A DLP-Printed 3D Bioceramplug Fabricated Using a Photocurable Negative Thermo-Responsive Bioceramic Slurry for...

Calcium phosphate (CaP) bioceramics remain underutilized in cranioplasty because of their intrinsic brittleness, limited impact/fatigue tolerance, and insufficient early fixation, which can compromise stable host-implant coupling. This study of 3D-printed β-tricalcium phosphate (β-TCP) burr-hole cover scaffold (3D Bioceramplug) engineered for mechanical reliability, controlled resorption, and well osteointegration in calvarial defect repair. A photocurable, negative thermo-responsive poly(N-isopropylacrylamide) (PNIPAM)-based ceramic slurry enabled digital light processing (DLP) printing of interconnected pores (300-500 μm) and high densification (94%), yielding compressive strength up to ∼38 MPa. It is worth mentioning that this novel slurry enables rapid dewatering within ∼1 h, stabilizing the green body and enabling timely transfer to high-temperature sintering for densification, thereby shortening the post-printing drying/stabilization stage. In a rabbit critical-size calvarial defect model, micro-CT and histology at 12 weeks demonstrated preserved structural integrity, osteoid ingrowth, and intramembranous ossification-mediated osteointegration. Immunohistochemistry (CD68, COL-I, vWF) indicated balanced remodeling, mature bone matrix deposition, and neovascularization. In a subsequent large-animal translational evaluation, implants with or without drainage ports were placed into 10 mm pig calvarial defects. Blood biochemistry and organ function markers remained within physiological ranges for 6 months, supporting systemic biocompatibility. CT/micro-CT enabled robust longitudinal assessment and showed synchronized scaffold degradation (16-19%) with progressive bone formation. Morphometric analysis revealed 70-80% defect occupancy by newly formed bone plus residual scaffold, compared with <25% in controls. Histology further confirmed bone ingrowth, osteoblastic differentiation (ALP), vascular formation (vWF), and minimal inflammation (CD68). Therefore, 3D Bioceramplug provides a mechanically stable, biologically safe, and osteoconductive platform for long-term calvarial (cranial) defect reconstruction while offering a substantially accelerated, personalized manufacturing route for sintered bioceramic bone substitutes.