In the 21st century the focus of tissue engineering/regenerative medicine (TE/RM) strategies did change its aim from repair to regeneration [1–4]. In concert, interdisciplinary teams composed of scientists, engineers and clinicians in the field of TE/RM are now applying the principles of cell transplantation, biomaterial science, and bioengineering to design and fabricate tissue engineered constructs (TEC) that can restore and maintain normal function in diseased and injured tissues [5, 6]. In biology, regeneration is the process of renewal and restoration that makes genomes, cells, tissues, and organs, resilient to natural fluctuations or events that cause trauma and/or injury [7]. The benchmark for tissue engineers working on limb regeneration is the newt. For example, an adult salamander can regenerate a lost arm or leg over and over again; regardless of how many times the part is amputated [8]. Frogs can regenerate a limb during tadpole stages when their limbs are first growing out, but they leave behind this regeneration potential in adulthood [9]. Even mammalian embryos have some ability to replace developing limb buds, but that competence is lost well before birth. Indeed, this trend toward declining regenerative capacity over the course of an organism’s development is mirrored in the evolution of higher animal forms, leaving newts such as a salamander as the only vertebrate still able to regrow tissues/organs throughout its lifetime. The very first responses of tissues at an amputation site are not that different in salamanders and in humans, but eventually human tissues form a scar, whereas the newt’s reactivate a kind of embryonic development plan which allows the cells to access an encoding programme designed to build a new limb. It is hypothesised that understanding firstly how to recognise and subsequently instruct the human wound environment to trigger salamander-like healing patterns combined with advanced surgical treatment concepts, biomaterials, tissue engineering technologies and stem cell expertise could make it possible to regenerate large volume tissue-interfaces (bone, muscle, neurovascular bundle) of a human limb such as an upper arm or lower leg. Many different types of tissue can be found in a human limb: bone, ligaments, tendons, muscle, nerves, skin, and blood vessels. All of these different tissues have to work together immaculately. Growing new arms just isn’t possible yet, though we are making progress toward helping many patients in need of a single new tissue. Currently, we can build tissue engineered constructs (TECs) that replace a few simple functions of very complex organs. For example, engineered skin is available on the market that can adequately perform the job of real skin as a barrier against the environment [9]. We can also make significant amounts of engineered bone [10] and cartilage [11, 12] and several groups around the world have concepts in place for engineering tendons, ligaments, muscles, peripheral nerves and blood vessels, which have been tested in rodents and some in preclinical animal studies [13]. Although it is clear that much remains to be studied and understood in limb regeneration research, we as scientists are heading in the right direction by taking the necessary D. W. Hutmacher (&) Science and Engineering Faculty, Regenerative Medicine Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia e-mail: dietmar.hutmacher@qut.edu.au
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