Non Clinical Model to Assess the Mechanism of Action of a Combined Hyaluronic Acid, Chondroitin Sulfate and Calcium Chloride: HA+CS+CaCl 2 Solution on a 3D Human Reconstructed Bladder Epithelium

• Published in: Medical devices (Auckland, N.Z.) Vol. 17; p. 47
• Main Authors: Brambilla, Laura, Frangione, Valeria, Meloni, Marisa
• Format: Journal Article
• Language: English
• Published: New Zealand 2024
• Subjects: E. coli UPEC; chondroitin sulphate; film forming properties; E. coli biofilm; recurrent cystitis; reconstructed 3D human bladder epithelium; urinary tract infections; anti-bacterial adhesion; hyaluronic acid
• ISSN: 1179-1470; 1179-1470

Medical Device Regulation (EU) 2017/745 requires the principal mode of action (MoA) to be demonstrated by experimental data. The MoA of Ialuril Prefill (combined as HA+CS+CaCl : sodium hyaluronate 1.6%, sodium chondroitin sulphate 2% w/v and calcium chloride 0.87%) Class III medical device, indicated for intravesical instillation to reduce urinary tract infections, has been evaluated on a 3D reconstructed human bladder epithelium (HBE). Three experimental designs; i) strain selection (DSM 103538, DSM 1103) to investigate the HA+CS+CaCl properties in modifying bacterial growth in liquid broth (CFU 4h and 24h) at 80%, 50% and 25% concentrations; ii) evaluation of film forming properties on HBE after 15 min exposure by quantifying caffeine permeation across the epithelium; iii) capacity to counteract adhesion and biofilm formation on colonized HBE by viable counts and ultrastructural analysis by scanning electron microscopy (SEM) using ciprofloxacin as the reference antimicrobial molecule. No significant differences were observed in bacterial viability for both the strains. HA+CS+CaCl reduced caffeine permeation of 51.7% and 38.1% at 1h and 2h, respectively and determined a significant decrease in caffeine permeation rate at both timepoints supporting HA+CS+CaCl capacity to firmly adhere to the bladder epithelium creating a physical barrier on the surface. The viable counts in HBE treated tissues then infected with resulted not different from the negative control suggesting that the device did not inhibit growth. SEM images showed homogenous product distribution over the HBE surface and confirmed the capacity of HA+CS+CaCl to adhere to the bladder epithelium, counteracting biofilm formation. The results support the capacity of HA+CS+CaCl to counteract bacterial invasion by using a physico-mechanical mode of action: this medical device represents a valid alternative to antibiotics in the treatment of recurrent UTIs.