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Microscale Bioadhesive Hydrogel Arrays for Cell Engineering Applications

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Abstract

Bioengineered hydrogels have been explored in cell and tissue engineering applications to support cell growth and modulate its behavior. A rationally designed scaffold should allow for encapsulated cells to survive, adhere, proliferate, remodel the niche, and can be used for controlled delivery of biomolecules. Here we report a microarray of composite bioadhesive microgels with modular dimensions, tunable mechanical properties and bulk modified adhesive biomolecule composition. Composite bioadhesive microgels of maleimide functionalized polyethylene glycol (PEG-MAL) with interpenetrating network (IPN) of gelatin ionically cross-linked with silicate nanoparticles were engineered by integrating microfabrication with Michael-type addition chemistry and ionic gelation. By encapsulating clinically relevant anchorage-dependent cervical cancer cells and suspension leukemia cells as cell culture models in these composite microgels, we demonstrate enhanced cell spreading, survival, and metabolic activity compared to control gels. The composite bioadhesive hydrogels represent a platform that could be used to study independent effect of stiffness and adhesive ligand density on cell survival and function. We envision that such microarrays of cell adhesive microenvironments, which do not require harsh chemical and UV crosslinking conditions, will provide a more efficacious cell culture platform that can be used to study cell behavior and survival, function as building blocks to fabricate 3D tissue structures, cell delivery systems, and high throughput drug screening devices.

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Acknowledgments

The authors would like to acknowledge financial support by Grants from the National Institutes of Health (1R21CA185236-01) and the Cornell University-Ithaca and Weill Cornell Medical College seed grant. The authors also thank Prof. Marjolein C.H. van der Meulen in the Department of Biomedical Engineering and the Sibley School of Mechanical and Aerospace Engineering for providing cells. The authors also thank Dr. Brian Kirby in Sibley School of Mechanical and Aerospace Engineering at Cornell University for access to the cells, microscopy facility and spectrophotometer. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Conflict of interest

Ravi Ghanshyam Patel, Alberto Purwada, Leandro Cerchietti, Giorgio Inghirami, Ari Melnick, Akhilesh Gaharwar, and Ankur Singh declare that they have no conflicts of interest.

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No animal or human studies were carried out by the authors for this article.

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Authors and Affiliations

  1. Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, 14853, USA

    Ravi Ghanshyam Patel & Ankur Singh

  2. Department of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA

    Alberto Purwada

  3. Division of Hematology and Medical Oncology, Weill Cornell Medical College, Cornell University, New York, NY, 10065, USA

    Leandro Cerchietti & Ari Melnick

  4. Department of Pathology, Weill Cornell Medical College, Cornell University, New York, NY, 10065, USA

    Giorgio Inghirami

  5. Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77843, USA

    Akhilesh K. Gaharwar

  6. Department of Materials Science & Engineering, Texas A&M University, College Station, TX, 77843, USA

    Akhilesh K. Gaharwar

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  1. Ravi Ghanshyam Patel
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Correspondence to Ankur Singh.

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Associate Editor David Mooney oversaw the review of this article.

This paper is part of the 2014 Young Innovators Issue.

Ankur Singh is an Assistant Professor in the Sibley School of Mechanical & Aerospace Engineering at Cornell University, where he directs the Immunotherapy and Cell Engineering Laboratory. Dr. Singh has expertise in the engineering of biomaterials based platforms for immune cell modulation, cell-biomaterial interactions, cell adhesion, nanoengineered materials, and stem cells. He received his postdoctoral training at Georgia Institute of Technology where he employed engineering and molecular cell biology principles to understand force response and mechanotransduction during the process of human stem cell reprogramming and differentiation. Dr. Singh received his Ph.D. in Biomedical Engineering at The University of Texas at Austin. His research has established multi-modal, synthetic immune priming centers and micro-nanoparticle vaccines for blood cancer and viral infections. His other relevant work includes developing self-assembly nanogels for protein therapeutic delivery to reduce osteoarthritis associated inflammation in knee joints. He has published peer-reviewed paper in Nature Methods, PNAS, Advanced Materials, Molecular Therapy, Biomaterials, Journal of Controlled Release, and Journal of Cell Science. His research is supported by the National Institutes of Health and National Cancer Institute.

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Patel, R.G., Purwada, A., Cerchietti, L. et al. Microscale Bioadhesive Hydrogel Arrays for Cell Engineering Applications. Cel. Mol. Bioeng. 7, 394–408 (2014). https://doi.org/10.1007/s12195-014-0353-8

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