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.

Histological and Immunohistochemical Evaluation of Rh-BMP2: Effect on Gingival Healing Acceleration and Proliferation of Human Epithelial Cells

“…A strong correlation between the intensity of proliferating cells and the rate of gingival healing was also discovered. Higher rates of proliferation and new cells formation are associated with faster rates of healing [29][30][31][32].…”

“…It has been used clinically to stimulate bone formation in various applications, including spinal fusion, fracture healing, and dental bone augmentation. outcomes [28][29][30][31].…”

“…Kawecki et al [31] reported that a BMP supplementation could enhance the in vitro osteogenic potential of the bone-like substitute, which later helps in better repair of alveolar bone repair after extraction.…”

Alveolar ridge preservation in rat tooth extraction model by chitosan-derived epigenetic modulation scaffold

“…Adequate dimensions of both hard and soft alveolar tissues, especially at the buccal aspect, are crucial for dental implants and prosthodontic treatment in a functionally optimal position. Ridge preservation is a surgical technique that prevents or minimizes dimensional changes in the alveolar process by dressing various bone grafts, barrier mem-branes, and/or biological agents in a fresh extraction socket [8][9][10].Bone tissue engineering (BTE) approaches with 3-dimensional porous scaffolds have long been considered in maxillofacial bone defect regeneration and alveolar ridge preservation [11][12][13]. Chitosan-based composite scaffolds incorporating ceramics such as hydroxyapatite or biphasic calcium phosphate (BCP) have been widely used as bone substitutes because of their excellent biocompatibility and mechanical property [14][15][16][17][18].The fundamental building blocks of chromatin called nucleosomes regulate gene expression by remodeling their 3-dimensional structure to perform gene regulation of eukaryotic cells.…”

“…Adequate dimensions of both hard and soft alveolar tissues, especially at the buccal aspect, are crucial for dental implants and prosthodontic treatment in a functionally optimal position. Ridge preservation is a surgical technique that prevents or minimizes dimensional changes in the alveolar process by dressing various bone grafts, barrier mem-branes, and/or biological agents in a fresh extraction socket [8][9][10].…”