MINE-MS for horizontal bone loss treatment

MINE-MS 用于水平骨丢失治疗

• 批准号: 10202801
• 负责人: Xiaohua Liu
• 金额: $ 35.6万
• 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/10202801
• 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; 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.

项目概要 牙周炎是美国成年人中一种非常流行的口腔疾病，也是导致牙齿丧失的主要原因。 恒牙。最近估计，30 岁或以上的美国成年人中有 42% 患有牙周炎，其中 7.8%患有严重牙周炎。破坏性牙周炎的特点是牙齿支持丧失 组织，包括牙槽骨。临床上，牙槽骨丢失大致可分为垂直（骨内）和 水平（骨上）骨质流失。令人惊讶的是，牙周炎中最常见的问题是水平骨质流失 面对临床医生但很少受到关注。目前尚无令人满意的产品 水平牙槽骨丢失的治疗结果。因此，开发具有临床意义的 用于水平牙槽骨再生的创新生物材料和技术。在初步研究中， 多功能可注射纳米纤维 ECM 模拟微球 (MINE-MS) 系统，具有多种独特的 设计并制造了特征。这些特性包括高机械强度、优异的可注射性 细胞相容性好，凝固时间快，抗菌活性强，骨诱导性高。此外，还有一个短 肽 E7 对骨髓间充质干细胞 (BMSC) 具有高特异性亲和力并排斥 鉴定出上皮细胞和牙龈成纤维细胞。当 E7 肽与 MINE-MS 缀合时 表面，MINE-MS 充当了极好的生物屏障，通过显着地选择性地重新填充细胞 在体外和体内增加 BMSC 并排出上皮细胞和成纤维细胞。此外，试点 实验表明，MINE-MS 成功提升了牙槽嵴并再生了比 牙釉质基质衍生物（一种用于牙周炎治疗的临床产品）在小鼠牙周炎诱导中的作用 水平骨丢失模型。这些令人兴奋的发现使 MINE-MS 成为治疗的绝佳候选者 牙周炎中水平牙槽骨丢失的研究。因此，拟议的项目是开发和优化 用于水平牙槽骨再生的 MINE-MS 系统。这项工作提出了三个具体目标。目的 1是合成MINE-MS并优化性能，包括可注射性、凝结时间、机械性能 强度、细胞相容性和抗菌活性。目标 2 侧重于整合 BMSC 亲和肽 到 MINE-MS 表面，评估和优化其作为选择性细胞生物屏障的功能 使用体外竞争性细胞粘附测定和牙周开窗缺陷大鼠模型进行再增殖。在 目标 3，载有成骨肽的纳米球将被纳入 MINE-MS 的核心及其 将检查增强骨再生的功能。最后，优化后的 MINE-MS 将进行测试 大鼠牙周炎诱导的水平骨丢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牙槽骨流失的挑战， 向临床牙周牙槽骨再生迈出重要一步。