BMPs have been frequently used in clinical trials with significant heterogeneity. A systematic review and metaanalysis on 11 trials observed comparable times to fracture healing between ABT 199 BMP and controls and confirmed some evidence of increased healing rates with BMP without a secondary procedure compared with usual care control in acute tibial fractures [47], but observed that achieving union for nonunited fractures was similar to bone graft substitutes. Other strategies such as local application of FGF2 were found to accelerate tibial shaft fractures [48], although no data are available in nonunions. Bone grafting is widely used in hospitals to repair injured, aged or diseased skeletal

tissue. In Europe, about one million patients encounter surgical bone reconstruction annually and the numbers are increasing due to our aging population. Bone grafting intends to facilitate bone healing through osteogenesis (i.e. bone generation) at the site of damage, I-BET-762 molecular weight but this is only attained when augmentation includes cells capable of forming bone. Other options to augment this bone repair include osteoinductive (i.e. bone inducers) and osteoconductive (i.e. bone guides) capabilities of the supplied coadjuvants to the surgical treatment. Bone autograft is the safest and most effective grafting procedure, since it contains a patient’s

own bone growing cells (to enhance osteogenesis) and proteins (to enhance osteoinduction), while providing a framework for the new bone to grow into (osteoconduction). However, bone autograft is limited in quantity (about 20 cm3) and its harvesting (e.g. from the iliac crest) represents an additional surgical intervention, with frequent consequences of pain and complications [49]. The next solution is allograft bone directly coming from tissue banks (fresh-frozen) or prepared to be conserved (dried or lyophilized). This solution does not contain

living cells and some matrix proteins are destroyed by virus-inactivation treatments and the freezing Glutathione peroxidase process, thus it only guarantees osteoconductive properties. Moreover, allograft bone may transfer disease or lead to immunological rejections [50]. An interesting alternative is to combine allograft with MSCs from concentrated bone marrow, as has been proposed in bone defects after revision hip surgery [51] but also preliminarily explored in long bone pseudarthrosis [52]. Yet the number of cells may be an issue, as the available evidence in preclinical models recommends a high number of cells [53] and many ongoing clinical trials are thus based on high number of MSCs that require cell expansion, as will be discussed later. Since both autograft and allograft have drawbacks, scientists have long searched for biocompatible materials that could be used in place of the transplanted bone [50] and [54].