| dc.description.abstract | Tissue engineering, or the construction of complex tissue-like structures for injured tissue replacement and regeneration, has been a subject of investigation over the last thirty years. In the last decade, there has been considerable interest in using additive manufacturing (3D printing) to achieve these goals. Despite such efforts, many key questions still need to be answered, particularly in relation to the scientific understanding of the printability and buildability of the biomaterial inks for targeted tissue-specific applications.
In addressing many unanswered questions, this dissertation reports the formulation and 3D bioprinting studies on hybridized bioinks with inorganic nanofillers based on the model baseline biomaterial, gelatin methacryloyl (GelMA), while demonstrating how they can be used as a potential scaffold for the transport of living cells as well as their maintenance for different tissue remodeling, particularly bone, cartilage, and nerve. Recognizing the importance of biophysical properties, printability toward shape fidelity, and biofunctionality, a significant focus has been centered around the qualitative and quantitative evaluation of the role of printing parameters, microrheological properties, and pore architectures on the mechanical properties, swelling kinetics, enzymatic degradation, and printability towards shape fidelity of biomaterial inks, in particular reference to 3D extrusion printing.
In order to identify the role of inorganic fillers in the scaffold buildability, varying amounts of hydrothermally synthesized phase pure rod-shaped nanocrystalline hydroxyapatite (HAp) powders were incorporated into pre-crosslinked GelMA matrix to fabricate a predesigned scaffold architecture using a custom-made 3D bioprinter. The HAp-incorporated GelMA compositions demonstrated superior printability and scaffold stability, with uniform distribution of HAp nanoparticles without any phase separation. Notably, the experimental results clearly suggested that the uniaxial compression properties, swelling behavior, and biodegradations can be regulated by optimizing the HAp content.
Further, we addressed the shortcomings of inferior printability of low-concentration GelMA by methacrylated carboxymethyl cellulose (mCMC), which has a significant impact on extrudability and buildability, sol-gel transition temperature, and yield stress. These photopolymerizable GelMA/mCMC ink served as the foundation for the growth and development of cartilage matrix after encapsulation of human mesenchymal stem cells (hMSCs). The inclusion of nHAp provided enhanced bioactivity and osteoinductive properties to promote the formation of a new bone matrix. Intriguingly, we incorporated poly(ethylene glycol)diacrylate (PEGDA) into the viscosity-modified GelMA to enhance compressive modulus and regulate cell (hMSCs) functionality. This knowledge contributed to optimizing the biomaterials ink formulation, ultimately improving the printability, buildability, and overall performance of the GelMA matrix in 3D bioprinting applications.
Next, we investigated the potential of GelMA to develop fully integrated, multilayered nerve conduits. We systematically incorporated carbon nanofiber (CNF), PEGDA, and gellan gum (GG) to synthesize an electroconductive bioink. We have semi-quantitatively analyzed the limitations of extrusion bioprinting to reconstruct freestanding thin hollow nerve conduits. Moreover, we critically evaluated the cytotoxicity and differentiation of encapsulated neuroblastoma cells (N2a) toward neurons in culture with differentiation inducers.
Taken together, our study unequivocally establishes a significant step forward in developing a broad spectrum of shape-fidelity compliant, biocompatible bioink for the 3D bioprinting of biomimetic bone, cartilage, and neural scaffolds. | en_US |
