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

Int J Biol Macromol. 2025 Sep;321(Pt 3):146297. doi: 10.1016/j.ijbiomac.2025.146297. Epub 2025 Jul 26.

Abstract

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.

Keywords: Anti-Adhesion; Sprayable; Thermal Sensitive Hyaluronic Acid Hydrogel.

MeSH terms

  • Animals
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Cell Movement / drug effects
  • Humans
  • Hyaluronic Acid* / chemistry
  • Hyaluronic Acid* / pharmacology
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Laparoscopy* / adverse effects
  • Lysine* / chemistry
  • Mice
  • Poloxamer* / chemistry
  • Poloxamer* / pharmacology
  • Rheology
  • Swine
  • Temperature
  • Tissue Adhesions / prevention & control
  • Viscosity
  • Wound Healing* / drug effects

Substances

  • Hyaluronic Acid
  • Hydrogels
  • Lysine
  • Poloxamer
  • Biocompatible Materials