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EAGER: Modulation of the Inflammatory Response for Accelerated Tissue Vascularization and Bone Regeneration

EAGER：调节炎症反应以加速组织血管化和骨再生

基本信息

批准号：
1631439
负责人：
Ehsan Jabbarzadeh
金额：
$ 11万
依托单位：
University of South Carolina at Columbia
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2017-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1631439&HistoricalAwards=false
关键词：
EAGER Modulation Inflammatory Response Accelerated

项目摘要

1631439-JabbarzadehThere is a profound need for bone regeneration strategies due to trauma and various musculoskeletal diseases. Current approaches to treat bone defects are associated with limitations such as shortage of donors and risk of disease transmission. Strategies built on tissue engineering offer alternative avenues to repair and regenerate bone tissue. The transfer of tissue engineering methodology from the lab to the clinic is limited by the inadequate vascular growth and host inflammatory response. This study establishes the proof of principle for the use of resveratrol, a natural compound found in berries and grapes, to harness the potential of immune cells to drive blood vessel growth. Through a systematic investigation of the effects of resveratrol on the interactions between immune cells and stem cells, this research will pave the way for a solution to the major clinical problem of bone regeneration. Successful completion of this work will impact a wide range of patients suffering from debilitating musculoskeletal conditions. The educational goals of this proposal are tightly linked to the scientific aims. The educational objectives of this proposal are to integrate research findings into a new course curriculum, facilitate the dissemination of results to both the scientific community and public, and promote participation of students from underrepresented groups in the field of biomedical engineering.This project addresses the profound need for bone regeneration strategies due to trauma and various musculoskeletal diseases. Current approaches to treat bone defects include autografts and allografts that are associated with limitations such as shortage of donors and risk of disease transmission. Strategies built on tissue engineering offer alternative approaches to repair and regenerate tissues. The transfer of tissue engineering methodology from the lab to the clinic is limited by the failure to adequately vascularize scaffolds following implantation. The goal of this project is to promote the neogenesis of bone and supporting vasculature in a synchronized manner similar to the physiological process of bone growth during maturation. The project is transformative in nature in that contrary to conventional methods, instead of trying to counteract inflammation, the proposed approach establishes the proof of principle for the use of resveratrol, a natural polyphenol, to regulate immune cell behavior and use their secreted signaling molecules to drive vasculogenesis and bone formation. The approach involves the use of (i) a resveratrol, a natural polyphenol found commonly in grapes and berries, (ii) a biomimetic scaffold with native bone extracellular matrix protein components, and (iii) mesenchymal stem cells. Rapid perfusion throughout an implanted scaffold is a critical issue for engineering the repair of a wide variety of tissues in addition to bone. The study delineate the potential of resveratrol as a potent physiological cue to control inflammatory response with many applications beyond the fields of tissue engineering and regenerative medicine (e.g. tumor inflammation). The educational goals include development of an elective course on principles of stem cells engineering and promoting participation of students from underrepresented groups in the field of biomedical engineering.

由于创伤和各种肌肉骨骼疾病，对骨再生策略的需求非常大。目前治疗骨缺损的方法存在局限性，如供体短缺和疾病传播风险。建立在组织工程上的策略为修复和再生骨组织提供了替代途径。组织工程方法从实验室到临床的转移受到血管生长不足和宿主炎症反应的限制。这项研究证实了使用白藜芦醇的原理，白藜芦醇是浆果和葡萄中发现的一种天然化合物，可以利用免疫细胞的潜力来驱动血管生长。通过系统研究白藜芦醇对免疫细胞和干细胞相互作用的影响，本研究将为解决骨再生的主要临床问题铺平道路。这项工作的成功完成将影响范围广泛的患有衰弱性肌肉骨骼疾病的患者。这项提议的教育目标与科学目标紧密相连。该提案的教育目标是将研究成果纳入新的课程，促进成果向科学界和公众传播，并促进来自代表性不足群体的学生参与生物医学工程领域。该项目解决了由于创伤和各种肌肉骨骼疾病对骨再生策略的深刻需求。目前治疗骨缺损的方法包括自体移植物和同种异体移植物，但存在供体短缺和疾病传播风险等局限性。建立在组织工程上的策略提供了修复和再生组织的替代方法。组织工程方法从实验室到临床的转移受到植入后支架血管化失败的限制。该项目的目标是促进骨的新生和支持血管系统以同步的方式类似于成熟过程中骨生长的生理过程。该项目在本质上具有变革性，因为与传统方法相反，该方法不是试图抵消炎症，而是建立了使用白藜芦醇（一种天然多酚）调节免疫细胞行为的原理证明，并利用其分泌的信号分子来驱动血管生成和骨骼形成。该方法涉及使用(i)白藜芦醇，一种常见于葡萄和浆果中的天然多酚，（ii）具有天然骨细胞外基质蛋白成分的仿生支架，以及（iii）间充质干细胞。除骨外，快速灌注整个植入支架是修复多种组织工程的关键问题。该研究描述了白藜芦醇作为一种有效的生理线索来控制炎症反应的潜力，在组织工程和再生医学（如肿瘤炎症）领域之外的许多应用。教育目标包括开发干细胞工程原理的选修课程，并促进来自代表性不足群体的学生参与生物医学工程领域。