BioPulp: Bioengineeering approaches for dental pulp regeneration

BioPulp：牙髓再生的生物工程方法

• 批准号: 7674167
• 负责人: Jeremy Mao
• 金额: $ 17.39万
• 依托单位: INNOVATIVE ELEMENTS, LLC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-09 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7674167
• 关键词: Animal Model; Be++ element; Beryllium; Biocompatible; Biocompatible Materials; Biological Assay; Biologically Based Therapy; Biomedical Engineering; Biotechnology; Blood Vessels; Businesses; Cell Differentiation process; Cell Lineage; Cell Proliferation; Cells; Classification; Clinical Trials; Connective and Soft Tissue; Data; Dental; Dental Pulp; Dental caries; Dentists; Development; Distress; Dose; Drug Formulations; Elements; Endodontics; Enzyme-Linked Immunosorbent Assay; Esthesia; Expenditure; Extravasation; Foundations; Goals; Homeostasis; Homing; Host Defense; Human; Immunohistochemistry; In Vitro; Incidence; Individual; Infection; Intellectual Property; Kinetics; Lead; Literature; Modality; Multi-Institutional Clinical Trial; Mus; Natural regeneration; Nature; Neurons; Nonvital Tooth; Organ; Outcome Assessment; Patients; Phase; Phase II Clinical Trials; Plant Roots; Postoperative Period; Procedures; Pulp Canals; Pulpitis; Quantitative Evaluations; Randomized; Root Canal Therapy; Safety; Science; Side; Technology; Tooth Fractures; Tooth structure; Trauma; United States; Universities; base; controlled release; cytokine; cytokine therapy; deciduous tooth; design; implantation; in vivo; innovation; instrument; interdisciplinary approach; nerve supply; permanent tooth; prototype; public health relevance; research and development; scaffold; secondary infection

DESCRIPTION (provided by applicant): Dental pulp is soft connective tissue in the central core of a tooth, and maintains homeostasis of the tooth as a biologically viable organ. When caries or trauma involves dental pulp, endodontic therapies are indicated. In irreversible pulpitis, the dentist or endodontist extirpates dental pulp, and obturates the instrumented root canal with bioinert materials. A total of approximately 16 million endodontic procedures are performed each year in the United States alone, with an annual total expenditure of approximately $15 to $25 billion dollars. Whereas root canal therapy is considered one of the successful dental treatments, complications have been repeatedly documented in the literature. Secondary infections due to coronal leakage or undetected accessory root canals are not uncommon, and cause additional distress to both patients and dentists. A substantial amount of tooth structure is removed during root canal treatment, leading to increased incidences of tooth fracture. Root canal treated teeth are devoid of innervation and pulpal sensation, and thus are deprived of the ability to detect secondary infections. In deciduous teeth or young permanent teeth with incomplete root apex formation, endodontic treatment is either contra-indicated or may lead to the cessation of root development. Scientifically, these complications may be attributed to the end result of the current root canal treatment leading to a devitalized tooth that has lost the mechanisms for homeostasis and host defense of a native tooth. Our preliminary data demonstrate that endodontically treated human teeth are recellularized and revascularized in vivo upon cytokine- induced cell homing approaches following in vivo ectopic implantation of the entire human teeth in mice. These findings provide the proof of concept that dental pulp of endodontically treated human tooth may be revascularized and recellularized orthotopically in vivo. Accordingly, our overall hypothesis is that various elements of dental pulp, including the angiogenic, odontoblastic and neuronal, can be regenerated by cytokine-induced cell homing. The overall goal of this 6-month SBIR/Phase-I proposal is to prepare formulations of singular and combinatory cytokines in biocompatible material scaffolds towards dental pulp regeneration. Our long-term goal is twofold: 1) to determine the efficacy and safety of biologically based dental pulp regeneration in small and large animal models, and 2) to perform randomized and controlled, multi-center clinical trials in endodontic patients, and determine the efficacy and safety of biologically based endodontic therapies. We envision that biologically based therapies will regenerate dental pulp in endodontic patients. PUBLIC HEALTH RELEVANCE: This SBIR/Phase I project will develop prototypes for bioengineered therapies for the regeneration of dental pulp resulting from infection or trauma. A total of approximately 16 million endodontic procedures are performed each year in the United States alone. Current root canal therapy has complications such as secondary infections, post-operative tooth fracture, and a lack of efficacy in deciduous teeth or young permanent teeth. Our preliminary data demonstrate that endodontically treated human teeth are recellularized and revascularized in vivo. We have designed interdisciplinary approaches with a strong potential to regenerate dental pulp in human teeth.

描述（由申请人提供）：牙髓是牙齿中心核心的软结缔组织，并保持牙齿的体内平衡为生物学上可行的器官。当龋齿或创伤涉及牙髓时，请指出牙髓疗法。在不可逆的牙髓炎中，牙医或牙医灭绝的牙髓，并用生物渗透材料堵塞仪器的根管。仅在美国，每年总共进行约1600万个牙髓牙齿程序，年总支出约为15至250亿美元。尽管根管治疗被认为是成功的牙科疗法之一，但文献中反复记录并发症。由于冠状动脉泄漏或未发现的辅助根管引起的继发感染并不少见，并且会给患者和牙医带来额外的困扰。在根管治疗期间，去除大量的牙齿结构，导致牙齿骨折的发生率增加。根管处理的牙齿没有神经和牙髓感觉，因此被剥夺了检测继发感染的能力。在具有不完全根尖的落叶牙齿或年轻的牙齿形成中，牙髓治疗要么是矛盾的，要么可能导致根发育的停止。从科学上讲，这些并发症可能归因于当前根管治疗的最终结果，导致牙齿失去现实的牙齿，该牙齿失去了体内平衡和宿主防御天然牙齿的机制。我们的初步数据表明，经过细胞因子诱导的细胞归巢方法在体内植入小鼠中整个人牙齿后，经过细胞因子诱导的细胞归巢方法，在体内进行了细胞化和血运重建。这些发现提供了一个概念证明，即接受牙髓治疗的人牙齿的牙髓可以在体内进行血运重建和重新细胞的原位化。因此，我们的总体假设是牙髓的各种元素，包括血管生成，牙胶细胞和神经元，可以通过细胞因子诱导的细胞归位来再生。这个为期6个月的SBIR/I期建议的总体目标是准备生物相容性材料支架中奇异和组合细胞因子的配方，以朝牙纸浆再生。我们的长期目标是双重的：1）确定基于生物学的小动物模型中基于生物学的牙髓再生的功效和安全性，以及2）在牙髓患者中执行随机和控制的多中心临床试验，并确定基于生物学的牙髓治疗的功效和安全性。我们设想，基于生物学的疗法将在牙髓患者中再生牙髓。 公共卫生相关性：该SBIR/I期项目将开发用于生物工程疗法的原型，用于再生感染或创伤引起的牙髓。仅在美国，每年总共进行约1600万个牙髓手术。目前的根管治疗具有继发性感染，术后牙齿骨折以及落叶牙齿或年轻恒牙的功效。我们的初步数据表明，经过牙齿治疗的人牙被延迟和体内血运重建。我们设计了跨学科的方法，具有强大的潜力，可以再生牙齿中的牙髓。