• Daniel Chaverri, Santiago Gallardo-Villares, Javier A Pinto, Luciano Rodríguez, Margarita Codinach, Joan García-López, Sergi Querol, Ruth Coll, Joaquim Vives, and Fernando Granell-Escobar.
• Department of Orthopaedic Surgery and Traumatology, ASEPEYO Sant Cugat Hospital, Avinguda Alcalde Barnils, 54-60, Sant Cugat del Vallès, Barcelona 08174, Spain.
• Injury. 2024 Jul 1; 55 (7): 111596111596.

BackgroundAtrophic pseudoarthrosis is a serious complication with an incidence of 5-10 % of bone fractures located in the diaphysis of long bones. Standard treatments involve aggressive surgical procedures and re-interventions requiring the use of autografts from the iliac crest as a source of bone-forming biological activity (Standard of Care, SoC). In this context, regenerative ex vivo expanded osteogenic cell-based medicines could be of interest. Particularly, Mesenchymal Stromal Cells (MSC) offer new prospects to promote bone tissue repair in pseudoarthrosis by providing biological activity in an osteoconductive and osteoinductive environment.MethodsWe conducted a phase IIa, prospective, randomised, parallel, two-arms, open-label with blinded assessor pilot clinical trial to compare SoC vs. a tissue-engineered product (TEP), composed of autologous bone marrow (BM)-derived MSCs loaded onto allogeneic decellularised, lyophilised spongy bone cubes, in a cohort of 20 patients with non-hypertrophic pseudoarthrosis of long bones. Patients were followed up for 12 months. Radiological bone healing was evaluated by standard X-ray and computed tomography (CT) scanning. Quality of life was measured using the EUROQOL-5D questionnaire.ResultsTen patients were randomized to TEP and 10 to SoC with iliac crest autograft. Manufacturing of TEP was feasible and reproducibly achieved. TEP implantation in the bone defect was successful in all cases and none of the 36 adverse events (AE) reported were related to the treatment. Efficacy analyses were performed in the Full Analysis Set (FAS) population, which included 17 patients after 3 patients withdrew from the study. The degree of consolidation, estimated by measuring Hounsfield units (HU) on CT, showed no significant differences between the two treatment groups at 12 months post treatment (main efficacy variable) (p = 0.4835) or at 6 months.ConclusionsAlthough only a small number of patients were included in our study, it is notable that no significant differences were observed between the experimental treatment and SoC, thus suggesting TEP as an alternative where autograft is not available or contraindicated.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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