IN VIVO PERFORMANCE OF THE EXPERIMENTAL CHITOSAN BASED BONE SUBSTITUTE--ADVANCED THERAPY MEDICINAL PRODUCT. A STUDY...

When evaluating a novel bone substitute material, advanced in vivo testing is an important step in development and safety affirmation. Sheep seems to be a valuable model for human bone turnover and remodeling activity. The experimental material composed with the stem cells is an advanced therapy medicinal product (acc. to EC Regulation 1394/2007). Our research focuses on histological differences in bone formation (guided bone regeneration--GBR) in sheep maxillas after implantation of the new chitosan/tricalcium phosphate/alginate (CH/TCP/Alg) biomaterial in comparison to the commercially available xenogenic bone graft and a/m enhanced with the stem cells isolated from the adipose tissue. Twelve adult female sheep of BCP synthetic line, weighing 60-70 kg were used for the study. The 11 mm diameter defects in maxilla bone were prepared with a trephine bur under general anesthesia and then filled with the bone substitute materials: CH/TCP/Alg, BioOss Collagen, Geistlich AG (BO), CH/TCP/Alg composed with the stem cells (CH/S) or left just with the blood clot (BC). Inbreeding cycle of the animals terminated at 4 months after surgery. Dissected specimens of the maxilla were evaluated histologically and preliminary under microtomography. Histological evaluation showed early new bone formation observed around the experimental biomaterial and commercially available BO. There were no features of purulent inflammation and necrosis, or granulomatous inflammation. Microscopic examination after 4 months following the surgery revealed trabecular bone formation around chitosan based bone graft and xenogenic material with no significant inflammatory response. Different results--no bone recreation were observed for the negative control (BC). In conclusion, the tested materials (CH/TCP/Alg and BO) showed a high degree of biocompatibility and some osteoconductivity in comparison with the control group. Although the handiness, granules size and setting time of CHffCP/Alg may be refined for future clinical tests. The relevant beneficial influence of using the adipose derived stem cells in GBR was not confirmed in this model.