Micro 3D cell culture systems for cellular behavior studies: Culture matrices, devices, substrates, and in‐situ sensing methods

Abstract

Microfabricated systems equipped with 3D cell culture devices and in-situ cellular biosensing tools can be a powerful bionanotechnology platform to investigate a variety of biomedical applications. Various construction substrates such as plastics, glass, and paper are used for microstructures. When selecting a construction substrate, a key consideration is a porous microenvironment that allows for spheroid growth and mimics the extracellular matrix (ECM) of cell aggregates. Various bio-functionalized hydrogels are ideal candidates that mimic the natural ECM for 3D cell culture. When selecting an optimal and appropriate microfabrication method, both the intended use of the system and the characteristics and restrictions of the target cells should be carefully considered. For highly sensitive and near-cell surface detection of excreted cellular compounds, SERS-based microsystems capable of dual modal imaging have the potential to be powerful tools; however, the development of optical reporters and nanoprobes remains a key challenge. We expect that the microsystems capable of both 3D cell culture and cellular response monitoring would serve as excellent tools to provide fundamental cellular behavior information for various biomedical applications such as metastasis, wound healing, high throughput screening, tissue engineering, regenerative medicine, and drug discovery and development.

Fabricating large‐scale three‐dimensional constructs with living cells by processing with syringe needles

“…One prominent challenge in tissue engineering is establishing a readily available technology for shaping 3D cell constructs . To this end, we attempted to fabricate large‐scale cell constructs in this study.…”

Microfluidics‐based 3D cell culture models: Utility in novel drug discovery and delivery research

“…These papers can later be destacked for layer‐by‐layer molecular analysis . Several reports suggest culture of cancerous and endothelial cells by this fashion to validate their proliferation profiles . Recently, paper‐based devices have been compared with 3D spheroid culture of MDA‐MB 231 cells.…”

“…72 Several reports suggest culture of cancerous and endothelial cells by this fashion to validate their proliferation profiles. 73 Recently, paper-based devices have been compared with 3D spheroid culture of MDA-MB 231 cells. Whatman filter papers were used to pattern 96 multilayer array consisting cells and were further tested against different cell based assays to provide information regarding their migration ( Figure 5).…”

Hydrogel‐based three‐dimensional cell culture for organ‐on‐a‐chip applications

“…Replicating such complex in vivo microenvironments is difficult to achieve in a 2D cell culture, which is thought to cause unnatural changes in the nuclear shape, gene expression, and protein synthesis of cells . These changes affect cellular proliferation and differentiation, making it difficult to accurately predict the efficacy of drugs and therapeutic agents . In contrast, 3D cell culture is known to improve cellular functions by creating an environment that is physiologically more similar to in vivo microenvironments than 2D cell culture .…”

“…2 These changes affect cellular proliferation and differentiation, making it difficult to accurately predict the efficacy of drugs and therapeutic agents. 3 In contrast, 3D cell culture is known to improve cellular functions by creating an environment that is physiologically more similar to in vivo microenvironments than 2D cell culture. 4 Although the superiority of 3D cell culture is not universal, the intracellular signaling, proliferation, and differentiation that occur in vivo is thought to be more accurately reproduced through various cell-cell and cell-ECM contacts.…”