Optimized DLP 3D-Printed High-Resolution Nano Zirconia-Hydroxyapatite Scaffold with Craniomaxillofacial Soft Tissue Invasion Resistance and Pro-Osteogenic Properties Via Dectin-1/Syk Inflammatory Axis

One major challenge of craniomaxillofacial bone regeneration is the direct contact of subcutaneous fibrous tissue towards bone regenerative region, which results in fast fibroblast invasion and suppression of bone regeneration. Dectin-1, a pattern recognition receptor expressed on activated macrophages, is crucial for directing fibrous invasion. Targeting Dectin-1 and its downstream signaling cascade could be an effective strategy to resist “craniomaxillofacial soft tissue invasion”. Nano zirconia can shelter the essential amino acids of Dectin-1 and was reported to deactivate the inflammation signals. Herein, we succeeded in incorporating nano zirconia into high-resolution 3D hydroxyapatite (HA) scaffolds via modified digital light processing (DLP) technique system. The incorporation of nano zirconia can endow high-resolution HA scaffolds with the capacity of regulating the key structure of extracellular C-type lectin-like domain (CTLD) of dectin-1, proved by computational simulation. This results in inhibiting the dectin-1/syk axis and pro-soft tissue proliferation cytokines production. In vivo experiments further validated the effects of HA/nano zirconia resisting craniomaxillofacial soft tissue invasion and promoting bone regeneration. Our work practices the concept of “soft tissue invasion resisting capacity” via targeting in manipulating dectin-1, which succeeds in attenuating fibrous invasion and craniomaxillofacial bone regeneration. The “soft tissue invasion resisting capacity” could become a valuable biological paradigm of craniomaxillofacial bone biomaterials.