| dc.description.abstract | The incidences of bone-related disorders is growing steeply worldwide because of acute trauma, diseases related to aging, and obesity. Bone has a natural regenerative capacity to repair and regenerate fractures and small defects. However, surgical intervention is required in the case of large bone defects and non-union fractures. Conventionally, substitutes such as bone grafts are used to treat the aforementioned bone defects. Drawbacks associated with bone grafts, such as low donor availability, immune rejection, multiple surgeries, etc., have created a huge demand for bone tissue substitute development. Bone tissue engineering aims to fabricate a scaffold that closely mimics the bone tissue microenvironment and thus stimulates bone regeneration and integration with the host tissue. Over the years, studies have shown that degradable polymer nanocomposites provide a better combination of properties to scaffolds over polymer alone. Also, it has been reported that oxidative stress can hamper the bone repair process. With its unique redox properties, cerium oxide (ceria) is increasingly being studied in biomedical applications but its potential in orthopedic applications is minimally explored. Ceria can be used to fabricate multifunctional polymer nanocomposites. Thus, ceria-based composite scaffolds could be developed and investigated as scaffolds that potentially offer multifunctional benefits for bone tissue engineering.
This thesis comprises seven chapters. Chapter 1 briefly introduces the concept of bone tissue engineering, polymer nanocomposites, oxidative stress in bone repair, and the unique properties of ceria. The chapter further outlines the literature review on the use of degradable polymeric nanocomposites for bone tissue engineering. Furthermore, the applications of ceria nanoparticles in the biomedical field are discussed with special attention to the antioxidant property that offers protection against oxidative stress in several degenerative disorders.
Chapters 2, 3, and 4 focus on synthesizing olive oil-based degradable polymer nanocomposites. Chapter 2 describes a combinatorial approach to prepare a library of polyesteramides from olive oil with tuneable properties. Polyesteramides are polymers with ester groups that provide degradability, whereas amide groups offer thermo-mechanical properties. The degradation, mechanical, and release properties were tailored by varying the chain length of the diacid, curing time, and stoichiometric ratio of reactants. Further, the fabrication of ceria-infused nanocomposites prepared by compression molding is also discussed in this chapter. The synthesized polymers and nanocomposite were cytocompatible in nature. And the release studies confirmed that the composites could be used as delivery platforms, including for ceria nanoparticles.
Chapter 3 explains the synthesis of slower degrading polyurethanes compared to polyesteramides from olive oil that are better suited for engineering tissue scaffolds. Polyurethanes are widely used in biomedical applications based on their various physicochemical p= roperties and biocompatibility. Two different polyurethanes were synthesized from olive oil, optionally incorporating polyethylene glycol (PEG). Improvement in degradation while the reduction in the mechanical properties of polyurethanes was observed after adding PEG. The synthesized polyurethanes can be fabricated into various 2D substrates and 3D scaffolds by compression molding and particulate leaching techniques. Further, the cytocompatibility and osteogenesis studies were performed, which are presented in this chapter. The result showed both the polyurethanes were cytocompatible and supported osteogenesis. Thus, this chapter deals with olive oil-based polyurethanes as a promising biomaterial for developing scaffolds with tailored degradation and mechanical properties for tissue regeneration.
Chapter 4 describes the synthesis of hybrid nanoparticles containing ceria nanoparticles anchored to the graphene sheets using a hydrothermal process and its advantage in improving the bioactivity of olive oil-based polyurethane. The hybrid particles afford good dispersion and reduced agglomeration in contrast to ceria nanoparticles. The various nanocomposites were prepared by in situ polymerization process incorporating hybrid, graphene oxide, or ceria nanoparticles. All the composites showed minimal toxicity to preosteoblasts. Hybrid particle-infused nanocomposites demonstrated improved radical scavenging potential and osteogenic differentiation ability over other nanocomposites and neat polyurethane. Thus, the collaborative effect of graphene and ceria in hybrid particles provides multifunctional properties to olive oil-based polyurethanes for potential application in bone tissue regeneration.
Chapters 5 and 6 demonstrate the use of known degradable polymers such as polylactic acid (PLA) and polycaprolactone (PCL) to fabricate multifunctional composite scaffolds containing ceria for bone tissue engineering. Chapter 5 explains a strategy to surface decorate 3D printed PLA scaffold with ceria and its advantage in bone regeneration. The 3D porous PLA scaffold was fabricated using a fused filament fabrication-based method. A facile polyethylene imine-citric acid conjugation was used to the functionalized scaffold with ceria. The surface functionalization was nontoxic and helped protect human mesenchymal stem cells from oxidative stress. Further, the decorated scaffold exhibited improved osteogenic and antibacterial potential than unfunctionalized scaffolds. Thus, the current chapter display a simple method of surface decoration of 3D printed PLA scaffolds with ceria offering a viable route for improvement of its bioactivity for bone tissue engineering.
Chapter 6 describes the fabrication of ceria-infused PCL nanofibrous scaffolds and its benefit in bone tissue engineering in the older population. The older population has a greater number of senescent cells, which are responsible for delayed bone regeneration. Senescent cells are identified with the cell cycle arrest and oxidative microenvironment. Senescence was induced by exposing preosteoblasts to ionizing radiations. The potential to scavenge free radicles showed that the strategy of ceria incorporation in nanofibrous scaffolds could reduce the oxidative stress level in senescent and non-senescent cells. Ceria-infused fibers rescued the decreased osteogenic potential caused due to senescence. Thus, the addition of ceria nanoparticles provides multifunctional properties to nanofibers which could be used in bone regeneration in the geriatric population.
Chapter 7 summarizes the key outcomes of the different studies performed here. The future scope and extension of this work are also discussed in this chapter.
In conclusion, the current thesis focuses on enhancing the osteogenic activity along with the antioxidant potential of scaffolds. This was accomplished by developing ceria containing multifunctional degradable polymer nanocomposite for bone tissue regeneration. | en_US |
