An Asymmetric Dura-Inspired Collagen Hydrogel Patch with Integrated Dense-Porous Architecture Enabled by Dual-Channel Freeze Casting.

Dural defects can trigger severe complications such as brain herniation and cerebrospinal fluid (CSF) leakage. Poreless structures like curing sealants are effective in preventing CSF leakage in dural defects but are often biologically inert. Here, we report a dura-inspired collagen hydrogel (DICH) consisting of dense-porous heterogeneous bilayers fabricated via a dual-channel freeze casting (abbreviated as Freezing-While-Lifting, FWL), which enables biocompatibility without compromising CSF sealing. The dense layer (DL) is formed through directional collagen molecular self-assembly followed by cross-linking, while the porous layer (PL) originates from collagen Pickering emulsion-templated self-assembly without cross-linking. By tuning collagen concentration and cross-linking density, the DL achieves optimized mechanical strength, whereas increasing the emulsification shear rate enhances pore interconnectivity and porosity in the PL. Compared with dense patches, DICH effectively prevents CSF leakage while promoting tissue compatibility and a minimal inflammatory response. At day 28, implantation studies in a rat model show histocompatibility comparable to that of the commercial DuraGen membrane, suggesting its potential as a dural substitute. This work establishes a facile biomimetic strategy for constructing dense-porous hydrogels with potential applications in tissue engineering.