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.

Ex vivo engineered immune organoids for controlled germinal center reactions

“…1D, E). While gelatin-based 3D hydrogels have existed for decades, mostly as chemically modified system that require UV exposure (methacrylate functionalities [47]), we have engineered hydrogels of polyampholytic gelatin that ionically interacts with the anisotropically distributed opposite charges on the synthetic SiNP resulting in hydrogels [48–50] that remain stable and do not liquefy at 37 °C (Fig. 1E).…”

Integrin αvβ3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells

“…We adapted a hydrogel system 15,16 by combining functionalized polyethylene glycol with a crosslinker peptide containing an integrin avb3 binding site and a collagenase degradable sequence. As inert stromal cellular component, we used irradiated human tonsil-derived HK follicular dendritic cells (supplemental Figure 3).…”

Biomaterial-Based Modulation of Cancer

“…Thus, hydrogels and scaffolds in which ECM stiffness and cell-matrix adhesion can be independently controlled can be apt models for studying the tumor environment and various mechanisms to modulate its physiological properties. We recently reported a facile approach to micro-manufacture composite bio-adhesive microgels of maleimidefunctionalized polyethylene glycol (PEG-MAL) with an interpenetrating network of ionically cross-linked gelatin and silicate nanoparticles (gelatin-NP) based on Michael-type addition polymerization and ionic gelation processes [34]. In these studies ( Fig.…”