Microfluidic Approach to Cell Microencapsulation

Sharma, Varna; Hunckler, Michael D.; Ramasubramanian, Melur K.; Opara, Emmanuel C.; Katuri, Kalyan C.

doi:10.1007/978-1-4939-6364-5_5

Cited by 9 publications

(6 citation statements)

References 11 publications

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“…Solid beads can be produced by a variety of methods [30][31][32], among which electrospraying is advantageous in terms of scaling up the process and the possibility for precise control over the size of the solid beads in the micro-and macroscopic range. This method yields in a low diameter variation given by the adjusted process parameters, such as electric field strength (the applied voltage over the spraying distance).…”

Section: Introductionmentioning

confidence: 99%

Coaxial Alginate Hydrogels: From Self-Assembled 3D Cellular Constructs to Long-Term Storage

Gryshkov

Mutsenko

Tarusin

et al. 2021

IJMS

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Alginate as a versatile naturally occurring biomaterial has found widespread use in the biomedical field due to its unique features such as biocompatibility and biodegradability. The ability of its semipermeable hydrogels to provide a favourable microenvironment for clinically relevant cells made alginate encapsulation a leading technology for immunoisolation, 3D culture, cryopreservation as well as cell and drug delivery. The aim of this work is the evaluation of structural properties and swelling behaviour of the core-shell capsules for the encapsulation of multipotent stromal cells (MSCs), their 3D culture and cryopreservation using slow freezing. The cells were encapsulated in core-shell capsules using coaxial electrospraying, cultured for 35 days and cryopreserved. Cell viability, metabolic activity and cell–cell interactions were analysed. Cryopreservation of MSCs-laden core-shell capsules was performed according to parameters pre-selected on cell-free capsules. The results suggest that core-shell capsules produced from the low viscosity high-G alginate are superior to high-M ones in terms of stability during in vitro culture, as well as to solid beads in terms of promoting formation of viable self-assembled cellular structures and maintenance of MSCs functionality on a long-term basis. The application of 0.3 M sucrose demonstrated a beneficial effect on the integrity of capsules and viability of formed 3D cell assemblies, as compared to 10% dimethyl sulfoxide (DMSO) alone. The proposed workflow from the preparation of core-shell capsules with self-assembled cellular structures to the cryopreservation appears to be a promising strategy for their off-the-shelf availability.

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Section: Introductionmentioning

confidence: 99%

Coaxial Alginate Hydrogels: From Self-Assembled 3D Cellular Constructs to Long-Term Storage

Gryshkov

Mutsenko

Tarusin

et al. 2021

IJMS

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“…In the context of islet/SC-β research, lab-on-a-chip platforms have been used in select studies examining the prevention of endothelial cell loss in islets post-isolation, dynamic imaging studies, insulin/glucagon/somatostatin secretion studies, differentiation of human embryonic stem cells into SC-β and endocrine spheroid microencapsulation (Sankar et al, 2011;Silva et al, 2013;McMillan et al, 2016;Nourmohammadzadeh et al, 2016;Lenguito et al, 2017;Sharma et al, 2017;Lee G. et al, 2018;Jun et al, 2019). These novel systems are remarkable for small-scale discovery research but one stark omission in most studies has been a comparison to conventional culture methods to see if these systems improve endocrine spheroid viability or function.…”

Section: Microfluidic Culture Platformsmentioning

confidence: 99%

The Importance of Proper Oxygenation in 3D Culture

Tse

Gardner

Domínguez‐Bendala

et al. 2021

Front. Bioeng. Biotechnol.

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Cell culture typically employs inexpensive, disposable plasticware, and standard humidified CO2/room air incubators (5% CO2, ∼20% oxygen). These methods have historically proven adequate for the maintenance of viability, function, and proliferation of many cell types, but with broad variation in culture practices. With technological advances it is becoming increasingly clear that cell culture is not a “one size fits all” procedure. Recently, there is a shift toward comprehension of the individual physiological niches of cultured cells. As scale-up production of single cell and 3D aggregates for therapeutic applications has expanded, researchers have focused on understanding the role of many environmental metabolites/forces on cell function and viability. Oxygen, due to its role in cell processes and the requirement for adequate supply to maintain critical energy generation, is one such metabolite gaining increased focus. With the advent of improved sensing technologies and computational predictive modeling, it is becoming evident that parameters such as cell seeding density, culture media height, cellular oxygen consumption rate, and aggregate dimensions should be considered for experimental reproducibility. In this review, we will examine the role of oxygen in 3D cell culture with particular emphasis on primary islets of Langerhans and stem cell-derived insulin-producing SC-β cells, both known for their high metabolic demands. We will implement finite element modeling (FEM) to simulate historical and current culture methods in referenced manuscripts and innovations focusing on oxygen distribution. Our group and others have shown that oxygen plays a key role in proliferation, differentiation, and function of these 3D aggregates. Their culture in plastic consistently results in core regions of hypoxia/anoxia exacerbated by increased media height, aggregate dimensions, and oxygen consumption rates. Static gas permeable systems ameliorate this problem. The use of rotational culture and other dynamic culture systems also have advantages in terms of oxygen supply but come with the caveat that these endocrine aggregates are also exquisitely sensitive to mechanical perturbation. As recent work demonstrates, there is a strong rationale for the use of alternate in vitro systems to maintain physio-normal environments for cell growth and function for better phenotypic approximation of in vivo counterparts.

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“…6). While microcapsule fabrication is achieved by droplet-generating techniques such as electrospray [316][317][318], emulsion-based strategies [319,320], submerged jet extrusion [321], or microfluidic systems [322,323], nanoencapsulation methods typically feature direct polymer deposition on the islet surface. Many techniques have been developed from early approaches in employing PEG as a polymer coating; in addition, the layer-by-layer (LBL) method has been used to produce versatile islet polymer films.…”

Section: Nanoencapsulationmentioning

confidence: 99%

Nanotechnology in cell replacement therapies for type 1 diabetes

Ernst

Bowers

Wang

et al. 2019

Advanced Drug Delivery Reviews

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Islet transplantation is a promising long-term, compliance-free, complication-preventing treatment for type 1 diabetes. However, islet transplantation is currently limited to a narrow set of patients due to the shortage of donor islets and side effects from immunosuppression. Encapsulating cells in an immunoisolating membrane can allow for their transplantation without the need for immunosuppression. Alternatively, "open" systems may improve islet health and function by allowing vascular ingrowth at clinically attractive sites. Many processes that enable graft success in both approaches occur at the nanoscale level-in this review we thus consider nanotechnology in cell replacement therapies for type 1 diabetes. A variety of biomaterial-based strategies at the nanometer range have emerged to promote immune-isolation or modulation, proangiogenic, or insulinotropic effects. Additionally, coating islets within nano-thin polymer films has burgeoned as an islet protection modality. Materials approaches that utilize nanoscale features manipulate biology at the molecular scale, offering unique solutions to the enduring challenges of islet transplantation.

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Microfluidic Approach to Cell Microencapsulation

Cited by 9 publications

References 11 publications

Coaxial Alginate Hydrogels: From Self-Assembled 3D Cellular Constructs to Long-Term Storage

Coaxial Alginate Hydrogels: From Self-Assembled 3D Cellular Constructs to Long-Term Storage

The Importance of Proper Oxygenation in 3D Culture

Nanotechnology in cell replacement therapies for type 1 diabetes

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