Periodontal Engineering Using Biomimetic Nano Scaffolds

使用仿生纳米支架的牙周工程

• 批准号: 7932524
• 负责人: PETER X MA
• 金额: $ 7.54万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-22 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932524
• 关键词: Address; Adult; Architecture; Area; BMP7 gene; Biological Assay; Biological Factors; Biology; Biomimetics; Blood Transfusion; Canis familiaris; Cell Differentiation process; Cell Proliferation; Cell-Matrix Junction; Cells; Cementoblast; Cementum Formation; Chronic; Collagen; Computer-Aided Design; Computer-Assisted Manufacturing; Coupled; Defect; Dental; Dental Cementum; Deposition; Development; Disease; Dose; Doxycycline; Drug Formulations; Engineering; Environment; Epithelial Cells; Fibroblasts; Genes; Grant; Growth Factor; Healed; Histologic; Human; Immune response; Immune system; Infection; Inflammatory; Inflammatory Response; Laboratories; Left; Lesion; Maps; Matrix Metalloproteinases; Modality; Modeling; Molds; Mus; Nanosphere; Natural regeneration; Nature; Nutrient; Osteoblasts; Osteogenesis; Patients; Periodontal Diseases; Periodontal Ligament; Periodontitis; Periodontium; Phase; Polymers; Population; Process; Rodent; Shapes; Side; Signal Transduction; Site; Staging; Stem cells; Structure; Surface; System; Techniques; Technology; Testing; Time; Tissue Differentiation; Tissue Engineering; Tissues; Tooth Loss; Tooth structure; Treatment outcome; United States; Wound Healing; alveolar bone; angiogenesis; antimicrobial; antimicrobial drug; base; bioimaging; bone; bone morphogenetic protein 7; cell motility; controlled release; design; dosage; healing; implantation; improved; in vivo; in vivo regeneration; microbial; mineralization; nano; novel; pathogen; patient population; platelet-derived growth factor BB; progenitor; public health relevance; regenerative; regenerative therapy; repaired; response; scaffold; self assembly; soft tissue; tissue processing; tomography; wound

DESCRIPTION (provided by applicant): Periodontitis results in loss of tooth-supporting tissues including bone, cementum, and periodontal ligament (PDL), ultimately leading to tooth loss if left untreated. Dental tissue loss represents the second largest patient population next to blood transfusion. With current therapies, these tooth-supporting defects can be repaired to some degree, but the results are often disappointing. Growth factors stimulate bone and soft tissue repair when delivered to periodontal bone lesions. However, human trials have failed to show consistent results in promoting regeneration. During our initial grant period, we have demonstrated that the mode of delivery and the coordination of growth factors such as BMP7 (osteoinductive) and PDGF (angiogenic and mitogenic) are critical for tissue engineering of alveolar bone defects. The hallmark of periodontal disease is the chronic and inflammatory nature of the process. However, current technologies for periodontal tissue engineering have only focused on the use of singular regenerative factors or cells, without addressing the host response or influence of contaminating microbiota. Approaches that can not only control the regenerative processes of tissue neogenesis, but also address exuberant inflammatory responses and microbial infection may be valuable. In this competing renewal proposal, we hypothesize that the robust regeneration of chronic inflammatory periodontal lesions can be achieved by coordinating the regenerative activities with the anti- matrix metalloproteinase (MMP) and anti-microbial activities via a growth factor-enhanced bioactive scaffold. For our studies, the following specific aims are proposed: SA 1. Develop nanospheres incorporated into nano-fibrous scaffolds for controlled local delivery of MMP- inhibitory/antimicrobial agents. SA 2. Develop nano-fibrous scaffold with triple-loaded nanospheres to deliver PDGF, BMP7, and MMP- inhibitory/antimicrobial agents; and optimize the combination of their release profiles to maximize periodontal regeneration in vivo. SA 3. Confirm that the nanosphere/nano-fibrous scaffold, selected based on the results from aims 1 and 2, provides a superior environment for regeneration of periodontal tissues in chronic pathogen-induced periodontal wound models. PUBLIC HEALTH RELEVANCE: Periodontitis afflicts over 50% of the adult population in the United States without a predictable treatment outcome due to its chronic inflammatory nature, with approximately 10% displaying severe disease concomitant with early tooth loss. This project should significantly advance our capacity to design a modality for restoring periodontal wounds resulted from periodontitis, leading to advanced new regenerative therapies.

描述（由申请人提供）：牙周炎会导致牙齿支持组织的损失，包括骨、牙骨质和牙周韧带 (PDL)，如果不及时治疗，最终会导致牙齿脱落。牙齿组织损失是仅次于输血的第二大患者群体。通过目前的治疗方法，这些牙齿支撑缺陷可以在一定程度上得到修复，但结果往往令人失望。当生长因子输送到牙周骨病变时会刺激骨和软组织修复。然而，人体试验未能在促进再生方面显示出一致的结果。在我们最初的资助期间，我们已经证明了 BMP7（骨诱导）和 PDGF（血管生成和有丝分裂）等生长因子的输送方式和协调对于牙槽骨缺陷的组织工程至关重要。牙周病的特点是该过程的慢性和炎症性质。然而，当前的牙周组织工程技术仅集中于单一再生因子或细胞的使用，而没有解决宿主反应或污染微生物群的影响。不仅可以控制组织新生的再生过程，而且可以解决旺盛的炎症反应和微生物感染的方法可能是有价值的。在这个竞争性的更新提案中，我们假设慢性炎症性牙周病变的强劲再生可以通过协调再生活性与抗基质金属蛋白酶（MMP）和通过生长因子增强的生物活性支架的抗微生物活性来实现。对于我们的研究，提出了以下具体目标： SA 1.开发纳入纳米纤维支架的纳米球，用于受控局部递送 MMP 抑制剂/抗菌剂。 SA 2. 开发具有三重负载纳米球的纳米纤维支架，以递送 PDGF、BMP7 和 MMP 抑制剂/抗菌剂；并优化其释放曲线的组合，以最大限度地提高体内牙周再生。 SA 3.确认根据目标1和2的结果选择的纳米球/纳米纤维支架为慢性病原体诱导的牙周伤口模型中的牙周组织再生提供了优越的环境。 公共健康相关性：牙周炎困扰着美国 50% 以上的成年人，由于其慢性炎症性质，治疗结果无法预测，其中约 10% 的人表现出严重的疾病并伴有早期牙齿脱落。该项目将显着提高我们设计修复牙周炎引起的牙周伤口的方式的能力，从而带来先进的新再生疗法。