Periodontal Engineering Using Biomimetic Nano Scaffolds

描述（由申请人提供）：牙周炎导致牙齿支持组织（包括骨、牙骨质和牙周韧带（PDL））的丧失，如果不治疗，最终导致牙齿丧失。牙齿组织缺损是仅次于输血的第二大患者群体。使用目前的治疗方法，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。生长因子刺激骨和软组织修复时交付牙周骨病变。然而，人体试验未能显示出促进再生的一致结果。在我们最初的资助期间，我们已经证明了骨形成蛋白7（骨诱导）和血小板衍生生长因子（血管生成和有丝分裂）等生长因子的传递模式和协调对于牙槽骨缺损的组织工程至关重要。牙周病的特点是慢性和炎症性的过程。然而，目前用于牙周组织工程的技术仅集中于使用单一的再生因子或细胞，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，而且还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。在这种竞争性的更新建议中，我们假设慢性炎症性牙周病变的稳健再生可以通过生长因子增强的生物活性支架协调再生活性与抗基质金属蛋白酶（MMP）和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。开发掺入纳米纤维支架中的纳米球，用于MMP抑制剂/抗微生物剂的受控局部递送。SA 2.开发具有三重负载纳米球的纳米纤维支架，以递送PDGF、BMP 7和MMP抑制剂/抗菌剂;并优化其释放曲线的组合，以最大化体内牙周再生。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上级环境。 公共卫生相关性：在美国，牙周炎折磨超过50%的成年人口，由于其慢性炎症性质，没有可预测的治疗结果，其中约10%显示伴随早期牙齿脱落的严重疾病。该项目将大大提高我们设计牙周炎导致的牙周伤口修复模式的能力，从而导致先进的新再生疗法。

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.