An overview on biofabrication

Biofabrication is defined as the production of intricate biological products from cells, molecules, and biomaterials for different purposes in regenerative medicine and tissue engineering. Biofabrication technologies are constantly evolving and open up many possibilities for the generation of highly complex cellular constructs. 1 2 3

A critical challenge for producing biological constructs is to support and guide cell growth toward their natural microenvironment, with the presence of specific biochemical and biophysical cues that drive cell behavior. To meet these requirements, different biofabrication techniques must provide the means to control cell position and tissue architecture in 3D constructions accurately. 1

The most used technologies in biofabrication include light-based technologies, such as selective laser sintering (SLS) and stereolithography (SLA); fused deposition modeling (FDM); extrusion bioprinting, inkjet, and valve jet bioprinting; as well as electrospinning. Some of these technologies were initially developed as additive manufacturing technologies for rapid prototyping but have been remodeled to act as biomanufacturing strategies for biomedical applications. 3

3D bioprinting techniques such as fused deposition modeling and stereolithography are widely applied to fabricate scaffolds for tissue engineering applications. They provide precise control over the external macrostructure and internal microstructure. For example, in a study by Neiman et al. (2015), stereolithography was employed to fabricate hydrogel scaffolds with open channels designed for post-seeding of hepatocytes. After seven days of perfused culture, the hydrogel supports remained intact and the primary hepatocytes exhibited higher levels of albumin production. 4

Figure 1: (a) The hydrogel scaffolds were chemically coupled to filters that were chemically activated by photopatterning with stereolithography. (b) The hydrogel scaffold was designed with open channels to organize cells and tissue formation in contact with the fluid flow to facilitate mass transport of oxygen and nutrients, while the filter distributes the fluid flow (b). 4

Using another biofabrication technique, the electrospinning, Castilho et al. (2017) developed ultra-fine fiber scaffolds combining the additive fabrication of a hydroxyl-functionalized polyester, (poly(hydroxymethylglycolide-co-ε-caprolactone) (pHMGCL), with melt electrowriting (MEW). Cardiac progenitor cells (CPCs) were seeded in this scaffold and presented the ability to align more efficiently along the preferred direction of scaffolds. This study endorses that biofabricated scaffolds can support and guide the growth of CPCs, enhancing their therapeutic potential. 5

Figure 2: a) Schematic of the custom-built MEW device and its main components. b) Produced melt electrospun fiber scaffolds based on pHMGCL polymer. c) Fiber scaffold infiltrated with CPCs/Collagen hydrogel. 5


1. Di Marzio, N., Eglin, D., Serra, T. & Moroni, L. Bio-Fabrication: Convergence of 3D Bioprinting and Nano-Biomaterials in Tissue Engineering and Regenerative Medicine. Front Bioeng Biotechnol 8, 326 (2020).

2. Tenenhaus, M., Rennekampff, H. O. & Mulder, G. 8 - Living cell products as wound healing biomaterials: Current and future modalities. in Wound Healing Biomaterials (ed. Ågren, M. S.) 201–225 (Woodhead Publishing, 2016).

3. Moroni, L. et al. Biofabrication: A Guide to Technology and Terminology. Trends Biotechnol. 36, 384–402 (2018).

4. Neiman, J. A. S. et al. Photopatterning of hydrogel scaffolds coupled to filter materials using stereolithography for perfused 3D culture of hepatocytes. Biotechnology and Bioengineering vol. 112 777–787 (2015).

5.Castilho, M. et al. Melt Electrospinning Writing of Poly-Hydroxymethylglycolide-co-ε-Caprolactone-Based Scaffolds for Cardiac Tissue Engineering. Adv. Healthc. Mater.6, (2017).

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