Biofunctional phosphorylated chitosan hydrogels prepared above pH 6 and effect of crosslinkers on gel properties towards biomedical applications

Though chitosan hydrogels have shown potential for numerous tissue regeneration applications, its insolubility above pH 6.0 have greatly limited applicability in encapsulation of live cells and pH sensitive bioactive agents. In this report an approach to overcome this limitation was tested with phosphorylated derivative of chitosan, N-methylene phosphonic chitosan (NMPC). NMPC is also known to possess efficacious gene delivery, biomineralization, and osteoinduction properties. NMPC hydrogels were synthesized by cross-linking NMPC with either glutaraldehyde (NMPC-GLU) or genipin (NMPC-GEN). An increase in pH from 3.0 to 6.8 reduced gelation time with both the agents, with the reduction more pronounced in NMPC-GLU. The results correlated with the reaction mechanisms of both agents with NMPC. Further NMPC-GEN gels demonstrated higher elastic modulus and compressive strength values. Cell culture studies showed higher cell proliferation on NMPC-GEN compared to NMPC-GLU.