3D-printed hydroxyapatite microspheres reinforced PLGA scaffolds for bone regeneration

Bone tissue engineering scaffolds with similar composition, structure, and mechanical properties to natural bone are conducive to bone regeneration. The objective of this study was to prepare hydroxyapatite/poly (lactic-co-glycolic acid) (HA/PLGA) three-dimensional porous scaffolds with HA content close to natural bone and strong mechanical strength to promote osteogenesis. To achieve this, we modified HA microspheres with polyvinyl alcohol to create an inorganic filler to endow the HA/PLGA printing ink with higher HA content and excellent printing fluidity for 3D printing. We successfully printed a series of HA/PLGA scaffolds with different HA contents. The highest HA content reached 60 wt%, which is close to the mineral percentage in natural bone. The composition, structure, mechanical properties, and in vitro degradability of the fabricated scaffolds were systematically characterized. The cytocompatibility and osteogenic activity of the fabricated HA/PLGA scaffolds were evaluated by in vitro cell culture and rabbit femoral defect repair experiments in vivo. The results indicated that the HA/PLGA composite scaffold with 45 wt% HA had the highest compressive strength of more than 40 MPa, which was six times higher than that of the pure PLGA scaffold. The incorporation of HA microspheres into the PLGA matrix significantly improved the cell adhesion, proliferation, and osteogenic differentiation of bone marrow stem cells (BMSCs) cultured on the surface of the scaffolds. Animal experiments showed that the HA/PLGA composite with 45 wt% HA exhibited the best structure maintenance and osteogenic performance in vivo. The prepared HA/PLGA composite 3D scaffold with HA microsphere reinforcement has considerable application potential in the field of large bone defect repair.