Periodontal Engineering Using Biomimetic Nano Scaffolds

描述（由申请人提供）：牙周病会导致包括骨、牙骨质和牙周韧带（PDL）在内的支持组织的丧失，如果不及时治疗，最终导致牙齿脱落。生长因子已被证明可以刺激骨和软组织修复，当输送到牙周骨病变。然而，人体试验未能证明临床成功的再生。成骨生长因子的输送方式对牙槽骨缺损的组织工程至关重要。本研究的长期目标是为牙周病的治疗发展最佳的重建模式。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），并含有微球用于传递生物活性因子（模仿发育和修复信号级联），将用于牙周骨缺损：促进愈合部位细胞的活动，例如成骨细胞、成水泥细胞和PDL成纤维细胞（及其祖细胞）；允许营养物质、代谢物和信号分子渗透；并在三维空间引导细胞增殖、分化和组织新生。具体目标是：1。测试纳米纤维孔壁聚合物支架是否优于“固体”孔壁支架，以及骨矿物模拟磷灰石是否促进体外钙化组织形成。2. 开发一种复合纳米纤维支架/可生物降解微球递送系统，允许控制释放并提高假定的牙周再生因子的生物利用度，并在体外评估其再生功能。3. 为了证实基于目标1和目标2的研究结果所选择的微球/支架系统在体内为牙周组织的再生提供了优越的环境。通过实现这些具体目标，我们对设计原则的理解将大大提高，用于开发一种“理想”的方式来修复被牙周疾病破坏的组织，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传递的速率和类型，该系统为多种组织工程应用的因子、基因和细胞传递方法提供了潜力。

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.