Development of Bioactive Composites for Maxillofacial (Orbital Floor) Fracture Repair and Regeneration

Alhamoudi, Fahad (2021) Development of Bioactive Composites for Maxillofacial (Orbital Floor) Fracture Repair and Regeneration. PhD thesis, UNSPECIFIED.

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Abstract

The restoration of maxillofacial (orbital floor) bone requires materials that are biodegradable, bioactive and biocompatible. The materials possess good bonding properties that show a particular biological response at the material interface. This forms a bond between the tissue and material to encourage angiogenesis that improves bone repair and regeneration. Polyurethane and nano-hydroxyapatite have been used in a variety of dental and bone regeneration applications. The interfacial linkage between polyurethane and nano-hydroxyapatite play a pivotal role in determining the bioactive composite's properties. In addition, the ionic substitution of hydroxyapatite plays an essential role in the bioactivity and biocompatibility of the final composite. This study investigated four aspects that present the project novelty: (i) the synthesis of multi-substituted nano-hydroxyapatite; (ii) varying the nano-hydroxyapatite concentration in the composite; (iii) bonding between the polyurethane and nano-hydroxyapatite (PU/HA); and (iv) PU/HA with multi ionic substations and its impact on bone fracture repair and regeneration. Substituted nano-hydroxyapatite, including (fluoride, carbonate and citrate), were synthesised by employing a hydrothermal flow system. Chemical structural, physical and biological properties were evaluated. Biocomposite scaffolds were fabricated by particles leaching using the room temperature mixing method, leading to the development of a condenser fabrication method that chemically bonded the hydroxyapatite to the polyurethane and controlled interconnected porosity was obtained. The concentration of nano-hydroxyapatite was ranged from 25, 40, and 60% in polyurethane. The resultant materials were fully characterised, chemically, physically, mechanically and biologically (with two different cells human osteoblast cell line MG-63 and human telomerase reverse transcriptase-immortalised bone marrow mesenchymal stromal cells (hTERT-BMSCs)). Finally, the resulting synthesis hydroxyapatites were nano-sized. The fluoride/carbonate and fluoride/citrate nano hydroxyapatites were the most promising materials, as these materials have the best biocompatibility and bioactivity. The resulting scaffolds were biocompatible, bioactive, and have well-interconnected porosity (the pore size ranging from 10 μm to 450 μm). The spectroscopic investigation confirmed the possibility of covalent bonds formed between the functional groups of polyurethane and nano-hydroxyapatite. The scaffolds with nano-hydroxyapatite have shown better cell viability and proliferation, collagen formation and VEGF protein production. With the increase in the nano-hydroxyapatite concentration, the scaffolds showed better biological responses. However, the mechanical test showed that 40% was the optimum concentration, which was confirmed by employing Chick Chorioallantoic Membrane (CAM) Assay. The obtained vascularisation with polyurethane/nano-hydroxyapatite 40% was higher than those of neat polyurethane scaffolds. The scaffolds with fluoride/citrate nano-hydroxyapatites were the most promising compared to all other scaffolds produced. In summary, the current study found a possible improvement in the bioactive effect, mainly mechanical properties, of scaffolds with a higher concentration of HA (> 40%), but no significant improvement in biologic behaviour. The noticeable effect was on forming new blood vessels compared to PU only. However, the impact of HA substitution (fluoride, carbonate and citrate) showed a significant improvement in biological behaviour, such as cell viability, collaging production, and VEGF release. It is believed that the polyurethane/ fluoride/citrate nano-hydroxyapatites scaffolds have the required properties for a wide range of bone fracture repair and regeneration applications, specifically for maxillofacial (orbital floor) bone.