Fabrication of Radio-Opaque and Macroporous Injectable Calcium Phosphate Cement.

The aim of this work was the development of injectable radio-opaque and macroporous calcium phosphate cement (CPC) to be used as a bone substitute for the treatment of pathologic vertebral fractures. A CPC was first rendered radio-opaque by the incorporation of zirconium dioxide (ZrO2). In order to create macroporosity, poly lactic-co-glycolic acid (PLGA) microspheres around 100 µm were homogeneously incorporated into the CPC as observed by scanning electron microscopy. Physicochemical analyses by X-ray diffraction and Fourier transform infrared spectroscopy confirmed the brushite phase of the cement. The mechanical properties of the CPC/PLGA cement containing 30% PLGA (wt/wt) were characterized by a compressive strength of 2 MPa and a Young's modulus of 1 GPa. The CPC/PLGA exhibited initial and final setting times of 7 and 12 min, respectively. Although the incorporation of PLGA microspheres increased the force necessary to inject the cement and decreased the percentage of injected mass as a function of time, the CPC/PLGA appeared fully injectable at 4 min. Moreover, in comparison with CPC, CPC/PLGA showed a full degradation in 6 weeks (with 100% mass loss), and this was associated with an acidification of the medium containing the CPC/PLGA sample (pH of 3.5 after 6 weeks). A cell viability test validated CPC/PLGA biocompatibility, and in vivo analyses using a bone defect assay in the caudal vertebrae of Wistar rats showed the good opacity of the CPC through the tail and a significant increased degradation of the CPC/PLGA cement a month after implantation. In conclusion, this injectable CPC scaffold appears to be an interesting material for bone substitution.

Development of new biocompatible 3D printed graphene oxide-based scaffolds.

The aim of this work was to develop a bioresorbable, biodegradable and biocompatible synthetic polymer with good mechanical properties for bone tissue engineering applications. Polylactic acid (PLA) scaffolds were generated by 3D printing using the fused deposition modelling method, and reinforced by incorporation of graphene oxide (GO). Morphological analysis by scanning electron microscopy indicated that the scaffold average pore size was between 400 and 500 µm. Topography imaging revealed a rougher surface upon GO incorporation (Sa = 5.8 µm for PLA scaffolds, and of 9.9 µm for PLA scaffolds with 0.2% GO), and contact angle measurements showed a transition from a hydrophobic surface (pure PLA scaffolds) to a hydrophilic surface after GO incorporation. PLA thermomechanical properties were enhanced by GO incorporation, as shown by the 70 °C increase of the degradation peak (thermal gravimetric analysis). However, GO incorporation did not change significantly the melting point assessed by differential scanning calorimetry. Physicochemical analyses by X-ray diffraction and Raman spectroscopy confirmed the filler presence. Tensile testing demonstrated that the mechanical properties were improved upon GO incorporation (30% increase of the Young's modulus with 0.3% GO). Cell viability, attachment, proliferation and differentiation assays using MG-63 osteosarcoma cells showed that PLA/GO scaffolds were biocompatible and that they promoted cell proliferation and mineralization more efficiently than pure PLA scaffolds. In conclusion, this new 3D printed nanocomposite is a promising scaffold with adequate mechanical properties and cytocompatibility which may allow bone formation.

Boron Nitride Based Nanobiocomposites: Design by 3D Printing for Bone Tissue Engineering.

Here, we produced a synthetic polymer having adequate biocompatibility, biodegradability, and bioresorbability, as well as mechanical properties for applications in bone tissue engineering. We used the fused deposition modeling (FDM) based 3D printing approach in order to produce biomimetic biodegradable scaffolds made of polylactic acid (PLA). We strengthened these scaffolds by addition of exfoliated boron nitride (EBN) as filler. We demonstrated the presence of EBN by physicochemical analysis using Raman spectroscopy and X-ray diffraction (XRD). Using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), we found that EBN incorporation did not influence the transition temperature, but reduced the polymer crystallinity. Scanning electron microscopy for morphology evaluation showed a mean scaffold pore size of 500 µm. EBN incorporation did not affect the scaffold mechanical properties (tensile test), but modified the surface roughness. Moreover, contact angle quantification indicated that the surface of PLA/EBN scaffolds was hydrophilic and that of PLA scaffolds hydrophobic. Finally, the results of the cytotoxicity, cell attachment, and proliferation experiments using MG-63 and MC3T3 cells indicated that PLA scaffolds filled with EBN were nontoxic and compatible with osteoblastic cells and also promoted the scaffold mineralization by MG-63 cells. Altogether, our results suggest that this 3D printed nanocomposite scaffold is suitable for tissue engineering.