Development of novel hydrogels with controlled adhesion and degradation properties for bone tissue engineering.

摘要

Tissue engineering, which is the regeneration of tissues to replace those damaged or lost as a result of disease, trauma, or congenital abnormalities, has the potential to restore function and health to millions of people. Specific control over cell behavior may be necessary to guide the process of tissue formation. Thus, the hypothesis of this thesis is that osteoblast cellular behavior may be positively modulated when engineering bone tissue by regulating adhesion ligand presentation and controlling polymer degradation.; The hypothesis was investigated using alginate, which is naturally non-adhesive to cells. Alginate was covalently modified with specific adhesive properties and ionically crosslinked to form hydrogels. Varying the adhesion peptide sequence type and density controlled osteoblast proliferation and differentiation in vitro. Compared to unmodified alginate controls, peptide-modified cell delivery vehicles significantly increased the amount of bone tissue formed in vivo following implantation with cells. This finding marks the first time regulation of biomaterial adhesive properties has been shown to control bone tissue regeneration in vivo.; Chondrocytes were then transplanted in vivo using this peptide-modified alginate system to test whether controlling biomaterial adhesion characteristics could improve the formation of another tissue type. Cartilaginous tissue was formed that grew in volume over time. Once a growing cartilaginous anlage was engineered, osteoblasts and chondrocytes were co-transplanted within peptide-modified alginate to partially recreate the cellular milieu present in endochondral ossification. Growing bony tissues resulted with regions resembling growth plate-like structures. This result suggests that co-transplantation of several cell types may be required in order to fully replicate the structure and function of many complicated tissues.; Once some control over cell behavior and new tissue formation was achieved using this system, the effect of improved biomaterial degradation rate on tissue formation was examined. Increasing the rate of biomaterial biodegradation resulted in improved rate, quality, and quantity of engineered bone tissue formation. The results of this thesis provide convincing evidence supporting the design of biomaterials that are bioactive and provide stimulatory signals to transplanted cells and surrounding host tissue. Enhanced tissue regeneration may also be achieved with biomaterials that degrade in concert with the formation of new tissue.