In vitro biocompatibility and cellular interactions of a chitosan/dextran‐based hydrogel for postsurgical adhesion prevention

Abstract

In this paper, we report the in vitro biocompatibility and cellular interactions of a chitosan/dextran-based (CD) hydrogel and its components as determined by mutagenicity, cytotoxicity, cytokine/chemokine response, and wound healing assays. The CD hydrogel, developed for postsurgical adhesion prevention in ear, nose, and throat surgeries, was shown by previously published experiments in animal and human trials to be effective. The hydrogel was synthesized from the reaction between succinyl chitosan (SC) and oxidized dextran (DA). Cytotoxicity was assessed in an xCELLigence system and cytokine/chemokine responses were measured by ELISA in human macrophage, nasopharyngeal epithelial, and dermal fibroblast cells. A wound healing model utilized nasopharyngeal epithelial cells. CD hydrogel and DA were nonmutagenic in the Ames test. CD hydrogel showed moderate cytotoxicity for the cell lines, DA being the cytotoxic component. Some inhibition of wound healing occurred due to the cytotoxic nature of DA. Cells cultured with CD hydrogel showed no increase in TNF-α, IL-10, and IL-8 levels. It is hypothesized that the cytotoxicity of DA is moderated when reacted with SC and that CD hydrogel inhibits unwanted fibroblastic invasion preventing scarring and adhesions. Together with the previously published human and animal trial data, the results indicate CD hydrogel is biocompatible in the setting of endoscopic sinus surgery. This work represents the first study of CD hydrogel with human cell lines and provides essential information for its future application in biomedicine.

In vitro genotoxicity assessment of an oxidized dextrin‐based hydrogel for biomedical applications

“…In our study, the low number of positive wells and the lack of a dose‐response, either in the presence or absence of S9 fractions suggest that the HG and its metabolites lack mutagenic activity at the concentrations tested. Negative mutagenicity results have been also reported for an HG composed by succinyl chitosan and aldehyde dextran (0.5‐8 mg/mL) as assessed by the Ames test (Aziz et al, ).…”

“…In fibroblasts, DA displayed a strong decrease of cell viability at conditions greater than 5 mg/mL. After the combination between DA and succinyl chitosan to obtain the dextran‐based hydrogel, this showed a strong and immediate cytotoxic effect in epithelial cells, in contrast to the macrophage and fibroblast cells, which exhibited a more moderate response with a ~40% overall reduction in cell viability (Aziz et al, ). The cytotoxic effect of aldehydes is most likely due to their reaction with amino acids of the culture medium and free amines in the cell, causing a negative effect on cellular growth (Hyon et al, ; Rousseau & Gagnieu, ).…”

“…This phenomenon can also explain the stronger cytotoxic effect of ODEX when used alone compared to the HG, in TK6 cells exposed to higher concentrations of these agents (C4, C5 and C6), i.e., ODEX by itself is more reactive than in the presence of ADH as all its aldehyde groups are free, while during formation of the HG some of the aldehydes react with ADH, thus reducing the number of free aldehydes. The toxicity of other types of aldehyde-modified polysaccharides has been already reported for other cell types, such as human and murine fibroblasts (Aziz et al, 2015;Draye et al, 1998;Hyon, Nakajima, Sugai, & Matsumura, 2014;Rousseau & Gagnieu, 2002), macrophage cells (THP-1 and RAW 264.7) (Aziz et al, 2015;Sokolsky-Papkov, Domb, & Golenser, 2006), epidermal keratinocytes, endothelial cells (Draye et al, 1998) and nasopharyngeal epithelial cells (Aziz et al, 2015). For instance, Aziz et al (2015) assessed the cytotoxicity of the aldehyde-modified dextran (DA; 1.25-30 mg/mL) using the xCELLigence system for 98 hours.…”

Characterization of the in vivo host response to a bi‐labeled chitosan‐dextran based hydrogel for postsurgical adhesion prevention

“…Fluorescence optical imaging was chosen due to its sensitivity to visualize compounds at surgical concentrations as well as provide high signal to noise ratios with low background. 29 Imaging using NIR-sensitive probes conjugated to hydrogels have been used successfully to target cancer cells, 30 35 The bioactivity of DA combined with the barrier function of the hydrogel was thought to explain the anti-adhesion mechanism of the CD hydrogel. In order to develop the CD hydrogel as a post-operative adhesion preventing adjunct for surgeries other than ESS, a lower oxidized and less cytotoxic DA, DA-25, was developed 20 and mixed with SC to create the CD-25 formulation.…”

Bacterial-derived biopolymers: Advanced natural nanomaterials for drug delivery and tissue engineering

“…They showed that co-encapsulation of several GFs in macroporous scaffolds of dextran and simultaneous release of them can be dramatically enhance the size and number of newly-formed functional vessels in in vivo conditions. Furthermore, dextran NPs themselves and dextran grafted with different biomaterials such as 2-hydroxyethyl methacrylate (HEMA), poly-l-lysine, chitosan, pullulan, gelatin, PEG derivatives and poly(anhydride) have been used as tissue bioadhesives in tissue regeneration [25][26][27].…”