Over the past decade, the tissue engineering paradigm has gained attention as a potential means to restore native tissue functionality. Although attractive, the wide variety of scaffold materials, cell sources, and mechanical conditioning regimes coupled with the paucity of structurally-based, finite deformation framework constitutive models found in the literature hinders the elucidation of extracellular matrix (ECM) formation and remodeling in engineered tissues. Therefore, the overall objective of this work is to develop structurally guided generalized finite deformation based constitutive models than can be used to gain an understanding of tissue formation and remodeling in tissue engineering applications. Further, it is the intent of this work to apply such an approach to investigate tissue formation and remodeling in tissue engineered pulmonary arteries.In the first part of this work, a novel technique for acquiring and quantifying high resolution three dimensional structural data was used on bone-marrow stem cell-seeded polymeric scaffold composites, and it was shown that the continuous anisotropic scaffold phase transitioned to a highly discontinuous isotropic scaffold phase after twelve weeks in vivo. Next, structural constitutive models were developed based on the scaffold continuity. For continuous scaffold composites, scaffold-ECM interactions were included in the model as extensional and shearing terms, while it was shown that such effects were negligible in the discontinuous scaffold composites. A parameter estimation and model validation procedure was described using a tunable tissue-analog system of polyacrylamide (PAM) gel. It was found that the scaffold-ECM interaction due to fiber extension was highly non-linear, showing a reinforcing effect larger than from rule of mixtures predictions. Experimental validation with PAM gel supported the models. Finally, both models were used to investigate tissue formation and remodeling in in vivo engineered pulmonary arteries. At early timepoints (7 days), little change in ECM mechanical properties was observed. In later timepoints (42 to 140 days), the collagen effective modulus and collagen recruitment parameters changed substantially, suggesting collagen maturation via increased cross-linking and crimp organization. Ultimately, a methodical approach to understanding tissue formation and remodeling via structural constitutive models was presented and successfully applied to a clinically-relevant tissue engineering system.
展开▼
