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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

基本信息

批准号：
8473067
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
项目类别：
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/8473067
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

项目摘要

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（由申请人提供）：该奖项将使申请人能够获得出生后牙髓干细胞再生医学的培训，重点是牙髓-牙本质复合物的组织工程。 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，该计划包括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 逐步实现研究独立性，开发利用生物材料的再生牙科（牙髓病）方法。该研究的中心假设是，基于天然水凝胶的生物基质，接种了丰富的牙髓源性成牙本质细胞干细胞/祖细胞群，将促进牙髓组织的再生和修复性牙本质屏障的沉积，以维持牙齿活力。文献表明，美国每年进行约 400 万例根管手术。因此，需要新的治疗干预来促进牙髓组织的快速愈合，并产生用于牙髓再生的新的牙本质屏障，从而可以避免传统的根管治疗（包括整体去除牙髓组织并制备牙根牙本质）或拔恒牙。这种治疗将能够保留牙齿，并减少与更严厉措施相关的牙科护理费用。本研究的具体目标是（1）鉴定牙本质-牙髓复合物对应激条件的生物反应，从而获得富集祖细胞以修复牙髓组织的新方法的参数； (2)合成透明质酸类似物，包括祖牙髓细胞，以促进其增殖、分化和生物矿化； (3)测定仿生水凝胶复合材料中递送的富集牙髓干细胞再生牙髓-牙本质复合物的能力。这个跨学科研究项目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骨干队伍。 (a) 治疗方式中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法情态。