Synthesis, Characterisation and 3D Printing of an Isosorbide Based, Light Curable, Degradable Polymer for Potential Application in Maxillofacial Reconstruction

Although emergence of bone tissue engineering techniques has revolutionised the field of maxillofacial reconstruction, the successful translation of such products, especially concerning larger sized defects, still remains a significant challenge. Light curable methacrylate based polymers have ideal properties for bone repair. These materials are also suitable for 3D printing which can be applicable for restoration of both function and aesthetics. The main objective of this research was to synthesise a mechanically stable and biologically functional polymer for reconstruction of complex craniofacial defects. The experimental work initially involved synthesis of (((3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane-2,1-diyl) bis((4-methyl-3-oxopent-4-en-1-yl)carbamate), CSMA-1, and ((((((((((((3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane-2,1 diyl))bis(oxy))bis(carbonyl))bis(azanediyl))bis(methylene))bis(3,3,5-trimethylcyclohexane-5,1-diyl))bis(azanediyl))bis(carbonyl))bis(oxy))bis(ethane-2,1-diyl) bis(2-methylacrylate), CSMA-2; Nuclear Magnetic Resonance (NMR) analysis confirmed formation of the monomers and composite samples were fabricated respectively by exposing 11 mm diameter discs to blue light. Modulus of the tensile elasticity was tested using a biaxial flexural test and the values were found to be between 1 and 3 GPa in CMA-1, CSMA-2 and their composites. In vitro cell culture, using human Bone Marrow Derived Mesenchymal Stem Cells (BMSCs), confirmed non-toxicity of the samples and finally 3D printing allowed direct extrusion and setting of the bio ink into a mesh-like construct

Zinc and Strontium based Phosphate glass beads: a novel material for bone tissue engineering

Degradable phosphate-based glasses that contain strontium, zinc and calcium were investigated to examine its function as an osteoconductive material. Glass beads of the general formula of (P2O5)-(Na2O)-(TiO2)-(CaO)-(SrO) or (ZnO) were prepared by melt quench technique followed by milling and spheroidisation. Glass bead size distribution was initially measured by SEM. Then, some of these samples were immersed in deionized water to evaluate both the surface changes and measure the ion release rate, whereas other glass beads samples were incubated in culture media to determine pH changes. Furthermore, human osteoblast-like osteosarcoma cells MG-63 and human mesenchymal stem cells were seeded on the glass beads to determine its cytocompatibility via applying CCK assay, ALP assay and Ca assay. SEM images and fluorescence images of confocal microscopy were performed for the cellular studies. While mass degradation and ion release results displayed a significant increase with zinc and strontium incorporation within time, pH results showed an initial increase in pH followed by a decrease. Cellular studies emphasised that all formulations enhanced cellular proliferation. More specifically, ZnO5 and SrO17.5 displayed more promising results although they were insignificantly different from that of control (p>0.05). This may suggest their applicability in hard tissue engineering

Physical properties and biocompatibility effects of doping SiO2 and TiO2 into phosphate-based glass for bone tissue engineering

Phosphate glass is continuing to gain more attention as potential bone substitutes. The ternary (P2O5-CaO-Na2O) is investigated in terms of both physical properties and biocompatibility by doping different percentages of SiO2 and TiO2. Two groups were prepared; the first has different percentages of TiO2 and SiO2, whereas the second group compositions have 5 mol% TiO2 and 5 mol% SiO2 being added to compensate the network-forming oxide P2O5 and the network-modifying oxide CaO. Density, mass loss, pH, DTA, XRD, and cation release experiments were performed to study the physicochemical properties of the compositions, while MG63 and hMS cells were used within in vitro cell culture to study their biocompatibility. Results showed that an increase in TiO2 content correlated with an increase in glass density, decreased mass loss, increased trend of Tg and Tm values, and Na+ and Ca2+ release in group 1. There was no improvement in the MG63 viability or the ability of hMSCs to differentiate into osteoblasts where TiO2 decreased in favour of SiO2. Furthermore, in group 2, 50P2O5-25CaO was less dense than 45P2O5-30CaO, degraded dramatically less, had lower Tg and Tm values and released less Na+ and Ca(2+). The synergistic effect of doping 5 mol% TiO2 and 5 mol% SiO2 increased the MG63 viability in both compositions and was found 45P2O5-30CaO to have promising results in terms of the ability of hMSCs to differentiate into osteoblasts. To conclude, substituting TiO2 in place of SiO2 improved the physical properties and the biocompatibility of (P2O5-CaO-Na2O) glass system, whereas doping 5 mol% SiO2 and 5 mol% TiO2 together in place of P2O5 and CaO had a synergistic effect in controlling their degradation rate and improving their biological responses