A Comparative Study of 2 Doses of BM Autologous H-MSC+Biomaterial vs Iliac Crest AutoGraft for Bone Healing in Non-Union

Bone injuries represent an important world medical problem producing significant healthcare and societal expenditure. While most bone injuries are not severe and are capable of healing through bone regeneration by natural callus formation with standard treatments, severe bone injuries may not heal, becoming an important unmet clinical need.

Non-unions, or pseudarthrosis, may occur in 5% to 20% of long-bone fractures that fail to heal properly after more than 6 months, with morbidity, prolonged hospitalization, and increased expenses. The most commonly accepted standard augmentation to procure fracture and non-union healing consists of autologous bone grafting, obtained from the same patient in a different surgical site and transplanted to the reconstruction site. However, autologous bone grafting has some drawbacks (such as persistent pain, scar, late recovery, limited amount of bone, etc) and a limited regeneration efficacy (success rate of about 74%) and high societal cost. Culture-expanded autologous MSCs combined with biphasic calcium phosphate (BCP) biomaterial granules have been claimed as a solid regenerative medicine alternative to autologous bone grafting in non-unions, although current data are limited. In this context, the ORTHOUNION initiative focuses on the opportunity to test the hypothesis of superiority of MSC, the investigational ATMP, versus the currently accepted standard therapy, iliac crest bone autograft to biologically augment surgical treatment of long-bone non-unions.

Inclusion criteria

• Age 18 years and older, both sexes
• 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 non-union.
• Able to understand, accept and sign informed consent
• Medical health coverage
• Able to understand and accept the study constraints

Exclusion criteria

• Hypertrophic non-unions
• Segmental bone loss requiring specific therapy (bone transport, vascularized graft, large structural allograft, megaprosthesis, etc)
• Unrecovered vascular or neural injury
• Other fractures causing interference with weight bearing
• Visceral injuries or diseases interfering with callus formation (severe cranioencephalic trauma, etc.)
• Active infection of any location and aetiology
• Surgical contraindication of any cause
• Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control.
• Malignant tumour (past history or concurrent disease)(except carcinoma in situ or basalioma in remission)
• History of bone harvesting on iliac crest contraindicating new iliac crest bone graft harvesting or bone marrow collection
• Insulin dependent diabetes
• Any evidence (confirmed by PCR) of active infection with HIV, Hepatitis B or Hepatitis C infection
• Any evidence of Syphilis
• Known allergies to products involved in the production process of MSC
• Corticoid or immunosuppressive therapy more than one week in the three months prior to study inclusion
• Autoimmune inflammatory disease
• Current treatment by biphosphonates not stopped three months prior to study inclusion
• Impossibility to meet at the appointments for the follow up
• Participation in another therapeutic trial in the previous 3 months
• Second non-union in case of bilateral or multiple non-unions (only one non-union per patient will be included in the trial)