Fish Gelatin-Based Absorbable Dural Sealant with Anti-inflammatory Properties

Cerebrospinal fluid (CSF) leakage from the dura mater during craniotomy is a common complication, which is associated with infection, meningitis, pneumocephalus, and delayed wound healing. In the present study, we developed an absorbable fish gelatin-based anti-inflammatory sealant for dura mater sealing to prevent CSF leakage. Gelatin derived from Alaska pollock (ApGltn) was modified with α-linolenic acid (ALA), an omega-3 fatty acid that exhibits anti-inflammatory properties, and cross-linked with a poly(ethylene glycol)-based cross-linker to develop ALA-ApGltn sealant (ALA-Seal). ALA-Seal demonstrated a higher storage modulus and tangent delta (tan δ) compared with those of the original ApGltn sealant (Org-Seal). The swelling ratio of ALA-Seal was markedly lower than that of DuraSeal, a commercially available dural sealant. Ex vivo burst strength measurements using porcine dura mater indicated that there was no significant difference between DuraSeal and ALA-Seal, despite ALA-Seal having an order of magnitude lower storage modulus. The anti-inflammatory properties of ALA-Seal, evaluated using brain microglial cells, were considerably higher than those of DuraSeal and Org-Seal, with a minimal adverse effect on cell viability. Therefore, compared to DuraSeal, ALA-Seal is a potential dural sealant with a lower swelling ratio, similar burst strength, and higher anti-inflammatory properties, which may prevent CSF leakage.