Bone graft substitutes are used to fill bone defects. Their function in treatment of bone defects is to act as void filler, provide initial mechanical support, and to enhance bone formation by osteoconduction and some stimulation of biological activity in specific materials.(105)
In larger bone defects, osteoconduction alone will not be sufficient and additional ingredients are necessary to achieve healing. An osteoconductive scaffold needs to be applied in combination with growth factors, osteogenic cells, adequate mechanical stability, and sufficient vascularization in order to achieve healing.(110-165)
These factors may be endogenous or exogenous, but are requirements in the treatment of these often challenging conditions. When the biological condition of the patient is considered insufficient, addition of growth factors or osteogenic cells to an osteoconductive scaffold should be considered.(166)
Combinations of treatment concepts are currently finding their way into clinical application. Still, development of a clinically applicable combination is difficult, with many factors interacting and leading to surprising outcomes in translational research. (163)
The successful application of combined implants, especially those with osteogenic cells, depends largely on the biology of the host. Vascularization of the implant, and consequently the survival of the cells, is a concern in larger implants. So far this has hampered the translation from preclinical concepts to the clinical situation, in particular for scaffolds seeded with osteogenic cells. Other factors that influence survival of cells in these implants are porosity and scaffold characteristics.(172)
The combination of resorbable materials with drugs or other substances has theoretical advantages. First, the purpose of the material can be extended: for example, in a bone defect after an infected non-union osteoconduction of the implanted material can be combined with antibiotics to treat the infection simultaneously. Second, the release of a drug can be determined by the resorption rate of the material, leading to a slow release of the material and a longer mean residual time (MRT) of the drug at the site of interest.(182)
By adding growth factors to osteoconductive materials, osteoinduction is added to the treatment protocol. In this manner, tissue engineering is taken from bench to bedside, and the contributing factors and circumstances are difficult to understand for clinicians who are used to working with screws, plates and nails. The use of resorbable materials makes decisions for specific products even more difficult. Still, several aspects have to be taken into account for each group of materials. (166)
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