Date of Award

8-2008

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Bioengineering

Advisor

Wen, Xuejun

Committee Member

Gao , Zhi

Committee Member

Webb , Ken

Committee Member

Zhang , Ning

Abstract

Chitosan, a naturally occurring polysaccharide, and its derivatives have been widely explored for biomedical applications due to their biocompatibility and biodegradability. In our studies, we developed a series of chitosan derivatives through chemical modifications. These chitosan derivatives not only possess better processibility in scaffolds fabrication, but also show excellent potentials in tissue engineering applications, including blood vessel and bone tissue engineering.
The excellent antithrombogenic property is crucial for vascular engineering applications, especially in engineering small-diameter blood vessels. In our studies, chitosan was chemically modified by phthalization and the phthalized chitosan exhibited great antithrombogenic property. Through a wet- phase-inversion process, tubular constructs of varying sizes, morphology, and permeability were fabricated from phthalized chitosan, suggesting its potential as a scaffold for vascular engineering.
The excellent osteoconductivity of chitosan and some of its derivatives make them good candicates for orthorpaedic applications. In our studies, we synthesized novel photocurable chitosans which possess great processibility compared to raw chitosan and can be fabricated into scaffolds with desired shape, pore size and topography upon light exposure. These photocured porous chitosan scaffolds showed great osteoconductivity in vivo. Moreover, the photocured chitosan scaffolds were developed into osteoinductive scaffolds through immobilizing heparin on the surface followed by loading BMP-2. Ectopic bone growth is observed when subcutaneously implanted. All of these indicated that the newly developed photocurable chitosan have great potential in solving some thorny problems in bone repair, such as non-union bone defects and long bone defects with irregular shapes.
In order to mimic the structure of extracellular matrix, the hybrid scaffolds containing photocurable chitosan and gelatin were developed. It is very interesting to note that the interaction between chitosan and gelatin, and the photocuring process can control the morphology of the complex scaffolds. Heparin can also be effectively immobilized on the surface of complex scaffolds. Loaded with BMP-2, the heparinized complex scaffolds can be used as osteoinductive scaffolds, as indicated by the ectopic bone growth in vivo. Moreover, this complex scaffold shows intriguing elasticity. Combined with the potential ability of delivering various growth factors, this complex scaffolds have great potentials in tissue engineering, especially in cartilage tissue engineering.

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