Gas modulating microcapsules for spatiotemporal control of hypoxia

Abstract

Oxygen is a vital molecule involved in regulating development, homeostasis, and disease. The oxygen levels in tissue vary from 1 to 8% with deviations having major biological consequences. In this work, we developed an approach to encapsulate enzymes and nanozymes, at an unprecedented loading capacity, which precisely controls the oxygen content in cell culture. Here, a single microcapsule is able to locally perturb the oxygen balance, and varying the concentration and distribution of matrix embedded microcapsules provides spatiotemporal control. We demonstrate attenuation of hypoxia signaling in populations of stem cells, cancer cells, endothelial cells, and cancer spheroids. Capsule containing hydrogel films applied to chick chorioallantoic membranes encourage neovascularization, providing scope for topical treatments or hydrogel wound dressings. We further demonstrate versatility by loading capsules with ceria nanorods as nanozymes to modulate active oxygen species with potential as a cytoprotective treatment. The approach can be used in multiple formats, including deposition in hydrogels, as granular solids for 3D bioprinting, and as injectable biomaterials. Overall, this platform's simplicity and flexibility will prove useful for fundamental studies of oxygen-mediated processes in virtually any in vitro or in vivo format, with scope for inclusion in biomedical materials where controlling hypoxia may be clinically advantageous.

Enzyme Bioink for the 3D Printing of Biocatalytic Materials

“…18 They are ideal candidates for adding functionality to biocatalytic hydrogels, due to their biocompatibility and high substrate specificity and selectivity, respectively. Examples of enzyme-based functionalities include the support of wound healing processes by quenching reactive oxygen species (ROS) and oxygen generation, [31][32][33] the prevention of microbial infections, 21,34 and improved wound repair by controlled degradation of wound dressings. 18,35 Notably, in all mentioned studies, enzymes were physically entrapped or coincubated within hydrogels.…”