A Janus-type polycaprolactone/chitosan scaffold with dual functions of leakage prevention and osteogenesis for skull base defect repair

A novel Janus bilayer scaffold is designed for simultaneous prevention of cerebrospinal fluid leakage and bone regeneration in skull base defects. • It consists of two layers: a simvastatin-loaded chitosan-hydroxyapatite porous layer for bone growth and a polycaprolactone electrospun barrier for sealing. • In vitro tests show the osteogenic layer promotes mineralization, increases alkaline phosphatase activity, and exhibits good hemostatic properties. • In vivo studies confirm enhanced bone formation in mice and effective leakage prevention in rabbits. To address the critical scientific challenge of achieving synergistic repair of cerebrospinal fluid leakage prevention and bone regeneration in skull base defects, an innovative Janus-type bilayer scaffold with dual functions of “leakage prevention and osteogenesis” was designed and fabricated by electrospun and freeze-drying technology. The scaffold consists of a simvastatin-loaded chitosan-hydroxyapatite porous scaffold (CS-HA-SIM) as the osteogenic layer, and a polycaprolactone (PCL) electrospun fiber membrane as the watertight barrier, forming a structurally and functionally integrated three-dimensional repair system. In vitro studies demonstrate that the osteogenic layer exhibits excellent hemostatic capability, significantly promotes the deposition of calcium phosphate minerals, and markedly upregulates the expression of alkaline phosphatase (ALP) in osteoblasts. Meanwhile, in vitro leakage prevention experiments demonstrate that the PCL membrane can effectively prevent cerebrospinal fluid leakage under intracranial pressure. In vivo experiments also confirm that the scaffold system significantly enhances new bone formation in a mouse calvarial defect model and demonstrates reliable anti-leakage performance in a rabbit cerebrospinal fluid leakage model. This novel bilayer scaffold, combining biological functionality and clinical applicability, provides an innovative solution for the regenerative repair of skull base defects and holds significant potential for clinical translation. Download: Download high-res image (338KB) Download: Download full-size image