Peritoneal application of chitosan and UV‐cross‐linkable chitosan

Abstract

The suitability of chitosan and UV-cross-linkable chitosan for intraperitoneal use, for example as a barrier device for preventing peritoneal adhesions or for drug delivery, was examined. In vitro experiments using two major cell types present in the peritoneal cavity (mesothelial cells and peritoneal macrophages) revealed neither attractive interactions between cross-linked chitosan gels and the cells nor a proliferative effect. However, the same UV-cross-linked chitosan applied in the peritoneal cavity of rabbits caused a granulomatous reaction with adhesion formation within two weeks in all animals, which persisted up to 4 weeks after exposure. Unmodified chitosan also caused adhesions, while UV irradiation did not. UV-cross-linkable chitosan induced significant elevations in MIP-2 and TNF-alpha from peritoneal macrophages, suggesting that soluble mediators could play a role in inducing adhesion formation. These results reinforce the view that the predictive value of in vitro cytotoxicity assays in matters of biocompatibility may not be sufficient, and suggest that other assays such as cytokine levels may be of value in predicting outcomes in situations involving multiple cell types (i.e. in vivo).

Polymers in the prevention of peritoneal adhesions

“…Chitosan-One initial approach was to use a UV cross-linkable chitosan hydrogel [55], based on the view that chitosan was generally considered to be biocompatible [56,57]. We demonstrated in vitro that it had excellent properties in terms of cohesiveness and macromolecule release kinetics (data not shown).…”

Microparticles and nanoparticles for drug delivery

“…In addition, it is important to study the mechanisms by which biomaterials cause tissue injury. Often, the simple in vitro tests that are commonly used to assess cytotoxicity do not predict outcome in vivo (Yeo et al, 2006a). However, in vivo screening of biomaterials is expensive, tedious, and has the ethical problem of involving living creatures.…”

Polymeric Biomaterials in Tissue Engineering

“…Of note, a material's apparent lack of cytotoxicity does not necessarily predict biocompatibility. For example, a cross-linked chitosan that was minimally toxic to mesothelial cells in vitro caused marked adhesions when placed in the peritoneum (11).…”

“…Direct action of putatively inert materials is seen in the following examples relating to carbohydrate-based matrices. In the crosslinked chitosan mentioned above that caused severe peritoneal adhesions, it was found that the material itself caused marked increases in the expression of MIP-2 (a murine IL-8 analogue) and tumor necrosis factor alpha (TNF-␣) in mesothelial cells (11). A cross-linked hyaluronic acid (35) used to prevent peritoneal adhesions (61) was shown to cause a small increase in tissue plasminogen activator in mesothelial cells, which might have contributed to the anti-adhesion efficacy.…”