Pre-clinical Models of Odontic Analogs by Endogenous Stem Cells

内源干细胞的牙类似物的临床前模型

基本信息

批准号：
8901766
负责人：
JEREMY J MAO
金额：
$ 71.38万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-10 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8901766
关键词：
Address Adult Affect American Animal Model Animals Area Biocompatible Materials Biomedical Engineering Bone Transplantation Cell Culture Techniques Cell Transplantation Cells Clinical Clinical Trials Cues Data Dental Dental Implants Dental crowns Dentures Development Devices Digestion Dimensions Edentulous Mouth Embryo Failure Family suidae Future Germ Cells Goals Growth Factor Harvest Homing Human Hypersensitivity Implantation procedure In Vitro Institutional Review Boards Literature Mastication Mechanical Stress Mechanics Metals Modeling Mouth Diseases Natural regeneration Oral cavity Organ Organ Transplantation Organ failure Patients Periodontal Ligament Physical Function Physiological Plant Roots Pre-Clinical Model Property Prosthesis Rattus Reporting Research Project Grants Shapes Speech Stem cell transplant Stem cells Technology Time Tissues Tooth Germ Tooth Loss Tooth regeneration Tooth root structure Tooth structure Translations Transplantation Work alveolar bone analog base clinical application cost design end of life implantation in vivo in vivo regeneration innovation migration novel novel strategies physical property postnatal pre-clinical preclinical study public health relevance regenerative research study response scaffold self esteem standard care stem tumorigenesis

项目摘要

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.

描述（由申请人提供）：内源性干细胞的牙齿类似物的临床前模型项目摘要牙齿脱落是最常见的器官衰竭。许多野生动植物物种的完全牙齿脱落等同于生命的尽头。对于人类而言，牙齿流失会对一个人的自尊产生负面影响，并损害多种生理功能，包括咀嚼，消化和/或语音。在此应用程序中，该应用是专门设计的对于PA-10-009，生物工程研究补助金（BRG），我们建议在临床前模型中基于天然牙根的形状和尺寸的生物材料支架开发牙齿类似物。目前，牙齿或牙齿植入物是部分或完全厌食的患者的首选治疗方法。但是，许多缺点与义齿和牙齿植入物有关，包括失败，金属过敏和过度成本。我们在初步数据中证明了牙根类似物在体内植入解剖上正确的3D生物材料支架后，用推定的牙周韧带和牙槽骨再生。该R01提案的总体目标是在临床前模型中生成概念验证数据，该模型代表了进一步开发最终临床应用的负担得起技术的强制性步骤。作为与先前涉及干细胞移植有功方法的先前牙齿再生研究的背离，所提出的实验旨在包括两种主要的创新方法。首先，所有提出的研究都将基于通过细胞多线提示寄宿内源性干细胞的归巢。不会移植细胞。如果在临床前模型和未来的临床试验中证明有效，则通过干细胞归巢的再生可能会避免与离体细胞培养，潜在污染和肿瘤发生有关的时间和成本过多的问题。其次，我们采用一种新的方法来确定脚手架生物材料的物理特性如何影响内源性茎/祖细胞的募集和分化，这种方法尚未在牙齿再生中进行研究。如果在体内开发牙齿类似物，它是生物镜的各种特性的函数，而无需传递细胞术提示或细胞，则可以进一步加速临床翻译。这些在临床前模型中提出的研究代表了牙根再生最严格的翻译工作，缺少人类临床试验，只能在临床前研究以及FDA和IRB批准后进行。