Hydrophilic surface-modified 3D printed flexible scaffolds with high ceramic particle concentrations for immunopolarization-regulation and bone regeneration.

Bioceramic scaffolds used in bone tissue engineering suffer from a low concentration of ceramic particles (<50 wt%), because the high concentration of ceramic particles increases the brittleness of the composite. 3D printed flexible PCL/HA scaffolds with high ceramic particle concentrations (84 wt%) were successfully fabricated in this study. However, the hydrophobicity of PCL weakens the composite scaffold hydrophilicity, which may limit the osteogenic ability to some extent. Thus, as a less time-consuming, less labour intensive, and more cost-effective treatment method, alkali treatment (AT) was employed to modify the surface hydrophilicity of the PCL/HA scaffold, and its regulation of immune responses and bone regeneration were investigated in vivo and in vitro. Initially, several concentrations of NaOH (0.5, 1, 1.5, 2, 2.5, and 5 mol L-1) were employed in tests to determine the appropriate concentration for AT. Based on the comprehensive consideration of the results of mechanical experiments and hydrophilicity, 2 mol L-1 and 2.5 mol L-1 of NaOH were selected for further investigation in this study. The PCL/HA-AT-2 scaffold dramatically reduced foreign body reactions as compared to the PCL/HA and PCL/HA-AT-2.5 scaffolds, promoted macrophage polarization towards the M2 phenotype and enhanced new bone formation. The Wnt/ß-catenin pathway might participate in the signal transduction underlying hydrophilic surface-modified 3D printed scaffold-regulated osteogenesis, according to the results of immunohistochemical staining. In conclusion, hydrophilic surface-modified 3D printed flexible scaffolds with high ceramic particle concentrations can regulate the immune reactions and macrophage polarization to promote bone regeneration, and the PCL/HA-AT-2 scaffold is a potential candidate for bone tissue repair.

Photo-crosslinked bioactive BG/BMSCs@GelMA hydrogels for bone-defect repairs.

The clinical treatments of bone defects remain a challenge. Hydrogels containing bone marrow mesenchymal stem cells (BMSCs) are extensively used to bone regeneration because of excellent biocompatibility and hydrophilicity. However, the insufficient osteo-induction capacity of the BMSC-loaded hydrogels limits their clinical applications. In this study, bio-active glass (BG) and BMSCs were combined with gelatin methacryloyl (GelMA) to fabricate composite hydrogels via photo-crosslinking, and the regulation of bone regeneration was investigated. In vitro experiments showed that the BG/BMSCs@GelMA hydrogel had excellent cytocompatibility and promoted osteogenic differentiation in BMSCs. Furthermore, the BG/BMSCs@GelMA hydrogel was injected into critical-sized calvarial defects, and the results further confirmed its excellent angiogenetic and bone regeneration capacity. In addition, BG/BMSCs@GelMA promoted the polarization of macrophages towards the M2 phenotype. In summary, this novel composite hydrogel demonstrated remarkable potential for application in bone regeneration due to its immunomodulatory, excellent angiogenetic as well as osteo-induction capacity.

Pore Size of 3D-Printed Polycaprolactone/Polyethylene Glycol/Hydroxyapatite Scaffolds Affects Bone Regeneration by Modulating Macrophage Polarization and the Foreign Body Response.

3D-printed porous bioactive ceramic scaffolds have been widely used in bone defect repair. However, material implantation is often accompanied by a foreign body response (FBR), which may affect host tissue regeneration. The physical properties of biomaterials, including shape, pore size, and porosity, control the relevant immune responses during tissue regeneration. To the best of our knowledge, the effect of the pore size of 3D-printed scaffolds on the immune response and bone-biomaterial integration has not been studied in vivo. Polycaprolactone/polyethylene glycol/hydroxyapatite (PCL/PEG/HA) bioactive scaffolds with different pore sizes, including 209.9 ± 77.1 µm (P200), 385.5 ± 28.6 µm (P400), and 582.1 ± 27.2 µm (P600), were prepared with a pneumatic extrusion 3D printer. Compared with other pore sizes, P600 significantly reduced the FBR and induced more M2 macrophage infiltration, vascular ingrowth, and new bone formation. Immunohistochemical staining revealed that the MyD88 protein might be involved in macrophage polarization-related signal transduction in response to the pore size. Based on these results, bone regeneration requires the active participation of the immune response, and the P600 PCL/PEG/HA scaffold is a preferable candidate for the repair of bone defects.