Designing of Chitosan-Based Scaffolds for Biomedical Applications
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Chitosan is a favorable natural polymer for biomedical application for its biocompatible, biodegradable, non-toxic, and hydrophilic properties. It has a chemical structure analogous to glycosaminoglycans, a component of extracellular matrix, indicating its potential bioactivity. However, chitosan's low mechanical strength precludes pristine chitosan scaffolds from tissue engineering. To achieve higher mechanical strength, different reinforcing agents are incorporated into the scaffold system; however, improved mechanical properties are obtained at the cost of compromised structure, porosity, and biological properties of the scaffold. Therefore, pristine chitosan is often preferred over its composites in biomedical applications due to its superior biological properties. This dissertation research presents several novel approaches such as controlling chitosan concentration in scaffold, applying the right temperature gradient, and developing a modular-collector electrospinning system to fabricate chitosan scaffolds with higher mechanical properties and appropriate morphology, pore size, and porosity for different tissue engineering uses, including bone and muscle. In the first approach, we controlled chitosan concentration in acidic solution to increase the crystallinity of chitosan scaffolds and thus fabricate stiffer scaffolds. Scaffolds of increased chitosan concentration, i.e., with greater mechanical strength, showed efficient bone tissue engineering with improved adhesion, proliferation, and osteogenic activity of MG-63 osteoblast cells. In the second approach, we applied appropriate temperature gradients to control pore size and porosity of the scaffold by regulating the rate of ice crystal formation in chitosan solution. Thus, we produced uniaxial tubular porous chitosan scaffolds with pore size and mechanical properties comparable to those of native skeletal muscle tissues. These scaffolds demonstrated the ability to align muscle cells, guide and promote cell fusion, and produce thick myotubes. In the third approach, we developed a novel portable electrospinning system with a modular-collector to control scaffold shape. This approach produced chitosan-based aligned nanofibrous cylindrical, tubular, and membrane scaffolds for different tissue engineering. In a model application, muscle cells cultured on chitosan-based cylindrical and tubular scaffolds showed their effectiveness in producing highly aligned and densely populated myotubes required for muscle tissue engineering. In the fourth approach, we developed a novel hybrid substrate in which a stripe-pattern chitosan substrate, several microns in thickness, is overlaid on a chitosan-based aligned nanofibrous membrane paralally to mimic native micro/nano environment. The results from muscle cell culture showed a higher level of expression of later-stage differentiation genes such as myogenin and myosin heavy chain on the hybrid substrate compared to that found on only nanofibrous membrane or stripe-pattern chitosan substrate. Finally, we stacked cell-cultured substrates to produce 3D tissue-engineered scaffold constructs. These findings prove chitosan's effectiveness as a material that can be used to design and develop scaffolds of required native forms with controlled structure, size, porosity, and mechanical properties for different tissue engineering needs.