Tendon and ligament injuries place a significant burden on the United States economy. Tissue-engineering is an emerging field that may potentially contribute to the development of novel therapeutic strategies in areas of ligament and tendon reconstruction surgery. Currently there is a limited supply of donor tendons available for surgical reconstruction. The goal of tissue engineering is to develop scaffolds to replace damaged and injured tissues. The major components of tissue engineering approaches include cells, biomaterials, and an appropriate environment for promoting tissue remodeling. The work in this thesis is based on the development of a novel decellularization and oxidation protocol. The data presented characterize both allogenic and xenogenic scaffolds using histological, mechanical and structural analyses. Scaffolds prepared using this protocol demonstrate decreased immunogenic potential, are biocompatible in vitro and in vivo, retain tensile properties compared to native source tissue, possess a modified ultrastructure, have a decreased risk of disease transmission through viral load elimination, and remodel and preserve functionality in vivo. Because these decellularized scaffolds provide the necessary microstructure and extracellular cues for cell attachment, they were successfully seeded and cultivated in a bioreactor. Cyclic preconditioning restored tensile properties compared to fresh-frozen tendons. In summary, the application of this novel decellularization and oxidation process is broadly applicable to create scaffolds from several sources for tendon and ligament reconstruction. Bioreactor conditioning facilitates tissue remodeling and improves the performance of scaffolds, making this construct a potential design to reconstruct tendons and ligaments with sufficient load-bearing capacity for rapid return of functionality.
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