Collaborative Research: GCR: Infection-Resisting Resorbable Scaffolds for Engineering Human Tissue

合作研究：GCR：用于工程人体组织的抗感染可吸收支架

• 批准号: 2219014
• 负责人: Matthew Libera
• 金额: $ 132.5万
• 依托单位: Stevens Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2027-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2219014&HistoricalAwards=false
• 关键词: Collaborative; Research; GCR; Infection; Resisting

Tissue engineering is a thought-provoking concept made compelling by the need to replace failed, damaged, or defective body parts. Unlike the more mature field of traditional medical-device development (e.g., joint replacement), tissue engineering is young and evolving. This project can thus change the established tissue-engineering paradigm to not only address the development of healthy tissue (associated with healing) but simultaneously address the need to inhibit bacterial colonization (associated with infection). A convergent team of researchers with expertise in microbiology, polymer science, biomaterials science, computational chemistry, veterinary medicine, and medical-device development will develop a new and flexible approach to infection control within a resorbable scaffold for tissue engineering. The research plan encorporates three synergistic research thrusts which will converge around a specific testbed, namely a new scaffold designed to regrow hard tissue that simultaneously resists bacterial colonization. To mimic the extracellular matrix, Thrust 1 will exploit 3D printing to additively create fiber-based scaffolds with controllable fiber size/spacing using combinations of resorbable polymers together with signaling factors to influence stem-cell differentiation. Thrust 2, using synergistic computational and experimental approaches, will explore fundamental concepts of polyelectrolyte complexation and directed self-assembly to render these scaffolds self-defensive (able to release antimicrobials only if, when, and where there is a bacterial challenge). Thrust 3 will employ lab-on-a-chip concepts to understand the competition between mammalian cells and bacteria and, in Phase 2 of project, include small-animal infection models able to recapitulate a complex physiological response.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.

组织工程是一个发人深省的概念，由于需要更换失效、损坏或有缺陷的身体部位而变得引人注目。与更成熟的传统医疗设备开发领域（例如关节置换）不同，组织工程还很年轻且不断发展。因此，该项目可以改变已建立的组织工程范式，不仅解决健康组织的发育（与愈合相关），而且同时解决抑制细菌定植（与感染相关）的需求。一个由微生物学、聚合物科学、生物材料科学、计算化学、兽医学和医疗设备开发专业知识的研究人员组成的汇聚团队将开发一种新的、灵活的方法，在组织工程的可吸收支架内控制感染。该研究计划包含三个协同研究重点，这些研究重点将集中在一个特定的测试平台上，即一种新的支架，旨在再生硬组织，同时抵抗细菌定植。为了模拟细胞外基质，Thrust 1 将利用 3D 打印技术，利用可吸收聚合物与信号因子的组合，以附加方式创建具有可控纤维尺寸/间距的纤维支架，以影响干细胞分化。 Thrust 2将使用协同计算和实验方法，探索聚电解质络合和定向自组装的基本概念，以使这些支架具有自我防御能力（​​只有在存在细菌挑战时、何时、何地才能够释放抗菌药物）。 Thrust 3 将采用芯片实验室概念来了解哺乳动物细胞和细菌之间的竞争，并在项目的第二阶段包括能够重现复杂生理反应的小动物感染模型。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

Self-Defensive Antimicrobial Surfaces Using Polymyxin-Loaded Poly(styrene sulfonate) Microgels

使用负载多粘菌素的聚（苯乙烯磺酸盐）微凝胶的自我防御抗菌表面

• DOI: 10.1021/acsbiomaterials.2c00783
• 发表时间: 2022
• 期刊: ACS Biomaterials Science & Engineering
• 影响因子: 5.8
• 作者: Xiao, Xixi;Ji, Jingjing;Wang, Haoyu;Nangia, Shikha;Wang, Hongjun;Libera, Matthew
• 通讯作者: Libera, Matthew