Towards the Development of Artificial Bone Grafts: Combining Synthetic Biomineralisation with 3D Printing

Abstract

A synthetic technique inspired by the biomineralisation process in nacre has been previously reported to be effective in replicating the nanostructural elements of nacre in 2D chitosan hydrogel films. Here we evaluate the applicability of this synthetic biomineralisation technique, herein called the McGrath method, in replicating the flat tabular morphology of calcium carbonate and other nanostructural elements obtained when 2D chitosan hydrogel films were used, on a 3D porous chitosan hydrogel-based scaffold, hence developing 3D chitosan-calcium carbonate composites. Nozzle extrusion-based 3D printing technology was used to develop 3D porous scaffolds using chitosan hydrogel as the printing ink in a custom-designed 3D printer. The rheology of the printing ink and print parameters were optimised in order to fabricate 3D cylindrical structures with a cubic lattice-based internal structure. The effects of various dehydration techniques, including air-drying, critical point-drying and freeze-drying, on the structural integrity of the as-printed scaffolds from the nano to macroscale, were evaluated. The final 3D composite materials were characterised using scanning electron microscopy, X-ray diffraction and energy dispersive X-ray spectroscopy. The study has shown that McGrath method can be used to develop chitosan-calcium carbonate composites wherein the mineral and matrix are in intimate association with each other at the nanoscale. This process can be successfully integrated with 3D printing technology to develop 3D compartmentalised polymer-mineral composites.

Granular Honeycombs Composed of Carbonate Apatite, Hydroxyapatite, and β-Tricalcium Phosphate as Bone Graft Substitutes: Effects of Composition on Bone Formation and Maturation

“…All HCGs had uniformly sized macropores (∼115 μm on a side) that were regularly arranged and penetrated straight through granules (Figure ). Conventionally, synthetic macroporous BG materials are fabricated by sintering powders around a transient porogen or foaming agent. − In principle, however, the macroporous structures formed by these methods are intricate and hamper cellular penetration into the materials. − To fabricate ordered macroporous BG materials, three-dimensional printing is a valid alternative. ,,− However, this method cannot currently be used to produce macroporous structures with sizes of less than 500 μm. Because, in the clinical setting, the typical size of BG granules ranges between 250 and 2000 μm, macroporous structures with sizes equal to or exceeding 500 μm are too large for the fabrication of granules or may produce granules with insufficient macropores.…”

“…To facilitate the penetration of cells and tissues into materials, the network of channels connecting macropores should ideally not be intricate. However, in most synthetic BG materials, macropores are not entirely connected and the paths are complex because of the method used to produce the macropores, such as the removal of porogens from the compact composed of ceramic powder and porogens. − Ideally, macropores penetrate straight into the material. From this perspective, a honeycomb (HC) structure, which is an array of hollow cells formed between thin vertical walls, is ideal. − …”

Application Progress of Modified Chitosan and Its Composite Biomaterials for Bone Tissue Engineering

“…Owing to the aqueous solubility of CS in an acidic environment, it is largely utilized for bioprinting applications, where it accounts for 4% of total polymer distribution used for bioink preparation [ 90 ]. The CS chains expand into a semi-rigid rod confirmation due to ionic repulsion between the charged groups (NH3+), and thus the CS ink exhibits shear thinning behavior under low shear rates at 25 °C, leading to better flow through the needle [ 91 ], which is beneficial for the extrusion-based 3D bioprinting [ 92 ]. CS-based hydrogels hold great promise for the development of 3D bioprinting inks to fabricate engineered constructs [ 93 ].…”

Novel chitosan-poly(vinyl acetate) biomaterial suitable for additive manufacturing and bone tissue engineering applications

“…28 Scaffolds containing CS for tissue engineering applications have been fabricated using AM in the past. These AM processes include material extrusion such as fused deposition modelling, [29][30][31] bioprinting [31][32][33] and low-temperature deposition manufacturing. 34,35 Other processes include binder jetting 36,37 and vat polymerisation.…”