Novel Biocompatible Material Formulations for 3D-Microfabrication of Porous Scaffolds for Bone Regenerative Engineering

Abstract

Abstract Many patients suffer yearly from bone fractures and defects worldwide. Projections have shown that three million osteotomies will be carried out by 2028. Whether it is a bone fracture (or defect) or a disease (such as osteosarcoma), patients will have to deal with a traditionally long healing process. 3D-microfabrication has emerged as a high-resolution method in clinical practice for fabrication of a broad range of osteoconductive bone tissue scaffolds. In addition, stem cell therapy has emerged as a clinically viable method, allowing for implantation of autologous cell-seeded scaffolds for tissue regeneration. However, patient-specific treatment of bone fractures is a complex clinical problem, governed by a wide range of factors, such as biomaterial formulation, 3D-fabrication process dynamics, as well as stem cell-driven osteogenesis. Therefore, there is a need for investigation of the influence of biomaterial formulation, among other factors, on the functional properties of fabricated bone scaffolds. In the absence of such knowledge, fabrication of bone scaffolds will not tailor to the medical needs of patients and thus will remain sub-optimal. The long-term goal of this research work is to fabricate patient-specific, biocompatible, and porous bone tissue scaffolds with low immunogenicity for the treatment of bone pathology. In pursuit of this goal, the overall objective of the work is to synthesize, fabricate, and characterize the mechanical and biomedical properties of bone tissue scaffolds, synthesized based on novel biomaterial formulations and fabricated using a pneumatic micro-extrusion (PME) process; a high-resolution additive manufacturing method. To realize this objective, porous bone tissue scaffolds are 3D-fabricated with a polysaccharide base containing chitosan, nanoclay, and hydroxyapatite at various concentrations as binary, ternary, and quaternary mixtures. These are natural-origin and biocompatible materials for bone regenerative engineering. In this study, the PME fabrication of bone scaffolds was performed with a microcapillary nozzle, having a diameter of 840 μm with material deposition on an unheated glass substrate using a flow pressure in the range of 75–175 kPa for laminar deposition of the formulated bone scaffolding materials. Finally, the fabricated bone scaffolds were freeze-dried to avoid intrinsic shrinkage and structural crack formation to obtain scaffolds with the highest level of dimensional accuracy. It was observed that the presence of hydroxyapatite as well as nanoclay (to a lesser extent) in the polysaccharide matrix not only facilitated the material deposition process in terms of viscosity, but also led to the formation of mechanically strong porous scaffolds compared to the influence of the other biomaterials used. Overall, the outcomes of this project will pave the way for patient-specific fabrication of scaffolds for bone regeneration and ultimately effective recovery of patients, who have suffered from bone-related injuries.