Electrohydrodynamic Fabrication of Triple-layered Polycaprolactone Dura Mater Substitute with Antibacterial and Enhanced Osteogenic Capability

In the field of dura mater repair, it is essential to employ artificial substitutes mimicking the multilayered microarchitecture and multiple functions of native dura mater for effective neurosurgery. However, existing artificial dura mater substitutes commonly cause complications because of mismatched structural and mechanical properties as well as the lack of antibacterial activity or osteogenic capability. In this study, a triple-layered dura mater substitute was fabricated by electrohydrodynamic (EHD) jetting techniques, including electrospinning and melt-based EHD printing processes. Highly aligned polycaprolactone (PCL) nanofibers loaded with gentamicin sulfate (GS) were prepared by electrospinning to form the inner layer, which can mimic the aligned collagen fibers of the native dura mater. Random PCL-GS nanofibers were then deposited by electrospinning to form the middle layer. They were intended to enhance the mechanical properties of the fabricated scaffolds. The outer layer involving PCL microfibers doped with nano-hydroxyapatite (nHA) at various angles was printed by the melting-based EHD method, which can enhance osteogenic capability and promote the fusion between the dura mater substitute and the skull. The tensile strength of the triple-layered drug-loaded biomimetic dura mater substitute was 22.42 ± 0.89 MPa, and the elongation at break was 36.43% ± 2.00%. The addition of GS endowed the substitutes with an anti-infection property without influencing their cytocompatibility. Furthermore, the incorporation of nHA promoted the osteogenic differentiation of MC3T3-E1 cells seeded on the triple-layered scaffolds. This work offers a promising strategy to manufacture multilayered dura mater substitutes with the desired antibacterial and enhanced osteogenic capability performance, possibly providing a novel candidate for dural tissue repair.