Aspiration-assisted bioprinting of the osteochondral interface

Ayan, Bugra; Wu, Yang; Karuppagounder, Vengadeshprabhu; Kamal, Fadia; Özbolat, İbrahim T.

doi:10.1038/s41598-020-69960-6

Cited by 56 publications

(35 citation statements)

References 60 publications

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“…[66][67][68] Aspiration-assisted bioprinting was employed to 3D bioprint a representative tumor model in fibrin highlighting the effect of proximity of multiple tumors on collective tumor angiogenesis and cancer invasion. [69][70][71][72] Tumor spheroids were aspirated from media by applying a critical lifting pressure, which was determined by the surface tension of spheroids. Surface tension correlates well with the mechanical properties and compactness of spheroids.…”

Section: Discussionmentioning

confidence: 99%

Studying Tumor Angiogenesis and Cancer Invasion in a Three‐Dimensional Vascularized Breast Cancer Micro‐Environment

et al. 2021

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Metastatic breast cancer is one of the deadliest forms of malignancy, primarily driven by its characteristic micro‐environment comprising cancer cells interacting with stromal components. These interactions induce genetic and metabolic alterations creating a conducive environment for tumor growth. In this study, a physiologically relevant 3D vascularized breast cancer micro‐environment is developed comprising of metastatic MDA‐MB‐231 cells and human umbilical vein endothelial cells loaded in human dermal fibroblasts laden fibrin, representing the tumor stroma. The matrix, as well as stromal cell density, impacts the transcriptional profile of genes involved in tumor angiogenesis and cancer invasion, which are hallmarks of cancer. Cancer‐specific canonical pathways and activated upstream regulators are also identified by the differential gene expression signatures of these composite cultures. Additionally, a tumor‐associated vascular bed of capillaries is established exhibiting dilated vessel diameters, representative of in vivo tumor physiology. Further, employing aspiration‐assisted bioprinting, cancer–endothelial crosstalk, in the form of collective angiogenesis of tumor spheroids bioprinted at close proximity, is identified. Overall, this bottom–up approach of tumor micro‐environment fabrication provides an insight into the potential of in vitro tumor models and enables the identification of novel therapeutic targets as a preclinical drug screening platform.

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Section: Discussionmentioning

confidence: 99%

Studying Tumor Angiogenesis and Cancer Invasion in a Three‐Dimensional Vascularized Breast Cancer Micro‐Environment

et al. 2021

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“…Subsequently, another layer of chondrogenic spheroids was deposited onto a previous osteogenic layer. It is worth noting that the spheroids in individual layers can fuse together and the phenotypes in both zones can maintain through the study ( Figure 3(b) ) [ 27 ]. Similar to cell spheroids, different microgels encapsulating stem cells can be utilized as building blocks to form a predefined tissue with a spatial controlled cell type and gradient structure [ 12 , 28 , 29 ].…”

Section: Overcoming Clinical Challenges From Administration and DImentioning

confidence: 99%

“…(b) Characteristics of the bioprinted OC interface and the zone of cartilage and subchondral bone. Reproduced with permission [ 26 , 27 ].…”

Section: Figurementioning

confidence: 99%

Bioengineering Approaches to Accelerate Clinical Translation of Stem Cell Therapies Treating Osteochondral Diseases

Wang

Luo

et al. 2020

Stem Cells International

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The osteochondral tissue is an interface between articular cartilage and bone. The diverse composition, mechanical properties, and cell phenotype in these two tissues pose a big challenge for the reconstruction of the defected interface. Due to the availability and inherent regenerative therapeutic properties, stem cells provide tremendous promise to repair osteochondral defect. This review is aimed at highlighting recent progress in utilizing bioengineering approaches to improve stem cell therapies for osteochondral diseases, which include microgel encapsulation, adhesive bioinks, and bioprinting to control the administration and distribution. We will also explore utilizing synthetic biology tools to control the differentiation fate and deliver therapeutic biomolecules to modulate the immune response. Finally, future directions and opportunities in the development of more potent and predictable stem cell therapies for osteochondral repair are discussed.

