title: Microscale Bioadhesive Hydrogel Arrays for Cell Engineering Applications.
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.
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Ravi Ghanshyam
authors.initials: RG
authors.lastname: Patel
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Purwada
authors.affiliation: Division of Hematology and Medical Oncology, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
authors.forename: Leandro
authors.initials: L
authors.lastname: Cerchietti
authors.affiliation: Department of Pathology, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Inghirami
authors.affiliation: Division of Hematology and Medical Oncology, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.
authors.forename: Ari
authors.initials: A
authors.lastname: Melnick
authors.affiliation: Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA ; Department of Materials Science & Engineering, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Gaharwar
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Ankur
authors.initials: A
authors.lastname: Singh
keywords: Bioadhesive; Cancer; Cell adhesive; Composite hydrogels; Leukemia; Michael-type addition; Microgels