An Injectable Low-Swelling and Mechanically Robust Bioadhesive Sealant for Sutureless Watertight Dural Repair

Watertight dural closure is essential for successful cranial and spinal surgery but remains a major clinical challenge due to persistent cerebrospinal fluid (CSF) leakage and associated complications. Conventional dural suturing is particularly challenging in cases involving fragile dura or anatomically complex defects, while existing sealants often suffer from delayed gelation, inadequate wet-tissue adhesion, and excessive swelling that may cause neural tissue compression. Herein, we report an injectable, biocompatible, low-swelling bioadhesive sealant (DLSS) based on N-hydroxysuccinimide-activated tetra-armed poly(ethylene glycol) and amine-functionalized gelatin for sutureless dural repair. The optimized hydrogel exhibits rapid in situ gelation, robust mechanical properties, effective wet-tissue adhesion, high burst pressure resistance, and limited swelling (13.2% volumetric swelling ratio in artificial CSF). Furthermore, DLSS demonstrates cytocompatibility and hemocompatibility, supports fibroblast migration, and undergoes controlled biodegradation. Ex vivo testing on rabbit dura demonstrated rapid and durable sutureless sealing of dural defects by DLSS. In vivo evaluation in rat cranial and spinal dural defect models demonstrated that DLSS enabled effective dural closure and tissue repair without detectable CSF leakage, showing improved performance compared with commercial fibrin glue. Its translational potential was validated in clinically relevant beagle models. Collectively, DLSS offers a promising strategy for sutureless dural repair.