Prevention of peritoneal adhesions using polymeric rheological blends

Abstract

The effectiveness of rheological blends of high molecular weight hyaluronic acid (HA) and low molecular weight hydroxypropyl methylcellulose (HPMC) in the prevention of peritoneal adhesions post-surgery is demonstrated. The physical mixture of the two carbohydrates increased the dwell time in the peritoneum while significantly improving the injectability of the polymer compared with HA alone. HA-HPMC treatment decreased the total adhesion area by ∼ 70% relative to a saline control or no treatment in a repeated cecal injury model in the rabbit. No significant cytotoxicity and minimal inflammation were associated with the blend. Furthermore, no chemical or physical processing was required prior to their use beyond simple mixing.

Keywords: Hyaluronic acid; Hydroxypropyl methylcellulose; Peritoneal adhesions; Rheological blends.

Figure 1

Cell viability (relative to media-only control) of MeT-5A mesothelial cells in the presence of HA only, HPMC only, and HA-HPMC blends at all tested concentrations

Figure 2

Intraperitoneal HA-HPMC blends in mice (a) Frontal view of translucent abdominal wall musculature and peritoneum (after reflection of the skin), 6 days after injection of HA₆HPMC₄. Viscera separated by fluid can be seen through the abdominal wall. (b) Effect of polymer concentration on the volume of fluid recovered from the peritoneal cavity as a function of time (n = 3 at each time point). (c) “Foamy” macrophages in peritoneal fluid 2 days after injection of HA₆HPMC₄. The lucent intracellular areas are ingested material. (d) Parietal peritoneal surface 2 days after injection of HA₆HPMC_4. The basophilic material in the upper part of the panel is the gel, with scattered macrophages). Histological findings were similar in all blends tested.

Figure 3

Rheological response of recovered HA₆HPMC₄ after varying retention times in the peritoneum: (a) viscosity versus shear rate; (b) elastic modulus versus oscillation stress. Elastic modulus data for HA₆ and HPMC₄ (open points) are also shown for comparison.

Figure 4

In vivo assessment of adhesion prevention by HA₆HPMC₄ in a rabbit double injury model (a) application of the HA₆HPMC₄ blend immediately following the second injury (b) adhesion formation seven days after repeated injury following treatment with HA₆HPMC₄ (c) adhesion formation seven days after repeated injury following treatment with saline only.