Light-responsive Pullulan-based dural adhesive with enhanced anti-fibrotic properties, in vitro

Abstract

The incidence of dural tears is becoming increasingly common in spinal laminectomy procedures, particularly those involving nerve decompression surgeries or tumor resections. Therefore, ensuring proper sealing of the injured dura is crucial to prevent postoperative complications such as cerebrospinal fluid leakage, neural damage, epidural fibrosis, and local inflammation. This study presents the development of a UV-responsive pullulan-based sealant, chemically grafted with dopamine (DOPLS), which demonstrates rapid gelation capabilities of less than 30 s. The developed DOPLS sealant exhibited good adhesive strength on porcine skin (0.331.6 ± 0.05 MPa) and glass slides (1.6 ± 0.24 MPa). Furthermore, its ability to bond with wet tissue surfaces was tested on ex vivo tissues, including caprine dural tissue, porcine heart, and murine kidney. The burst pressure testing on caprine tissue revealed that DOPLS (442.78 ± 88.9 mm Hg) could withstand sevenfold higher pressure compared to the unconjugated pullulan sealant (63.75 ± 32.8 mm Hg). Moreover, the DOPLS sealant demonstrated superior viscoelastic characteristics, such as a wider linear viscoelastic regime, a higher elastic modulus, and improved structural stability compared to its unmodified counterpart. Its excellent shear-thinning behaviour, which is essential for injectable sealants, facilitates the delivery of DOPLS through narrow-gauge needles. Further, the DOPLS sealant was loaded with naringin (NDOPLS), a natural flavanone glycoside known for its pharmaceutical properties, which showed a sustained release of over 75% within 48 h. Naringin-loaded DOPLS also exhibited excellent anti-fibrotic activity in vitro, demonstrated by a notable reduction in α-SMA expression, and good cytocompatibility, with cell viability exceeding 90%. Overall, these findings suggest that this pullulan-based light-curable sealant incorporating dopamine and naringin could be an effective option for repairing spinal dural injuries by providing strong sealing, cytocompatibility, and promoting scarless healing.