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

Abstract

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.