With the rising risk of drug resistance and increasing chronic diseases, there is a surge in demand for novel biopharmaceuticals across the globe. Drug discovery remains an indispensable part of the healthcare system to combat developing drug resistance. However, it takes years of research, clinical trials, investment, and final approval from the FDA to use on humans. Traditional drug discovery involves animal testing and physical volunteers that pose a risk of drug failure due to inappropriate results. Moreover, animal cell cultures are morphologically and physiologically different from humans. Since cell culture is crucial for drug discovery, researchers have introduced a 3D cell culture that demonstrates the replica of the in vivo physiology of humans. 3D cell models and their applications have been in practice to understand the disease mechanism and drug action.
3D cell culture systems exhibit differentiated cellular function and easily simulate microenvironment conditions such as nutrient gradient and hypoxia. Owing to its significance, several researchers are using 3D cell models for clinical trials and drug development studies. Currently, 3D cell culture marketplayers are exploring different application areas, such as drug discovery, cancer research, and tissue engineering.
An Overview of 3D Cell Culture
3D cell culture is an artificial culture environment that enables the cell to grow and interact with an extracellular framework within three dimensions. In comparison to 2D cell cultures that grow on monolayer, 3D cell culture can be grown without a supporting scaffold and with the scaffold.
1. Scaffold Based 3D Cell Culturing
The most popular type of scaffold used for cell culturing includes:
▪ Hydrogels
These are polymeric materials that have a network of cross-linked polymer chains that have the potential to retain water. It can be derived from animals (collagen), plants (agarose), and chemically synthesized (matrix).
▪ Inert Matrices
Sponge-like membranes are made of polystyrene that contains minute pores for cells to grow and proliferate in vitro.
2. Scaffold Free 3D Cell Culturing
3D cell cultures can also be grown without scaffold support as they mainly rely on cells to assemble in clusters and spheroids format. Some of the common scaffold-free methods include:
▪ Hanging Drop
In this method, cells are placed in a suspended drop of nutrient medium, enabling cells to aggregate and make a spheroid shape at the bottom of droplets.
▪ Low-Adhesion Plates
The non-adhesion plates are coated with hydrophilic polymers that prevent the sticking of cells to the surface, enabling the clustering of cells together and forming an extracellular matrix.
▪ Micro Patterned Surfaces
Plastic surfaces are altered to generate multi-wells and a micro-pattern that induces cells to grow into clusters.
What Are the Advantages of 3D Cell Culture?
Cellular growth in 3D cell culture offers several benefits, including:
⬝ Stem cells that are grown in a 3D cell model have higher differentiation potential.
⬝ The study of drug efficacy and safety becomes relatively easier with 3D cell cultures, significantly reducing the time researchers spend on drug development.
⬝ 3D cell culture enables the study of drug-induced hepatotoxicity.
⬝ 3D cell cultures offer better drug resistance prediction.
⬝ Viral pathogenesis, such as viral infection, growth, and pathogen-host interactions, can be studied easily using 3D models.
Types of 3D Cell Models Used in Drug Discovery
With technological advancements, several 3D models have been created by the 3D cell culture market players to facilitate drug discovery studies. Examples of different types of 3D cell cultures include
▪ Microfluidic Organ-On-a-Chip Models
A 3D microfluidic cell culture chip designed to imitate the physiology of an organ is called an organ-on-a-chip. Within the compartments of a microchip, scaffolds supporting 3D cell growth are used. Microliter to picoliter amounts of liquid may move and disperse nutrients or other compounds throughout cells via tiny channels. Microfluidic, when combined with organ-on-a-chip, enables real-time microenvironment control such as gas exchange, nutrient flow, molecular gradients, mechanical phenomena, and fluid flow. The dynamic model enables drug action and mechanism study to be relatively easier, consequently saving plenty of time required for drug development with high precision.
▪ Organoids
Organoids have been isolated either from healthy individuals or diseased adult stem cells. The isolated organoid is then induced by pluripotent stem cells that resemble the cellular heterogeneity of the particular tissue and organ. Researchers are continually exploring new opportunities of synergistically combining organoids and organ-on-a-chip to provide advanced in-vitro technology that can be used for therapeutic applications.
What Are The 3D Cell Culture Applications in Different Drug Discovery?
3D cell cultures market players such as 3D Biotek, Advanced BioMatrix, Lena Biosciences, and TissUes have developed different 3D cell models that enable the study of cell behavior in micro-environment reflecting in vivo conditions to study a wide range of applications, including:
▪ 3D Cell Model for Drug Testing
3D cell culture has been exploited for drug development during clinical trials and non-clinical trials. It emerges as a precise cultural technique to screen drugs in a cost-effective manner. For instance, the organ-on-a-chip model can be used in biomedical research and cancer therapeutic studies.
▪ 3D Cell Culture For Tissue Engineering
The 3D cell model is widely accepted in tissue engineering applications such as organoid development, cartilage, and skin. It enables researchers to study complex behavior in a more physiological context. The spatial arrangement of a cluster of cells inside the 3D cell model influences gene expression and cell signaling pathways, thereby enabling the study of cellular behavior easily.
Recent Developments in 3D Cell Culture
Several research studies and developments have been undertaken in the 3D cell culture to explore more applications of the 3-D cell models. Some of the recent developers in the 3D cell culture market include:
⬝ In May 2023, AMSBIO announced the launch of Matrimix, an advanced 3D cell culture substrate that enables researchers to culture a broad range of tissues.
⬝ In September 2023, Inventia Life Science inked a distribution agreement with Biotron Healthcare to offer Inventia’s RASTRUM miniaturized 3D cell culturing platform within the Indian market.
3D Cell Culture: Paving Into the Future of Biomedicines
In a nutshell, 3D cell culture serves as a promising technique in tissue engineering, offering a controlled biometric environment for the study of cellular behavior and functional tissues used for regenerative medicine applications. Driven by the significance of using 3D cell culture in drug discovery, 3D cell culture market players are currently exploring more in-vitro technology combined with advanced computational technology that facilitates the study of drug action data in real-time. Considering the ongoing developments and active participation of market players, the 3D cell culture market holds a promising future.
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