Reducing the Use of Animal Models with Tissue Engineering

Since the dawn of medicine, the use of animals as scientific research models has been a cause of heated public, scientific, and philosophical discussion even though it is an essential source of contributions to our days’ medical progress. Over the 20th century, and with the rise of technologies available to access new scientific discoveries such as developing new drugs, the number of animals used for experimentation increased significantly. In the tissue engineering (TE) field, animal models play an essential role; they are used in primary experiments as well as in secondary testing before clinical application [1,2].


The principle of replacement, an approach developed by Russell and Burch, based on reduction and refinement strategies (3Rs), has been guiding animal experiments’ ethical treatment over the past decades. According to this principle, researchers should try to replace sentient animals with non-sentient ones, computer models, or in vitro cultures to reduce the number of animals used and to refine their techniques to minimize animal suffering [1,4].


Some countries like Japan have several laboratory animal welfare regulations. These regulations aim to cause the minimum pain and distress possible to the animal, taking into consideration the definition of animal experimentation as the use of animals for scientific purposes, following the 3Rs principle [3].


It is undeniable that TE‐based research is a promising new technology that still results in suffering and loss of animal lives; however, this field also has excellent potential for developing alternatives to animal experiments for multiple research fields. TE constructs have essential advantages over other cell-based options currently in use due to this technique’s potential to establish constructs with a 3D structure. These constructs can be designed using human cells, allowing scientists to investigate interactions between cells and the extracellular matrix since obtaining whole human tissues and organs for ex vivo culturing is very difficult. Thus, tissue engineering can translate better findings to human physiology/pathology and also can help decrease the use of animals as models [4,5]


Several companies have also created commercially available tissue models for animal replacement, mainly as a replacement strategy for animal experiments on toxicological tests using skin tissue engineering. However, TE skins still present relatively simpler structures compared to more complex organ tissues, such as vascularized parenchymal tissues.

Corporations, including L’Oréal® and Proctor & Gamble (P&G), are currently developing 3D bioprinted skin models to achieve more accuracy on tests and as an alternative to replacing animals on experiments since legislations are prone to ban animal experiments for testing cosmetic products worldwide.


Figure 1: L’Oreal’s current skin cell technology, based on skin patches grown for cells donated by plastic surgery patients [6].

Another promising technology, the organ-on-a-chip systems, are adding even more potential to the use of TE as an alternative to animal experimentation. This technology consists of 3D microfluidic cell culture chips that simulate entire organs’ behavior, mainly regarding the physiological functions. Also, it can act as a screening platform for drug development [4].


A study on the reconstitution of organ-level lung functions on a chip was performed by Huh et al. (2010). The authors designed a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung, which can provide direct visualization and quantitative analysis of the lung’s diverse biological processes in ways that have not been possible in traditional cell culture or animal models [7]. Tissue engineering approaches can originate truly representative tissue models and bring more accurate results to preclinical research, therefore presenting outstanding potential to replace animal models and end animal suffering.

Figure 2: A human organs-on-a-chip device developed by Wyss Institute at Harvard University. Credit: Wyss Institute at Harvard University.




REFERENCES


1. Nordgren, A. Moral imagination in tissue engineering research on animal models. Biomaterials 25, 1723–1734 (2004).

2. Franco, N. H. Animal Experiments in Biomedical Research: A Historical Perspective. Animals (Basel) 3, 238–273 (2013).

3. Kurosawa, T. M. Japanese regulation of laboratory animal care with 3Rs. AATEX 14, 317 (2007).

4. Liguori, G. R., Jeronimus, B. F., de Aquinas Liguori, T. T., Moreira, L. F. P. & Harmsen, M. C. Ethical Issues in the Use of Animal Models for Tissue Engineering: Reflections on Legal Aspects, Moral Theory, Three Rs Strategies, and Harm–Benefit Analysis. Tissue Engineering Part C: Methods vol. 23 850–862 (2017).

5. de Vries, R. B. M. et al. The potential of tissue engineering for developing alternatives to animal experiments: a systematic review. J. Tissue Eng. Regen. Med. 9, 771–778 (2015).

6. Scott, A. P&G funds project to 3D-print human skin. Focus Surfactants 2015, 5 (2015).

7. Huh, D. et al. Reconstituting organ-level lung functions on a chip. Science 328, 1662–1668 (2010).


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