OCLC: 1242436675
Tissue engineering has played an exceptionally important role in addressing the increasing need for suitable tissue and organ replacements over the past few decades. Successful engineering of tissues that physiologically mimic their native counterparts relies on design and fabrication of temporary templates known colloquially as scaffolds. Scaffolds are commonly made of porous, biocompatible and often biodegradable biomaterials that enhance the cell and tissue growth and functionality. Among many scaffold engineering techniques, three-dimensional (3D) bioprinting is commonly used due to its ease of use and high speed of fabrication. In 3D bioprinting, a suspension of biomaterial, also known as bio-ink, is deposited in a layer-by-layer fashion to create the desired scaffold geometry according to a computer-aided design. An ideal bio-ink must be both “biocompatible” and “printable”: it must not impede the cell and tissue growth and it must retain the user-defined spatial arrangement following deposition from the printhead.
It has been proven that all-natural bio-inks have high biocompatibility and reduced toxicity during degradation. Chitosan, starch, and agarose have all been used either on their own or as a blend with other natural and synthetic polymers to create high performance bio-inks. The binary mixture of chitosan-starch and N,O-Carboxymethyl Chitosan (NOCC)-agarose have not been investigated for bioprinting applications of neurons. The objectives of this thesis are:
To achieve objective 1, the printability and biocompatibility of chitosan and starch blend bio-inks were investigated using a systematic framework. To consider the effects of flattening of filaments following deposition, the conventional framework was revised. Varying compositions of chitosan and starch blends were used to print scaffolds to grow neuron cells, and printability, cytotoxicity and cell viability for each scaffold were monitored. It was observed that, although increasing the potato starch content contributes to better printability of the bio-ink, more chitosan must be added to achieve higher biocompatibility. Therefore, a compromise in printability and biocompatibility must be made when starch and chitosan blends are used for scaffold fabrication.
To achieve objective 2, the suitability of bio-inks composed of pure NOCC, pure agarose and their binary blends for applications in 3D bioprinting was investigated. The loss and storage moduli of each bio-ink were characterized, and it was observed that increasing the NOCC concentration enhances the rheological properties. The printability number for each bio-ink was determined and compared to the rheology results. The printability calculation was in agreement with the rheological studies. It was observed that while increasing the agarose concentration leads to a decrease in the rheological and printability properties of the bio-inks, it leads to an increase in cell viability. Therefore, when mixtures of agarose and NOCC are used, a balanced mixture of AG40NC60 is a suitable bio-ink in terms of biocompatibility as well as printability.
With further development, these bio-inks could be used for a wide range of applications in the field of tissue engineering. In particular, in the long term, the scaffolds developed in this thesis can be used to create in-vitro models of the blood brain barrier (BBB). These models have the potential to be used for drug testing and consequently save the lives of many people who suffer from neurodegenerative diseases.