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“…[ 2,6 ] Cell spheroids have also been trending as tissue engineering building blocks to replace single‐cell printing, [ 7 ] where their complex composition, prolonged survival and fusion capacity are used to reconstruct various tissues, from branched blood vessel [ 8 ] to thyroid gland [ 9 ] and osteochondral interface. [ 10 ]…”

Section: Introductionmentioning

confidence: 99%

“…[2,6] Cell spheroids have also been trending as tissue engineering building blocks to replace single-cell printing, [7] where their complex composition, prolonged survival and fusion capacity are used to reconstruct various tissues, from branched blood vessel [8] to thyroid gland [9] and osteochondral interface. [10] The scalable application of spheroids in the above-mentioned studies necessitates a high-throughput production method with consistent physiological and morphological characteristics. The standard spheroid formation methods include hanging droplets, agitation-based systems, culture on non-adherent surfaces, and scaffold-based fabrication.…”

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confidence: 99%

Rapid Formation of Multicellular Spheroids in Boundary‐Driven Acoustic Microstreams

Rasouli

Tabrizian

2021

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cell-matrix. These unique characteristics render spheroids the optimal candidate for numerous fundamental studies and biomedical applications including the development of pre-clinical models for drug discovery, regenerative medicine, and tissue engineering. [1,2] Spheroids of cancer cells, also known as tumoroids, are emerging as preferred models for the investigation of anticancer therapeutics' response, as they provide analogous spatial architecture, diffusion gradient, tumor dynamics, metabolic activity, and drug resistance behavior of solid tumors. [3][4][5] In a similar vein, spheroids of stem cells are also largely investigated owing to their higher cell viability, proliferation, stemness, and regenerative characteristic compared to 2D culture. [2,6] Cell spheroids have also been trending as tissue engineering building blocks to replace single-cell printing, [7] where their complex composition, prolonged survival and fusion capacity are used to reconstruct various tissues, from branched blood vessel [8] to thyroid gland [9] and osteochondral interface. [10] The scalable application of spheroids in the above-mentioned studies necessitates a high-throughput production method with consistent physiological and morphological characteristics. The standard spheroid formation methods include hanging droplets, agitation-based systems, culture on non-adherent surfaces, and scaffold-based fabrication. [11,12] These methods are generally labor-intensive, low-yield, time-consuming, and show heterogeneous spheroids in shape and size due to poor control of the process which limits their scaled-up application. [13,14] Microfluidics has shown the capacity to overcome some of the technical hurdles in spheroid formation by offering controlled physical conditions, minimized cells and reagent consumption, high sensitivity in drug screening, precise manipulation of cells, continuous perfusion, and regulation of the nutrients and oxygen supply. [15][16][17] These advantages coupled with decreasing user-device interaction, compatibility for automation, low fabrication and operation costs make microfluidics an attractive tool for producing high throughput and uniform spheroids desirable for clinical translation. [18,19] Generally, spheroid formation starts with the physical agglomeration of cells. Next, cell-membrane integrins bind to long-chain extracellular matrix (ECM) fibers of adjoining cells 3D cell spheroid culture has emerged as a more faithful recreation of cell growth environment compared to conventional 2D culture, as it can maintain tissue structures, physicochemical characteristics, and cell phenotypes. The majority of current spheroid formation methods are limited to a physical agglomeration of the desired cell type, and then relying on cell capacity to secrete extracellular matrix to form coherent spheroids. Hence, apart from being time-consuming, their success in leading to functional spheroid formation is also cell-type dependent. In this study, a boundarydriven acoustic microstreaming tool is presented that can si...

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Aspiration-assisted bioprinting of the osteochondral interface

Cited by 56 publications

References 60 publications

Studying Tumor Angiogenesis and Cancer Invasion in a Three‐Dimensional Vascularized Breast Cancer Micro‐Environment

Studying Tumor Angiogenesis and Cancer Invasion in a Three‐Dimensional Vascularized Breast Cancer Micro‐Environment

Bioengineering Approaches to Accelerate Clinical Translation of Stem Cell Therapies Treating Osteochondral Diseases

Rapid Formation of Multicellular Spheroids in Boundary‐Driven Acoustic Microstreams

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