Abstract
Bioprinting is a rapidly developing technology that enables the exact positioning of living cells embedded in bio-materials in precise spatial arrangements to fabricate engineered tissues and organs. While the ultimate goal of bioprinting approaches is to produce organs for transplantation purposes, bioprinted organ models also hold great potential for research purposes to serve as alternatives to animal experiments. By using human cells, humanized organ models can be generated that may produce more relevant results for human (patho-)physiology than animal models. However, standard bioprinting procedures currently use numerous hidden animal components. Virtually all studies published in the field to date make use of cells grown in media with fetal bovine serum (FBS). In addition, Matrigel, the extracellular matrix (ECM) harvested from Engelbreth-Holm-Swarm sarcoma grown in mice, is widely employed to cultivate stem cells and 3D organ models. Finally, most bioinks currently in use contain gelatin or comparable animal components to improve cell viability and adhesion. The present review will give an introduction to the potential of bioprinting to fabricate 3D models that may be substituted for animal experiments and will go on to describe strategies to replace animal components currently included in standard procedures of bioprinting. These approaches comprise the adaptation of cells to FBS-free media, the use of bioinks composed of synthetic or plant material, and the replacement of animal ingredients by materials of human origin. We propose denoting bioprinting strategies devoid of animal components as clean bioprinting.
Highlights
The current biomedical research paradigm is based on initial studies in 2D cell culture followed by animal experiments
6.1 Fetal bovine serum Fetal bovine serum (FBS), known as fetal calf serum (FCS), is a commonly added supplement used in cell culture media in virtually all life science laboratories around the world
Two-dimensional cell cultures and animal models have been the dominating tools in biomedical research
Summary
The current biomedical research paradigm is based on initial studies in 2D cell culture followed by animal experiments. Animal models provide the opportunity to study (patho-)physiological phenomena in a functional biological system Their major scientific drawbacks are species-specific differences that limit the relevance of animal studies to humans. The degree of this problem is highly controversial. The high failure rate of drug candidates in clinical testing can, at least to some degree, be ascribed to differences in animal and human physiology. The main reasons for failure in clinical development are low efficacy and unexpected toxicity, which is to a certain extent due to species-specific differences in physiology between test animals and humans. Due to the uncertainties involved in predicting human toxicity, our current approach to investigate properties of drug candidates in pre-clinical development with animal experiments is under debate (Van Norman, 2019). We will argue that this concept will only have a chance to become widely established in the scientific community if the advantages of avoiding human-animal chimeric systems for obtaining human-relevant research results can be demonstrated, rather than just citing the singular consideration of improved animal welfare
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