Preclinical Evaluation of BMP-9-Treated Human Bone-like Substitutes for Alveolar Ridge Preservation following Tooth Extraction

Abstract

The success of dental implant treatment after tooth extraction is generally maximized by preserving the alveolar ridge using cell-free biomaterials. However, these treatments can be associated with inflammatory reactions, leading to additional bone volume loss hampering dental implant positioning. Our group developed a self-assembled bone-like substitute constituted of osteogenically induced human adipose-derived stromal/stem cells (hASCs). We hypothesized that a bone morphogenetic protein (BMP) supplementation could improve the in vitro osteogenic potential of the bone-like substitute, which would subsequently translate into enhanced alveolar bone healing after tooth extraction. ASCs displayed a better osteogenic response to BMP-9 than to BMP-2 in monolayer cell culture, as shown by higher transcript levels of the osteogenic markers RUNX2, osterix (OSX/SP7), and alkaline phosphatase after three and six days of treatment. Interestingly, BMP-9 treatment significantly increased OSX transcripts and alkaline phosphatase activity, as well as pro-angiogenic angiopoietin-1 gene expression, in engineered bone-like substitutes after 21 days of culture. Alveolar bone healing was investigated after molar extraction in nude rats. Microcomputed tomography and histological evaluations revealed similar, or even superior, global alveolar bone preservation when defects were filled with BMP-9-treated bone-like substitutes for ten weeks compared to a clinical-grade biomaterial, with adequate gingival re-epithelialization in the absence of resorption.