Bioengineered 3D Tooth Constructs for Whole Tooth Regeneration

用于全牙再生的生物工程 3D 牙齿结构

• 批准号: 9189150
• 负责人: Elizabeth Erin Smith
• 金额: $ 4.01万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-16 至 2018-05-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9189150
• 关键词: Alveolar Bone Loss; Biological; Biomedical Engineering; Biomimetics; Cell Communication; Cell Differentiation process; Cells; Cellular Morphology; Data; Dental; Dental Cementum; Dental Enamel; Dental Pulp; Dentin; Development; Effectiveness; Enamel Organ; Encapsulated; Endothelial Cells; Epithelial; Epithelial Cells; Exhibits; Failure; Fracture; Gelatin; Gingiva; Goals; Growth; Health; Histological Techniques; Human; Hydrogels; Impairment; Implant; In Vitro; Jaw; Life; Mastication; Measures; Mechanics; Mesenchymal; Mesenchymal Stem Cells; Metabolic; Methods; Modeling; Nerve; Oral health; Organ; Outcome; Patients; Periodontal Ligament; Physiological; Plant Roots; Process; Production; Property; Rattus; Research; Sensory; Shapes; Specific qualifier value; Testing; Tissue Engineering; Tissues; Tooth Crowns; Tooth Germ; Tooth Loss; Tooth Tissue; Tooth regeneration; Tooth structure; Umbilical vein; Validation; Vascularization; Work; alveolar bone; base; body system; clinical application; clinically relevant; design; experience; implantation; improved; in vivo; methacrylamide; mineralization; novel; novel strategies; scaffold; social; subcutaneous

Currently, there are no replacement tooth therapies that provide the function and sensory responsiveness of natural teeth. Our long-term goal is to design and develop functional bioengineered, vital, whole tooth constructs for clinical applications as an improved alternative to synthetic dental implants. The objective of the proposed study is to fabricate biomimetic tooth constructs of specified size and shape using post-natal dental cells encapsulated in gelatin methacrylamide (GelMA) hydrogel scaffolds. We hypothesize that “tunable” GelMA hydrogel constructs will promote improved dental cell interactions leading to the formation of mineralized dental tissues. The rationale for the proposed research includes the significant health need, our strong preliminary data, and the need for alternatives to currently used replacement tooth therapies. Results from the proposed studies could also be used to develop other bioengineered tissue and organ systems that require proper epithelial and mesenchymal cell interactions. We will test the hypothesis with the following specific aims: 1. Identify growth factors that can be incorporated into GelMA constructs to promote dental cell differentiation and mineralized dental tissue formation. 2. Identify scaffold design for improved DE cell differentiation and enamel production. 3. Characterize biomimetic GelMA tooth bud constructs grown in an in vivo rat jaw implant model. The analyses that we will use to investigate the effectiveness of these different fabrication strategies of GelMA tooth bud constructs include 3D radiographic techniques, and histological and immunohistochemical methods, to measure the extent of polarized dental cell morphology, differentiation, and organized construct mineralization. The expected outcomes of the proposed study include an improved biomimetic 3D tooth bud model that facilitates the formation of organized, functional, bioengineered teeth of specified size and shape. Validation of a functional biomimetic 3D tooth bud will have a significant impact on the tooth tissue engineering field by providing a clinically relevant alternative to artificial dental implants. The contribution of the proposed research is significant as it aims to enhance the quality of dental and oral health for people suffering from tooth loss as well as contribute to other studies aiming to bioengineer similar organs and tissues.

目前，还没有提供功能和感觉的替代牙齿疗法。 天然牙齿的响应性。我们的长期目标是设计和开发功能生物工程，至关重要的， 用于临床应用的全牙结构，作为合成牙种植体的改进替代品。这个 这项拟议的研究的目标是制造特定大小和形状的仿生牙齿结构 出生后的牙细胞被包裹在明胶甲基丙烯酰胺(GelMA)水凝胶支架中。我们假设 这种可调节的GelMA水凝胶结构将促进牙齿细胞相互作用的改善，从而导致形成 矿化的牙齿组织。建议研究的理由包括重大的健康需求，我们的 强劲的初步数据，以及需要替代目前使用的替代牙齿疗法。结果 也可用于开发其他生物工程组织和器官系统 需要适当的上皮细胞和间充质细胞的相互作用。我们将通过以下几点来检验这一假设 具体目标： 1.确定可整合到GelMA构建体中以促进牙细胞分化的生长因子 和矿化的牙齿组织形成。 2.确定可促进DE细胞分化和牙釉质产生的支架设计。 3.研究在大鼠颌骨种植模型中生长的仿生GelMA牙蕾结构。 我们将使用这些分析来调查这些不同制造策略的有效性 GelMA牙蕾构造包括3D放射成像技术、组织学和免疫组织化学 方法：测量极化牙细胞的形态、分化和有组织结构的程度 矿化作用。这项拟议研究的预期结果包括改进的仿生3D牙蕾 便于形成特定大小和形状的有组织的、有功能的生物工程牙齿的模型。 功能仿生三维牙蕾的验证将对牙齿组织工程产生重大影响 通过提供一种临床上相关的替代人工牙种植体。建议项目的贡献 这项研究具有重要意义，因为它旨在提高牙齿患者的牙齿和口腔健康质量 这对旨在利用类似器官和组织进行生物工程的其他研究也有帮助。