GCR: Infection-Resisting Resorbable Scaffolds for Engineering Human Tissue

组织工程是一个发人深省的概念，由于需要替换失败，受损或有缺陷的身体部位而引人注目。与更成熟的传统医疗器械开发领域（如关节置换术）不同，组织工程是一个年轻且不断发展的领域。因此，该项目可以改变现有的组织工程范式，不仅解决健康组织的发展（与愈合有关），而且同时解决抑制细菌定植（与感染有关）的需要。一个汇集了微生物学、高分子科学、生物材料科学、计算化学、兽医学和医疗设备开发等专业知识的研究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。该研究计划包括三个协同研究重点，它们将围绕一个特定的试验台，即设计一种新的支架，用于再生硬组织，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，利用可吸收聚合物和影响干细胞分化的信号因子的组合，制造纤维大小/间距可控的纤维基支架。推力2将使用协同计算和实验方法，探索多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（仅在有细菌攻击时、何时和何地才能释放抗菌剂）。Thrust 3将采用芯片实验室的概念来了解哺乳动物细胞和细菌之间的竞争，在项目的第二阶段，包括能够概括复杂生理反应的小动物感染模型。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。

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.