MINE-MS for horizontal bone loss treatment

MINE-MS 用于水平骨丢失治疗

• 批准号: 10542374
• 负责人: Xiaohua Liu
• 金额: $ 35.56万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10542374
• 关键词: Acceleration; Address; Adult; Affect; Affinity; Alveolar; Alveolar Bone Loss; Animals; Anti-Bacterial Agents; Area; Attention; Biocompatible Materials; Biological; Biomedical Engineering; Bone Regeneration; Bone Resorption; Cell Adhesion; Cells; Chemical Structure; Clinic; Clinical; Clinical Trials; Data; Defect; Dental; Dental Enamel; Development; Engineering; Epithelium; Evaluation; Extracellular Matrix; Fibroblasts; Future; Gingiva; Goals; Health; In Situ; In Vitro; Injectable; Mandible; Mechanics; Membrane; Mesenchymal Stem Cells; Microfabrication; Microspheres; Modality; Modeling; Modification; Morphology; Mouth Diseases; Mus; Nanosphere; Natural regeneration; Outcome; Peptides; Periodontal Ligament; Periodontitis; Persons; Population; Porosity; Procedures; Property; Rattus; Regenerative capacity; Shapes; Surface; System; Technology; Testing; Therapeutic; Time; Tissues; Tooth Loss; Tooth root structure; Treatment outcome; Work; aged; alveolar bone; bone; bone loss; bone marrow mesenchymal stem cell; 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.

项目摘要 牙周炎是美国成年人中高度普遍的口腔疾病，是丧失的主要原因 永久牙齿。最近估计，有42％的美国30岁以上的美国成年人患有牙周炎，患有 7.8％患有严重牙周炎。破坏性牙周炎的特征是牙齿支撑失去 包括牙槽骨在内的组织。临床上，牙槽骨流失可以大致分为垂直（内部）和 水平（肩部）骨质流失。令人惊讶的是，牙周炎的水平骨质流失是最常见的问题 面对临床医生，但受到了很少的关注。目前，没有提供令人满意的产品 治疗水平肺泡骨质流失的结果。因此，发展是临床意义 用于水平肺泡骨再生的创新生物材料和技术。在初步研究中 多功能注射纳米纤维ECM模拟微球（Mine-MS）系统具有多个独特的 功能是设计和制造的。这些功能包括高机械强度，出色的注射性 和细胞相容性，快速设定时间，较强的抗菌活性和较高的骨诱导率。另外，一小段 肽E7与骨髓具有高特异性的衍生性间充质干细胞（BMSC）并排斥的肽E7 鉴定出上皮和牙龈成纤维细胞。当将E7肽连接到矿山时 表面，矿山是通过显着重新填充细胞的极好的生物屏障 在体外和体内增加BMSC并驱除上皮和成纤维细胞。此外，飞行员 实验表明，矿山成功升高了牙槽波峰，并再生的骨头比 小鼠牙周炎诱导的搪瓷基质衍生物（用于牙周炎治疗的临床产品） 水平骨质流失模型。这些令人兴奋的发现使矿山成为治疗的绝佳候选者 牙周炎水平肺泡骨质流失。因此，拟议的项目是开发和优化 水平肺泡骨再生的矿山系统。这项工作提出了三个具体目标。目的 1是合成矿山，并优化属性，包括注射性，设定时间，机械 强度，细胞相容性和抗菌活性。 AIM 2专注于合并BMSC亲和肽 进入Mine-MS表面，评估并优化其作为选择性细胞的生物屏障的功能 在体外使用竞争性细胞粘附测定和牙周发射缺陷大鼠模型的重生。在 AIM 3，将成骨的肽纳米球纳入了矿山及其核心及其核心 将检查增强骨骼再生的功能。最后，优化的矿山将进行测试 大鼠牙周炎诱导的水平骨质流失模型中的牙周牙槽骨再生。成功的 该项目的完成将解决牙周炎引起的水平肺泡骨质流失的挑战， 在临床上迈出了牙周牙槽骨再生的重要一步。