The utility of biomedical scaffolds laden with spheroids in various tissue engineering applications

Chae, SooJung; Hong, Jisu; Hwangbo, Hanjun; Kim, GeunHyung

doi:10.7150/thno.58421

Cited by 38 publications

(58 citation statements)

References 108 publications

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“…This is probably due to the fact that cells in 3D culture experience a heterogeneous environment in regards to nutrient supply, oxygen availability, and waste disposal which is ultimately dictated by spheroid size. 22,45,48,49 As cell number increases, poor oxygenation and nutrient depletion lead to the formation of a necrotic core. 9,28,45,50 It has been suggested that the limit of oxygen diffusion in vivo is 200 µm with poor conditions found at the core of spheroids larger than 400 µm.…”

Section: Discussionmentioning

confidence: 99%

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Human iPSC-Vascular Smooth Muscle Cell Spheroids Demonstrate Size-dependent Alterations in Cellular Viability and Secretory Function

Islam

Parker

Dash

et al. 2022

Preprint

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Human induced pluripotent stem cells and their differentiated vascular cells have been revolutionizing the field of regenerative wound healing. These cells are shown to be rejuvenated with immense potentials in secreting paracrine factors. Recently, hiPSC-derived vascular smooth muscle cells (hiPSC-VSMC) have shown regenerative wound healing ability via their paracrine secretion. The quest to modulate the secretory function of these hiPSC-VSMC is an ongoing effort and involves the use of both biochemical and biophysical stimuli. This study explores the development and optimization of a reproducible, inexpensive protocol to form hiPSC-VSMC derived spheroids to investigate the implications of spheroid size on viability and paracrine secretion. Our data shows the successful formation of different sizes of spheroids using various amount of hiPSC-VSMC. The hiPSC-VSMC spheroids formed with 10000 cells strike an ideal balance between overall cell health and maximal paracrine secretion. The conditioned medium from these spheroids was found to be bioactive in enhancing human dermal fibroblast cell proliferation and migration. This research will inform future studies on the optimal spheroid size for regenerative wound healing applications.

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Section: Discussionmentioning

confidence: 99%

“…3,4,6,8,9,[18][19][20][21] They also have higher levels of tissue-specific gene expression and increased exosome production. 10,22 Overall, spheroids enhance biological processes relating to immunity, inflammation, angiogenesis, and wound healing. 14,[23][24][25][26] A previous study by Murphy et.…”

Section: Introductionmentioning

confidence: 99%

Human iPSC-Vascular Smooth Muscle Cell Spheroids Demonstrate Size-dependent Alterations in Cellular Viability and Secretory Function

Islam

Parker

Dash

et al. 2022

Preprint

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“…Although spheroids were not widely explored in AF tissue engineering, recent developments expanded the possibilities for spheroid-biomaterial seeding in related areas of musculoskeletal repair. In bone tissue engineering, foaming/freeze-drying techniques were used to produce scaffold microporosity that promoted spheroid penetration into the scaffold and fixed them in place [ 16 , 17 ]. Spheroids were also generated in situ in a novel porous PLGA/CS scaffold obtained after lyophilization.…”

Section: Spheroid-based Cell Therapies For Degenerative Disc Diseasementioning

confidence: 99%

“…Recent developments in other fields of tissue engineering demonstrate that spheroid-based approaches could help overcome some of these challenges due to their superior regenerative performance and/or resistance when compared to single cells [ 16 , 17 ]. Spheroids are self-assembling living microtissues based on multicellular aggregates that mature by the formation of intercellular contacts on non-adhesive substrates [ 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

“…Spheroids have the intrinsic capacity to fuse, which allows for structural and functional integration of spheroid-based grafts. Spheroids have been used in combination with biomaterials or alone as scaffold-free products [ 17 ]. Spheroid-based technology is in clinical use for articular cartilage repair and under investigation for regeneration of skin, blood vessels, and other tissues, supporting the feasibility and translational potential of this strategy for IVD regeneration [ 17 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Spheroid-Based Tissue Engineering Strategies for Regeneration of the Intervertebral Disc

Kasamkattil

Gryadunova

Martin

et al. 2022

IJMS

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Degenerative disc disease, a painful pathology of the intervertebral disc (IVD), often causes disability and reduces quality of life. Although regenerative cell-based strategies have shown promise in clinical trials, none have been widely adopted clinically. Recent developments demonstrated that spheroid-based approaches might help overcome challenges associated with cell-based IVD therapies. Spheroids are three-dimensional multicellular aggregates with architecture that enables the cells to differentiate and synthesize endogenous ECM, promotes cell-ECM interactions, enhances adhesion, and protects cells from harsh conditions. Spheroids could be applied in the IVD both in scaffold-free and scaffold-based configurations, possibly providing advantages over cell suspensions. This review highlights areas of future research in spheroid-based regeneration of nucleus pulposus (NP) and annulus fibrosus (AF). We also discuss cell sources and methods for spheroid fabrication and characterization, mechanisms related to spheroid fusion, as well as enhancement of spheroid performance in the context of the IVD microenvironment.

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Remote Magnetic Microengineering and Alignment of Spheroids into 3D Cellular Fibers

Demri

Dumas

Nguyen

et al. 2022

Adv Funct Materials

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Developing in vitro models that recapitulate the in vivo organization of living cells in a 3D microenvironment is one of the current challenges in the field of tissue engineering. In particular for anisotropic tissues where alignment of precursor cells is required for them to create functional structures. Herein, a new method is proposed that allows aligning in the direction of a uniform magnetic field both individual cells (muscle, stromal, and stem cells) or spheroids in a thermoresponsive collagen hydrogel. In an all-in-one approach, spheroids are generated at high throughput by magnetic engineering using microfabricated micromagnets and are used as building blocks to create 3D anisotropic tissue structures of different scales. The magnetic cells and spheroids alignment process is optimized in terms of magnetic cell labeling, concentration, and size. Anisotropic structures are induced to form fibers in the direction of the magnetic alignment, with the respective roles of the magnetic field, the mechanical stretching of hydrogel or co-culture of the aligned cells with non-magnetic stromal cells, being investigated. Over days, spheroids fuse into 3D tubular structures, oriented in the direction of the magnetic alignment. Moreover, in the case of the muscle cells model, multinucleated cells can be observed within the fibers.

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The utility of biomedical scaffolds laden with spheroids in various tissue engineering applications

Cited by 38 publications

References 108 publications

Human iPSC-Vascular Smooth Muscle Cell Spheroids Demonstrate Size-dependent Alterations in Cellular Viability and Secretory Function

Human iPSC-Vascular Smooth Muscle Cell Spheroids Demonstrate Size-dependent Alterations in Cellular Viability and Secretory Function

Spheroid-Based Tissue Engineering Strategies for Regeneration of the Intervertebral Disc

Remote Magnetic Microengineering and Alignment of Spheroids into 3D Cellular Fibers

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