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Abstract
Acute injuries to the anterior cruciate ligament (ACL) are common among young, active people. When fully disrupted, the ACL does not heal, which may contribute to the development of osteoarthritis. Trauma, congenital deformities, and the removal of cancerous tumors result in soft tissue defects. Most notably in the case of the breast, such defects can be psychologically troubling. In cases of both ACL disruptions and soft tissue defects, the preferred method of reconstruction is with autologous tissue. Such procedures, however, are plagued by complications, the most serious of which is donor site morbidity. Reconstructions with synthetics and allograft tissues are also less than ideal. Tissue engineering offers the possibility of reconstructing soft tissues without many of the complications associated with current treatment options. Because of its ubiquity in the body and inherent biocompatibility, collagen is an obvious choice for a scaffolding material to create soft connective tissues in vitro. In this dissertation, engineered ligament tissue was created in vitro by combining collagen fiber scaffolds with fibroblast-seeded collagen gels. Single collagen fibers, collagen fiber scaffolds, and collagen fiber composite scaffolds demonstrated mechanical behavior similar to that of natural ligament tissue. Combining collagen fiber scaffolds with the cell-seeded collagen gels and maintaining them in culture for up to 20 days resulted in constructs that had similar mechanical and viscoelastic properties to natural tissue. Histological analyses likewise demonstrated ligament-like organization. Engineered tissues to treat soft-tissue defects were created in vitro by embedding short collagen fibers in cell-seeded collagen gels. Cultured constructs seeded with fibroblasts maintained their initial size and shape in a predictable manner, and had permeabilities 100 to 1000 times greater than similar constructs created without short collagen fibers. Short fiber composite constructs seeded with preadipocytes demonstrated similar contractile behavior. Preadipocytes also matured and accumulated lipid after 21 days in culture as demonstrated by FTIR and histological analyses. These results demonstrate the general promise of collagen-based biomaterials for engineering soft tissues. Extensive research, however, is necessary before such a vision can be realized.
