Abstract
Hydrogel-based artificial scaffolds play a vital role in shifting in vitro models from two-dimensional (2D) cell culture to three-dimensional (3D) cell culture. Microfluidic 3D cell culture systems with a hydrogel matrix encourage biomedical researchers to replace in vivo models with 3D in vitro models with a cellular microenvironment that resembles physiological conditions with greater fidelity. Hydrogels can be designed as an artificial extracellular matrix scaffold for providing spatial orientation and promoting cellular interactions with surroundings. Selecting the appropriate hydrogels and their fabrication techniques are the key to mimic the in vivo mechanical environment. Moreover, combining a microfluidic technique with a hydrogel-based 3D cell culture system can create a complex and controlled microenvironment for the cells by placing small biosamples inside the microchannel. This paper provides an overview of the structural similarities of the hydrogels as an extracellular matrix (ECM), their classification and fabrication techniques as an ECM, and their use in microfluidic 3D cell culture systems. Finally, the paper presents the current challenges and future perspectives of using hydrogel scaffolds in microfluidic 3D cell culture systems.
Highlights
The cellular microenvironment plays a vital role in substantial cellular morphology and the activation of a wide range of factors for regulating cell growth, proliferation, and migration
The results suggested that the membrane with a large surface pore facilitated the cell incorporation while interconnected small porous structure was suitable for nutrients and oxygen diffusion, along with the waste removal
The success of cell culture in microchannels mostly depends on the selection and fabrication of a preferred hydrogel as extracellular matrix (ECM) structure
Summary
The cellular microenvironment plays a vital role in substantial cellular morphology and the activation of a wide range of factors for regulating cell growth, proliferation, and migration. In a 3D cell culture, an arti cial cellular microenvironment is created as a biological scaffold to provide mechanical support for cell growth by promoting cellular interactions with the surroundings. Different biomaterials such as patterned glass substrates, elastomeric lms, hydroxyapatite ceramics, hydrogels, and brillar foams are employed as the alternative of physical scaffold for cells These materials create the complexity, mechanical support, composition, and structural orientation similar to the native tissue during the in vitro cell culture process.[5] Among these materials, biocompatible hydrogels have gained popularity because of their crosslinkable, highly hydrated porous network for the cellular. To have the similar structure of mammalian ECM, hydrogels must possess a hydrated protein and polysaccharide network.[15,17] Like native ECM, hydrogels from natural polymers contain growth factors and integrin binding sites (Fig. 1B) for promoting cellular functions. By introducing new functional groups, matrix stiffness can be tuned for cellular support, and pore architecture can be optimized to promote tissue formation.[6]
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