A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol
(1) Age 18 to 65, both sexes (2) Traumatic isolated closed or open Gustilo I and II, IIIA and IIIB humerus, tibial or femur diaphyseal, or metaphysodiaphyseal fracture with a status of atrophic, oligotrophic, or normotrophic nonunion. A nonunion is defined as a fracture not healed at least 9 months after the originating trauma that meets the following criteria: (i) Insufficient bone bridging to stabilize the fracture (ii) Insufficient bone biological activity in the fracture (iii) Failure of previous treatment (including bone grafting) (3) At least 9 months from acute fracture (4) Able to understand, accept, and sign informed consent (5) Medical health coverage (6) Able to understand and accept the study constraints
Exclusion criteria
(1) Hypertrophic nonunions (2) Segmental bone loss requiring specific therapy (bone transport, vascularized graft, large structural allograft, megaprosthesis, etc.) (3) Unrecovered vascular or neural injury (4) Other fractures causing interference with weight bearing (5) Visceral injuries or diseases interfering with callus formation (severe cranioencephalic trauma, etc.) (6) Active infection of any location and aetiology (7) Surgical contraindication of any cause (8) Pregnancy, breast-feeding women, and women who are of childbearing age and not practicing adequate birth control. The following methods are considered adequate: (i) Combined hormonal contraception (ii) Injected hormonal contraception (iii) Implanted hormonal contraception (iv) Progesterone-only hormonal contraception associated with inhibition of ovulation (v) Placement of an intrauterine device (IUD) (vi) Placement of intrauterine hormone-releasing system (IUS) (9) Malignant tumour (past history or concurrent disease) (except carcinoma in situ or basalioma in remission) (10) History of bone harvesting on iliac crest contraindicating new iliac crest bone graft harvesting or bone marrow collection (11) Insulin-dependent diabetes (12) Any evidence (confirmed by PCR) of active infection with HIV, hepatitis B, or hepatitis C (13) Any evidence of syphilis (14) Known allergies to products involved in the production process of MSC (15) Corticoid or immunosuppressive therapy more than one week in three months prior to study inclusion (16) Autoimmune inflammatory disease (17) Current treatment by bisphosphonates not stopped three months prior to study inclusion (18) Impossibility to meet at the appointments for the follow-up (19) Participation in another therapeutic trial in the previous 3 months (20) Second nonunion in case of bilateral or multiple nonunions (only one nonunion per patient will be included in the trial)
