Efficacy and safety of autologous or allogeneic mesenchymal stromal cells from adult adipose tissue expanded and combined with tricalcium phosphate biomaterial for the surgical treatment of atrophic nonunion of long bones: a phase II clinical trial.

BACKGROUND: Autologous bone grafting is the standard treatment for the surgical management of atrophic nonunion of long bones. Other solutions, such as bone marrow mesenchymal stem cells (BM-MSC) combined with phospho-calcium material, have also been used. Here we evaluate the safety and early efficacy of a novel procedure using autologous or allogenic adipose tissue mesenchymal stromal cells (AT-MSC) seeded in a patented tricalcium phosphate-based biomaterial for the treatment of bone regeneration in cases of atrophic nonunion. METHODS: This was a prospective, multicentric, open-label, phase 2 clinical trial of patients with atrophic nonunion of long bones. Biografts of autologous or allogenic AT-MSC combined with a phosphate substrate were manufactured prior to the surgical procedures. The primary efficacy was measured 6 months after surgery, but patients were followed for 12 months after surgery and a further year out of the scope of the study. All adverse events were recorded. This cohort was compared with a historical cohort of 14 cases treated by the same research team with autologous BM-MSC. RESULTS: A total of 12 patients with atrophic nonunion of long bones were included. The mean (SD) age was 41.2 (12.1) years and 66.7% were men. Bone healing was achieved in 10 of the 12 cases (83%) treated with the AT-MSC biografts, a percentage of healing similar (11 of the 14 cases, 79%) to that achieved in patients treated with autologous BM-MSC. Overall, two adverse events, in the same patient, were considered related to the procedure. CONCLUSIONS: The results of this study suggest that AT-MSC biografts are safe for the treatment of bone regeneration in cases of atrophic nonunion and reach high healing rates. TRIAL REGISTRATION: Study registered with EUDRA-CT (2013-000930-37) and ClinicalTrials.gov (NCT02483364).

Orthobiologics: Current role in Orthopedic Surgery and Traumatology.

Orthobiologics are organic and synthetic materials that help in the cure of musculo-skeletal problems and are utilized in Orthopaedic Surgery, both in and out of the surgical theater, to augment the possibilities of curing bone and soft tissue lesions. Taking into account that their effect is frequently multifactorial and, in some occasions not entirely comprehended, together with the insufficient clinical information, orthobiologics should be scrupulously assessed against other secure and clinically accepted options. The fundamental orthobiologics today ready for use in Orthopedic Surgery are the following: osseous hollow fillers, extracellular matrix (ECM) substances, platelet-rich plasma (PRP), bone morphogenetic protein-2 (BMP-2), bone marrow aspirate (BMA), bone marrow aspirate concentrate (BMAC), and mesenchymal stem cells (MSCs). It is predictable that in the time to come we will have more secure and more efficacious orthobiologics. Meanwhile, it is paramount that orthopedic surgeons have appropriate information of contemporary orthobiologics (biological adjuvants) so that they can utilize them correctly.