BackgroundTissue engineering appears to be an attractive alternative to the traditional approach in the treatment of fracture non-unions. Mesenchymal stromal cells (MSCs) are considered an appealing cell source for clinical intervention. However, ex vivo cell expansion and differentiation towards the osteogenic lineage, together with the design of a suitable scaffold have yet to be optimized. Major concerns exist about the safety of MSC-based therapies, including possible abnormal overgrowth and potential cancer evolution.AimsWe examined the long-term efficacy and safety of ex vivo expanded bone marrow MSCs, embedded in autologous fibrin clots, for the healing of atrophic pseudarthrosis of the upper limb. Our 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.Methods and FindingsBone marrow MSCs isolated from 8 patients were expanded ex vivo until passage 1 and short-term osteo-differentiated in autologous-based culture conditions. Tissue-engineered constructs designed to embed MSCs in autologous fibrin clots were locally implanted with bone grafts, calibrating their number on the extension of bone damage. Radiographic healing was evaluated with short- and long-term follow-ups (range averages: 6.7 and 76.0 months, respectively). All patients recovered limb function, with no evidence of tissue overgrowth or tumor formation.ConclusionsOur study indicates that highly autologous treatment can be effective and safe in the long-term healing of bone non-unions. This tissue engineering approach resulted in successful clinical and functional outcomes for all patients.

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Pelvic fractures account for 4-5% of all fracturated patients, and they occur in 4-5% of polytraumatized patients. In the most of the cases, they are consequent to high-energy trauma with a high percentage of lesions of other organs (cerebral, thoracic, and abdominal lesions. The most of the patients (80%) who die are dying within the first hours after trauma for a massive hemorrhagic shock. When the pelvic fracture and the patient's hemodynamic conditions are both unstable, osteosynthesis of the fracture is mandatory. Fracture stabilization should be performed within the first hour after trauma (as soon as possible), and it should be considered as part of the resuscitation procedure. We usually make an urgent stabilization of pelvic fracture with an anterior external fixator technique. We have revised all unstable pelvic fractures treated in our department (Orthopaedic Clinic Pisa University) from 2000 up to the 2005 to determine a correct treatment protocol for these lesions. Pelvic stabilization, reducing the pelvic volume and bleeding from the stumps of fracture, determines the arrest of the hemorrhage, as evidenced by the sharp decline in the number of transfusions in postoperative period. In these cases, there is an absolute indication for an urgent pelvic stabilization. Pelvic stabilization, whether temporary or permanent, allows to control the bleeding because it (1) leads to a reduction in the volume pelvis with a containment on the retro-peritoneal hematoma (2) reduces bleeding from the fracture fragments (3) reduces motility fracture promoting the blood clotting. The stabilization of the pelvis also makes it easier to manage the patient and his mobilization for the implementation of subsequent investigations. In our experience, external fixator accounts for its characteristics the gold standard approach for the urgent stabilization of these lesions, and, for most of them, it can be used as the definitive treatment. External fixation is a quick and easy procedure for pelvic fractures stabilization for surgeons with experience with this technique.

The choice of the most appropriate procedure for surgical treatment of type IV-V and VI dislocations of the acromioclavicular joint according to Rockwood's classification has always been troublesome because of complications such as residual instability of the joint, delayed arthrosis of the A-C, delayed osteolysis of the clavicle, host intolerance towards artificial ligaments and because of the need of early mobilization of the affected limb. In our study, 17 male patients, ranging in age from 21 to 79 years and affected by A-C dislocation grade IV and V, both acute and chronic, underwent surgical reconstruction of the A-C joint capsule and extra-articular ligaments with ligament augmentation and reconstruction system (LARS) artificial ligament. Following surgery, their affected limb was braced for 3 days and thereafter all patients began an early active and passive mobilization programme. Patients eventually all returned to their previous working and recreational activities. Throughout thorough clinical and radiographic evaluation and the use of both Constant score and Simple Shoulder test, the aim of our study is to prove that at mid-term follow-up, the reconstruction of the conoid and trapezoid ligaments with LARS is a valid and safe alternative to other procedures.

The use of growth factors and autologous mesenchymal stem cells through the enforcement of system for tissue regeneration is a valid and innovative biotechnology technique for the treatment long bone nonunions.