3D Bioprinting of Advanced Bioinks for Tissue Engineering Applications

Abstract

Organ transplantation would be the first option for those whose tissues/organs have been extremely injured. However, the growing gap between the number of organ donors and receivers has resulted in the long waiting list for organ transplantation. Regenerative medicine has emerged as a promising approach to tackle the crisis associated with organ shortage by employing the principle of engineering and biology. The regenerative medicine aims to support and accelerate the regeneration of defective tissue/organs through combining cells, scaffolds, and growth factors. Among various biofabrication methods, tremendous attention has been devoted to the recently emerged three-dimensional (3D) bioprinting technology for the fabrication of functional tissue-engineered scaffold loaded with cells due to its ability to assemble complex structures with meticulous control over the entire fabrication process. It is a computer-assisted technology that enables the direct fabrication of complex 3D constructs usually layers upon layers fashion according to a pre-designed structure. The 3D bioprinting concept was borrowed from 3D printing technology that has been primarily exploited in fabrication industries as a rapid prototyping technology. Harnessing the 3D printing technology in the generation of personalized implants, tissue-engineered scaffolds, drug delivery devices, tissue models has opened up a new avenue for the biofabrication methods. For bioprinting application, an ideal bioink should possess a set of desirable properties including biodegradability, biocompatibility, providing mechanical strength and rheological properties, and closely mimicking the native tissue microenvironment. The selection of materials to be used as bioinks remains the main bottleneck in the realization of 3D bioprinting technology. This thesis aims to develop novel bioinks to address the challenges associated with current bioinks by employing polymers and nanomaterials. The specific objectives of this thesis are organized into seven chapters that will be presented in the form of a collection of the published papers which are the results of the research. In addition, a literature review has been provided to establish the background of this research. Overall, the main contributions of this thesis to the 3D bioprinting field are as follows: ➢ Development of a novel bioink composed of methylcellulose/gelatin-methacryloyl (MC/GelMA) hydrogel with high shape integrity and improved biological stability (paper 1). ➢ Extending the usage territory of MXene nanosheets to the 3D bioprinting field owing to its favorable features (paper 2).➢ Addressing the poor electrical conductivity of current bioinks by employing poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) conductive polymer for neural tissue engineering (paper 3). ➢ Development of bioink with potent antibacterial activity toward Gram-positive (S. aureus) and Gram-negative (P. aeruginosa) bacterial, while supporting the cellular functions (paper 4).