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

描述（由申请人提供）：该奖项将使申请人获得出生后牙髓干细胞再生医学的培训，重点是牙髓-牙本质复合体的组织工程。PI将通过一个提议的校际项目，包括在知名研究人员的实验室进行培训，将他的科学技能扩展到再生牙髓学这一新的研究领域。拟议研究的总体目标是发展再生牙科（牙髓学）方法与生物材料的PI进展到研究独立。本研究的中心假设是，天然的水凝胶生物基质，植入丰富的牙髓源性成牙干细胞/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。文献显示，在美国，每年约有400万例根管治疗。因此，需要新的治疗干预措施来促进牙髓组织的快速愈合，并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（包括整体去除牙髓组织和准备根牙本质）或拔牙。这种疗法将使牙齿保持，并减少与更激烈的措施相关的牙科护理费用。本研究的具体目的是：(1)确定牙本质-牙髓复合体对应力条件的生物学反应，从而获得一种新的方法来丰富用于牙髓组织修复的祖细胞的参数；(2)合成透明质酸类似物，包括祖髓细胞，促进其增殖、分化和生物矿化；(3)测定以仿生水凝胶复合材料递送的富集牙髓干细胞再生牙髓-牙本质复合物的能力。这项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共同导师，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，代表了具有拟议培训所需专业知识的科学家骨干。(a)与透明质酸的细胞相互作用治疗方式，(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等方面的专家将确保PI作为独立科学家成功开发先进的牙齿修复治疗方式。

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.