Cell Modulation Using Biomaterials with a Negative Poisson's Ratio

该奖项的研究目标是创造一类新的纳米结构生物支架，表现出负泊松比（拉胀表面），并研究其调节细胞形状，粘附，增殖和细胞骨架重新定向的能力。生物材料支架支撑和传递细胞和组织力的能力可以通过其弹性模量和泊松比来定量描述。最近的研究表明，弹性模量可以调节多种细胞类型。然而，泊松比对细胞行为的影响在很大程度上被忽略了。虽然大多数天然材料具有正泊松比并且当在某一方向上拉伸（压缩）时横向收缩（膨胀），但拉胀材料表现出具有负泊松比的不寻常性质，即，它们在拉伸时横向膨胀，反之亦然。为了实现研究目标，该团队将设计，制造和表征纳米级拉胀表面形貌，使用聚乙二醇生物材料表现出负泊松比。该团队将研究纳米支架对脂肪来源的人类干细胞的粘附、细胞骨架组织和形状的拉胀效应。如果成功的话，这项工作将是该领域第一个开发负泊松比纳米级支架和研究细胞对这种新型支架的反应。PI在纳米纤维、生物材料和细胞与微环境的相互作用方面有着出色的研究记录。加州大学圣地亚哥分校和PI的实验室为这个项目提供了一流的设施和资源。 拉胀支架可以匹配宿主组织的弹性刚度和泊松比，并且可能更好地与天然组织整合并更好地促进临床组织再生。在这项工作中开发的方法可以扩展到其他生物材料和细胞类型，以研究改变泊松比对动脉内皮细胞，心肌补片，皮肤和脂肪组织工程，医用缝合线和伤口管理的各种细胞方面的影响。因此，这项工作直接有助于科学进步，使医疗保健和整个社会受益。拟议的研究是高度跨学科的，涉及组织工程，纳米制造和生物材料。该项目的成果将成为本科生和研究生的优秀教材。对K-12和少数民族学生的强有力的教育努力将吸引更多的年轻学生和代表性不足的学生进入工程，特别是进入工程和生物学之间的跨学科领域。

The research objective of this award is to create a new class of nanostructured biological scaffolds that exhibit a negative Poisson's ratio (auxetic surfaces), and study their ability to modulate the cell shape, adhesion, proliferation and cytoskeletal re-orientation. The ability of a biomaterial scaffold to support and transmit cell and tissue forces can be quantitatively described by its elastic modulus and Poisson's ratio. Recent studies have shown that elastic modulus can modulate a variety of cell types. However, the effect of Poisson's ratio on cell behavior has been largely ignored. While most natural materials have a positive Poisson's ratio and contract (expand) transversally when stretched (compressed) in a certain direction, auxetic materials exhibit an unusual property of having a negative Poisson's ratio, i.e., they expand transversally when stretched and vice versa. To achieve the research objectives, the team will design, fabricate, and characterize nanoscale auxetic surface topographies that exhibit a negative Poisson's ratio using polyethylene glycol biomaterial. The team will investigate the auxetic effect in the nanoscaffolds on the adhesion, cytoskeletal organization, and shape of adipose derived human stem cells. If successful, this work will be the first in the field for developing nanoscale scaffolds with a negative Poisson's ratio and studying the cellular responses to such novel scaffolds. The PI has an outstanding track record of research in nanofabrication, biomaterials, and cell interactions with microenvironments. UC San Diego and the PI's laboratories offer excellent facilities and resources for this project. An auxetic scaffold could match both the elastic stiffness and the Poisson's ratio of the host tissue and would likely better integrate with native tissues and better promote clinical tissue regeneration. Methodology developed in this work can be extended to other biomaterials and cell-types to investigate effects of altering the Poisson's ratio on a variety of cellular aspects for arterial endothelium, myocardial patch, skin and fat tissue engineering, medical sutures, and in wound management. Thus this work directly aids scientific progress, benefits healthcare and society at large. The proposed research is highly interdisciplinary, involving tissue engineering, nanomanufacturing, and biomaterials. Results from this project will be excellent teaching materials for undergraduate and graduate students. The strong educational efforts for K-12 and minority students will attract more young students and under-represented students into engineering, and particularly into the interdisciplinary field between engineering and biology.