Periodontal Engineering Using Biomimetic Nano Scaffolds

使用仿生纳米支架的牙周工程

基本信息

批准号：
8105112
负责人：
PETER X MA
金额：
$ 36.39万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-30 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8105112
关键词：
Address Adult Architecture Area BMP7 gene Biological Assay Biological Factors Biology Biomimetics Blood Transfusion Bone Tissue 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

项目摘要

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撑组织的损失，包括骨骼，牙骨质和牙周韧带（PDL），如果未治疗，最终会导致牙齿脱落。牙科组织损失代表了第二大患者群体接近输血。通过当前的疗法，可以在某种程度上修复这些支撑牙齿的缺陷，但结果通常令人失望。当递送到牙周骨折时，生长因子刺激骨骼和软组织修复。但是，人类试验未能显示出促进再生的一致结果。在我们的最初赠款期间，我们证明了生长因子（例如BMP7（骨诱导）和PDGF（血管生成和有丝分裂）等生长因子的交付方式和协调方式对于肺泡骨缺陷的组织工程至关重要。牙周疾病的标志是该过程的慢性和炎症性质。但是，当前用于牙周组织工程的技术仅着眼于使用奇异再生因子或细胞的使用，而无需解决污染微生物群的宿主反应或影响。不仅可以控制组织新生成的再生过程的方法，而且还解决了炎症的炎症反应和微生物感染可能是有价值的。在这项相互竞争的更新建议中，我们假设可以通过与抗基因质金属蛋白酶（MMP）的再生活性和抗微生物活性通过生长因素增强因子增强性生长因子效应的生物活性造成活性来实现慢性炎症性牙周病变的稳健再生。在我们的研究中，提出了以下特定目标：SA 1。开发纳米球并纳入纳米纤维脚架中，以控制MMP-抑制/抗菌剂的局部递送。 SA 2。使用三重纳米球发展纳米纤维脚手架，以提供PDGF，BMP7和MMP-抑制/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，基于AIMS 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牙周组织的再生提供了卓越的环境。公共卫生相关性：牙周炎遭受了美国超过50％的成年人口，没有可预测的治疗结果，这是由于其慢性炎症性质，大约10％表现出严重的疾病与早期牙齿丧失。该项目应大大提高我们设计用于牙周炎导致牙周伤口的方式的能力，从而导致高级新的再生疗法。

项目成果

期刊论文数量（43）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Novel antibacterial nanofibrous PLLA scaffolds.

DOI：
10.1016/j.jconrel.2010.05.035
发表时间：
2010-09-15
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
0
作者：
Feng K;Sun H;Bradley MA;Dupler EJ;Giannobile WV;Ma PX
通讯作者：
Ma PX

The influence of three-dimensional nanofibrous scaffolds on the osteogenic differentiation of embryonic stem cells.

DOI：
10.1016/j.biomaterials.2009.01.009
发表时间：
2009-05
期刊：
BIOMATERIALS
影响因子：
14
作者：
Smith, Laura A.;Liu, Xiaohua;Hu, Jiang;Ma, Peter X.
通讯作者：
Ma, Peter X.

Effects of hypoxias and scaffold architecture on rabbit mesenchymal stem cell differentiation towards a nucleus pulposus-like phenotype.

缺氧和支架结构对兔间充质干细胞向髓核样表型分化的影响。

DOI：
10.1016/j.biomaterials.2011.07.049
发表时间：
2011-11
期刊：
BIOMATERIALS
影响因子：
14
作者：
Feng, Ganjun;Jin, Xiaobing;Hu, Jiang;Ma, Haiyun;Gupte, Melanie J.;Liu, Hao;Ma, Peter X.
通讯作者：
Ma, Peter X.

Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering.