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. The proposed project, therefore, is to develop and optimize the
MINE-MS system for horizontal alveolar bone regeneration. Three specific aims are proposed in this work. Aim
1 is to synthesize the MINE-MS and optimize the properties, including the injectability, setting time, mechanical
strength, cytocompatibility, and antibacterial activity. Aim 2 focuses on incorporating the BMSC affinity peptide
onto the MINE-MS surface, evaluating and optimizing its function as a biological barrier for selective cell
repopulation using a competitive cell adhesion assay in vitro and a periodontal fenestration defect rat model. In
Aim 3, an osteogenic peptide-loaded nanospheres will be incorporated into the core of the MINE-MS and its
function for enhanced bone regeneration will be examined. Lastly, the optimized MINE-MS will be tested for
periodontal alveolar bone regeneration in a rat periodontitis-induced horizontal bone loss model. Successful
completion of this project will address the challenge of periodontitis-induced horizontal alveolar bone loss,
making a significant step towards periodontal alveolar bone regeneration in clinic.