Versatile, cell and chip friendly method to gel alginate in microfluidic devices

Håti, Armend Gazmeno; Bassett, D. C.; Ribe, Jonas M.; Sikorski, Pawel; Weitz, David A.; Stokke, Bjørn Torger

doi:10.1039/c6lc00769d

Cited by 71 publications

(83 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A more rigorous analysis of the application of CLEX to the microencapsulation of both eukaryotic and prokaryotic cells is described in detail elsewhere. 29 By way of demonstration, CLEX was also applied to form larger scale bulk gels by casting (Fig 4B) into an injection mould using a dual syringe to deliver equal volumes of alginate solution. A homogenous, bubble free gel was obtained.…”

Section: Resultsmentioning

confidence: 99%

Competitive ligand exchange of crosslinking ions for ionotropic hydrogel formation

et al. 2016

Self Cite

View full text Add to dashboard Cite

Currently there are limitations to gelation strategies to form ionically crosslinked hydrogels, derived in particular from a lack of control over the kinetics of release of crosslinking ions, which severely restrict applications. To address this challenge, we describe a new approach to form hydrogels of ionotropic polymers using competitive displacement of chelated ions, thus making specific ions available to induce interactions between polymer chains and form a hydrogel. This strategy enables control of ion release kinetics within an aqueous polymer solution and thus control over gelation kinetics across a wide range of pH. The described technique simplifies or facilitates the use of ionotropic hydrogels in a range of applications, such as 3D printing, microfluidic-based cell encapsulation, injectable preparations and large scale bubble and solid free mouldable gels. We investigate a range of chelatorion combinations and demonstrate this powerful method to form hydrogels across a wide range of pH and µm -cm length scales. We highlight our findings by applying this gelation strategy to some of the more challenging hydrogel application areas using alginate and polygalacturonate as model polymer systems.

show abstract

Section: Resultsmentioning

confidence: 99%

Competitive ligand exchange of crosslinking ions for ionotropic hydrogel formation

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although the availability of binding sites for cells is critical for cell attachment and function, the bulk properties of hydrogels play an equally important role. Alginate is widely used as a platform to study the effect of mechanical cues because the gelation [31,32], swelling ratio [33], crosslinking density, and resultant moduli [34] can be easily tuned by calcium ion concentration.…”

Section: Discussionmentioning

confidence: 99%

Tunable Fibrin-Alginate Interpenetrating Network Hydrogels to Guide Cell Behavior

Gonzalez-Fernandez

Joshee

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Hydrogels are effective platforms for use as artificial extracellular matrices, cell carriers, and to present bioactive cues. Two common natural polymers, fibrin and alginate, are broadly used to form hydrogels and have numerous advantages over synthetic materials. Fibrin is a provisional matrix containing native adhesion motifs for cell engagement, yet the interplay between mechanical properties, degradation, and gelation rate is difficult to decouple. Conversely, alginate is highly tunable yet bioinert and requires modification to present necessary adhesion ligands. To address these challenges, we developed a fibrin-alginate interpenetrating network (IPN) hydrogel to combine the desirable adhesion and stimulatory characteristics of fibrin with the tunable mechanical properties of alginate. We tested its efficacy by examining capillary network formation with entrapped co-cultures of mesenchymal stromal cells (MSCs) and endothelial cells (ECs). We manipulated thrombin concentration and alginate crosslinking density independently to modulate the fibrin structure, mesh size, degradation, and biomechanical properties of these constructs. In IPNs of lower stiffness, we observed a significant increase in total cell area (1.72´10 5 ± 7.9´10 4 µm 2 ) and circularity (0.56 ± 0.03) compared to cells encapsulated in stiffer IPNs (3.98´10 4 ± 1.49´10 4 µm 2 and 0.77 ± 0.09, respectively). Fibrinogen content did not influence capillary network formation. However, higher fibrinogen content led to greater retention of these networks confirmed via increased spreading and presence of F-actin at 7 days. This is an elegant platform to decouple cell adhesion and hydrogel bulk stiffness that will be broadly useful for cell instruction and delivery.

show abstract

“…In these techniques, the introduction of the spacer flow was necessary, as it modulates the high gelation speed of alginate. Another interesting approach was recently reported by Hati et al (2016), wherein an in-situ gelation method based on ion-exchange was reported, which was called competitive ligand exchange crosslinking. Two types of metal complexes-Ca-EDTA and Zn-EDDA-were used, which were individually introduced into aqueous solutions of Na-alg.…”

Section: Droplet Micro Uidics To Produce Alginate Particlesmentioning

confidence: 99%

Multiphase Microfluidic Processes to Produce Alginate-Based Microparticles and Fibers

Yamada

Seki

2018

Journal of Chemical Engineering of Japan

View full text Add to dashboard Cite

With the recent developments in micro uidic instruments and devices, various types of micrometer-sized materials have been produced by employing multiphase ow patterns formed in the microchannel. In particular, microparticles and micro bers, which are compatible with biomolecule incorporation or living cell encapsulations, have been gaining signi cant attention as new tools for biochemical analysis, cellular physiological studies, tissue engineering, cell transplantation, and controlled drug delivery. Herein, we introduce recent developments in micro uidic systems to produce alginate-based hydrogel microparticles and micro bers. By utilizing droplet dispersions either in equilibrium or nonequilibrium states, or by employing parallel laminar ows, microengineered functional materials that are di cult to generate using conventional devices and operations can be obtained. New and interesting multiphase phenomena are reviewed, together with the pros and cons of these systems and their applications. Furthermore, the fundamentals of multiphase micro uidics and the materials used to prepare particles and bers are brie y introduced.

show abstract

Versatile, cell and chip friendly method to gel alginate in microfluidic devices

Cited by 71 publications

References 58 publications

Competitive ligand exchange of crosslinking ions for ionotropic hydrogel formation

Competitive ligand exchange of crosslinking ions for ionotropic hydrogel formation

Tunable Fibrin-Alginate Interpenetrating Network Hydrogels to Guide Cell Behavior

Multiphase Microfluidic Processes to Produce Alginate-Based Microparticles and Fibers

Contact Info

Product

Resources

About