Project Summary Periodontitis is a highly prevalent oral disease among US adults and is the primary cause of the loss of permanent teeth. It was recently estimated that 42% of US adults aged 30 years or older have periodontitis, with 7.8% having severe periodontitis. Destructive periodontitis is characterized by the loss of dental supporting tissues including alveolar bone. Clinically, alveolar bone loss can be broadly divided into vertical (intrabony) and horizontal (suprabony) bone loss. Surprisingly, horizontal bone loss in periodontitis is the most common problem confronting clinicians but has received scant attention. Currently, there are no products offering satisfactory outcomes for the treatment of horizontal alveolar bone loss. Therefore, it is clinical significance to develop innovative biomaterials and technology for horizontal alveolar bone regeneration. In the preliminary studies, a multifunctional injectable nanofibrous ECM-mimicking microsphere (MINE-MS) system with several unique features was designed and fabricated. These features include high mechanical strength, excellent injectability and cytocompatibility, fast setting time, strong antibacterial activity, and high osteoinductivity. In addition, a short peptide E7 that has high specific affinity to bone marrow derived mesenchymal stem cells (BMSCs) and repels epithelial and gingival fibroblast cells was identified. When the E7 peptide was conjugated to the MINE-MS surface, the MINE-MS served as an excellent biological barrier to selectively repopulate cells by significantly increasing BMSCs and expelling epithelia and fibroblasts both in vitro and in vivo. Furthermore, the pilot experiment shows that the MINE-MS successfully elevated the alveolar crest and regenerated more bone than enamel matrix derivative (a clinical product for periodontitis treatment) in a mouse periodontitis-induced horizontal bone loss model. These exciting findings make the MINE-MS an excellent candidate for the treatment of horizontal alveolar bone loss in periodontitis..........
