New Hydrogel Sealant Effective at Sealing Dural Defects and Preventing Postoperative Adhesion

The dura mater is a fibrous membrane of connective tissue that envelops the brain and spinal cord. In neurosurgical procedures that require access to the brain or spinal cord, opening the dura mater often leads to complications, one of which is the leakage of cerebrospinal fluid (CSF). CSF leakage can result in a variety of severe complications, including postural headaches, pseudodural cysts, dural fistulas, cerebral or spinal hernias, meningitis, intracranial hemorrhages, epidural fibrosis, and postoperative adhesions. To address this, the standard clinical practice involves suturing the area where the dura mater has been opened. However, suturing can be time-consuming and challenging, particularly when dealing with hard-to-reach defects. The process also damages the dura mater, and the needle holes can hinder the achievement of a watertight seal. Consequently, there has been significant interest in developing tissue adhesives and sealants that can provide sutureless wound closure, achieve hemostasis, and seal against leaks more effectively, offering benefits like ease of use, reduced tissue damage, and suitability for urgent medical situations.

Scientists at the Chinese Academy of Sciences (Beijing, China) have developed an innovative injectable hydrogel sealant that is tissue-adhesive and exhibits minimal swelling. This sealant, based on o-phthalaldehyde (OPA)/amine chemistry, is designed specifically for dural sealing and repair. The hydrogel forms when gelatin is mixed with OPA-terminated 4-armed PEG (4aPEG-OPA). In this reaction, the OPA groups from the 4aPEG-OPA react with the amine groups in the gelatin, forming phthalimidine linkages that create a stable, low-swelling cross-linking network. Additionally, the OPA groups can also bond with amine groups on the tissue surface, enhancing the hydrogel’s adhesion to the tissue and ensuring a watertight seal over the dural defects. The adhesive strength of this 4aPEG-OPA/gelatin hydrogel on porcine tissue has shown to be significantly stronger than that of fibrin glue, and its ability to withstand pressure exceeds that of postoperative CSF pressure fluctuations.

Further evaluations, including in vitro swelling and degradation tests, have demonstrated that the 4aPEG-OPA/gelatin hydrogel has a considerably lower swelling ratio compared to other commercially available dural sealants. In vivo studies using rat and rabbit models have shown that when applied to lumbar and cerebral dural incisions, the hydrogel effectively seals the defects and prevents CSF leakage without exerting undue pressure on the central nervous system. Additionally, the use of this hydrogel has been associated with reduced local inflammation, decreased epidural fibrosis, and fewer postoperative adhesions in the areas of the dural defect. These findings highlight the significant potential of the 4aPEG-OPA/gelatin hydrogel as a multifunctional sealant for effectively sealing dural defects and preventing postoperative complications.

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Chinese Academy of Sciences

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