Mechanical Analysis of Injury and Repair: An Experimental Approach

Abstract

The goal of the work described herein was to initiate development of new theoretical and experimental tools specifically designed to improve bio-fidelity in the mechanical performance of tissue-engineered constructs. Of particular interest was addressing present challenges in producing tissue-engineered constructs that are biomimetic with respect to mechanical behavior. Presently, there are no ASTM/ISO standards focused on the mechanical characterization of tissue-engineered therapies. The absence of such a standard is important exhibitory evidence of the need in this area. With this general understanding, the specific effort described herein was motivated by the desire to develop the theoretical and technological advances necessary to produce biomimetic tissue-engineered grafts for both off-the-shelf and patient specific print-on-demand applications. Evidence acquired in conducting this work suggests that the deficit in this area is vast and will ultimately require contributions from many within the mechanics and tissue engineering communities. As a first step, the work was focused on one-dimensional analysis of non-linear stress-strain behavior with allowance for spatially varying properties along the one dimension. Several conventional and well established non-linear models were compared. The approach of Freed-Rajagopal was determined to be the most useful for tissue engineering applications based on several factors. Employment of this model in a subsequent study was sufficient to conclusively demonstrate that tissues described as biomimetic using conventional approaches gleaned from the tissue engineering literature fail to mimic the mechanical behavior of the native tissue when more appropriate non-linear models are used, e.g. the Freed- Rajagopal 1-D Fiber model, to analyze the experimental data. Thus, considerable effort was focused on the development of a more effective method and protocol for performing one-dimensional tests on biologic tissues. The resulting protocol is presented in a format suitable for development into an ASTM/ISO standard, i.e. as an ASTM/ISO proto-standard. Finally, the ability to characterize the mechanical properties of a tissue using MRI elastography was investigated with emphasis on the ability to map the spatial variation in mechanical properties. The approach used here was based on an open source application. While the results of that study revealed that there is potential to use MRI for this purpose, the open-source algorithm was not sufficient for the intended application, and a more sophisticated method will need to be developed.