• Bone nonunion
• Expanded Human Mesenchymal Stem Cells
• Tissue engineering

Mesenchymal stem cells (MSCS) are probably the most interesting adult stem cells for orthopedic applications because of their potential to differentiate to both bone and cartilage.
In treating musculoskeletal disorders, cell therapy has been used mainly for bone grafting in the management of nonunions, replacement of lost bone tissue as large bone defects usually caused by trauma, infection, or tumors .
The focus of this study is to better understand the result of expanded bone marrow MSCs, embedded in autologous fibrin clots, for the healing of atrophic nonunions. The research work relied on three main issues: use of an entirely autologous context (cells, serum for ex vivo cell culture, scaffold components), reduced ex vivo cell expansion, and short-term MSC osteoinduction before implantation. Our aims was also to examine the long-term efficacy and safety of this procedure.
The method is standardized and requires the cooperation of the Haematology Unit and was in all cases associated to a surgical procedure.
We clinically demonstrate the efficacy of our construct in an autologous context. The fibrin gel texture of the clot permitted easy diffusion of the nutrients and differentiation of the inner cells towards the osteogenic lineage. The long-term follow-up of the patients proved the safety and effectiveness of our procedures: no episodes of ectopic neoformation, infection or overgrowth, neoplastic transformation or re-fracture were detected .
Our preliminary results are encouraging both in terms of bone repair efficacy and patients safety. While the surgical approach still remains first choice for the management of nonunions, our data confirm that tissue engineering using MSCs could provide a very useful tool to accelerate and complete the healing process. We believe that the minimal ex vivo MSC expansion and short-term osteoinduction used in this study strongly contributed to reduce risks of implant overgrowth due to uncontrolled proliferation of transplanted cells.