An essential requirement for osteoclasts in refined bone-like tissue reconstruction in vitro.

One crucial but often disregarded problem in tissue-engineered bone is that osteoblasts in culture significantly differ in function and behavior from their counterparts in vivo. This difference is represented as an inability of cultured osteoblasts to form lamellar bone-like structures and deposit the characteristic mineral of native bone, as well as their loss of polarity of matrix secretion, marked by tissue growth bridging the pore interconnections of scaffolds. These abnormalities of in vitro bone formation are a major cause of the current failure to yield functional and mechanically competent bone. Recent studies with osteoclast deficient animal models have definitely revealed that the regulatory effect of osteoclasts is essential for normal bone formation. The abnormalities of bone formation present in osteoclast deficient animals are largely reflected in current tissue-engineered bone. Reasonably, the abnormalities of in vitro bone formation most likely result from the absence of osteoclasts in current bone formation strategies. Therefore, it is hypothesized that osteoclast introduction will provide a necessary solution to the critical problems in bone tissue engineering. The way of osteoclast introduction is the first challenge in exploring its roles in bone tissue engineering. In vivo studies have shown that maturation of preosteoclasts, the cells just before fusion to form multinucleated cells, requires formation and accumulation of bone matrix despite the independence of preosteoclast appearance and bone formation. Thus, the application of preosteoclasts to biomineralized matrix for osteoclastogenesis is a physiologically relevant strategy for osteoclast introduction. In conclusion, osteoclast introduction holds the promise of structural and functional improvement of tissue-engineered bone.