Development of a sprayable thermosensitive lysine-modified pluronic hyaluronic acid hydrogel for enhanced wound healing and adhesion prevention in laparoscopic applications.

Postoperative adhesions remain a considerable clinical challenge in both general and high-risk minimally invasive procedures. Although hyaluronic acid (HA) is widely used in clinical practice for adhesion prevention by forming a highly hydrated, viscoelastic barrier over damaged tissues, conventional HA-based products suffer from rapid degradation and limited mechanical strength. To overcome these constraints, we developed novel amino-acid-modified Pluronic F127 hyaluronic acid hydrogels with lysine-modified F127 (Lys127/HA); thereby, emerging as the optimal formulation owing to its unique thermosensitivity and improved rheological behavior. This hydrogel remains flowable at low temperatures for sprayability and transitions to a gel under physiological temperature via physical crosslinking through electrostatic interactions and hydrogen bonding. The resulting gel exhibits enhanced viscosity, extended retention, and improved mucoadhesion. When administered using a precision sprayable device in a porcine laparoscopic model, Lys127/HA significantly reduced adhesion formation, outperforming commercial crosslinked HA-based barriers. Additionally, Lys127/HA improved wound healing, suppressed inflammation, and effectively prevented fibroblast migration. Comprehensive in vitro and in vivo investigations demonstrated excellent biocompatibility with no observable side effects. These findings establish Lys127/HA as a promising candidate for postoperative adhesion prophylaxis, especially in laparoscopic surgeries, with the potential to address limitations of existing clinical anti-adhesion strategies.