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Scaffolding
The key components of tissue engineering have remained the same since the start of the practice in the 1980s. These include cells, scaffolds, and growth-stimulating signals. Scaffolds are generally made of polymeric biomaterials, materials used to construct artificial organs or to replace tissue, and serve as structural support for cell attachment and subsequent tissue development. Over the past few decades, four major scaffolding approaches have become prevalent in the field of tissue engineering. These include pre-made porous scaffolds, decellularized extracellular matrix (ECM), cell sheets with secreted extracellular matrix, and cells encapsulated in self-assembled hydrogel.

Pre-Made Porous Scaffolds
This is the most well-known and frequently used scaffolding approach in tissue engineering. It involves seeding or implanting therapeutic cells into porous scaffolds made of synthetic or natural degradable biomaterials. These scaffolds are created when porogens (particles used to make pores) are incorporated into moulded structures. These pre-made porous scaffolds can be used for both soft and hard tissues.

Some noted advantages of this technique include that it provides the most diversified choices for materials and allows for the precise design for microstructure and architecture. However, this technique can be time consuming and may result in an uneven distribution of cells.

Decellularized Extracellular Matrix (ECM)
This technique uses tissues of either allogeneic or xenogeneic origin to provide a nature-simulating scaffold approach. Allogeneic tissues are those that are derived from the same species, whereas xenogeneic tissues are derived from a different species. These scaffolds are created by processing extracellular matrix from different tissues and removing cellular components, while preserving the ECM components. These preserved ECM components are referred to as decellularized extracellular matrix. This decellularized ECM approach is best used for tissues with high extracellular matrix content.

Noted benefits of decellularized ECM include that it allows for the most natural scaffolding approach as it possesses many of the natural mechanical and biological properties of the original tissue. But there are also some drawbacks to using this method, as it may also result in an uneven distribution of cells and could trigger an immune response if the original tissue is not properly decellularized.

Cell Sheets with Secreted Extracellular Matrix (ECM)
Cell sheet engineering is a technique which removes the need for enzymes and uses excreted extracellular matrix from cells cultured on a thermoresponsive polymer. Here, cells are cultured and regulated until the cells cover the entire surface of the polymer, or reach confluence. This is repeated with multiple layers to form a thicker matrix. Thickening the matrix causes the cells to form tight junctions and secrete ECM. This scaffolding approach can be applied to various types of tissues including epithelial tissues, endothelial tissues, and thin layer tissues.

The main benefit of this technique is that the ECM from these cell sheets is biocompatible as it does not harm living cells, whereas the main drawback of this approach is that multiple laminations are required for this technique to be effective.