**2. Biomimetic models**

Tissue engineering is an interdisciplinary field that applies the principles of biology and engineering to the development of functional substitutes for damaged tissue [1]. The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in human health care. By applying the basic principles of engineering and cell biology tissue engineering is helping us to move toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ [2]. The new tissues can be used as test beds in basic research and development and have potential for future use in transplan‐ tation and reconstructive surgery [3].

Biomimetics is defined as the study of the structure and function of biological systems as models for the design and engineering of biomaterials. The term biomimetics was coined by Otto Schmitt in the 1950s for the transfer of ideas and analogues from biology to technology [4]. It generally refers to human-made and engineered processes, substances, devices, or systems that imitate and therefore *mimic* natural processes and biological systems. It extends to the study of the formation, structure and function of biological substances and materials (i.e. enzymes, polymers, surfaces) and biological mechanisms or processes (i.e. catalysis, protein synthesis) aimed at synthesizing similar products by artificial mechanisms that mimic natural ones. Therefore, a biomimetic model aims to *mimic* the structure and function of a biological system in its structure or function.

Organ, tissue and cell culture have been used for decades as biomimetic models of cells, tissues and organs. The pioneering work of eminent scientists such as Sydney Ringer, Wilhelm Roux and Ross Harrison from 1880 to the early 1900s helped to establish the principles and meth‐ odology of tissue culture. Ringer developed salt solutions containing the chlorides of sodium, potassium, calcium and magnesium suitable for developing organ culture. He used this model to maintain the beating of an isolated animal heart outside of the body. Roux maintained a portion of the medullary plate of an embryonic chicken in a warm saline solution for several days, establishing the principle of tissue culture. Harrison published the first paper that successfully introduced tissue culture to settle the argument of how nerve fibres originated [5]. Although other scientists had examined cells *in vitro* several decades earlier, none of them had successfully manage to culture them and it was Harrison who first successfully overcame basic culture problems and created a technique that other investigators could follow [6]. The first permanent fibroblast-like cell line was developed by Earle in 1943 from subcutaneous mouse tissue [7]. This allowed the development of techniques for generating the first human "trans‐ formed" cell line, the HeLa cell, derived from a cervical carcinoma [8]. This resulted in the advent of cell and tissue culture. This technique is arguably one of the best and earliest examples of biomimetics and has become one of the foundations of modern biomedical research. It has been used for decades to grow tissues and cells isolated from living organisms. Tissue culture generally refers to the growth of human or animal cells *in vitro*. However, the term tissue culture can also be used to refer to the culturing of pieces of tissue, i.e. explants or whole organs in culture. It is an invaluable tool for the study of cell biology and pathology.

Organ, tissue and cell culture are powerful reductionist techniques that have allowed us to study the function of biological systems. However, they are not suitable models for every type of biological question. For example results from cell culture are often not comparable to those derived from *in vivo* studies using whole animals e.g. in studies of drug action and metabolism since the drugs are metabolized *in vivo* but not *in vitro*. Furthermore, primary or derived culture is rarely able to accurately model the physiological functions of an organ because of the difficulties associated with re-creating neural, circulatory and endocrine signals *in vitro*. Nevertheless, tissue culture remains a powerful technique and has many animal sparing applications.
