In silico biology of bone modelling and remodelling: regeneration.

Bone regeneration is the process whereby bone is able to (scarlessly) repair itself from trauma, such as fractures or implant placement. Despite extensive experimental research, many of the mechanisms involved still remain to be elucidated. Over the last decade, many mathematical models have been established to investigate the regeneration process in silico. The first models considered only the influence of the mechanical environment as a regulator of the healing process. These models were followed by the development of bioregulatory models where mechanics was neglected and regeneration was regulated only by biological stimuli such as growth factors. The most recent mathematical models couple the influences of both biological and mechanical stimuli. Examples are given to illustrate the added value of mathematical regeneration research, specifically in the in silico design of treatment strategies for non-unions. Drawbacks of the current continuum-type models, together with possible solutions in extending the models towards other time and length scales are discussed. Finally, the demands for dedicated and more quantitative experimental research are presented.