3D bio-etching of a complex composite-like embryonic tissue

Abstract

Morphogenesis involves a complex series of cell signaling, migration and differentiation events that are coordinated as tissues self-assemble during embryonic development. Collective cell movements such as those that occur during morphogenesis have typically been studied in 2D with single layers of cultured cells adhering to rigid substrates such as glass or plastic. In vivo, the intricacies of the 3D microenvironment and complex 3D responses are pivotal in the formation of functional tissues. To study such processes as collective cell movements within 3D multilayered tissues, we developed a microfluidic technique capable of producing complex 3D laminar multicellular structures. We call this technique "3D tissue-etching" because it is analogous to techniques used in the microelectromechanics (MEMS) field where complex 3D structures are built by successively removing material from a monolithic solid through subtractive manufacturing. We use a custom-designed microfluidic control system to deliver a range of tissue etching reagents (detergents, chelators, proteases, etc.) to specific regions of multilayered tissues. These tissues were previously isolated by microsurgical excision from embryos of the African claw-toed frog, Xenopus laevis. The ability to shape the 3D form of multicellular tissues and to control 3D stimulation will have a high impact on tissue engineering and regeneration applications in bioengineering and medicine as well as provide significant improvements in the synthesis of highly complex 3D integrated multicellular biosystems.

Chemotactic Responses of Jurkat Cells in Microfluidic Flow-Free Gradient Chambers

“…Microtechnology provides novel tools that allow precise spatiotemporal control over microenvironments to better understand the operation of complex biologic systems [13][14][15]. Advances in microfabrication over the last two decades have enabled the development of sophisticated microfluidic chemotaxis systems where dynamic and complex movement of chemotactic cells can be studied in precisely defined microenvironments [16].…”

Multifunctional Peroxidase-Encapsulated Nanoliposomes: Bioetching-Induced Photoelectrometric and Colorimetric Immunoassay for Broad-Spectrum Detection of Ochratoxins

“…In the presence of a hole-trapping reagent of AA, the photocorrosion of CdS/ZnO NRs/rGO could be effectively avoided, thus ensuring a stable and efficient photocurrent. More importantly, CdS could be irreversibly bioetched by HRP-induced enzymatic catalysis in the presence of H 2 O 2 . , After that, a weak photoelectric conversion was obtained since the ZnO NRs can only adsorb UV light. Therefore, the photocurrent intensity of CdS/ZnO NRs/rGO decreased with the amount of HRP, achieving the “signal-off” PEC detection.…”

“…More importantly, CdS could be irreversibly bioetched by HRP-induced enzymatic catalysis in the presence of H 2 O 2 . 38,39 After that, a weak photoelectric conversion was obtained since the ZnO NRs can only adsorb UV light. Therefore, the photocurrent intensity of CdS/ZnO NRs/rGO decreased with the amount of HRP, achieving the "signal-off" PEC detection.…”

Nanomedicines for endothelial disorders

“…This integrative approach can be applied to optimize nanoparticles and study their potentials in a range of other diseases, including cancer, diabetes, and inflammation. In the future, the ability to create physiologically realistic microsystems that can mimic in vitro microvessels [225, 226], and manipulate in vivo small organisms [227] or ex vivo embryonic tissue excised from live embryos [228–231], will allow the identification and prediction of the potential of nanomedicines and pave the path for their rapid clinical translation.…”