Cytocompatible chitosan based multi-network hydrogels with antimicrobial, cell anti-adhesive and mechanical properties.

Hydrogel with good mechanical and biological properties has great potential and promise for biomedical applications. Here we fabricated a series of novel cytocompatible chitosan (CS) based double-network (DN) and triple-network (TN) hydrogels by physically-chemically crosslinking methods. Natural polysaccharide CS with abundant resources was chosen as the first network due to its good antimicrobial activity, biocompatibility and easy cross-linking reaction. Zwitterionic sulfopropylbetaine (PDMAPS) was chosen as the second network due its good biocompatibility, antimicrobial and antifouling properties. And nonionic poly(2-hydroxyethyl acrylate) (PHEA) was chosen as the final network due to its good biocompatibility, excellent nonfouling and mechanical properties. Cross-section SEM images showed that both CS/PHEA (DN1, the molar ratio of glutaraldehyde to structural unit of CS is 0.2/3.0) and CS/PDMAPS/PHEA (TN1, the molar ratio of glutaraldehyde to structural unit of CS is 0.2/3.0) hydrogels exhibited a smooth and uniformly dispersed porous microstructures with pore size distribution in the range of 20∼100 µm. The largest compressive stress and tensile stress of DN1 hydrogels reached 84.7 MPa and 292 kPa, respectively, and largest compressive stress and tensile stress of TN1 hydrogels could reach 81.9 MPa and 384 kPa, respectively. Moreover, the value of failure strain for TN1 gels reached 1020%. Besides excellent mechanical properties, DN1 and TN1 gels exhibited good antimicrobial, cytocompatible and antifouling properties due to introduction of antimicrobial chitosan, cell anti-adhesive PDMAPS and PHEA. The combination of the excellent mechanical and biological properties of multiple network hydrogels can provide a potential pathway to develop biomedical hydrogels as promising bioapplications in wound dressing and other biomedical applications.

Enhanced water-solubility, antibacterial activity and biocompatibility upon introducing sulfobetaine and quaternary ammonium to chitosan.

Chitosan (CS) has attracted much attention due to its good antibacterial activity and biocompatibility. However, CS is insoluble in neutral and alkaline aqueous solution, limiting its biomedical application to some extent. To circumvent this drawback, we have synthesized a novel N-quaternary ammonium-O-sulfobetaine-chitosan (Q3BCS) by introducing quaternary ammonium compound (QAC) and sulfobetaine, and its water-solubility, antibacterial activity and biocompatibility were evaluated compare to N-quaternary ammonium chitosan and native CS. The results showed that by introducing QAC, antibacterial activities and water-solubilities increase with degrees of substitution. The largest diameter zone of inhibition (DIZ) was improved from 0 (CS) to 15mm (N-Q3CS). And the water solution became completely transparent from pH 6.5 to pH 11; the maximal waters-solubility was improved from almost 0% (CS) to 113% at pH 7 (N-Q3CS). More importantly, by further introducing sulfobetaine, cell survival rate of Q3BCS increased from 30% (N-Q3CS) to 85% at 2000µg/ml, which is even greater than that of native CS. Furthermore, hemolysis of Q3BCS was dropped sharply from 4.07% (N-Q3CS) to 0.06%, while the water-solution and antibacterial activity were further improved significantly. This work proposes an efficient strategy to prepare CS derivatives with enhanced antibacterial activity, biocompatibility and water-solubility. Additionally, these properties can be finely tailored by changing the feed ratio of CS, glycidyl trimethylammonium chloride and NCO-sulfobetaine.