Early orthodontic correction of skeletal malocclusion takes advantage of mechanical force to stimulate unclosed suture remodeling and to promote bone reconstruction; however, the underlying mechanisms remain largely unclear. Gli1+ cells in maxillofacial sutures have been shown to participate in maxillofacial bone development and damage repair. Nevertheless, it remains to be investigated whether these cells participate in mechanical force-induced bone remodeling during orthodontic treatment of skeletal malocclusion. In this study, rapid maxillary expansion (RME) mouse models and mechanical stretch loading cell models were established using two types of transgenic mice which are able to label Gli1+ cells, and we found that Gli1+ cells participated in mechanical force-induced osteogenesis both in vivo and in vitro. Besides, we found mechanical force-induced osteogenesis through inositol 1,4,5-trisphosphate receptor (IP3R), and we observed for the first time that inhibition of Gli1 suppressed an increase in mechanical force-induced IP3R overexpression, suggesting that Gli1+ cells participate in mechanical force-induced osteogenesis through IP3R. Taken together, this study is the first to demonstrate that Gli1+ cells in maxillofacial sutures are involved in mechanical force-induced bone formation through IP3R during orthodontic treatment of skeletal malocclusion. Furthermore, our results provide novel insights regarding the mechanism of orthodontic treatments of skeletal malocclusion.
Mineralization has found widespread use in the fabrication of composite biomaterials for hard tissue regeneration. The current mineralization processes are mainly carried out in neutral aqueous solutions of biomineral counter-ions (a pair of cation and anion that form the corresponding minerals at certain conditions), which are stable only at very low concentrations. This typically results in inefficient mineralization and weak control over biomineral formation. Here, we find that, in the organic solvent glycerol, a variety of biomineral counter-ions (e.g., Ca/PO 4 , Ca/CO 3 , Ca/SO 4 , Mg/PO 4 , or Fe/OH) corresponding to distinct biominerals at significantly high concentrations (up to hundreds-fold greater than those of simulated body fluid (SBF)) are able to form translucent and stable solutions (mineralizing solution of highly concentrated counter-ions (MSCIs)), and mineralization can be triggered upon them with external solvents (e.g., water or ethanol). Furthermore, with pristine bacterial cellulose (BC) membrane as a model, we demonstrate an effective and controllable mineralization performance of MSCIs on organic substrates. This approach not only forms the homogeneous biominerals on the BC fibers and in the interspaces, but also provides regulations over mineralization rate, mineral content, phase, and dopants. The resulting mineralized BC membranes (MBCs) exhibit high cytocompatibility and favor the proliferation of rat bone marrow mesenchymal stem cells (rBMSC). Following this, we prepare a mineralized bone suture (MBS) from MBC for non-weight bearing bone fixation, which then is tested on a rabbit median sternotomy model. It shows firm fixation of the rabbit sternum without causing discernible toxicity or inflammatory response. This study, by extending the mineralization to the organic solution system of highly concentrated counter-ions, develops a promising strategy to design and build targeted mineral-based composites.
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