Elucidation of 3D cell growth and its applications for periodontal regeneration therapy

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Tissue engineering offers a promising new approach to regenerating lost periodontal tissues. In periodontal tissue engineering, however, the sourcing of most of the relevant cells is limited by poor accessibility, whereas the use of readily available gingival fibroblasts is hampered because of their inhibitory effects on bone formation. T address the latter drawback, we developed a new graft composed of fibronectin (FN) matrix-based multilayered cell sheets of human gingival fibroblasts modified to express alkaline phosphatase(ALP). This study was undertaken to invest the effects of this graft, called the FN-ALP transplant, on the healing of periodontal defects in a rat model. After implantation, the FN-ALP transplants healed alveolar bone defects by intramembraneous ossification, with formation of cementum and periodontal ligament. FN-ALP transplants increased new bone formation, by endochondral ossification, on the mandibular cortex adjacent to the defect. Grafted fibroblasts were located near host osteoblasts and chondrocyte precursor cells early in the ossification process but were undetectable on and in newly formed bone and cartilage. These results indicate that the FN-ALP transplants support alveolar bone regeneration within the defect and augment bone formation outside the defect through the recruitment of host osteo/chondrogenic cells, suggesting their potential for periodontal tissue engineering applications.