
TL;DR: Organ printing can be defined as layer-by-layer additive robotic biofabrication of three-dimensional functional living macrotissues and organ constructs using tissue spheroids as building blocks.
Abstract: Organ printing can be defined as layer-by-layer additive robotic biofabrication of three-dimensional functional living macrotissues and organ constructs using tissue spheroids as building blocks. The microtissues and tissue spheroids are living materials with certain measurable, evolving and potentially controllable composition, material and biological properties. Closely placed tissue spheroids undergo tissue fusion - a process that represents a fundamental biological and biophysical principle of developmental biology-inspired directed tissue self-assembly. It is possible to engineer small segments of an intraorgan branched vascular tree by using solid and lumenized vascular tissue spheroids. Organ printing could dramatically enhance and transform the field of tissue engineering by enabling large-scale industrial robotic biofabrication of living human organ constructs with "built-in" perfusable intraorgan branched vascular tree. Thus, organ printing is a new emerging enabling technology paradigm which represents a developmental biology-inspired alternative to classic biodegradable solid scaffold-based approaches in tissue engineering.

942 citations