3D-Printed Poly(Lactic-co-Glycolic Acid) Binder-Based Self-Hardening Calcium Phosphate Bone Scaffolds.

Three-dimensionally (3D)-printed alpha-tricalcium phosphate (α-TCP) scaffolds, fabricated through a low-temperature hydrothermal dissolution-precipitation process, replicate the structural and compositional features of native bone. Reinforcing hydrothermally processed α-TCP with poly(lactic-co-glycolic acid) (PLGA) as a binder has previously been shown to confer distinct mechanical advantages, supporting its potential as a viable material for bone regenerative scaffolds. Although the hydrothermal processing of α-TCP scaffolds and PLGA-based mechanical reinforcement have each been characterized individually in earlier studies, this work represents the first pre-clinical in vivo assessment of osseoconduction and biocompatibility of 3D-printed, PLGA-reinforced, self-hardening calcium phosphate scaffolds in a large translational animal model. A ceramic ink suitable for extrusion was prepared by combining a 30 wt/vol% poloxamer 407 solution with α-TCP powder at a 0.45 wt/wt ratio (CTRL). A second extrudable ink, consisting of an α-TCP ceramic suspension incorporating a 35 wt/wt% PLGA binder, was formulated at a 0.5 wt/wt ratio (EXP). Cylindrical scaffolds (6 mm × 6 mm) were fabricated at room temperature using a custom-built Direct Ink Write 3D printer, then hydrothermally treated via submersion in water and thermal consolidation at 121 °C. Osteotomies were created in the ilium of adult sheep, with two cylindrical defects (7 mm × 6 mm) per animal, each receiving either a CTRL or EXP scaffold. Animals were euthanized at 3 and 12 weeks post-surgery (n = 6 animals per time point), and samples were collected en bloc for analysis. For both scaffold formulations, hard tissue formed by 12 weeks displayed high cellularity and active vascularization, consistent with early woven bone formation. Quantitative analysis revealed no significant between-group differences in bone formation at either time point (p > 0.05). These findings indicate that 3D-printed, PLGA-reinforced, self-hardening α-TCP scaffolds are osseoconductive and biocompatible, supporting their potential use in orthopedic and craniomaxillofacial bone defect repair.