MINE-MS for horizontal bone loss treatment

MINE-MS 用于水平骨丢失治疗

• 批准号: 10364700
• 负责人: Xiaohua Liu
• 金额: $ 35.22万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-05 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10364700
• 关键词: Address; Adult; Affect; Affinity; Alveolar; Alveolar Bone Loss; Animals; Anti-Bacterial Agents; Area; Attention; Biocompatible Materials; Biological; Biomedical Engineering; Bone Marrow; Bone Regeneration; Bone Resorption; Cell Adhesion; Cells; Chemical Structure; Clinic; Clinical; Clinical Data; Clinical Trials; Data; Defect; Dental; Dental Enamel; Development; Engineering; Epithelial; Evaluation; Extracellular Matrix; Fibroblasts; Future; Gingiva; Goals; Health; In Situ; In Vitro; Injectable; Mandible; Marrow; Mechanics; Membrane; Mesenchymal Stem Cells; Microspheres; Modality; Modeling; Modification; Morphology; Mouth Diseases; Mus; Nanosphere; Natural regeneration; Outcome; Peptides; Periodontal Ligament; Periodontitis; Persons; Population; Procedures; Property; Rattus; Regenerative capacity; Surface; System; Technology; Testing; Therapeutic; Time; Tissues; Tooth Loss; Tooth root structure; Treatment outcome; Work; aged; alveolar bone; bone; bone loss; cell type; clinical application; clinically significant; design; experimental study; improved; in vitro Assay; in vivo; innovation; mechanical properties; nanofabrication; nanofiber; novel; osteogenic; permanent tooth; pre-clinical; regenerative; regenerative therapy; stem cell differentiation; tissue regeneration

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.

项目总结