CAREER: Programmable Cell-Matrix Interactions for Regenerative Engineering

再生工程汇集了材料科学和生物学的概念，目的是修复和再生组织。通常，再生工程师使用生物材料来指导细胞行为。然而，生物材料引导细胞行为的能力受到天然细胞信号传导途径的限制，限制了控制细胞对调节再生和减少炎症的复杂信号的反应的潜力。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共同作用以改善组织再生。研究结果将有助于确定细胞和天然和合成生物材料如何对环境做出反应以修复组织。这可能会导致未来的策略，工程细胞表达自己的治疗在有效剂量的慢性炎症性疾病，如类风湿性关节炎。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，对生物材料特征和细胞功能之间相互作用的深刻理解导致研究人员生产设计生物材料，与天然信号通路接口，以指导细胞行为。这些努力本质上是有限的，因为它们依赖于天然信号传导通道来控制对调节细胞功能的许多输入的关键细胞反应，例如增殖，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推进再生工程，以建立一个可编程的通信通道，允许细胞，其所在的天然或人工基质及其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个多功能平台，使定制的细胞反应，以天然可溶性因子感知的背景下，无论是生物材料支架或通过靶组织的独特功能，如风湿性关节炎关节结构。该项目将探索人工信号网络如何允许工程细胞，人工或天然基质和可溶性信号介质之间的设计师相互作用。该提案的成功将使定制生物材料或天然组织协调的可预测细胞行为成为可能，这将有助于开发可靠的组织工程和再生医学策略来治疗各种疾病。这项建议还将研究与教育和外联紧密结合起来。它为培养研究生和吸引高中生获得实践研究经验提供直接支持，同时还协助为课外学术和一般公众推广活动开发教育材料。该奖项反映了NSF的法定使命，并通过使用基金会的智力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.