Transplantation of engineered bone tissue using a rotary three-dimensional culture system

• Published in: In vitro cellular & developmental biology. Animal 2007-02, Vol.43 (2), p.49-58
• Main Authors: Hidaka, Miyoko, Su, George Nan-Chang, Chen, Joy Kuan-Hao, Mukaisho, Ken-ichi, Hattori, Takanori, Yamamoto, Gaku
• Format: Article
• Language: English
• Subjects: 3-D culture system; Allogenous transplantation; Animals; Bone and Bones - blood supply; Bone and Bones - cytology; Bone and Bones - physiology; Bone defect model; Bone Matrix - cytology; Bone Matrix - physiology; Bone Regeneration; Bone Substitutes; Bone tissue engineering; Bone Transplantation; Bones; Calcification, Physiologic; Calcium; CELL AND TISSUE MODELS; Collagens; Japanese culture; Laboratory staining techniques; Mice; Mice, Nude; Osteoblast; Osteoblasts; Osteoblasts - cytology; Osteoblasts - metabolism; Osteogenesis - physiology; Rats; Rats, Wistar; Tissue Culture Techniques; Tissue engineering; Tissue Engineering - methods; Tissue Transplantation; Transplantation
• ISSN: 1071-2690; 1543-706X
• DOI: 10.1007/s11626-006-9005-1

Bone is a complex, highly structured, mechanically active, three-dimensional (3-D) tissue composed of cellular and matrix elements. We previously published a report on in situ collagen gelation using a rotary 3-D culture system (CG–RC system) for the construction of large tissue specimens. The objective of the current study was to evaluate the feasibility of bone tissue engineering using our CG–RC system. Osteoblasts from the calvaria of newborn Wistar rats were cultured in the CG–RC system for up to 3 wk. The engineered 3-D tissues were implanted into the backs of nude mice and calvarial round bone defects in Wistar rats. Cell metabolic activity, mineralization, and bone-related proteins were measured in vitro in the engineered 3-D tissues. Also, the in vivo histological features of the transplanted, engineered 3-D tissues were evaluated in the animal models. We found that metabolic activity increased in the engineered 3-D tissues during cultivation, and that sufficient mineralization occurred during the 3 wk in the CG–RC system in vitro. One mo posttransplantation, the transplants to nude mice remained mineralized and were well invaded by host vasculature. Of particular interest, 2 mo posttransplantation, the transplants into the calvarial bone defects of rats were replaced by new mature bone. Thus, this study shows that large 3-D osseous tissue could be produced in vitro and that the engineered 3-D tissue had in vivo osteoinductive potential when transplanted into ectopic locations and into bone defects. Therefore, this system should be a useful model for bone tissue engineering.