Single-Cell Microgels: Technology, Challenges, and Applications

Kamperman, Tom; Karperien, Marcel; Gac, Séverine Le; Leijten, Jeroen

doi:10.1016/j.tibtech.2018.03.001

Cited by 73 publications

(65 citation statements)

References 108 publications

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“…To enhance residence time, Mao et al recently demonstrated a microencapsulation technique, in which individual MSCs were encapsulated in alginate-poly- d -lysine (PDL)-alginate (APA) microgels (particulate hydrogels with dimensions in the range of 30 to 50 μm). Using a single-cell microgel encapsulation approach has several distinct advantages compared to typical larger multicellular hydrogels for systemic administrations: The advantages include a reduced fibrotic capsule formation, a reduction in diffusion limitations that lead to hypoxic effects, and a higher surface area to volume ratio, which facilitates the release of biologics from encapsulated cells ( 125 ). Specifically, in the study by Mao et al , unlike a regular hydrogel that has a large volume and is not suitable for intravenous injection, the encapsulating microgel layer is on the order of 10 μm and can be easily injected intravenously.…”

Section: Overcoming Clinical Challenges From Administrationmentioning

confidence: 99%

Shattering barriers toward clinically meaningful MSC therapies

et al. 2020

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More than 1050 clinical trials are registered at FDA.gov that explore multipotent mesenchymal stromal cells (MSCs) for nearly every clinical application imaginable, including neurodegenerative and cardiac disorders, perianal fistulas, graft-versus-host disease, COVID-19, and cancer. Several companies have or are in the process of commercializing MSC-based therapies. However, most of the clinical-stage MSC therapies have been unable to meet primary efficacy end points. The innate therapeutic functions of MSCs administered to humans are not as robust as demonstrated in preclinical studies, and in general, the translation of cell-based therapy is impaired by a myriad of steps that introduce heterogeneity. In this review, we discuss the major clinical challenges with MSC therapies, the details of these challenges, and the potential bioengineering approaches that leverage the unique biology of MSCs to overcome the challenges and achieve more potent and versatile therapies.

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Section: Overcoming Clinical Challenges From Administrationmentioning

confidence: 99%

Shattering barriers toward clinically meaningful MSC therapies

et al. 2020

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“…The bottom‐up assembly of microtissues allows in situ printing or implantation of replacement organs or therapeutic agents such as stem cells to be delivered in a noninvasive or mini‐invasive manner. Hydrogel microparticles encapsulating therapeutic stem cells has been found to significantly increase the retention rate of such cells at the transplant site . Scarless wound healing has been a challenge associated with many surgical procedures, but may be avoided by in situ assembly of modular microtissues via mini‐invasive transplantation.…”

Section: Challenges and The Future Directionsmentioning

confidence: 99%

“…Scarless wound healing has been a challenge associated with many surgical procedures, but may be avoided by in situ assembly of modular microtissues via mini‐invasive transplantation. Moreover, it was found that the cell‐laden microgels (soft microtissues) smaller than 100 µm in diameter had dramatically reduced effect as implants to induce fibrosis, compared with larger implants . Finally, microgels are capable of providing immunoprotection and meanwhile allowing efficient insulin release from encapsulated islet cells …”

Section: Challenges and The Future Directionsmentioning

confidence: 99%

Microfluidics Fabrication of Soft Microtissues and Bottom‐Up Assembly

Mukherjee

2018

Adv. Biosys.

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recapitulate the structure, cellular organization, and functions of their native counterparts. Though the size is usually up to three orders of magnitude smaller than the native organs, the miniaturized organ model retrieves the multicellular and cellmatrix interactions, and holds the promise to recapitulate some critical functions of native organs. [8] On the other hand, shortage of organs available for transplantation, and the risk of infection and organ rejection coupled with allotransplantation-associated immunosuppression call for the development of engineered organs based on acceptor's genetic information and tissue material (like patient-induced pluripotent stem cell derived differentiated cell lines). [11,12] Modular assembly of microtissues, [13] either in vitro followed by culture and transplantation, or in vivo, such as in situ printing, [14] has become a promising approach to engineer artificial organs across a wide range of scales for regeneration or repair purposes.Hydrogels are a class of polymeric materials that hold large amounts of water in the 3D networks, and have been widely used as the artificial biomaterial to mimic the cellular environment supporting the living tissue networks. [15][16][17] Hydrogels can be either natural or synthetic. [17] Here, we will primarily introduce the microfluidics-based fabrication of hydrogel microtissues in the form of modular structures and microfibers, with a particular focus on one specific class of materials that provides a more native environment to cells, the extracellular matrix (ECM) or ECM-like materials. [18] Microfluidics is a revolutionary platform that manipulates fluids across a wide range of viscosity, [19,20] and has emerged as a powerful technique to miniaturize fluids into microscale and manipulate the fluids online, including mixing, merging, splitting and reaction, etc. [20][21][22] The continuous flow manner can produce various microfibers, [23] whereas droplet-based microfluidics which carriers the hydrogel precursor in discrete manners allows the high-throughput production of monodisperse modular microstructures variable in size, shape, and composition. [24] Microfluidics Fabrication of Soft Microtissues and the Bottom-Up AssemblyMicrotissues are cell-laden solid microstructures gelled from hydrogel precursor solutions, adopting and maintaining identical shapes before and after gelation. Normally, cells are loaded into Soft microtissues comprising living cells and supportive matrices have attracted the attention of researchers for their potential as in vitro organ models that represent the patient's tissue heterogeneity, as well as building blocks for artificial organs or regenerative tissues. Microfluidics is known for its capability to produce monodisperse microstructures in high-throughput. This review summarizes the progress on microfluidics fabrication of hydrogel-based microstructures and soft microtissues, and the challenges faced by this field. It mainly focuses on the strengths and limitations of microfluidics fabrication of ex...

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“…This deepened understanding of tissue‐specific microenvironments and recognition of their fundamental modular nature has revealed that different cell populations and their supportive extracellular matrix (ECM) represent the core effectors in human biological systems and are essential for life . During the processes of organogenesis and morphogenesis, such elements self‐orchestrate tissue development from a nano‐ to macrostructural organization in a dynamic mode involving both cell–cell crosstalk (e.g., via soluble mediators, vesicles, etc.)…”

Section: Introductionmentioning

confidence: 99%

Advanced Bottom‐Up Engineering of Living Architectures

et al. 2019

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Bottom‐up tissue engineering is a promising approach for designing modular biomimetic structures that aim to recapitulate the intricate hierarchy and biofunctionality of native human tissues. In recent years, this field has seen exciting progress driven by an increasing knowledge of biological systems and their rational deconstruction into key core components. Relevant advances in the bottom‐up assembly of unitary living blocks toward the creation of higher order bioarchitectures based on multicellular‐rich structures or multicomponent cell–biomaterial synergies are described. An up‐to‐date critical overview of long‐term existing and rapidly emerging technologies for integrative bottom‐up tissue engineering is provided, including discussion of their practical challenges and required advances. It is envisioned that a combination of cell–biomaterial constructs with bioadaptable features and biospecific 3D designs will contribute to the development of more robust and functional humanized tissues for therapies and disease models, as well as tools for fundamental biological studies.

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Single-Cell Microgels: Technology, Challenges, and Applications

Cited by 73 publications

References 108 publications

Shattering barriers toward clinically meaningful MSC therapies

Shattering barriers toward clinically meaningful MSC therapies

Microfluidics Fabrication of Soft Microtissues and Bottom‐Up Assembly

Advanced Bottom‐Up Engineering of Living Architectures

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