A model of human bone regeneration: morphological, cellular and molecular aspects

Aim The postoperative healing of the cystic cavity was chosen as experimental model of bone regeneration. The morphological, cellular and molecular events characterizing the stages of regeneration, from the clot to the bone formation within the cystic cavity were investigated. Materials and methods Samples of regenerating tissue taken 15 days, 1, 2 and 4 months after surgery were analyzed. A total of 8 samples were collected, 4 of which were from the same patient (longitudinal study) and 4 from different patients (cross-sectional study). The investigations performed were: SEM analysis of all samples; transmission electron microscopy of samples taken after 15 days and 1 month; primary cell cultures of samples taken after 15 days and 1 month; Western blotting of cell lysates to highlight the presence of proteins characteristic of osteoblasts, such as osteocalcin, BMP2 and transglutaminase. Clinical and radiographic examinations completed the analyses. Results Results confirm that a spontaneous bone regeneration occurs after enucleation of jaw cysts, even in patients with large bone defects. The bone healing process is slow, in particular bone maturation, which is still not completed after 4 months. Remodeling of the matrix begins after 15 days and is evident after 1 month, also demonstrated by the high expression level of transglutaminase in the preosteoblastic cells isolated from the samples. The first phase of bone healing, characterized by an osteoid matrix replacing the osteo-coagulum, can be considered completed after about 2 months. Conclusion The basic conditions for spontaneous bone regeneration are: migration of undifferentiated mesenchymal cells from the overhanging periosteum and of osteoblasts from the surrounding endostium; fibrin matrix supporting the amplification and the differentiation of pluripotent mesenchymal cells; cooperation of platelets, macrophages and immunocompetent cells; significant neoangiogenesis ensuring new tissue vascularization.