Mineralization of regenerated cellulose hydrogels induced by human bone marrow stromal cells.

The proliferation of cultured human bone marrow stromal cells (HBMSC) on regenerated cellulose hydrogels was assessed. Regenerated cellulose hydrogels showed good rates of HBMSC proliferation, the cells exhibiting a flattened morphology, and after 22 days in culture, the cells had homogeneously colonized the surface of the materials. Moreover, since the early days in culture, between the surface of the materials and attached cells a continuous granulated hydroxyapatite layer was formed. It has been previously demonstrated in vitro, but without cells, that these materials did not mineralize. Hence, it seems that HBMSC promoted the mineralization of the surface.

Cellulose phosphates as biomaterials. In vivo biocompatibility studies.

Femoral implantation of regenerated cellulose hydrogels revealed their biocompatibility, but a complete osseointegration could not be observed. Phosphorylation was therefore envisaged as the means to enhance cellulose bioactivity. In vitro studies showed that regenerated cellulose hydrogels promote bone cells attachment and proliferation but do not mineralize in acellular simulated physiological conditions. On the contrary, phosphorylated cellulose has shown an opposite behavior, by inducing the formation of a calcium phosphate layer in simulated physiological conditions, but behaving as a poor substrate for bone cells attachment and proliferation. In order to investigate the in vivo behavior of these materials, and assess the influence of mineralization induction ability vs. bone cells compatibility, unmodified and phosphorylated cellulose hydrogels were implanted in rabbits for a maximum period of 6 months and bone regeneration was investigated. Despite the difficulties arising from the retraction of cellulose hydrogels upon dehydration during the preparation of retrieved implants, histological observations showed no inflammatory response after implantation, with bone intra-spongious regeneration of cells and the integration of the unmodified as well as the phosphorylated cellulose implants. After a maximum implantation period of 6 months, histological observations, histomorphometry and the measurement of the amount of 45Ca incorporated in the surrounding tissue indicated a slightly better osseointegration of phosphorylated cellulose, although no significant differences between the two materials were found.

Mineralization of regenerated cellulose hydrogels.

Due to their high water swelling, regenerated cellulose hydrogels and sponges were pre-incubated in a Ca-containing solution, and their mineralization was investigated. Results obtained demonstrate that a simple pre-incubation treatment in a Ca containing solution can induce mineralization in materials with limited or no tendency to mineralize. The minerals formed had an apatitic carbonated and poorly crystalline structure, resembling carbonated hydroxyapatite found in bone mineral. The apatitic layer formed showed a relatively accelerated growth using this technique, exhibiting nodules in their macroscopic structure, which seem to indicate lateral growth. The porous structure of regenerated cellulose sponges was also homogeneously mineralized using this technique.