3D Cell Culture Scaffolding Developments: Scaffold-based and Scaffold-Free Tissue Engineering New Developments in Cell Scaffolding and Scaffold-Free 3D Culture

Since the earliest days of biomedical laboratory research, a primary goal for many researchers has been figuring out how to move from simply culturing cells to growing the tissues composed of these cells and, from there, how to grow the organs composed of these tissues.

One of the biggest breakthroughs in this process has been the use of cell scaffolding. These scaffolds provide a structure on which cell and tissue growth can proceed in an organized fashion. Cell scaffolding techniques have enabled discoveries in cancer biology, drug discovery, the physiology of human diseases, and other areas. In addition, recent years have seen the emergence of a wider variety of non-scaffold-based approaches to 3D cell culturing and tissue engineering.

Scaffold-based and non-scaffold-based approaches each offer certain benefits but also come with limitations, according to the Journal of Biomedical Science. Some applications favor the scaffold-free approach, which tends to be cheaper and simpler to set up. Others, such as more complex tissue cultures and organoid models, tend to require cell scaffolding for success.

Over time, scientists and engineers hope to create such a wide variety of highly specific growth analogues that virtually any biological condition can be recreated in culture. Today, researchers are studying organs from the bone to the heart in 3D cultures, and, according to the Journal of Burn Care & Research, some applications are undergoing clinical testing.

Scaffold-Free Cell Culture Options Are Growing

The primary form of the non-scaffold-based platform is the spheroid platform. Researchers can cultivate spheroids from various cell types, but each spheroid forms as a multicellular aggregate composed of a single cell type. Corning's spheroid growth platforms, including Corning^® spheroid microplates and Corning^® Elplasia^® microplates and flasks, use Corning's Ultra-Low Attachment (ULA) surface coating and well geometry to enable uniform and reproducible spheroid formation. Other non-scaffold-based spheroid growth techniques include the hanging drop method, spinner cultures, and magnetic levitation.

Scaffold-free growth environments are well-suited for culturing cancer cells. As a result, spheroid cultures are widely used in cancer research. Additionally, scaffold-free cultures have been used in toxicology research and for certain stem cell experiments.

On the other hand, many cell and tissue types are highly dependent on the environment created by other cells in the body, making it more challenging for them to grow in vitro. These are the perfect candidates for a scaffold-based approach.

Recent Developments in Scaffold-Based Cell Culture Platforms

A traditional scaffolding technique involves using biological hydrogels, such as Corning^® Matrigel^®Matrix, to maintain a stable protein matrix that can mimic the extracellular matrix found within a living animal. This provides the perfect environment for 3D culturing of many cell types, similar to in vivo biological conditions. However, there are limitations. Natural hydrogels can be difficult to manipulate to the researcher's specifications, and their composition can vary from batch to batch.

Cellular growth scaffolds now come in a wide variety of forms with natural, synthetic, or hybrid origins to facilitate a broader range of 3D applications. For example, Corning's Synthegel^® 3D matrix kits provide a defined growth substrate, resulting in no lot-to-lot variability, which supports the growth of induced pluripotent stem cells, cancer spheroids, and other 3D cultures.

Different cellular scaffoldings enable various cellular processes to progress in a more physiologically relevant manner, providing meaningful experimental data about in vivo behavior. One type of scaffold is the permeable support, a device containing a porous membrane that separates cells growing in an insert from cells in a well below, while allowing for gases and liquids to pass through. Permeable supports create a more in vivo-like environment for cells, and researchers can use them in co-culture, drug transport, and cell migration and invasion experiments. Additional examples include electrospun fibrous scaffolds and decellularized tissues.

In Some Cases a More Complex Cell Culture Model is Needed

Some types of tissue can be well characterized with a single technique, but most complex biological structures require greater specificity in their growth environment. A complex of multiple cell culturing technologies is often needed to accurately simulate the action of multi-tissue organs. For example, a research team recently developed a tendon-on-a-chip model that uses a combination of collagen scaffolds and porous membrane barriers to simulate interactions between tendon, immune system, and vascular tissues. The team is using the model to study tendon inflammation and disease. Today, an increasing number of organ-on-a-chip models are available to study various body systems in 3D.

Learn More with Corning's Cell Culture Resources

Corning has invested in 3D culture research for more than 25 years and continues to advance scaffold-based and scaffold-free culture techniques. Explore Corning's 3D cell culture resources or sign up for 3D culture technical updates to learn more.