Bioengineered 3D Tooth Constructs for Whole Tooth Regeneration

目前，还没有替代牙齿治疗提供功能和感觉， 天然牙齿的反应。我们的长期目标是设计和开发功能性生物工程，重要的， 作为合成牙植入物的改进替代物的用于临床应用的全牙构造。的 本研究的目的是利用生物材料制造特定尺寸和形状的仿生牙齿结构。 封装在明胶甲基丙烯酰胺（GelMA）水凝胶支架中的出生后牙细胞。我们假设 “可调”GelMA水凝胶构建体将促进改善的牙细胞相互作用，导致牙本质细胞的形成， 矿化的牙齿组织拟议研究的理由包括重大的健康需求，我们的 强有力的初步数据，以及对目前使用的替代牙齿治疗的替代品的需求。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相互作用。我们将通过以下方式来检验假设 具体目标： 1.鉴定可掺入GelMA构建体以促进牙细胞分化的生长因子 和矿化的牙齿组织形成。 2.确定用于改善DE细胞分化和釉质产生的支架设计。 3.表征在体内大鼠颌骨植入物模型中生长的仿生GelMA牙芽结构。 我们将用来研究这些不同制造策略的有效性的分析， GelMA牙芽结构包括3D射线照相技术、组织学和免疫组织化学 方法，以测量极化牙细胞形态，分化和组织结构的程度 成矿这项研究的预期成果包括改进的仿生3D牙芽 该模型有助于形成特定尺寸和形状的有组织的、功能性的生物工程牙齿。 功能性仿生三维牙芽的验证将对牙齿组织工程产生重要影响 通过提供与临床相关的替代人工牙种植体的方法，提议的捐助 这项研究意义重大，因为它旨在提高患有牙病的人的牙齿和口腔健康质量。 损失以及有助于其他旨在生物工程类似器官和组织的研究。

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.