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The creation of engineered intestinal tissue has recently stimulated new endeavors with the ultimate goal of intestinal replacement for massive resections of bowel. In this context, we investigated the effect of hyaluronic acid (HA) on the physicochemical characteristics of gelatin-collagen scaffolds and its cytocompatibilty to the human intestinal epithelial Caco-2 cell line in vitro. Gelatin/collagen hybrid scaffolds with different concentrations of HA were prepared by solvent casting and freeze-drying techniques and subsequent chemical crosslinking by genipin. The morphologies of the scaffolds were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. In vitro tests were carried out in phosphate-buffered saline (PBS) solution to study the swelling ratio and the biostability of the scaffolds. It was found that the porous structure of the scaffolds could be tailored by further addition of HA. Moreover, both the swelling ratio and the degradation rate of the scaffold increased by addition of HA. A resazurin-based cell viability assay was employed to determine the viability and estimate the number of scaffold-adherent Caco-2 cells. The assay indicated that the scaffolds were all cytocompatible. We concluded that addition of less than 15% HA to scaffolds with a composition of 9:1 gelatin:collagen results only in incremental improvement in the structural characteristics and cytocompatibility of the gelatin-collagen scaffolds. However, the scaffolds with 25% HA exhibited remarkable enhancement in physicochemical characteristics of the scaffolds including cell viability, growth, and attachment as well as their physical structure.

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