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

1631439-Jabbarzadeh由于创伤和各种肌肉骨骼疾病，迫切需要骨再生策略。目前治疗骨缺损的方法与供体短缺和疾病传播风险等限制有关。建立在组织工程基础上的策略为修复和再生骨组织提供了替代途径。组织工程学方法从实验室到临床的转移受到血管生长和宿主炎症反应不足的限制。这项研究为白藜芦醇的使用建立了原则上的证据，白藜芦醇是一种在浆果和葡萄中发现的天然化合物，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之间相互作用的影响，这项研究将为解决骨再生这一临床主要问题铺平道路。这项工作的成功完成将影响到大量患有衰弱肌肉骨骼疾病的患者。这项提案的教育目标与科学目标紧密相连。这项建议的教育目标是将研究成果整合到新的课程课程中，促进研究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而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和同种异体移植，这些方法与供体短缺和疾病传播风险等限制有关。建立在组织工程基础上的策略提供了修复和再生组织的替代方法。组织工程学方法学从实验室到临床的转移受到植入后支架不能充分血管化的限制。该项目的目标是以类似于成熟期间骨生长的生理过程的同步方式促进骨的新生和支持血管的形成。该项目本质上是变革性的，因为与传统方法相反，拟议的方法不是试图抗炎，而是建立了使用白藜芦醇(一种天然多酚)来调节免疫细胞行为并使用它们分泌的信号分子来驱动血管生成和骨形成的原则证据。该方法包括使用(I)白藜芦醇，一种常见于葡萄和浆果中的天然多酚，(Ii)含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。在植入支架的整个过程中快速灌流是工程修复除骨骼之外的各种组织的关键问题。这项研究描述了白藜芦醇作为一种有效的生理信号控制炎症反应的潜力，在组织工程和再生医学(例如，肿瘤炎症)领域以外的许多领域都有应用。教育目标包括开发一门关于干细胞工程原理的选修课，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。

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.