Periodontal Engineering Using Biomimetic Nano Scaffolds

描述（由申请人提供）：牙周病导致支持组织（包括骨、牙骨质和牙周韧带（PDL））的损失，如果不治疗，最终导致牙齿脱落。 生长因子已被证明刺激骨和软组织修复时，交付到牙周骨病变。 然而，人体试验未能证明临床上成功的再生。 成骨生长因子的输送方式是牙槽骨缺损组织工程的关键。 这项研究的长期目标是开发最佳的牙周病治疗重建模式。 我们提出了一种新的仿生/组织工程方法。 在这种方法中，独特的纳米纤维聚合物支架（模仿胶原结构），用表面磷灰石（模仿骨矿物质）改性，并含有用于递送生物活性因子（模仿发育和修复信号级联）的微球，将用于牙周骨缺损，以：成骨细胞、成牙骨质细胞和PDL成纤维细胞（及其祖细胞）;允许营养物、代谢物和信号分子渗透;并在三维中引导细胞增殖、分化和组织新生。 具体目标是：1.测试具有纳米纤维孔壁的聚合物支架是否上级具有“固体”孔壁的支架，以及骨矿物质模拟磷灰石是否在体外促进钙化组织形成。 2.开发一种结合纳米纤维支架/生物可降解微球的递送系统，其允许控制释放并提高推定的牙周再生因子的生物利用度，并在体外评价其再生功能。 3. 确认根据目标1和2的研究结果选择的微球/支架系统为体内牙周组织再生提供了上级环境。 通过实现这些特定的目标，我们对设计原则的理解，用于开发一个“理想”的方式来恢复牙周病破坏的组织将显着推进，从而导致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递送因子的速率和类型，该系统为多种组织工程应用的因子、基因和细胞递送方法提供了潜力。

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.