Inductive co-crosslinking of cellulose nanocrystal/chitosan hydrogels for the treatment of vertebral compression fractures

Vertebral compression fractures are a very common consequence of osteoporosis for which injection of a non-biodegradable, non-bioactive, mechanically-stiff polymer bone cement into the vertebral body is the most common treatment. Recently, there has been growing interest in using bioactive, degradable, and bone biomechanics-matching products as an alternative approach for treating these fractures. In this research, we focused on creating injectable, chitosan-based hydrogels that can convey mechanical strength similar to vertebral bone as well as possess inherent osteoinductivity. First, we investigated the effects of three different factors - 1) bioactive phosphate ionic crosslinking; 2) genipin covalent crosslinking; 3) mechanically reinforcing cellulose nanocrystal incorporation - on the material properties of chitosan-based hydrogels. Mesenchymal stem cells were then exposed to hydrogels with optimum mechanical properties and stability in order to assess the biological effects of the bioactive phosphate ionic crosslinker. Our results show that hydrogels with higher ionic and covalent crosslinking ratios supplemented with neutral cellulose nanocrystals possessed desirable compressive strength and stability. Also, the significant osteoinductivity of these composite hydrogels demonstrated their potential to function as an injectable system for the future treatment of vertebral compression fractures.