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

• 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
• 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

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）：内源干细胞的牙类似物的临床前模型 项目摘要 牙齿缺失是最常见的器官衰竭。许多野生动物的牙齿完全脱落就等于生命的终结。对于人类来说，牙齿缺失会对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/或言语。在此应用程序中专门针对响应而设计 根据 PA-10-009，生物工程研究补助金 (BRG)，我们建议在临床前模型中开发基于生物材料支架的牙齿类似物，其形状和尺寸与天然牙根相同。目前，假牙或种植牙是部分或完全无牙颌患者的首选治疗方法。然而，假牙和牙种植体存在许多缺点，包括失败、金属过敏和成本过高。我们在初步数据中证明，在体内植入解剖学上正确的 3D 生物材料支架后，牙根类似物可以通过假定的牙周膜和牙槽骨再生。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，这是进一步开发可负担技术以实现最终临床应用的必要步骤。与之前的牙齿再生研究总是涉及干细胞移植的优点方法不同，所提出的实验旨在包括两种主要的创新方法。首先，所有拟议的研究都将基于细胞抑制信号对宿主内源干细胞的归巢。不会移植任何细胞。如果在临床前模型和未来的临床试验中证明干细胞归巢再生有效，则可以避免诸如与离体细胞培养相关的过多时间和成本、潜在污染和肿瘤发生等问题。其次，我们采用一种新方法来确定支架生物材料的物理特性如何影响内源干/祖细胞的招募和分化，这种方法尚未在牙齿再生中进行研究。如果牙类似物是根据生物支架的各种特性在体内开发的，并且无需传递细胞趋向信号或细胞，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牙根再生方面最严格的转化努力， 缺乏人体临床试验，只能在临床前研究以及 FDA 和 IRB 批准后进行。