3D Cell Culture to Model a New Structure for the Field of Medical Science

Growing and developing cells in an artificial environment to study their behavior in response to their environment is termed as cell culture. Depending on the properties and applications of cells, different kind of cell cultures are innovated in order to suit their environment. 3D cell culture is one of the many techniques that is widely used as it offers new and convenient features compared to other alternative cell culture method. This technique could be described as the culture of living cells within micro-assembled devices that support three dimensional structures creating an artificial implementation of tissue and organ specific microarchitecture.

Nearly all the cells in tissues are located in an extracellular matrix (ECM) which consists a complex three-dimensional architecture and interact with neighboring cells through biochemical and mechanical cues. The surrounding cellular microenvironment determines the key events in the live cycle of a cell. By implementing cell culture in two-dimensional environment diminishes or limits the features of cell including differentiation, cellular morphology, proliferation, response to stimuli, viability, drug metabolism, gene and protein expression, and general cell function. To overcome these limitations several 3D cell culture models have been developed. These developments have greatly accelerated the translation research in regenerative medicine, cancer biology, and tissue engineering. People from different fields such as material scientists, cell biologists, biomedical engineers, and others have come together in order to contribute to the 3D cell culture development.

The priority aspect of creating a 3D cell culture is the need to mimic specific aspects of cell behaviors that will enable accurate prediction of tissue development and morphogenesis, genotypic, cellular differentiation, and phenotypic response to compounds in drugs and toxicity screening. Of the various methods to cultivate cell in a three-dimensional environment are listed below­

• 3D Spheroid Cultures

3D spheroids are simple cellular models that are generated from a wide range of cell types. The spherical shape is chosen for the 3D environment as the cell types have the tendency of adherent cells to aggregate. Few of the known examples of mammospheres, embryoid bodies, neurospheres, and hepatospheres. If the cells are put under circumstances that impede adhesion to cell culture substrates, it triggers their natural tendency to aggregate and form spheroids. The matrix free method that is commonly used for optimizing spheroids consist of attachment resistant cell culture surfaces which maintains the cells as suspension cultures in media. The spheroids have a size of few hundred micrometers beyond which necrosis ensues within the core of spheroids.

• 3D Cultures using Hydrogels and Extracellular Matrices

A substance consisting of networks of cross-linked polymer chains or complex protein molecules of natural or synthetic origin is called as hydrogels. Hydrogels possess biophysical characteristics that are similar to natural tissue as they have significant water content. Due to this they are able to serve as highly effective matrices for 3D cell culture. They can be used as a coating reagent for various cell culture surfaces including solid scaffolds. Furthermore, the cells cultivated through this technique can be encapsulated in or sandwiched between these matrices. The functionality, morphology, and growth of the cells inside the hydrogel matrices are dependent on the presentation of biochemicals and biophysical cues along with its physical properties such as matrix stiffness and permeability.

• Natural Hydrogels and Extracellular Matrices (ECMs)

The natural hydrogels are derived from the natural sources such as laminin, collagen, chitosan, fibrin, and hyaluronic acid. These naturally occurring gels exhibit the properties of biocompatibility and bioactivity. As they also feature endogenous factors, they promote many cellular functions which can be advantageous for supporting proliferation, viability, function, and development of many cell types. Furthermore, it offers a complex, nanoscale architecture of structural proteins laminin, collagen, and fibronectin in order to create the mechanical properties inherent in the cellular microenvironment. This significantly helps in targeting the genes the include those production of matrix metalloproteinases (MMPs), enzymes that degrade ECM components and allow tumor cell invasion, and the parts that are affected due to cell sensitivity to anti-cancer drug., cell migration, and cell proliferation.

• Synthetic Hydrogels

3D cell culture applications can be performed effectively with the help of synthetic hydrogels, when naturally derived biological matrices are not suitable. The synthetic hydrogels are comprised of purely non-natural molecules such as polyvinyl alcohol, poly-di-hydroxy-ethyl-methacrylate, and poly-ethylene-glycol. These chemicals offer structural support for various cell types but are biologically inert in nature. As this field advances, there will be a need for matrices with combined properties of natural and synthetic hydrogels.

• Solid Scaffolds

A 3D cell culture can be fabricated over a broad range of materials such as ceramics, metal, glass, and polymers by implementing solid scaffolds. The benefiting factor to this process is that it generates solid scaffolds of varying size, diverse structure, permeability, stiffness and porosity.

Many research and development organization have deemed the field of 3D cell culture to be an opportunistic segment in the field of medicine. Several enterprises have decided to venture in the 3D cell culture market as this market has a promising future. According the research by Allied Market Research, the 3D cell culture market would garner $4.69 billion by 2022, growing exponentially at a CAGR of 29.4% from 2016-2022. The market of 3D cell culture has great potential and will increase at a steady pace as new technologies and innovative products are introduced in the market.

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