Bone tissue regeneration indento-alveolar surgery : clinical and experimental studies on biomaterials and bone graft substitutes

Abstract: Pathological processes in the alveolar and facial bones can lead to bone loss that may not heal with complete regeneration. Biomaterials can be used to facilitate the healing process and/or as a bone substitute, but the mechanisms are not fully understood. Persistent leakage of bacteria/bacterial toxins, after root canal treatment, may lead to a residual bone defect. The healing is dependent on a placed dental biomaterial providing a tight seal. The composition of the filling material may also influence the healing process. The general aim of this study is to investigate surface properties and biological interactions of biomaterials used in dento-alveolar surgery. A dental biomaterial, a bonded compomer (DAP) containing a corroding glass filler, was used as a root end filling material, promoting a new operation technique. The healing (assessed according to Molven´s x-ray criteria) demonstrates a significant improvement in healing results for the compomer group, compared to a commonly used technique. The surface properties and biological interactions of DAP were analyzed. ICP-OES of DAP cell culture medium extract demonstrated a significant release of Sr, Si and F from the dental biomaterial. Human periodontal ligament (PDL) cells grew on and around DAP specimens without any sign of toxic reactions. DAP extract stimulated proliferation of PDL cells, but caused an inhibition of osteoblastic gene expression in mouse bone marrow cells. The surface properties of the glass containing compomer may contribute to improved healing of the periapical lesions. A bovine inorganic bone graft substitute (BO) is commonly used as a treatment option in dento-alveolar surgery with new bone formation in immediate close contact with BO material. ICP-OES dissolution analysis of cell culture media, after incubation with BO particles, demonstrated a dosedependent release of Si and a decrease of Ca and P. An uptake of Ca from the medium to the BO particle was demonstrated with calcium-45 labeling. The Si dissolution varied between different batches, possibly reflecting a variation in food intake in the animals. Stimulated osteogenic response was seen in close contact to the BO particles in cell cultures. Furthermore, it was clearly demonstrated that the study design is a critical factor for correctly understanding biomaterials’ biological interactions. The surface properties of three bone graft substitutes reported to have good results in dento-alveolar surgery were investigated, in order to establish whether or not dissolution-precipitation reactions could contribute to the bone healing. Dissolution-precipitation extracts of BO, bioactive glass 45S5 (BG) and a marine algae hydroxyl apatite (AP) in cell culture media were analyzed. Dissolution of Si at significant levels was detected for BO and 45S5 over time. Significant uptake levels of Ca and P from the culture were seen for both 45S5, BO and AP but at different times. Surface analysis of the biomaterials with SEM/EDAX, before and after immersion in cell culture media, revealed a smoothing of the surface morphology for 45S5 over time. No obvious alterations for BO and AP were detected. Ca/P ratio decreased significantly for 45S5, but no major changes were detected by XPS for BO or AP. XPS further demonstrated a surface charge for BO, changing from negatively to positively charged when exposed to serum. 45S5 and AP had positive surface charges, both in the absence and the presence of serum. These demonstrated surface changes in biomaterials could contribute to adherence of cells and subsequently affect bone healing. Conclusion: Biomaterials used in dento-alveolar surgery interact with biological surroundings through surface and dissolution-precipitation reactions which may have implications for bone healing.