Pre-clinical Models of Odontic Analogs by Endogenous Stem Cells

描述（由申请人提供）：牙用内源性干细胞类似物的临床前模型项目总结牙齿缺失是最常见的器官衰竭。在许多野生动物物种中，牙齿完全脱落相当于生命的终结。对于人类来说，牙齿脱落会对一个人的自尊心产生负面影响，并损害多种生理功能，包括咀嚼，消化和/或言语。在这个应用程序中，是专门为响应 根据PA-10-009，生物工程研究赠款（BRG），我们提出在临床前模型中开发基于天然牙根形状和尺寸的生物材料支架的牙科类似物。目前，假牙或牙科植入物是部分或完全缺牙患者的治疗选择。然而，许多缺点与假牙和牙科植入物相关，包括失败、金属过敏和过高的成本。我们在我们的初步数据表明，牙根模拟再生与假定的牙周膜和牙槽骨植入解剖正确的三维生物材料支架在体内。R 01提案的总体目标是在临床前模型中生成概念验证数据，这是进一步开发经济实惠的技术以实现最终临床应用的必要步骤。作为从以前的牙齿再生研究，总是涉及干细胞移植的优点的方法出发，拟议的实验设计，包括两个主要的创新方法。首先，所有提出的研究将基于宿主内源性干细胞的归巢的cytotagic线索。不会移植任何细胞。通过干细胞归巢的再生，如果在临床前模型和未来的临床试验中被证明是有效的，则可以避免与离体细胞培养相关的过度时间和成本、潜在污染和肿瘤发生等问题。其次，我们采取了一种新的方法来确定支架生物材料的物理特性如何影响内源性干/祖细胞的招募和分化，这种方法在牙齿再生中尚未研究。如果牙科类似物在体内开发为生物支架的各种特性的函数，并且不递送细胞趋化因子或细胞，则可以进一步加速临床转化。这些在临床前模型中提出的研究代表了对牙根再生的最严格的转化努力， 除了人体临床试验，只有在临床前研究和FDA和IRB批准后才能进行。

DESCRIPTION (provided by applicant): Pre-clinical Models of Odontic Analogs by Endogenous Stem Cells Project summary Tooth loss is the most common organ failure. Complete tooth loss in many wildlife species equates to the end of life. For humans, tooth loss negatively impacts one's self-esteem and impairs multiple physiological functions including mastication, digestion and/or speech. In this application that is specifically designed in response to PA-10-009, Bioengineering Research Grants (BRG), we propose to develop odontic analogs based on biomaterial scaffolds in the shape and dimensions of native tooth roots in a preclinical model. Currently, dentures or dental implants are the treatments of choice for patients who are partially or completely edentulous. However, a number of drawbacks are associated with dentures and dental implants, including failure, metal allergy and excessive cost. We demonstrate in our preliminary data that a tooth root analog regenerated with putative periodontal ligament and alveolar bone upon implantation of anatomically correct 3D biomaterial scaffold in vivo. The overall goal of this R01 proposal is to generate proof-of-concept data in a preclinical model that represents an obligatory step for further development of an affordable technology towards eventual clinical applications. As a departure from previous tooth regeneration studies that invariably involve the meritorious approach of stem cell transplantation, the proposed experiments are designed to include two primary innovative approaches. First, all the proposed studies will be based on the homing of host endogenous stem cells by cytotatic cues. No cells will be transplanted. Regeneration by stem cell homing, if proven effective in pre-clinical models and future clinical trials, may circumvent issues such as excessive time and cost in association with ex vivo cell culture, potential contamination and tumoerigenesis. Second, we take a novel approach to determine how physical properties of scaffold biomaterials affect the recruitment and differentiation of endogenous stem/progenitor cells, an approach that has not been investigated in tooth regeneration. If odontic analogs are developed in vivo as a function of various properties of bioscaffolds and without the delivery of cytotactic cues or cells, clinical translation can be further accelerated. These proposed studies in a preclinical model represent the most rigorous translational effort on tooth root regeneration, short of a human clinical trial that can only be conducted after a preclinical study and after FDA and IRB approvals.