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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.

项目概述：牙齿脱落是最常见的器官衰竭。对许多野生动物来说，牙齿完全脱落就等于生命的终结。对人类来说，牙齿脱落会对自尊产生负面影响，并损害咀嚼、消化和/或语言等多种生理功能。在这个应用程序中，它是专门为响应而设计的