Stop-flow lithography to generate cell-laden microgel particles

Panda, Priyadarshi; Ali, Sher; Lo, Edward Chin Man; Chung, Bong Geun; Hatton, T. Alan; Khademhosseini, Ali; Doyle, Patrick S.

doi:10.1039/b804234a

Cited by 266 publications

(236 citation statements)

References 48 publications

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“…6,7 Several attempts have been proposed to solve this problem. [8][9][10][11][12] The Doyle group developed methods to generate hydrogel microparticles with specific shapes using continuous flow or stopflow lithography. 13 A droplet-based microfluidic system was proposed to construct alginate gel beads encapsulating cells.…”

Section: Introductionmentioning

confidence: 99%

Fabrication of Hydrogel Particles of Defined Shapes Using Superhydrophobic‐Hydrophilic Micropatterns

et al. 2016

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We report a method to rapidly fabricate alginate hydrogel particles of specific sizes and shapes.Our method is based on the formation of arrays of droplets of pre-hydrogel solutions on superhydrophobic-hydrophilic patterns using the process of discontinuous dewetting, followed by their gelation via the parallel addition of CaCl 2 to the individual droplets via the sandwiching method. We demonstrate that viability of living cells incorporated within the hydrogel particles is higher during the long-term cultivation than in the case of cells cultured in the bulk threedimensional hydrogel matrix. Incorporation of magnetic particles into the free-standing hydrogel particles containing living cells enabled ease manipulation of the particles using an external magnetic field.

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Section: Introductionmentioning

confidence: 99%

Fabrication of Hydrogel Particles of Defined Shapes Using Superhydrophobic‐Hydrophilic Micropatterns

et al. 2016

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“…Khademhosseini and co-workers used a stop-flow lithography approach within a microfluidic channel to make microscale hydrogel blocks contain embedded cells. [45] These types of cellular "building blocks" can be assembled or molded following manufacture into complex 3D shapes, as demonstrated by Takeuchi and co-workers. [46] Lee and coworkers have designed a microfluidic-based biofabrication tool that can generate cell-laden microfibers with spatially coded placement of multiple cell types.…”

Section: Microfluidic Systems For Biofabricationmentioning

confidence: 99%

Biomimicry, Biofabrication, and Biohybrid Systems: The Emergence and Evolution of Biological Design

Raman

Bashir

2017

Adv Healthcare Materials

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how the concept of bioinspiration, or imitating biological design and functionality in synthetic materials, created a new class of "smart" biomimetic materials. Then, we shall discuss how the continuing development of enabling manufacturing technologies, such as 3D printing and microfluidics, has established the separate subdiscipline of biofabrication for tissue engineering, or "building with biology." Finally, we shall investigate the convergence of these two fields into the emerging discipline of biohybrid design, the use of biological materials to power non-natural functional behaviors in synthetic machines. Throughout this report, we will revisit a single class of materials, hydrogels, as a case study of biological design in the context of each subfield, and discuss how the constraints, underlying principles, and end-use applications differ in each case. We will also discuss ethical considerations of biological design, with a special focus on forward engineering non-natural or hypernatural functional behaviors in biohybrid systems. We will conclude with recommendations for implementing biological design into educational curricula, ensuring effective and responsible practices for the next generation of engineers and scientists. Biomimicry and Bioinspired DesignA deeper understanding of the underlying design principles that govern biological systems has inspired the field of biomimicry. [1,2] Observing adaptive phenomena in nature, scientists and engineers have sought to extract the components of biological design responsible for this behavior and replicate the behavior in synthetic materials. Fundamentally, this involves understanding the building blocks or base units from which a biological material is built, the hierarchical assembly of these building blocks, and the interactions and interfaces between them.In this section, we will discuss strategies that engineers and scientists have employed to engineer bioinspired hierarchy, from bottom-up self-assembly and top-down engineered assembly. We will present several key demonstrations of stimulus-responsive hydrogels ranging from the micro-to the macroscale, and investigate novel demonstrations in biomimetic actuation and movement. We will conclude with the remaining challenges in the field of biomimicry and discuss the potential future impact of bioinspired design.The discipline of biological design has a relatively short history, but has undergone very rapid expansion and development over that time. This Progress Report outlines the evolution of this field from biomimicry to biofabrication to biohybrid systems' design, showcasing how each subfield incorporates bioinspired dynamic adaptation into engineered systems. Ethical implications of biological design are discussed, with an emphasis on establishing responsible practices for engineering non-natural or hypernatural functional behaviors in biohybrid systems. This report concludes with recommendations for implementing biological design into educational curricula, ensuring effective and responsible practice...

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“…As these approaches produce device-bound structures, they are useful for rather fundamental in vitro studies, but have limited translational potential. To increase microgel fabrication throughput and collection efficiency, cell encapsulation has also been demonstrated by stop flow lithography (SFL), a single-phase microfluidic technique for PEG microgel fabrication, at low throughput but with precise control over microgel shape and size 31 . SFL combined with hydrolytically degradable hydrogel networks can produce a cell or drug delivery scaffold with tunable properties and degradation profiles 32 .…”

Section: Introductionmentioning

confidence: 99%

A microfluidic-based cell encapsulation platform to achieve high long-term cell viability in photopolymerized PEGNB hydrogel microspheres

et al. 2017

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Cell encapsulation within photopolymerized polyethylene glycol (PEG)-based hydrogel scaffolds has been demonstrated as a robust strategy for cell delivery, tissue engineering, regenerative medicine, and developing in vitro platforms to study cellular behavior and fate. Strategies to achieve spatial and temporal control over PEG hydrogel mechanical properties, chemical functionalization, and cytocompatibility have advanced considerably in recent years. Recent microfluidic technologies have enabled the miniaturization of PEG hydrogels, thus enabling the fabrication of miniaturized cell-laden vehicles. However, rapid oxygen diffusive transport times on the microscale dramatically inhibit chain growth photopolymerization of polyethylene glycol diacrylate (PEGDA), thus decreasing the viability of cells encapsulated within these microstructures. Another promising PEG-based scaffold material, PEG norbornene (PEGNB), is formed by a step-growth photopolymerization and is not inhibited by oxygen. PEGNB has also been shown to be more cytocompatible than PEGDA and allows for orthogonal addition reactions. The step-growth kinetics, however, are slow and therefore challenging to fully polymerize within droplets flowing through microfluidic devices. Here, we describe a microfluidic-based droplet fabrication platform that generates consistently monodisperse cell-laden water-in-oil emulsions. Microfluidically generated PEGNB droplets are collected and photopolymerized under UV exposure in bulk emulsions. In this work, we compare this microfluidic-based cell encapsulation platform with a vortex-based method on the basis of microgel size, uniformity, post-encapsulation cell viability and long-term cell viability. Several factors that influence post-encapsulation cell viability were identified. Finally, long-term cell viability achieved by this platform was compared to a similar cell encapsulation platform using PEGDA. We show that this PEGNB microencapsulation platform is capable of generating cell-laden hydrogel microspheres at high rates with well-controlled size distributions and high long-term cell viability.

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Stop-flow lithography to generate cell-laden microgel particles

Cited by 266 publications

References 48 publications

Fabrication of Hydrogel Particles of Defined Shapes Using Superhydrophobic‐Hydrophilic Micropatterns

Fabrication of Hydrogel Particles of Defined Shapes Using Superhydrophobic‐Hydrophilic Micropatterns

Biomimicry, Biofabrication, and Biohybrid Systems: The Emergence and Evolution of Biological Design

A microfluidic-based cell encapsulation platform to achieve high long-term cell viability in photopolymerized PEGNB hydrogel microspheres

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