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）：牙髓是牙齿中央核心的软结缔组织，并作为生物活性器官维持牙齿的体内平衡。当龋齿或创伤涉及牙髓时，需要进行牙髓治疗。在不可逆的牙髓炎中，牙医或牙髓病医生拔除牙髓，并用生物惰性材料封闭器械根管。仅在美国，每年就进行总计约1600万次牙髓手术，年总支出约为150亿至250亿美元。虽然根管治疗被认为是成功的牙科治疗之一，并发症已被反复记录在文献中。由于冠渗漏或未被发现的副根管引起的继发感染并不少见，并给患者和牙医带来额外的痛苦。在根管治疗过程中，大量的牙齿结构被去除，导致牙齿骨折的发生率增加。根管治疗的牙齿缺乏神经支配和牙髓感觉，因此被剥夺了检测继发感染的能力。乳牙或年轻恒牙根尖形成不完全，根管治疗是禁忌或可能导致牙根发育停止。从科学上讲，这些并发症可能是由于目前根管治疗的最终结果导致失去了天然牙齿的体内平衡和宿主防御机制的失活牙齿。我们的初步数据表明，在小鼠体内异位植入整个人牙后，经牙髓治疗的人牙在体内通过细胞因子诱导的细胞归巢方法进行再细胞化和再血管化。这些发现提供了概念上的证据，牙髓治疗的人牙齿可以再血管化和再细胞原位在体内。因此，我们的总体假设是，牙髓的各种元素，包括血管生成，成牙本质细胞和神经元，可以再生的姜黄素诱导的细胞归巢。这个为期6个月的SBIR/I期提案的总体目标是在生物相容性材料支架中制备单一和组合细胞因子的制剂，以促进牙髓再生。我们的长期目标是双重的：1）在小型和大型动物模型中确定基于生物学的牙髓再生的有效性和安全性，以及2）在牙髓病患者中进行随机和对照的多中心临床试验，并确定基于生物学的牙髓治疗的有效性和安全性。我们设想，生物为基础的治疗将再生牙髓病人。 公共卫生关系：该SBIR/第一阶段项目将开发用于感染或创伤引起的牙髓再生的生物工程疗法的原型。仅在美国，每年就进行总计约1600万次牙髓手术。目前的根管治疗有并发症，如继发感染，术后牙骨折，乳牙或年轻恒牙缺乏疗效。我们的初步数据表明，牙髓治疗的人牙齿再细胞化和血管化在体内。我们设计了具有强大潜力的跨学科方法来再生人类牙齿中的牙髓。