Thermal stimuli-responsive hyaluronic acid loaded cellulose based physical hydrogel for post-surgical de novo peritoneal adhesion prevention

Effective strategies for post-surgical adhesion prevention have increasingly focused on injectable adhesion barriers due to their minimal invasiveness and wider applicability. In this study, a thermo-reversible hydrogel was developed by combining high molecular weight hyaluronic acid (HA) at various concentrations (0.05, 0.25, and 0.45% w/v) with tempo-oxidized nanocellulose (TOCN), methyl cellulose (MC) and polyethylene glycol (PEG) for anti-adhesion application. The hydrogel preparation time was short and did not require any chemical modification. TOCN ensured the mechanical stability of the hydrogel. MC confirmed thermo-sensitive feature. Higher amounts of HA increased the rate of hydrogel degradation. The HA 0.25 hydrogel was free-flowing, injectable at ambient temperature, capable of faster (40 ± 2 s), and reversible sol-gel (4 °C–37 °C) transition. A rat side-wall cecum abrasion model was used to confirm the complete de novo adhesion prevention efficacy of optimized HA 0.25 hydrogel, where the scratched abdominal wall of animals treated with HA 0.25 hydrogel healed after 14 days. During in vivo experiment, PEG in the hydrogel played a crucial role in adhesion prevention by minimizing friction between the surgical site and nearby organs. In a nutshell, HA 0.25 hydrogel, fabricated without crosslinking agent, is a potential candidate for tissue adhesion prevention strategies.