Synthetic Ceramic Bone Graft Substitutes
Brian Kwon, MD discussed what makes a synthetic bone graft substitute ideal during the North American Spine Foundation's biologics in spine care course.
Synthetic bone graft substitutes, specifically synthetic ceramics, was the topic presented by Brian Kwon, MD during the North American Spine Foundation’s course, Biologic Interventions for Spinal Pathologies: Stem Cells, Growth Factors and Novel Therapeutics. Dr. Kwon is an Assistant Clinical Professor of Orthopedic Surgery at Tufts University School of Medicine in Medford, MA.
What makes a synthetic bone graft substitute ideal was a rhetorical question for the audience. Essential characteristics include:
- Bioresorbable (broken down and absorbed by the body)
- Strong to withstand mechanical stresses, forces and loads—compression, tension, shear, bending and torsion.
- Osteoconductive (forms a scaffold for new bone growth)
- Osteoinductive (stimulate new bone growth)
- Be readily available with a shelf life, and easy to use
“What we're looking for is a resorption mechanism and really cell-mediated resorption obviously, which is the best,” stated Dr. Kwon.
Synthetic ceramics may be made up of collagen, calcium phosphate (CaP), calcium sulfate, and the products listed below.
- Synthetic hydroxyapatite (HA, a mineral component in bone and teeth). Dr. Kwon indicated, “Due to it’s chemical composition and crystalline structure, we know absorption rates are very low.”
- Beta-tricalcium phosphates (β-TCP), which may be one of the most widely used “calcium phosphate/ceramic products out there,” stated Dr. Kwon.
- Biphasic calcium phosphate (BCP; consists of HA and β-TCP)
Ceramics are formed by sintering; a process using high temperatures to extract individual crystals that fuse into grains (varying sizes).
Dr. Kwon commented, “We know bone itself has macro- and micropores [porosity] … where we know we need growth factors, red blood cells, microvasculature ultimately.” This is where grain size makes a difference—new bone needs something to grow onto. “We know osteoclasts preferentially tend to attach to areas on grain boundaries, in particular, where the grain boundaries are mismatched in terms of size,” said Dr. Kwon. In the field of ceramic chemistry, a great deal of work is being performed on the variability of grain size.” Another physical characteristic is shape; such as concave or convex.
Synthetic Ceramic Bone Graft Strength
Although ceramics can be produced to be tough, the problem is they are brittle. “Under repeated cyclical loading and certainly under situations such as shear torsion, they tend to be very brittle and break apart,” commented Dr. Kwon.
Question of Osteoinductivity
Osteoinductive, osteopromotive, osteopositive, and osteoactive were terms Dr. Kwon used to help describe a favorable biological environment. He pointed out, “We know there are certain characteristics, simple characteristics such as creating micropores, creating small pits. You put them in a biological environment, and it turns out cells will nest there. Again, you give them sort of an interesting place to go. Cells will go; they will nest, and they will begin to phenotypically modify what they do, and you can actually start to see bone growth simply based on the surface characteristics of your graft.”
Origination of Osteoinductivity
Where does osteoinductivity originate? Dr. Kwon stated, “It probably very likely parallels the injury cascade.” Cellular infiltration leads to an inflammatory response, tissue granulation, and foreign body reaction. In cellular aggregates, as early as day 7, blood vessels and pores develop. Granulation tissue, fibroblasts and macrophages are seen in days 7-14. “Within 30 or 45 to 60 days these cell aggregates will actually even start to recruit or become multinucleated giant cells and eventually see osteoblasts in bone,” stated Dr. Kwon.
“So, in the world of synthetics – and again just synthetics alone – the conclusion is that we're very close,” Dr. Kwon said. Furthermore, he indicated, “We have great materials; we have great scientists; we have a lot of great work being done.”