Antisolvent 3D Printing of Gene-Activated Scaffolds for Bone Regeneration

The use of 3D-printed gene-activated bone grafts represents a highly promising approach in the fields of dentistry and orthopedics. Bioresorbable poly-lactic-co-glycolic acid (PLGA) scaffolds, infused with adenoviral constructs that carry osteoinductive factor genes, may provide an effective alternative to existing bone grafts for the reconstruction of extensive bone defects. This study aims to develop and investigate the properties of 3D scaffolds composed of PLGA and adenoviral constructs carrying the BMP2 gene (Ad-BMP2), both in vitro and in vivo. The elastic modulus of the disk-shaped PLGA scaffolds created using a specialized 3D printer was determined by compressive testing in both axial and radial directions. In vitro cytocompatibility was assessed using adipose-derived stem cells (ADSCs). The ability of Ad-BMP2 to transduce cells was evaluated. The osteoinductive and biocompatible properties of the scaffolds were also assessed in vivo. The Young's modulus of the 3D-printed PLGA scaffolds exhibited comparable values in both axial and radial compression directions, measuring 3.4 ± 0.7 MPa for axial and 3.17 ± 1.4 MPa for radial compression. The scaffolds promoted cell adhesion and had no cytotoxic effect on ADSCs. Ad-BMP2 successfully transduced the cells and induced osteogenic differentiation in vitro. In vivo studies demonstrated that the 3D-printed PLGA scaffolds had osteoinductive properties, promoting bone formation within the scaffold filaments as well as at the center of a critical calvarial bone defect.