Photo-Crosslinked Hyaluronic Acid/Carboxymethyl Cellulose Composite Hydrogel as a Dural Substitute to Prevent Post-Surgical Adhesion

Abstract

A dural substitute is frequently used to repair dura mater during neurosurgical procedures. Although autologous or commercially available dural substitutes matched most of the requirements; difficulties during dural repair, including insufficient space for suturing, insufficient mechanical strength, easy tear and cerebrospinal fluid leakage, represent major challenges. To meet this need, a photo-crosslinked hydrogel was developed as a dural substitute/anti-adhesion barrier in this study, which can show sol-to-gel phase transition in situ upon short-time exposure to visible light. For this purpose, hyaluronic acid (HA) and carboxymethyl cellulose (CMC), materials used in abdominal surgery for anti-adhesion purposes, were reacted separately with glycidyl methacrylate to form hyaluronic acid methacrylate (HAMA) and carboxymethyl cellulose methacrylate (CMCMA). The HA/CMC (HC) hydrogels with different HA compositions could be prepared by photo-crosslinking HAMA and CMCMA with a 400 nm light source using lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photo-initiator. From studies of physico-chemical and biological properties of HC composite hydrogels, they are bio-compatible, bio-degradable and mechanically robust, to be suitable as a dural substitute. By drastically reducing attachment and penetration of adhesion-forming fibroblasts in vitro, the HC hydrogel can also act as an anti-adhesion barrier to prevent adhesion formation after dural repair. From in vivo study in rabbits, the HC hydrogel can repair dural defects as well as protect the dura from post-operative adhesion, endorsing the possible application of this hydrogel as a novel dural substitute.

Novel Trends in Hydrogel Development for Biomedical Applications: A Review

“…The HA/CMC hydrogel had good biodegradability, biocompatibility (>80% cell viability for 3T3 fibroblasts in vitro cultured for 24 h) and mechanical properties. In vivo experiments demonstrated that these hydrogels can act properly as dural substitutes to repair dural defects in rabbits [ 126 ].…”

Hemoadhican-Based Bioabsorbable Hydrogel for Preventing Postoperative Adhesions

“…From the thermogravimetric analysis (TGA), it was observed that HD and HD-based cross-linked hydrogels generally exhibited two stages of weight loss (Figure S2). The initial weight loss occurred at approximately 100 °C, which was attributed to the evaporation of water molecules that were initially bound to the HD polysaccharide. , The weight loss between 200 and 350 °C reflected the thermal stability at high temperatures. Similarly, the maximum thermal degradation temperatures of HD-L and HD-H hydrogels changed compared with those of the native polysaccharide.…”

Electrospun Nanofibers for Dura Mater Regeneration: A Mini Review on Current Progress

“…The isotropic surface properties of these substitutes are not well suited for cell attachment and proliferation, which results in poor performance of the material [ 74 ]. Among them, various tough hydrogels have been prepared, which possess a good load-bearing capacity to fit the desired mechanical properties for dural implants [ 53 , 82 , 83 , 84 , 85 , 86 , 87 ]. However, the poor biocompatibility and degradability of these synthetic polymers limit their application as a dural substitute.…”