3D-Printed Hydroxyapatite/Polycaprolactone Porous Scaffolds as Tarsus Substitutes for Eyelid Defects: A Preliminary Study in Rabbits

Purpose: Reconstruction of eyelid tarsal defects remains challenging due to donor-site morbidity, insufficient autologous tissue sources, and biomechanical mismatch between grafts and native tarsal plate. This study aimed to fabricate polyethylene glycol 400-plasticized 3D-printed hydroxyapatite/polycaprolactone (HA/PCL) porous scaffolds, and to compare the repair efficacy of scaffolds with 70% and 84% HA mass fractions in a rabbit eyelid tarsal defect model. Methods: Scaffolds were fabricated by pneumatic extrusion 3D printing and characterized for porosity, mechanics, hydrophilicity, and cytocompatibility with human umbilical vein endothelial cells (HUVECs). A rabbit tarsal defect model was used to evaluate ocular safety, inflammation, angiogenesis, and tissue integration at 4 and 8 weeks via corneal staining, hematoxylin and eosin (H&E), qPCR, and immunohistochemistry (IHC). Results: Both scaffolds achieved high porosity of 91.66% and exhibited favorable hydrophilicity and cytocompatibility. The elastic modulus of the 84% HA scaffold was 2.66 MPa, which was closer to that of a natural rabbit tarsal plate. No obvious corneal injury or immune rejection was observed in vivo. Compared with the 70% HA group, the 84% HA scaffold induced milder inflammation, more regular collagen arrangement, tighter tissue integration, and a more stable inflammatory-angiogenic microenvironment. Conclusions: The 3D‑printed HA/PCL scaffolds are promising for tarsal repair. The 84% HA scaffold offers superior mechanical compatibility, inflammatory regulation, angiogenesis, and tissue regeneration, providing an experimental basis for eyelid reconstruction biomaterials. Translational Relevance: This study translates basic biomaterial's research into clinical ophthalmic care by showing optimized 3D‑printed HA/PCL scaffolds match tarsal mechanics and enhance tissue repair, providing a promising alternative to autologous grafts for clinical eyelid defect reconstruction.