Assessment of Bone Healing Capacity and Osseointegration Potential of Bone Grafting Materials Loaded with Rabbit Mesenchymal Stem Cells Derived from Different Sources: in Vitro and in Vivo Studies

Dental implant therapy is a well-accepted treatment modality to replaced missing teeth. However, challenging clinical situations where insufficient amount of bone is present would decrease success rate of dental implants. Therefore, bone reconstruction (guided bone regeneration, GBR) is necessary for the successful placement of implants to avoid functional and esthetic problems. Among these bone grafting materials, synthetic bone graft materials (HA/TCP) are the most used in clinic because of the advantages of safety and efficacy. But, these materials have showed only osteoconduction capacity for bone regeneration. In order to overcome these problems, the concept of stem-cell-based regenerative therapy has been applied in recent yeas. Although the reconstruction of the craniofacial skeleton and bone regeneration demonstrated a few applications of stem-cell-based regenerative therapy, the application of mesenchymal stem cells (MSC) combined with HA/TCP scaffold in the treatment of peri-implant defects is still unclear. Moreover, the comparison of proliferative capacity and multi-lineage differentiation of MSC derived from different sources has not been fully explored. Thus, the primary aim of this study is to compare rabbit bone marrow mesenchymal stem cells (rBMSC)、rabbit adipose mesenchymal stem cells (rASC) and rabbit dental pulp mesenchymal stem cells (rDMSC) with regard to proliferation, differentiation, mineralization and gene expression when loaded in the HA/TCP in vitro. The second aim is to in vivo evaluate whether the combination of rabbit MSC derived different sources and HA/TCP scaffold could promote osseointegration of dental implants in the rabbit peri-implant defects model when comparing blood clot, HA/TCP along and autogenous bone. Based on this viewpoint, the present study was designed to assess (1) the osteogenic and mineralized potential of MSC by using cell culture methods, biochemical methods and real-time PCR (2) the bone healing capacity and osseointegration potential of the combination of scaffold and MSC by using implant stability detection, histomorphometric, fluorescence analysis, micro-CT analysis, microarray and gene expression analysis. With the completion of the two-year research project, we not only demonstrated the biochemical, biomechanical, histological and molecular evidences for the therapeutic abilities of MSC but also provide scientific information and references for the future clinical application of stem-cell-based regenerative techniques.