Force Spectroscopy Imaging and Constriction Assays Reveal the Effects of Graphene Oxide on the Mechanical Properties of Alginate Microcapsules

Abstract

Microencapsulation of cells in hydrogel-based porous matrices is an approach that has demonstrated great success in regenerative cell therapy. These microcapsules work by concealing the exogenous cells and materials in a robust biomaterial that prevents their recognition by the immune system. A vast number of formulations and additives are continuously being tested to optimize cell viability and mechanical properties of the hydrogel. Determining the effects of new microcapsule additives is a lengthy process that usually requires extensive in vitro and in vivo testing. In this paper, we developed a workflow using nanoindentation (i.e., indentation with a nanoprobe in an atomic force microscope) and a custom-built microfluidic constriction device to characterize the effect of graphene oxide (GO) on three microcapsule formulations. With our workflow, we determined that GO modifies the microcapsule stiffness and surface properties in a formulation-dependent manner. Our results also suggest, for the first time, that GO alters the conformation of the microcapsule hydrogel and its interaction with subsequent coatings. Overall, our workflow can infer the effects of new additives on microcapsule surfaces. Thus, our workflow can contribute to diminishing the time required for the validation of new microcapsule formulations and accelerate their clinical translation.

Preparation of Graphene Oxide/Polymer Hybrid Microcapsules via Photopolymerization for Double Self-Healing Anticorrosion Coatings

“…This was due to the introduction of GO, which enhanced the mechanical property of the microcapsule shell. 29 But, it should be noted that with further increase in GO concentration, the breakage ratios of GO-4/PUA and GO-8/PUA microcapsules did not further decrease, which were almost the same as that of the GO-2/ PUA microcapsule.…”

“…Graphene oxide (GO) has attracted much attention due to its high radius–thickness ratio, shielding property, high strength, and photothermal conversion properties, and researchers have already integrated GO into the shell to boost the microcapsule performance. − The introduction of GO in the shell could not only enhance the barrier property, solvent resistance property, and mechanical property of microcapsules but also endow the microcapsule with photothermal conversion performance , and thermal conductivity, which broadens the application fields of microcapsules. At present, GO microcapsules are mainly prepared by the Pickering emulsion method via thermal polymerization, , which requires long reaction time and high temperature.…”

Generation of Self-Induced Myocardial Ischemia in Large-Sized Cardiac Spheroids without Alteration of Environmental Conditions Recreates Fibrotic Remodeling and Tissue Stiffening Revealed by Constriction Assays

“… 9 To study spheroid stiffness, we applied a constriction assay methodology ( Figure 6 A–C) previously developed in our group for the mechanical characterization of alginate-based microcapsules. 26 , 27 Either 20.000 or 40.000 cell seeding spheroids were studied by this system. However, although 20.000 cell seeding spheroids were enough to generate spheroids over 500 μm, they were not retained in the constriction system, not allowing the quantification of the stiffness by this methodology ( Figure S4 ).…”

Layer-by-Layer Cell Encapsulation for Drug Delivery: The History, Technique Basis, and Applications

“…As indicated, pores are easily formed in the alginate capsules, thus still facilitating immune recognition and thereafter reactions [91]. Researchers proved that Ba 2+ -alginate could only exempt allogeneic grafts from immune attack, instead of the xenogeneic ones [92].…”