MINE-MS for horizontal bone loss treatment

项目摘要 牙周炎是一种在美国成年人中高度流行的口腔疾病，也是导致牙周炎的主要原因 恒牙。最近估计，30岁或30岁以上的美国成年人中有42%患有牙周炎， 有重度牙周炎的占7.8%。破坏性牙周炎的特征是失去牙齿支撑。 包括牙槽骨在内的组织。临床上，牙槽骨丢失大致可分为垂直(骨内)和 水平(上)骨丢失。令人惊讶的是，牙周炎的水平骨丢失是最常见的问题。 与临床医生对峙，但很少受到关注。目前，还没有提供令人满意的产品 水平牙槽骨丢失的治疗结果。因此，开展这项研究具有重要的临床意义。 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，一个 多功能可注射纳米纤维类ECM微球(MINE-MS)系统 特征是设计和制造的。这些特点包括高机械强度、优良的可注入性 细胞相容性好，固化时间快，抗菌活性强，骨诱导性强。此外，还有一段简短的 与骨髓间充质干细胞(BMSCs)具有高度特异性亲和力的E7肽和排斥肽 鉴定上皮细胞和牙周成纤维细胞。当E7多肽与MINE-MS偶联时 表面，MINE-MS作为一种极好的生物屏障，通过显著地 体内、外均可增加骨髓间充质干细胞，清除上皮细胞和成纤维细胞。此外，飞行员 实验表明，MINE-MS成功地抬高了牙槽骨的牙槽骨，再生了更多的骨。 牙釉质基质衍生物(临床牙周炎治疗产品)对小鼠牙周炎的治疗作用 水平骨丢失模型。这些令人兴奋的发现使MINE-MS成为治疗的极佳候选药物 牙周炎患者的水平牙槽骨丢失。因此，拟议的项目是开发和优化 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。目标 1、合成了MINE-MS，并对其性能进行了优化，包括注入性、凝结时间、机械性能等 强度、细胞相容性和抗菌活性。目的2专注于整合骨髓间充质干细胞亲和肽 在MINE-MS表面，评价和优化其作为选择细胞的生物屏障的功能 用竞争性细胞黏附实验和牙周开窗缺陷大鼠模型进行体外再繁殖。在……里面 目的3，将一种载骨多肽纳米球引入到MINE-MS的核心中，并将其 增强骨再生的功能将被检验。最后，对优化后的MINE-MS进行了测试 大鼠牙周炎诱导水平骨丢失模型的牙周牙槽骨再生。成功 该项目的完成将解决牙周炎引起的水平牙槽骨丢失的挑战， 在临床上向牙周牙槽骨再生迈出重要的一步。

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.