Skeletal tissue engineering-from in vitro studies to large animal models

Bone is a tissue with a strong regenerative potential. New strategies for tissue engineering of bone should therefore only focus on defects with a certain size that will not heal spontaneously. In the development of tissue-engineered constructs many variables may play a role, e.g. the source of the cells used, the design and mechanical properties of the scaffold and the concentration and mode of application of growth factor(s).Models for studying new strategies for tissue engineering of bone should be based on the target tissue to be restored. However, in light of the many potential variables, which may also interact if used in combination(s), there is also a large need for relatively simple models in which variables can be tested in a limited number of animals. Moreover, in compromised bone there may be a problem with the load-bearing capacity of the remaining healthy bone. In this light, an important prerequisite for tissue-engineering constructs is that they can be tested in loaded conditions. Particularly, this latter prerequisite is very difficult to achieve. Therefore, in vitro tests for mechanical stability are very useful for evaluating the mechanical consequences of a particular reconstruction procedure prior to the animal experiment. Before a tissue-engineered construct can be introduced into a clinical trial, a final test should be available in a large animal model that is as close and relevant to a particular problematic clinical situation as possible.In the past, a series of models were developed in our laboratory that are very useful for testing tissue-engineered constructs. In this paper, we focus on the use of relatively new simple in vitro and in vivo models for hip revision surgery, segmental bone defect restoration and tumour surgery.