Inclusion of calcium phosphate does not further improve in vitro and in vivo osteogenesis in a novel, highly biocompatible, mechanically stable and 3D printable polymer

Abstract

At a time of unpredictable challenges for health, one trend is certain: there is an exceedingly high demand for functional implants, particularly bone grafts. This has encouraged the emergence of bone tissue engineering substitutes as an alternative method to conventional bone grafts. However, the current approaches in the field face several limitations that have prevented the ultimate translation into clinical settings. As a result, many attempts have been made to fabricate synthetic bone implants that can offer suitable biological and mechanical properties.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 investigate the role of calcium phosphate (CaP) incorporation in a mechanically stable, biologically functional and 3D printable polymer for the reconstruction of complex craniofacial defects. The experimental work initially involved the synthesis of (((((((((((3R,3aR,6S,6aR)- hexahydrofuro[3,2-b]furan-3,6-diyl)bis(oxy))bis(ethane-2,1- 48 diyl))bis(oxy))bis(carbonyl))bis(azanediyl))bis(3,3,5-trimethylcyclohexane-5,1- 49 diyl))bis(azanediyl))bis(carbonyl))bis(oxy))bis(ethane-2,1-diyl) bis(2-methylacrylate) referred to as CSMA and fabrication of composite discs via a Digital Light Printing (DLP) method. The flow behaviour of the polymer as a function of CaP addition, surface remineralisation potential, in vitro cell culture, using MC3T3 and Adipose-Derived Mesenchymal Stem Cells (ADSCs) and ex ovo angiogenic response was assessed. Finally, in vivo studies were carried out to investigate neo-bone formation at 4- and 8-weeks post-implantation. Quantitative micro-CT and histological evaluation did not show a higher rate of bone formation in CaP filled CSMA composites compared to CSMA itself. Therefore, such polymeric systems hold promising features by allowing more flexibility in designing a 3D printed scaffold targeted at the reconstruction of maxillofacial defects.

Amorphous, Carbonated Calcium Phosphate and Biopolymer-Composite-Coated Si3N4/MWCNTs as Potential Novel Implant Materials

“…The Si 3 N 4 /3wt% MWCNT substrate was appropriately biocompatible and the caCP addition to the biopolymer matrix noticeably advanced the cell attachment. The obtained results here agree well with other research works, in which the amorphous CaP particles and different composites were studied and characterized concerning their boosted osteogenic level [57][58][59][60][61][62][63].…”

In Vivo Osteogenic and Angiogenic Properties of a 3D-Printed Isosorbide-Based Gyroid Scaffold Manufactured via Digital Light Processing

“…The combination of PLGA and poly(isosorbide sebacate) (PISEB) was shown to be cytocompatible with HUVEC and showed pro-angiogenic gene expression [ 28 ]. Moreover, CSMA-2 demonstrated an angiogenic response that can be observed via CAM assay and IHC analysis of CD-31 markers, with or without calcium phosphate addition [ 4 ].…”

“…Isosorbide can serve as the backbone for polymers with methacrylate or acrylate groups as the functional groups [ 3 ]. Several studies have demonstrated successful 3D printing with various isosorbide-based composites for hard tissue engineering [ 3 , 4 , 5 ].…”

Digital Light Processing 3D Printing of Gyroid Scaffold with Isosorbide-Based Photopolymer for Bone Tissue Engineering

“…Different from those of the OPN and OCN, the RUNX2 gene expressions in our result were not affected by the HA percentage on the scaffold. The presence of aliphatic side chains and cyclohexenes on the CSMA-2 that increased the surface charge of the 3D-printed scaffold might be able to promote differentiation without the help of HA [ 52 ]. Furthermore, the metabolic activity was significantly lower in the CSMA-2 scaffolds incubated with the osteogenic medium ( Figure 10 ).…”