Periodontal Engineering Using Biomimetic Nano Scaffolds

使用仿生纳米支架的牙周工程

• 批准号: 6897534
• 负责人: PETER X MA
• 金额: $ 36.4万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6897534
• 关键词: apatites; biodegradable product; bioengineering /biomedical engineering; biological signal transduction; biomimetics; bioreactors; biotechnology; bone morphogenetic proteins; cementum; collagen; dental pharmacology; dogs; drug delivery systems; gene expression; genetic mapping; laboratory rat; microcapsule; nanotechnology; osteoblasts; osteogenesis; periodontium; periodontium disorder; platelet derived growth factor; polymers; regeneration; restorative dentistry; technology /technique development; tissue engineering; tissue support frame

DESCRIPTION (provided by applicant): Periodontal diseases result in loss of supporting tissues including bone, cementum, and periodontal ligament (PDL), ultimately leading to tooth loss if left untreated. Growth factors have been shown to stimulate bone and soft tissue repair when delivered to periodontal bone lesions. However, human trials have failed to demonstrate clinically successful regeneration. The mode of delivery of osteogenic growth factors appears to be critical for tissue engineering of alveolar bone defects. The long-term goal of this research is to develop optimal reconstructive modalities for the treatment of periodontal diseases. We propose a novel biomimetic/tissue engineering approach. In this approach an unique nano-fibrous polymer scaffolding (mimicking collagen architecture), modified with surface apatite (mimicking bone mineral), and containing microspheres for delivery of bioactive factors (mimicking development and reparative signaling cascades) will be used in periodontal osseous defects to: promote activities of cells at the healing site, e.g., osteoblasts, cementoblasts, and PDL fibroblasts (and their progenitor cells); allow for nutrients, metabolites, and signal molecules to permeate; and guide cell proliferation, differentiation and tissue neogenesis in three dimensions. The specific aims are: 1. To test whether polymer scaffolds with nano-fibrous pore walls are superior to scaffolds with "solid" pore walls, and whether bone mineral-mimic apatite promotes calcified tissue formation, in vitro. 2. To develop a combined nano-fibrous scaffold/biodegradable microsphere delivery system that allows for controlled release and improve bioavailability of putative periodontal regenerative factors and to evaluate their regenerative function, in vitro. 3. To confirm that the microsphere/scaffold systems selected based on the results from studies under aims 1 and 2, provide a superior environment for regeneration of periodontal tissues, in vivo. By accomplishing these specific aims, our understanding of design principles to use for developing an "ideal" modality for restoring tissues destroyed by periodontal diseases will be significantly advanced, resulting in new and improved periodontal regenerative therapies. Furthermore, with our ability to manipulate the scaffolding structure and control the rate and types of factors delivered, this system offers potential for factor, gene and cell delivery approaches for multiple tissue engineering applications.

描述(申请人提供)：牙周病会导致支持组织的丢失，包括骨、牙骨质和牙周膜(PDL)，如果不治疗，最终导致牙齿脱落。已有研究表明，当生长因子被输送到牙周骨病变时，可以刺激骨和软组织的修复。然而，人体试验未能证明再生在临床上是成功的。成骨生长因子的输送方式对于牙槽骨组织工程修复牙槽骨缺损至关重要。这项研究的长期目标是开发治疗牙周病的最佳重建方式。我们提出了一种新的仿生/组织工程方法。在这种方法中，一种独特的纳米纤维聚合物支架(模仿胶原结构)、表面磷灰石修饰(模仿骨矿物质)并含有输送生物活性因子的微球(模仿发育和修复信号级联反应)将被用于牙周骨缺损中：促进愈合部位的细胞，如成骨细胞、成牙骨质细胞和PDL成纤维细胞(及其前体细胞)的活动；允许营养物质、代谢物和信号分子渗透；以及在三维空间引导细胞增殖、分化和组织新生。其具体目的是：1.在体外测试具有纳米纤维孔壁的聚合物支架是否优于具有“实心”孔壁的聚合物支架，以及类骨矿物磷灰石是否促进钙化组织的形成。2.研制一种复合纳米纤维支架/可生物降解微球给药系统，可控制释放牙周再生因子并提高其生物利用度，并对其体外再生功能进行评价。3.根据AIMS 1和AIMS 2的研究结果选择的微球/支架系统，为体内牙周组织的再生提供良好的环境。通过实现这些特定的目标，我们对用于开发修复被牙周病破坏的组织的“理想”模式的设计原则的理解将显著提高，从而产生新的和改进的牙周再生疗法。此外，由于我们能够操纵支架结构并控制因子输送的速度和类型，该系统为多种组织工程应用提供了因子、基因和细胞输送方法的潜力。