ABSTRACT
The field of bone tissue engineering aims to develop an effective and aesthetical bone graft substitute capable of repairing large mandibular defects. However, graft failure resulting from necrosis and insufficient integration with native tissue due to lack of oxygen and nutrient transportation remains a concern. To overcome these drawbacks, this study aims to develop a 3D printed polycaprolactone layered construct with a LEGO®-inspired interlocking mechanism enabling spatial distribution of biological components. To highlight itsin vitroosteogenic potential, human mesenchymal stromal cells are cultured onto Bio-Gide®Compressed collagen (Col) membranes, which are embedded within the layered construct for 28 d. The osteogenic response is assessed through the measurement of proliferation, relevant markers for osteogenesis including alkaline phosphatase (ALP) activity, expression of transcriptional genes (SP7, RUNX2/SOX9) as well matrix-related genes (COL1A1, ALPL IBSP, SPP1), osteoprotegerin secretion.In vitroosteogenic differentiation results showed increased levels of these osteogenic markers, indicating the layered construct's potential to support osteogenesis. In this study, a novel workflow of 3D printing a patient-specific LEGO®-inspired layered construct that can spatially deliver biological elements was successfully demonstrated. These layered constructs have the potential to be employed as a bone tissue engineering strategy, with particular focus on the repair of large mandibular defects.
Subject(s)
Collagen , Mandible , Mesenchymal Stem Cells , Osteogenesis , Polyesters , Printing, Three-Dimensional , Tissue Scaffolds , Humans , Polyesters/chemistry , Osteogenesis/drug effects , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effects , Collagen/chemistry , Tissue Scaffolds/chemistry , Tissue Engineering , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Bone Regeneration/drug effects , Cells, CulturedABSTRACT
The 3D printing process of fused deposition modelling is an attractive fabrication approach to create tissue-engineered bone substitutes to regenerate large mandibular bone defects, but often lacks desired surface porosity for enhanced protein adsorption and cell adhesion. Solvent-based printing leads to the spontaneous formation of micropores on the scaffold's surface upon solvent removal, without the need for further post processing. Our aim is to create and characterize porous scaffolds using a new formulation composed of mechanically stable poly(lactic-co-glycol acid) and osteoconductive ß-tricalcium phosphate with and without the addition of elastic thermoplastic polyurethane prepared by solvent-based 3D-printing technique. Large-scale regenerative scaffolds can be 3D-printed with adequate fidelity and show porosity at multiple levels analysed via micro-computer tomography, scanning electron microscopy and N2 sorption. Superior mechanical properties compared to a commercially available calcium phosphate ink are demonstrated in compression and screw pull out tests. Biological assessments including cell activity assay and live-dead staining prove the scaffold's cytocompatibility. Osteoconductive properties are demonstrated by performing an osteogenic differentiation assay with primary human bone marrow mesenchymal stromal cells. We propose a versatile fabrication process to create porous 3D-printed scaffolds with adequate mechanical stability and osteoconductivity, both important characteristics for segmental mandibular bone reconstruction.