Collaborative Research: 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，损坏或有缺陷的身体部位而变得引人注目。与传统医疗器械开发的更成熟领域（例如，关节置换），组织工程是年轻的和不断发展的。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。一个汇聚了微生物学、聚合物科学、生物材料科学、计算化学、兽医学和医疗器械开发方面专业知识的研究人员团队将开发一种新的、灵活的方法来控制组织工程可吸收支架内的感染。该研究计划包括三个协同研究重点，这些重点将集中在一个特定的试验平台上，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打印来添加创建具有可控纤维尺寸/间距的基于纤维的支架，使用可吸收聚合物与信号传导因子的组合来影响干细胞分化。推力2，使用协同的计算和实验方法，将探索生物复合和定向自组装的基本概念，使这些支架具有自我防御性（只有在细菌挑战的情况下，才能释放抗菌剂）。Thrust 3将采用芯片实验室概念来理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，并被认为值得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来支持。

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.