EAGER: (ST2) Peptide-Functionalized Hydrogels that Communicate with Preprogrammed Cells

EAGER：(ST2) 与预编程细胞通讯的肽功能化水凝胶

• 批准号: 2037055
• 负责人: Sebastian Vega
• 金额: $ 25万
• 依托单位: Rowan University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2037055&HistoricalAwards=false
• 关键词: EAGER; ST2; Peptide; Functionalized; Hydrogels

Non-technical abstract:Some tissues, such as cartilage, have limited capacity to repair or regenerate their matrix material when damaged. Self-healing materials with the ability to detect and replace damaged matrix would enable more effective and longer lasting therapies. This EArly-concept Grant for Exploratory Research (EAGER) project investigates the use of programmed cells within hydrogels as a new class of materials able to detect and replace matrix loss. This research aims to program cells within hydrogels to detect and respond to matrix loss by producing new matrix material as needed. The matrix produced by cells is tagged with an “OFF” signal that is used by the cells to detect when enough of matrix has been produced. As the “OFF” signal accumulates, the cells decrease and eventually stop production until more matrix is needed due to further damage or degradation. This project is designed to advance the fundamental understanding of biological feedback mechanisms and to provide multidisciplinary research opportunities for graduate and undergraduate students by supporting the Ph.D. training of two graduate students and undergraduate students in capstone project teams. This EAGER project is inspired by ideas developed at the Square Table 2 (ST2) workshop on Programmable Interfaces.Technical abstract:Although cells with stimulatory synthetic receptors that produce materials (e.g., antibodies, cytokines, etc.) upon peptide activation exist, these preprogrammed cells lack the ability to stop production once enough material is made. The goal of this EAGER project is to investigate stimulatory and inhibitory receptor-ligand communication as a novel biological feedback mechanism and to use these insights to develop adaptive materials with self-healing properties. This new class of materials consists of cells preprogrammed with stimulatory and inhibitory synthetic receptors encapsulated in enzymatically degradable hydrogels. Upon activation with spatially tethered stimulatory peptides, cells produce green fluorescent protein (GFP, measurable fluorescence) and a matrix protein tagged with inhibitory ligand. Stimulated cells then replace their surrounding hydrogel with cell-secreted matrix until a balance is reached between competing stimulatory and inhibitory signals. To confirm the self-healing capabilities of these materials, cell-produced matrix is removed locally, and cellular responses and material production are measured via 3D imaging of cellular GFP and fluorescently labeled nascent matrix.This Division of Materials Research (DMR) grant supports research to understand and develop stimulatory and inhibitory receptor-ligand communication as a novel biological feedback mechanism and to use these insights to develop adaptive materials with self-healing properties managed by the Condensed Matter Physics (CMP) Program in DMR of the Mathematical and Physical Sciences (MPS) Directorate.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.

非技术摘要：某些组织（例如软骨）在受损时修复或再生其基质材料的能力有限。能够检测和替换受损基质的自愈材料将实现更有效、更持久的治疗。这个早期概念探索性研究资助（EAGER）项目研究了水凝胶中程序化细胞的使用，作为一种能够检测和替代基质损失的新型材料。这项研究旨在对水凝胶内的细胞进行编程，通过根据需要生产新的基质材料来检测和响应基质损失。细胞产生的基质标有“OFF”信号，细胞使用该信号来检测何时产生了足够的基质。随着“关闭”信号的积累，细胞数量减少并最终停止生产，直到由于进一步损坏或降解而需要更多基质。该项目旨在促进对生物反馈机制的基本理解，并通过支持博士生和本科生提供多学科研究机会。在顶点项目团队中培训两名研究生和本科生。这个 EAGER 项目的灵感来自于 Square Table 2 (ST2) 可编程接口研讨会上提出的想法。技术摘要：尽管存在具有刺激性合成受体的细胞，这些受体在肽激活后产生材料（例如抗体、细胞因子等），但这些预编程细胞缺乏在产生足够材料后停止生产的能力。该 EAGER 项目的目标是研究刺激性和抑制性受体-配体通讯作为一种新型生物反馈机制，并利用这些见解来开发具有自我修复特性的适应性材料。这类新型材料由用刺激性和抑制性合成受体预先编程的细胞组成，这些受体封装在可酶降解的水凝胶中。在用空间束缚的刺激肽激活后，细胞产生绿色荧光蛋白（GFP，可测量荧光）和用抑制性配体标记的基质蛋白。然后，受刺激的细胞用细胞分泌的基质取代周围的水凝胶，直到竞争性刺激信号和抑制信号之间达到平衡。为了确认这些材料的自我修复能力，细胞产生的基质被局部去除，并通过细胞 GFP 和荧光标记的新生基质的 3D 成像来测量细胞反应和材料生产。材料研究部 (DMR) 拨款支持研究以理解和开发刺激性和抑制性受体-配体通讯作为一种新型生物反馈机制，并利用这些见解来开发适应性材料 具有自我修复特性，由数学和物理科学 (MPS) 理事会 DMR 的凝聚态物理 (CMP) 项目管理。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。

项目成果

Plant Tissue Parenchyma and Vascular Bundles Selectively Regulate Stem Cell Mechanosensing and Differentiation

• DOI: 10.1007/s12195-022-00737-9
• 发表时间: 2022-09
• 期刊: Cellular and Molecular Bioengineering
• 影响因子: 2.8
• 作者: K. Driscoll;Maya S. Butani;Kirstene A. Gultian;Abigail McSweeny;Jay M. Patel;Sebastián L. Vega

The living interface between synthetic biology and biomaterial design.

• DOI: 10.1038/s41563-022-01231-3
• 发表时间: 2022-04
• 期刊: Nature materials
• 影响因子: 41.2