Cellular Scaffolding and Modern Tissue Engineering | 3D Cell Culturing | Corning

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Since the beginning of biomedical science, one of researchers' primary goals has been figuring out how to progress cell culturing from growing cells to growing the tissues composed of these cells to growing the organs composed of these tissues. One of the biggest breakthroughs in this process has been the use of cellular scaffolding to provide a structure on which growth can proceed in an organized fashion.

Recent years have seen the emergence of a wide variety of non-scaffold-based approaches to 3D cell culturing and tissue engineering that offer benefits over — but also limitations not found in — scaffold-based alternatives. Some applications favor the scaffold-based approach; others are best-suited for a scaffold-free platform. Knowing the differences is crucial to saving time and money and avoiding the frustration of rerunning failed trials.

Over time, the hope is to create such a wide variety of highly specific growth analogues that virtually any biological condition can be recreated through a piecemeal recreation of each cell and tissue type that hierarchically governs in vivo cellular function.

Scaffold-Based Platforms Are Powerful, But Not Suited to Every Situation

Recently, labs have made incredible breakthroughs through the use of certain substances — hydrogels, in particular — to maintain a stable protein matrix that can mimic the extracellular matrix of a living animal. This provides the perfect environment for 3D culturing of many cell types, providing an environment similar to in vivo biological conditions.

But there are limitations. In particular, hydrogels are mostly homogeneous, meaning that they might not always mimic the gradients of in vivo conditions that real cells experience. Cells can also adhere to the protein matrix in some of these gels, and, as they grow along them, become less representative of real biological proliferation. Many processes rely on the extracellular matrix to proceed properly, but many do not — in particular many diseased cells that require specifically this type of research.

That's why cellular growth scaffolds now come in a wide variety of forms, such as hydrogels, permeable support wells, and electrospun fibrous scaffolds — to better provide analogues for the wide variety of cell types in the body. Organoid models often employ protein scaffolds to help cells grow properly throughout the test environment.

Different cellular scaffoldings allow different cellular processes to proceed healthily and provide meaningful experimental data about in vivo behavior.

Scaffold-Free Options Are Growing

As scientists have identified the limitations for scaffold-based growth, they have simultaneously invented new techniques to get the results they need. This has resulted in a wide and growing array of non-scaffold-based growth options.

The primary form of the non-scaffold-based platform is the spheroid platform, a multicellular aggregate that creates its own extracellular matrix. Spheroids can be created through various techniques, such as the hanging drop method, using spinner flasks, and magnetic levitation. Microplates use an ultra-low attachment surface and well geometry to form single spheroids and keep them in suspension.

More free-form growth environments allow for more representative growth of certain tissues — cancerous tissues, in particular — that naturally grow without strict adherence to a cellular scaffold. Non-scaffold-based growth offers a powerful tool to study tumor cells that ignore the cell's normal growth control mechanisms.

When they work, spheroids can provide more natural-looking results — but they only work when they can grow properly on their own or with synthetic help from scientists. Many cell types are simply too dependent on the environment created by other cells in the body, making them more difficult to grow in vitro. These are the perfect candidates for a scaffold-based approach.

For More Complex Models, a Synthesis 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 — some making use of cellular scaffolding and some not — will likely be needed to accurately simulate the action of multitissue organs.

It's these hierarchical interactions that have so confounded biomedical researchers, but remember that cells are hierarchical systems of systems, as are the organs they constitute. Any attempt to create a synthetic system will have to mimic at least the majority of these growth subsystems — and that's exactly what researchers are finally beginning to be able to do.