Techniques of 3D bioprinting for organ production

The applications of three-dimensional printing are endless. From prototyping to specialized manufacturing, 3D printing allows users to develop unique creations for specific purposes, without requiring skills in the manufacturing process (Shimizu et al., 2000). Its use is widespread through the manufacturing and technology industries, and shows great promise in other fields as well, including healthcare.

One of the key aims of 3D printing in medicine is the printing of functional tissues for transplantation (Figure 1). While traditional printing utilizes printing layers of plastic to form solid structure, bioprinting positions biological materials, biochemicals and even living cells to form tissues and organs (Nakamura et al., 2010). However, bioprinting adds another layer of complexity, as the cells must also be functional and viable (Zopf et al., 2013). There are currently three main approaches towards bioprinting: biomimicry, autonomous self-assembly and mini-tissue building blocks.

Figure 1: A step by step approach for bioprinting 3D tissues (Murphy and Atala, 2014). Row 1: Visualization of Biomimicry Approach. Row 2: Visualization of autonomous self-assembly approach. Row 3: Visualization of mini-tissues approach.

 

The biomimicry approach involves producing an identical replica of a target tissue or organ. In this approach, both the functions and the structure are made as close as possible to the original in the attempt to successfully print a viable organ (Murphy and Atala, 2014). This approach is theoretically perfect, as long as the printed organ is identical to the original. However, the accuracy of the model depends on the scale to which the cellular environment is understood, including the specific arrangement of functional and supporting cells, and the gradients of molecules in the environment. Thus the success of the biomimicry approach is highly dependent on extensive knowledge of the cellular environment (Ingber et al., 2006).

Another approach is the autonomous self-assembly (ASA) method. As opposed to producing an identical replica, the ASA approach prints organs using embryonic transcription factors to stimulate development that is self-directed (Jakab et al., 2010; Steer and Nigam, 2004). The cell determines the specifics in ASA, so this approach does not require an extensive understanding of organ structure and the cellular environment. ASA focuses instead on manipulating the signals of histogenesis, where it provides the general direction for which organs and tissues to produce. The cell then develops into the organ tissue with the proper internal environment (Marga, Neagu, Kosztin and Forgacs, 2007).

The mini-tissues approach is a combination of the biomimicry and autonomous self-assembly methods. A mini-tissue, the smallest functional unit of an organ (ie. The nephron of a kidney), is autonomously self assembled and then artificially organized into the final organ (Mironov et al., 2009). This approach benefits from an artificial and targeted design overall, but allows the specificities of organ generation and cellular environments, areas which currently lack adequate knowledge, to be autonomous (Kelm et al., 2010).

Bioprinting is a new and exciting area of research. While there are multiple techniques used, each with their own benefits and drawbacks, the overall goal of these approaches are the same. While fully functional, kidneys can be printed, our inability to produce blood vessels significantly limits their size and practicality. Though many roadblocks still exist before us, 3D bioprinting is an important advancement in our way of thinking about medicine, and in how we integrate multiple disciplines of science to save lives.

 

Works Cited:

Ingber, D.E. et al., 2006. Tissue engineering and developmental biology: going biomimetic. Tissue Engineering, [online] 12(12), pp.3265–3283. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/17518669>.

Jakab, K. et al., 2010. Tissue engineering by self-assembly and bio-printing of living cells. Biofabrication, [online] 2(2), p.022001. Available at: <http://stacks.iop.org/1758-5090/2/i=2/a=022001?key=crossref.9918c297563e99844c8fe50c8371d385> [Accessed 13 Mar. 2015].

Kelm, J.M. et al., 2010. A novel concept for scaffold-free vessel tissue engineering: self-assembly of microtissue building blocks. Journal of Biotechnology, [online] 148(1), pp.46–55. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/20223267>.

Marga, F., Neagu, A., Kosztin, I. and Forgacs, G., 2007. Developmental biology and tissue engineering. Birth Defects Research. Part C, Embryo Today: Reviews, [online] 81(4), pp.320–328. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/18228266>.

Mironov, V. et al., 2009. Organ printing: tissue spheroids as building blocks. Biomaterials, [online] 30(12), pp.2164–2174. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/19176247>.

Murphy, S. V and Atala, A., 2014. 3D bioprinting of tissues and organs. Nature Biotechnology, [online] 32(8), pp.773–785. Available at: <http://www.nature.com/doifinder/10.1038/nbt.2958> [Accessed 13 Mar. 2015].

Nakamura, M. et al., 2010. Biomatrices and biomaterials for future developments of bioprinting and biofabrication. Biofabrication, [online] 2(1), p.014110. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/20811125>.

Shimizu, T.S. et al., 2000. Molecular model of a lattice of signalling proteins involved in bacterial chemotaxis. Nature Cell Biology, [online] 2(11), pp.792–796. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/11056533>.

Steer, D.L. and Nigam, S.K., 2004. Developmental approaches to kidney tissue engineering. American Journal of Physiology. Renal Physiology, [online] 286(1), pp.F1–7. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/14656756>.

Zopf, D.A. et al., 2013. Bioresorbable airway splint created with a three-dimensional printer. The New England Journal of Medicine, [online] 368(21), pp.2043–2045. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/23697530>.