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Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Biomedical Engineering

Supervisor

Mequanint, Kibret

Abstract

Bone biomaterials prepared from a combination of biodegradable polymers and bioactive glasses offer several advantages, including favorable cell interactions, selective gene expression, and delivery of biomolecules. Furthermore, the interaction of the organic and inorganic phases at the molecular level results in a single-phase hybrid material possessing synergistic properties.

This research aimed to design bone biomaterials from α-amino acid-based poly(ester amide) (PEA) and tertiary bioactive glasses using a sol-gel process. Since incorporating calcium into the bioactive glass network is challenging at sol-gel reaction temperatures, calcium ethoxide and calcium chloride were studied as precursors, and the optimum reaction conditions were identified. Mesoporous silica nanoparticles loaded with a model drug were incorporated into the hybrid biomaterials during scaffold fabrication to provide drug delivery capability. In an alternative strategy, a hydrophobic model drug was loaded to the PEA, while a hydrophilic model drug was loaded to the bioactive glass during the hybrid sol-gel microparticle synthesis. Data presented in this thesis demonstrated the feasibility of delivering multiple biomolecules from these hybrid biomaterials. Owing to the presence of the amino acid L-phenylalanine, the hybrid microparticles were fluorescent with tunable emission by changing the excitation wavelengths ranging from 300 to 565 nm for potential multiplex imaging.

The PEA-bioactive glass hybrids were cytocompatible and promoted hydroxyapatite formation from simulated body fluid. Moreover, the hybrid microparticles induced osteogenic differentiation of 10T1/2 cells as a stand-alone system without biochemical factor supplements. Taken together, the data presented in this thesis demonstrated the potential of hybrid biomaterials for bone tissue engineering applications.

Summary for Lay Audience

The increase in the elderly segment of the population has made the need for bone substitutes a demanding task. Apart from age-related diseases, there are other reasons which can cause substantial bone loss, such as fractures, congenital diseases, and tumor resections. Bone has a high regenerative capacity; however, depending on the size of the defect, its anatomical location, age and health background of the patient, and the state of surrounding soft tissue, many defects do not heal spontaneously. For these defects, the current clinical approach is the use of autografts or allografts. Autografts are bone harvested from another site in the patient body to be transplanted into the defect site, while allografts are harvested from another human body, mostly a cadaver. There are certain limitations associated with these approaches, such as limited availability of healthy bone and disease transmission risk. Therefore, developing alternative solutions is essential to meet the ever-increasing demand. Bone tissue engineering attempts to provide bone substitutes by the use of natural or synthetic materials in combination with other elements such as (stem) cells and biomolecules.

In this research, hybrid biomaterials consisting of a biodegradable polymer derived from natural amino acids, namely poly(ester amide) and bioactive glass, were synthesized. Hybrid material scaffolds having silica nanoparticles embedded in them as a biomolecule delivery system were fabricated. To study the hybrid material for drug delivery capability, hybrid microparticles with a new synthetic approach were prepared. The microparticles could be loaded with two compounds and were bioactive.

The potential of the hybrid microparticles to promote progenitor cells differentiation to osteoblasts (bone cells) through the release of ions from their structure and/or the release of the loaded drug was investigated. Dexamethasone was loaded in the microparticles as the drug of interest.

In conclusion, this work introduced and investigated the potential of a specific organic-inorganic hybrid biomaterial in the form of scaffolds and microparticles for the application of bone tissue engineering.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Available for download on Friday, December 31, 2021

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