Measurement of Contractility-induced Residual Stress for Tissue Engineering

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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.