A Novel Approach for Biomaterials Assisted Regeneration of Pulp-Dentin Complex

生物材料辅助牙髓-牙本质复合体再生的新方法

• 批准号: 8681201
• 负责人: Satish B Alapati
• 金额: $ 13.76万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8681201
• 关键词: Adult; Advisory Committees; Apoptosis; Area; Award; Binding; Biocompatible Materials; Biological; Biological Preservation; Biology; Biomedical Engineering; Biomimetics; Blood Vessels; Bone Marrow; CD44 gene; Cell Adhesion Molecules; Cell Culture Techniques; Cell Signaling Process; Cell Surface Receptors; Cells; Chemicals; Chicago; Clinical Treatment; Complex; Dental; Dental Care; Dental Pulp; Dentin; Dentistry; Dentition; Deposition; Development; Embryo; Embryonic Development; Endodontics; Endothelial Cells; Engineering; Ensure; Epithelial Cells; Excision; Extracellular Matrix; Goals; Healed; Health Care Costs; Healthcare; Human; Hyaluronan; Hyaluronic Acid; Hydrogels; Illinois; In Vitro; Infection; Inflammation Process; Inflammatory; Interdisciplinary Study; Laboratories; Lead; Leukocytes; Literature; Longevity; Measures; Mechanics; Medical; Medicine; Mentors; Mesenchymal Stem Cells; Messenger RNA; Methods; Modality; Molecular; Molecular Genetics; Muscle Cells; Natural regeneration; Nerve Endings; Odontoblasts; Oral health; Plant Roots; Population; Preparation; Procedures; Process; Production; Proteins; Pulp Canals; Reaction; Regenerative Medicine; Regulation; Reporting; Research; Research Personnel; Role; Root Canal Therapy; Science; Scientist; Signal Transduction; Stem cells; Stress; Structure; Surgical Injuries; System; Techniques; Therapeutic; Tissue Engineering; Tissues; Tooth Extraction; Tooth Loss; Tooth structure; Training; Treatment Protocols; Universities; analog; base; biomineralization; bone; college; cost; design; embryonic stem cell; gene function; healing; maxillofacial; morphogens; novel; novel strategies; novel therapeutic intervention; novel therapeutics; outcome forecast; permanent tooth; postnatal; progenitor; programs; regenerative; repaired; response; restorative material; scaffold; skills; soft tissue; stem; stressor; success

DESCRIPTION (provided by applicant): This award will enable the applicant to obtain training in postnatal dental pulp stem cell-based regenerative medicine, with an emphasis on tissue-engineering the pulp-dentin complex. The PI will expand his scientific skills into this new research area of regenerative endodontics through a proposed intercollegiate program that involves training in the laboratories of well-known researchers. The overall objective of the proposed research is to develop regenerative dental (endodontics) approaches with biomaterials as the PI progresses into research independence. The central hypothesis of the proposed research is that a natural hydrogel-based biomatrix, seeded with an enriched population of dental pulp-derived odontoblast stem cells/progenitors, will promote regeneration of dental pulp tissue and deposition of a reparative dentin barrier to maintain tooth vitality. The literature suggests that ~4 million root canal procedures are performed annually in the US. Thus, novel therapeutic intervention is needed to promote rapid healing of dental pulp tissue and the production of a new dentin barrier for regeneration of the dental pulp, so that conventional root canal therapy (involving removal of pulp tissue in whole and preparation of root dentin) or permanent tooth extraction can be avoided. Such therapy will enable tooth retention and reduce dental care costs associated with more drastic measures. The specific aims of the proposed research are (1) identification of the biological responses of the dentin-pulp complex to stress conditions, thereby obtaining parameters for a novel method to enrich progenitor cells for repair of dental pulp tissue; (2) synthesis of hyaluronic acid analogues that include progenitor pulp cells to promote their proliferation, differentiation, and biomineralization; and (3) determination of the ability of enriched dental pulp stem cells delivered in a biomimetic hydrogel composite to regenerate the pulp-dentin complex. This interdisciplinary research program will involve mentors and co-mentors from the areas of cel biology, molecular genetics, bioengineering, and materials science, along with an advisory committee of senior medical scientists, to provide guidance to the PI. Training will be focused at the University of Illinois at Chicago (UIC) College of Dentistry, the UIC College of Medicine, and the Bioengineering Program, representing a cadre of scientists with the expertise needed for the proposed training. Experts in (a) cellular interactions with hyaluronic acid for treatment modalities, (b) tisue engineering and regenerative medicine, (c) molecular mechanisms and gene function in tooth development, (d) dental pulp stem cells and mesenchymal stem cells, and (e) dentin matrix proteins involved in biomineralization will ensure the PI's success as an independent scientist to develop the advanced dental restorative therapeutic modality.

描述(由申请者提供)：该奖项将使申请者能够获得出生后牙髓干细胞再生医学方面的培训，重点是牙髓-牙本质复合体的组织工程。PI将通过一个拟议的校际计划将他的科学技能扩展到这个新的再生牙髓研究领域，该计划涉及在知名研究人员的实验室进行培训。拟议研究的总体目标是随着PI发展到研究独立，利用生物材料开发再生牙科(牙髓)方法。这项拟议研究的中心假设是，以天然水凝胶为基础的生物基质，种植有丰富的牙髓来源的成牙本质干细胞/祖细胞，将促进牙髓组织的再生和修复性牙本质屏障的沉积，以维持牙齿的活力。文献表明，在美国，每年大约有400万例根管手术。因此，需要新的治疗干预措施来促进牙髓组织的快速愈合和为牙髓再生产生新的牙本质屏障，从而避免传统的根管治疗(包括全部去除牙髓组织和准备根部牙本质)或永久拔牙。这种疗法将使牙齿得以保留，并在采取更严厉措施的情况下降低牙齿护理成本。拟议研究的具体目标是：(1)鉴定牙本质-牙髓复合体对应激条件的生物学反应，从而获得用于修复牙髓组织的富集祖细胞的新方法的参数；(2)合成透明质酸类似物，包括促进其增殖、分化和生物矿化的前体牙髓细胞；(3)测定在仿生水凝胶复合材料中富含的牙髓干细胞再生牙髓-牙本质复合体的能力。这一跨学科研究计划将包括来自细胞生物学、分子遗传学、生物工程和材料科学领域的导师和联合导师，以及由资深医学科学家组成的咨询委员会，为PI提供指导。培训将集中在伊利诺伊大学芝加哥分校(UIC)牙科学院、UIC医学院和生物工程项目，代表一批拥有拟议培训所需专业知识的科学家。(A)治疗方法中与透明质酸的细胞相互作用，(B)组织工程和再生医学，(C)牙齿发育中的分子机制和基因功能，(D)牙髓干细胞和间充质干细胞，以及(E)参与生物矿化的牙本质基质蛋白，将确保PI作为独立科学家成功开发先进的牙科修复治疗方法。