**11. Conclusions and future perspectives**

The objective difficulty of those specific cases, evidenced or classified correctly by an elevated NUSS, cannot be representative in cases in which, in front of presumable mechanic necessities and correct surgical treatment, presents real biological difficulties.

This biologic difficulty is presumable to be searched in genetic expression [52, 53] but is difficult to assess in her real essential components and even more in the single clinical case.

The even more depth study of those which are the causes that can induce to non-union is today more important than ever. The new frontier will be the gene therapy or rather the possibility to transport inside the patient those genes acted to determine the succession of events that conduce to the formation of a bone callus and his maturation to strong bone.

Several studies, on animals, evidence today show that the gene therapy is viable both with the use of carrier virus [54, 55], both with the use of other non-viral carrier as for example particular pulsed electric fields (DNA electroporation) [56]. These therapies are still futuristic realities and provide an ulterior wide preclinic and clinic evaluation. A lot of road has been done until today on the ground of knowledge and of clinic treatment of non-union, and we think that in the near future there will be understanding of how the non-union pathology could be by herself a pathology on a vulnerable patient.

In these patients in which the regeneration possibilities are compromised, a valid solution is offered from the biological chamber and from the new mega prosthetic implants that can avoid the amputation and restoring the function to the patient.

Is today recognized the importance of a global and polyspecialists approach in the treatment of non-union and of large bone loss of the tibial pilon? Recent studies costs–benefits on the choice of the most appropriate treatment have demonstrate that the probabilities of a better outcome offered by multidisciplinary approach with biotechnology have a fewer impact on the sanitary economy compared to that expected for long-time care in case of repeated features [57].

It is therefore our opinion that the use of secure and trusted traditional techniques must be accompanied by the best is offered today by new technologies both on the respect of the quality of patient's life, both keeping in mind of the economic feasibility.
