CAREER: Programmable Cell-Matrix Interactions for Regenerative Engineering

再生工程将材料科学和生物学的概念结合起来，以修复和再生组织为目标。通常，再生工程师使用生物材料来指导细胞行为。然而，生物材料指导细胞行为的能力受到天然细胞信号通路的限制，限制了控制细胞对调节再生和减少炎症的复杂信号反应的潜力。这个教师早期职业发展（Career）项目的目标是设计具有理想信号通路的细胞，以了解细胞和材料如何协同工作以改善组织再生。研究结果将有助于确定细胞、天然和合成生物材料如何对环境做出反应来修复组织。这可能会导致未来的策略，即设计细胞以有效剂量表达它们自己的治疗方法，以治疗慢性炎症性疾病，如风湿性关节炎。该项目为培养下一代科学家和高中生合成生物学和工程学提供直接支持。学员将获得实践研究经验，同时也为其他学生和公众宣传开发教育材料。在再生工程领域，对生物材料特性和细胞功能之间相互作用的深刻理解促使研究人员生产出设计生物材料，这些材料与天然信号通路相结合，指导细胞行为。这些努力在本质上是有限的，因为它们依赖于自然信号通道来控制关键细胞对许多调节细胞功能的输入的反应，如增殖、分化和炎症消退。这个CAREER项目的目标是通过使用合成生物学来建立一个可编程的通信通道来推进再生工程，该通道允许细胞、其所在的天然或人工基质以及微环境中的可溶性因子之间的特权通信。该项目的具体目标是开发一种多功能平台，以实现在生物材料支架或通过目标组织（如风湿性关节结构）的不同特征的背景下，对天然可溶性因子的定制细胞反应。该项目将探索人工信号网络如何允许设计人员在工程细胞、人工或天然基质和可溶性信号介质之间进行交互。这一建议的成功将使可预测的细胞行为通过定制的生物材料或天然组织协调，这将有助于可靠的组织工程和再生医学策略的发展，以治疗各种疾病。该提案还将研究与教育和推广紧密结合。它为培训研究生和吸引高中生获得实践研究经验提供直接支持，同时也协助开发课外学术和一般公众外展活动的教育材料。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Regenerative engineering brings together concepts from materials science and biology with the goal of repairing and regenerating tissues. Often, regenerative engineers use biomaterials to instruct cell behaviors. However, the ability of biomaterials to guide cell behaviors is limited by natural cell signaling pathways, restricting the potential to control cellular responses to complex signals that regulate regeneration and reduce inflammation. The goal of this Faculty Early Career Development (CAREER) project is to design cells with desirable signaling pathways to understand how cells and materials can work together for improved tissue regeneration. The research outcomes will help to define how cells and natural and synthetic biomaterials can respond to their environment to repair tissue. This could lead to future strategies to engineer cells to express their own therapeutics at effective doses for chronic inflammatory diseases, such as rheumatoid arthritis. This project provides direct support for training next-generation scientists and high school students in synthetic biology and engineering. Trainees will gain hands-on research experience while also developing educational materials for other students and public outreach.Within the field of regenerative engineering, a deep appreciation for the interplay between biomaterial features and cell functions has led investigators to produce designer biomaterials that interface with native signaling pathways to instruct cell behaviors. Such efforts are intrinsically limited, because they rely on natural signaling channels to govern key cellular responses to numerous inputs that regulate cell functions, such as proliferation, differentiation, and inflammation resolution. The goal of this CAREER project is to advance regenerative engineering by using synthetic biology to establish a programmable channel of communication that allows for privileged communication between a cell, the native or artificial matrix on which it resides, and soluble factors in its microenvironment. The specific aims of this project are focused on developing a versatile platform to enable customized cellular responses to native soluble factors perceived in the context of either biomaterial scaffolds or via distinct features of targeted tissues, such as rheumatic articular joint structures. The project will explore how artificial signaling networks will allow designer interactions between engineered cells, artificial or native matrices, and soluble signaling mediators. Success in this proposal will enable predictable cell behaviors coordinated by bespoke biomaterials or native tissues, which will contribute to the development of reliable tissue engineering and regenerative medicine strategies to treat diverse disorders. This proposal also tightly integrates research with education and outreach. It provides direct support for training graduate students and for engaging high school students to gain hands-on research experiences while also assisting in the development of educational materials for extracurricular scholastic and general public outreach events.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.