Development of hydrogels based on oxidized cellulose sulfates and carboxymethyl chitosan

Abstract

Cellulose or chitosan represent highly abundant biopolymers possessing excellent biocompatibility that is required in tissue engineering. Both, cellulose and chitosan can be used to form hydrogels that can replace soft human tissues like cartilage. Hence, we developed here an approach to oxidize cellulose after sulfation, which was then crosslinked with carboxymethyl chitosan (CMCh). Sulfation was performed either by direct or acetosulfation reaching different sulfation degrees of DSSulf = 0.8–2.0. Subsequently oxidation of cellulose sulfate (CS) was performed with sodium periodate, which yielded aldehyde contents of DSAld = 0.1–0.3. Since oxidation requires the presence of vicinal hydroxyl groups in the anhydroglucose unit (AGU) of CS, higher sulfation degree as obtained by direct sulfation including hydroxyl groups at C2 and C3-position yielded lower aldehyde contents. On the contrary, regioselective sulfation at C6-position by acetosulfation was more suitable to achieve higher oxidation degrees of CS. Consequently, hydrogel formation obtained by chemical crosslinking of oxidized cellulose sulfate (oCS) with CMCh was fast within seconds when oxidation degree was high, but sulfation degree low. Moreover gel formation lasted almost 24 h when sulfation degree was high. It could also be shown that hydrogels based on oCS with a DSAld of 0.28 or higher were stable for 25 days when incubated in phosphate-buffered saline (PBS) or Dulbeccos modified Eagle medium (DMEM). Studies with pH dependent fluorescent tracer molecules could show that the intrinsic pH value in hydrogels was slightly acidic (sim pH 6.4) when they were incubated in PBS at pH 7.4. Mass transfer and homogeneity of the gel network was studied by NMR finding that diffusion of water molecules was not hindered inside the hydrogels.