Measurement of Contractility-induced Residual Stress for Tissue Engineering

组织工程和再生医学为移植和重建病变组织重建器官带来了希望。 组织工程的一个关键挑战是设计它们以模拟它们所替代的组织的机械特性的能力。生物细胞并不是被动的，而是主动地通过伸出手来改变周围的环境，抓住周围基于蛋白质的支架，并收缩以产生内应力。这些细胞产生的应力是人类健康和疾病的重要考虑因素，因为它们改变了组织的机械和失效行为。这项研究将使用一种综合的实验和建模方法来测量嵌入工程组织中的活细胞在收缩并不断改变机械行为时的效果。在这个项目中获得的知识将有助于预测整体组织工程产品的质量，从而促进国家的健康，繁荣和福利，同时促进生物力学科学的进步。为了确保这项研究产生更广泛的影响，计划开展广泛的宣传和教育活动，例如，通过教师研究经验计划培训K-12教师，并为公众制作“探索研究”视频。此外，还将资助佛罗里达大学的居里系列讲座，吸引杰出的女学者到该校学习。该研究的目的是利用创新的高分辨率在线技术，监测由生物相容性聚合物支架和嵌入的活细胞组成的工程组织的机械变化。 这些组织中的应力场将用显微拉曼光谱法以1微米的分辨率进行测量。此外，拉曼光谱数据将用于开发计算生物复合材料模型，量化细胞收缩的工程组织的组成性反应的贡献。这种在工程组织替代物上利用光谱学的方法是新颖的，并且为跟踪细胞周围的应力提供了潜在的变革手段。统一的实验和建模结果将突出基于凝胶、细胞形状、细胞密度和细胞收缩的设计差异，目的是为预期应用提供定制组织特性的新指南。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 and regenerative medicine hold the promise of rebuilding organs for transplants and reconstructing diseased tissues. A critical challenge for tissue engineering is the ability to design them to mimic mechanical properties of the tissues they replace. Biological cells are not passive but actively alter their surroundings by reaching out, grabbing onto the protein-based scaffold around them and contracting to cause internal stresses. These cell-generated stresses are an important consideration in human health and disease because they alter mechanical and failure behavior of tissues. This study will use an integrated experimental and modeling approach to measure the effect of living cells embedded in engineered tissues as they contract and continuously alter mechanical behavior. The knowledge gained in this project will help predict quality of overall tissue-engineered products, thereby advancing national health, prosperity, and welfare, while promoting the progress of biomechanical sciences. To ensure this research has broader impact, a wide range of outreach and educational activities are planned, e.g., training of K-12 teachers through the Research Experiences for Teachers program, and developing "Explore Research" videos for the public. In addition, the University of Florida Curie Lecture series, which brings in outstanding women scholars to the university, will be supported.The objective of this research is to monitor mechanical changes in engineered tissues composed of bio-compatible polymeric scaffolds with embedded living cells using innovative high-resolution, in-line techniques. Stress fields in these tissues will be measured with micro-Raman spectroscopy at one-micron resolution. Furthermore, Raman spectroscopy data will be used to develop computational bio-composite models that quantify the contributions of cell contraction to the constitutive response of engineered tissues. This approach of utilizing spectroscopy on engineered tissue surrogates is novel and provides a potentially transformative means for tracking stresses around cells. Consolidated experimental and modeling results will highlight design differences based on gel, cell shape, cell density, and cell contraction with the goal of providing new guidelines for customizing properties of tissues for intended applications.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.