Influence of polysaccharide composition on the biocompatibility of pullulan/dextran-based hydrogels.

The implantation of a biomaterial for tissue engineering requires the presence of a suitable scaffold on which the tissue repair and regeneration will take place. Polymers have been frequently used for that purpose because they show similar properties to that of the natural extracellular matrix. Scaffold properties and biocompatibility are modulated by the composition of the polymers used. In this work four polysaccharide-based hydrogels (PSH) made of dextran and pullulan were synthesized. Their in vitro properties were determined and then tested in vivo in a rat model. As pullulan concentration increased in dextran hydrogels, the glass transition temperature and the maximum modulus decreased. In vitro degradation studies for 30 days demonstrated no significant degradation of PSH except for 100% pullulan hydrogel. In vivo tissue response evaluated 30 days after PSH subcutaneous implantation in rats indicated that all PSH were surrounded by a fibrous capsule. Adding pullulan to dextran induced an increased inflammatory reaction compared to PSH-D(100% dextran) or PSH-D(75)P(25)(75% dextran). This in vitro and in vivo data can be used in the design of hydrogels appropriate for tissue engineering applications.

Development of a functionalized polymer for stent coating in the arterial delivery of small interfering RNA.

In patients receiving drug eluting stents, there is a growing concern about both the long-term toxicity/degradability of the polymers used for the coating, and the nature of the therapeutic agents. We hypothesized that the use of a functionalized biocompatible polymer for a stent coating could be appropriate for local arterial therapy. A cationized pullulan hydrogel was thus prepared to cover bare metal stents that could be further loaded with small interfering RNA (siRNA) targeted at MMP2 for gene silencing in vascular cells. The efficient coverage of the stent struts by a smooth polymeric layer, which can withstand the crimping of the stent on a balloon-catheter and its deployment, was demonstrated by fluorescence microscopy, scanning electron microscopy, and atomic force microscopy. The release of siRNA from the stents was modulated by the presence of the cationic groups, as compared to noncationized pullulan hydrogel. In vivo implantation of coated stents was successful and cationized pullulan-based hydrogels loaded with siRNA in rabbit balloon-injured carotid arteries induced an uptake of siRNA into the arterial wall and a decrease of pro-MMP2 activity. These results suggest that cationized pullulan-based hydrogel could be used as a new biocompatible and biodegradable stent coating for local gene therapy in the arterial wall.

A biocompatible polysaccharide hydrogel-embedded polypropylene mesh for enhanced tissue integration in rats.

Prosthetic materials are largely used in surgery and tissue engineering. However, many postoperative complications are due to poor integration of the materials, which delays the healing process. The objective of our study was to develop a synthetic scaffold that, according to histopathological and biomechanical criteria, would achieve both tolerance and efficiency. In this study, we evaluated the effect of intramuscular and subcutaneous implantation of a new hybrid mesh (HM) in rats. This HM was composed of clinical grade polypropylene mesh embedded in a polysaccharide hydrogel. Histological and biomechanical studies on the polysaccharide gel alone and on HM were performed 15 and 30 days after implantation, and then compared with two clinically used materials, porcine decellularized small intestinal submucosa and a polypropylene mesh. Results showed that the incorporation of a polypropylene mesh within the polysaccharide hydrogel led to the absence of adverse effects and better tissue organization. Thus, this new synthetic biocompatible HM with suitable properties for tissue repair appears to be a promising material for clinical applications.