Gene Therapy for Reconstructing Periodontal Tissues

牙槽骨缺损修复的一个主要挑战是 同时修复牙槽骨、牙骨质和功能性牙周韧带（PDL）。 到目前为止，主要的局限性存在的可预测性和程度的再生实现， 再生牙周治疗基因治疗已显示出强大的潜力， 靶向、递送和改善生长促进因子（如BMP和PDGF）生物利用度 来刺激牙周缺损的修复。这次竞争性更新的目标是 开发新的组合基因递送策略，并将其应用于口腔和 牙周病的治疗方法将采用方法优化基因 使用合适的载体递送系统和载体转移生长促进分子 修复相关牙槽骨（牙齿支撑）缺损的结构。具体目标是 建议如下： 具体目标1：确定组合基因递送策略向组织递送的能力 在大鼠实验性牙周病模型中构建牙周组织 作为体内基因治疗载体的全身生物分布的量度。 具体目标2：使用常规和非常规的基因递送策略来应用组合基因递送策略。 基于图像的支架在实验性牙齿再生医学中的应用 支持比格犬的骨缺损。 这些研究结果将有助于更好地了解持续生长因子和基因 牙周创伤修复的药物。该项目的长期目标将优化和验证 临床前基因治疗方法，以提供足够的证据，考虑应用于 人类临床条件下修复大牙周和口腔和颅面骨缺损。

A major challenge in the reconstruction of tooth-supporting alveolar bone defects is the simultaneous restoration of alveolar bone, cementum and a functional periodontal ligament (PDL). To date, major limitations exist with the predictability and extent of regeneration achievable via available regenerative periodontal therapies. Gene therapy has demonstrated strong potential to target, deliver, and improve bioavailability of growth-promoting factors (such as BMPs and PDGFs) to stimulate the re-engineering of periodontal defects. The goal of this competitive renewal is to exploit novel combinatorial gene delivery strategies and apply them to relevant models of oral and periodontal disease reconstructive modalities. Approaches will be employed to optimize gene transfer of growth promoting molecules using appropriate carrier delivery systems and vector constructs to repair relevant alveolar bone (tooth-supporting) defects. The specific aims of this proposal are: Specific Aim 1: To determine the ability of combinatorial gene delivery strategies to tissue engineer periodontal structures in an experimental periodontal disease model in rats as well as measure systemic biodistribution of gene therapy vectors in vivo. Specific Aim 2: To apply combinatorial gene delivery strategies using conventional and image-based scaffolding for regenerative medicine applications in experimental tooth- supporting bone defects in beagle dogs. Results from these studies will aid in the better understanding of sustained growth factor and gene delivery on periodontal wound repair. The long-term goal of this project will optimize and validate preclinical gene therapeutic approaches to provide sufficient evidence to consider application to human clinical conditions to repair large periodontal and oral and craniofacial bone defects.