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: 8240446
• 负责人: Satish B Alapati
• 金额: $ 13.61万
• 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/8240446
• 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; public health relevance; 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. PUBLIC HEALTH RELEVANCE: The proposed research will lead to development of a novel endodontic technique to regenerate dental pulp tissue and form reparative dentin, using a special biological substrate for proliferation and differentiation of progenitor pulp stem cells/mesenchymal stem cells to tissue-engineer the pulp-dentin complex. Ideally, the new material will also provide novel treatment of root formation in immature permanent dentition, and have uses in other maxillofacial structures.

描述（由申请人提供）：该奖项将使申请人获得在产后牙髓干细胞为基础的再生医学的培训，重点是组织工程牙髓牙本质复合体。PI将通过一项拟议的校际计划将他的科学技能扩展到再生牙髓学这一新的研究领域，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进入研究独立性，开发使用生物材料的再生牙科（牙髓病学）方法。拟议研究的中心假设是，一种天然的水凝胶基生物基质，与牙髓衍生的成牙本质细胞干细胞/祖细胞的富集群体接种，将促进牙髓组织的再生和修复性牙本质屏障的沉积，以保持牙齿的活力。文献表明，在美国每年进行约400万根管治疗。因此，需要新的治疗干预来促进牙髓组织的快速愈合和用于牙髓再生的新的牙本质屏障的产生，使得可以避免常规的根管治疗（包括全部去除牙髓组织和制备根牙本质）或永久性拔牙。这种疗法将使牙齿保持和减少与更激烈的措施相关的牙齿护理费用。该研究的具体目标是：（1）鉴定牙髓复合体对应力条件的生物学反应，从而获得用于富集牙髓组织修复祖细胞的新方法的参数;（2）合成透明质酸类似物，包括牙髓祖细胞，以促进其增殖、分化和生物矿化;和（3）测定在仿生水凝胶复合物中递送的富集的牙髓干细胞再生牙髓-牙本质复合物的能力。这个跨学科的研究计划将涉及来自细胞生物学，分子遗传学，生物工程和材料科学领域的导师和共同导师，沿着高级医学科学家的咨询委员会，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，代表了一批具有拟议培训所需专业知识的科学家。（a）透明质酸与治疗方式的细胞相互作用，（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的专家将确保PI作为独立科学家成功开发先进的牙科修复治疗方式。 公共卫生相关性：这项研究将导致一种新的牙髓技术的发展，以再生牙髓组织和形成修复性牙本质，使用一种特殊的生物基质的祖细胞牙髓干细胞/间充质干细胞的增殖和分化的牙髓-牙本质复合体的组织工程。理想情况下，这种新材料还将为未成熟恒牙列的牙根形成提供新的治疗方法，并可用于其他颌面结构。