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

1631439-由于创伤和各种肌肉骨骼疾病，对骨再生策略有着深刻的需求。目前治疗骨缺损的方法与诸如供体短缺和疾病传播风险等限制相关。建立在组织工程学基础上的策略提供了修复和再生骨组织的替代途径。组织工程方法从实验室向临床的转移受到血管生长不足和宿主炎症反应的限制。这项研究为使用白藜芦醇（一种在浆果和葡萄中发现的天然化合物）来利用免疫细胞的潜力来驱动血管生长建立了原理证明。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的主要临床问题铺平道路。这项工作的成功完成将影响到广泛的患者患有衰弱性肌肉骨骼疾病。这项建议的教育目标与科学目标紧密相连。该项目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的传播，并促进来自生物医学工程领域代表性不足的群体的学生的参与。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，这些方法存在局限性，例如供体短缺和疾病传播的风险。建立在组织工程学基础上的策略提供了修复和再生组织的替代方法。组织工程方法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。本项目的目标是促进骨和支持血管系统的新生，以同步的方式类似于成熟过程中骨生长的生理过程。该项目本质上是变革性的，与传统方法相反，该方法不是试图对抗炎症，而是建立了使用白藜芦醇（一种天然多酚）调节免疫细胞行为并使用其分泌的信号分子来驱动血管生成和骨形成的原理证明。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组分的仿生支架，以及（iii）间充质干细胞。整个植入支架的快速灌注是工程修复除骨外的各种组织的关键问题。这项研究描绘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，其应用超出了组织工程和再生医学领域（例如肿瘤炎症）。教育目标包括开设一门关于干细胞工程原理的选修课，并促进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.