In recent years a paradigm shift in understanding of human bone formation has 
occurred that starts to change current concepts in tissue engineering of bone 
and cartilage. New discoveries revealed that fundamental steps in 
biomineralization are enzyme driven, not only during hydroxyapatite deposition, 
but also during initial bioseed formation, involving the transient deposition 
and subsequent transformation of calcium carbonate to calcium phosphate mineral. 
The principal enzymes mediating these reactions, carbonic anhydrase and alkaline 
phosphatase, open novel targets for pharmacological intervention of bone 
diseases like osteoporosis, by applying compounds acting as potential activators 
of these enzymes. It is expected that these new findings will give an innovation 
boost for the development of scaffolds for bone repair and reconstruction, which 
began with the use of bioinert materials, followed by bioactive materials and 
now leading to functional regenerative tissue units. These new developments have 
become possible with the discovery of the morphogenic activity of bioinorganic 
polymers, biocalcit, bio-polyphosphate and biosilica that are formed by a 
biogenic, enzymatic mechanism, a driving force along with the development of 
novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting 
(3D cell printing) techniques that may allow a fabrication of customized 
implants for patients suffering in bone diseases in the future.