Modulation of osteogenic and haemostatic activities by tuning cationicity of genipin-crosslinked chitosan hydrogels

Chitosan as a natural cationic polysaccharide has drawn wide interests as surface modification materials in orthopedic applications, with the potential to achieve combined osteogenic, antimicrobial and haemostatic functions. The cationicity of chitosan has been reported to play an important role in modifying the osteoblastic cell responses and the antibacterial activities, while its effect on the haemostatic properties has been rarely studied. To this aim, we prepared carboxymethyl chitosan hydrogels with different cationicity through crosslinking with different concentrations of genipin (1%, 2.5%, 5% and 10%). The genipin concentration strongly influenced both mesenchymal stem cell (MSC) responses and blood coagulation activity for chitosan-hydroxyapatite samples. Increasing genipin concentration overall enhanced the osteogenic and haemostatic potentials, and an optimum window of chitosan cationicity (5% genipin in our case) led to both the best MSC response and coagulant activities. In particular, the cationicity had demonstrated a profound modulation effect on the haemostatic activities of chitosan samples, through influencing three different aspects of the coagulation processes, including intrinsic coagulation pathway, aggregation and activation of platelet, and activation of erythrocyte. Tuning the crosslinking degree thus provides a simple and effective approach to achieving combined osteogenic and haemostatic functions, which has great potential in surface modification of surgical implants.