As the size and complexity of 3D models increase, the need for scaffolds becomes more and more obvious. In addition to space control, cell aggregates also need to exchange nutrients and gases. When the aggregate thickness is 1-2 mm, the problem of cell death will occur due to lack of mass transfer, mainly through the exchange of nutrients and waste metabolites. This has been solved through the use of highly porous scaffolds, where the basic design considers shape, cell adhesion sites and the flow of gases, nutrients, and metabolites. Scaffolds can be made from either natural or synthetic materials. Many 3D culture systems are already available. Biomaterials can be used in 3D cell culture to enhance various forms of culture efficiency and cell function, including hydrogel, solid scaffold, acellular natural tissue and ultra-low attachment (ULA) surface.

Figure 1．Hydrogel-based artificial scaffold for cell culture (Akther, et al. 2020).

The scaffold-based techniques can realize organotypic co-culture and simulate layered tissue structure. In addition, it is compatible with existing plastic product formats and downstream analysis methods, with consistent structure, repeatability and high throughput. CD BioSciences can provide you with one-stop scaffold-based 3D cell culture service relying on our professional and experienced service support team. If you have any needs, please feel free to contact us.

Principle of Scaffold Design for 3D Cell Culture

Different cell types are embedded in scaffolds with different characteristics and shapes. For example, if engineering peripheral nerve, the natural structure of axons surrounded by soft uniaxially arranged lipoprotein myelin sheath must be considered. In contrast, osteoblasts adhere to a hard surface of bone within cuboidal sheets. Therefore, the design of the scaffold should not only reflect the tissue to be studied, but also adapt to the diversity of scaffold design of tissue engineering. An important consideration is the intended application and use. Clinical work requiring functional implants may only require a temporary biodegradable scaffold, which is remodeled by the body and replaced by natural tissue to restore the original function. In this case, the scaffold must support cell growth and differentiation, and there must be a physical match between the size of the scaffold and the size of the defect. In addition, scaffolds should be decomposed into metabolites without toxic or immunogenic reactions.

Types of Biomaterials Used in Scaffold-Based 3D Cell Culture

Type	Advantages	Disadvantages
Hydrogel	Tissue like flexibility Easily supplies water-soluble factors to cells	Low mechanical resistance
Solid scaffold	Various materials can be used Physical strength is easily adjusted	Difficulty in homogeneous dispersion of cells
Decellularized native tissue	Provides complex biochemistry, biomechanics and 3D tissues of tissue-specific extracellular matrix (ECM)	Decrease of mechanical properties (roughness, elasticity, and tension strength) of the tissues as compared to the native group
Ultra-low attachment surface	Provides an environment similar to in vivo conditions	Difficulty in mass production Lack of uniformity between spheroids

1. Haycock, John W. "3D cell culture: a review of current approaches and techniques." 3D cell culture (2011): 1-15.
2. Akther, Fahima, et al. "Hydrogels as artificial matrices for cell seeding in microfluidic devices." RSC Advances 10.71 (2020): 43682-43703.
3. Park, Yujin, Kang Moo Huh, and Sun-Woong Kang. "Applications of Biomaterials in 3D Cell Culture and Contributions of 3D Cell Culture to Drug Development and Basic Biomedical Research." International Journal of Molecular Sciences 22.5 (2021): 2491.

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