Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Biomedical Engineering

Supervisor

Mequanint, Kibret

Abstract

Electrically conductive carbon-based materials are emerging as potential biomaterials for bone tissue engineering. Their incorporation into organic-inorganic nanocomposites mimics the structural composition and electrically conductive nature of bone.

The aim of this research was to design bone biomaterials from gelatin-based polymers, tertiary bioactive glasses (BG) via a sol-gel method, and multiwall carbon nanotubes (MWCNT). The incorporation of calcium into organic-inorganic nanocomposites plays an essential role in the development of bioactive bone biomaterials. Calcium chloride and calcium ethoxide were investigated as calcium sources in gelatin-BG-MWCNT nanocomposites. The resulting surface elemental distribution was homogeneous, but the swelling, degradation and porosity properties of nanocomposites differed due to the fate of calcium ions within the organic-inorganic network. Mineralization on the surfaces of nanocomposites was observed after treatment in simulated body fluid. Favorable cell adhesion, spreading, and viability were observed on nanocomposites, with calcium ethoxide having more advantageous properties. Furthermore, an alternative synthesis strategy comprising gelatin methacryloyl (GelMA), sol-gel derived tertiary BG containing calcium ethoxide as calcium source, and MWCNT was developed to create nanocomposite organic-inorganic hydrogels. Using this strategy, biomaterials possessed mechanical and electrically conductive properties as a function of MWCNT loading. In addition, suitable electro-mechanical responses similar to that found in endogenous bone were observed without affecting their bioactive and biocompatibility properties. Nanocomposite hydrogels also supported mouse embryo multipotent mesenchymal progenitor (10T1/2) cells and drove differentiation into an osteogenic lineage.

Mesenchymal stem cells derived from human-induced pluripotent stem cells (iMSCs) were also able to attach to GelMA-BG-MWCNT nanocomposite hydrogels. Cell adhesion onto the surfaces of nanocomposite was improved when hydrogels were coated with fibronectin and seeding pre-differentiated iMSCs. Increased osteogenic differentiation and the formation of mature mineral deposition were observed in hydrogels with increasing MWCNT concentration. Overall, the data presented in this thesis demonstrated that nanocomposites containing MWCNT could potentially become promising bioactive biomaterials for bone repair and regeneration applications.

Summary for Lay Audience

Bone loss is clinically defined as a defect in the bone structure that is caused either by external factors or deformation of existing bone, causing structural deterioration. The repair of bone fractures and reconstruction of critical-size bone defects that exceed the healing capacity of the human body represent a significant challenge. Currently, treatment for cases of orthopedic intervention involves a grafting procedure that replaces the defected bone with autograft or allograft sources as well as xenograft or synthetic bone substitutes, however, these procedures often lead to complications causing hemorrhage and vascular lesions, limited quality of harvested bone as well as risk of disease transmission and immune response. In addition, patients display limited anatomical and functional recovery demonstrating the requirement for an alternative therapeutic solution that would ideally degrade at a similar rate to the formation of new tissue to maintain the integrity of the repaired region of bone. Although several materials such as organic polymers, inorganic phosphates, and organic-inorganic hybrids have been extensively studied for bone tissue engineering solutions, new generation of biomaterials that better mimic the bone's natural electrically conductive property may have significant advantages.

In this research, nanocomposite biomaterials comprised of gelatin, bioactive glass (BG) and multiwall carbon nanotubes (MWCNT) were developed to establish a favorable approach that incorporates all three components for the development of a bone biomaterial. Comparison of the role of different calcium sources in the gelatin-BG-MWCNT were evaluated. An improved strategy was further developed to prepare bioactive nanocomposite hydrogels composed of gelatin methacryloyl (GelMA), BG and MWCNT containing tunable electro-mechanical responses similar to those found in endogenous bone during its regeneration and healing. The nanocomposite hydrogels were able to induce osteogenic differentiation in mouse- and human-derived stem cells and enhanced protein expression and mineralization in pre-differentiation human-derived stem cells.

In conclusion, organic-inorganic nanocomposite biomaterials containing an electrically conductive component mimic the natural structural composition and electrical conductive properties of bone, and may be good candidates for bone tissue engineering.

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