Bone substitutes: An update
Introduction
Bone graft is the second most common transplantation tissue, with blood being by far the commonest.7, 65 More than 500,000 bone grafting procedures are happening annually in the United States and 2.2 million worldwide in order to repair bone defects in orthopaedics, neurosurgery and dentistry.42, 47
Furthermore, the treatment of posttraumatic skeletal complications, such as delayed unions, non-unions, malunions, are challenging.57 Bone-grafting is usually required to stimulate bone-healing. In addition, spinal fusions, filling defects following removal of bone tumors and several congenital diseases may require bone grafting. Several methods of reconstructing bone defects are available namely using autograft, allograft, demineralised bone matrix (DBM), hydroxyapatitecalcium phosphate (CP, TCP), autologous bone marrow aspirates, bone morphogenetic proteins, and several other related growth factors (VEGF, PDGF, etc.).
The gold standard of bone-grafting is harvesting autologous cortical and cancellous bone from the iliac crest. All other forms of bone grafting have disadvantages compared to autograft and as such their use is sub-optimal. Technological evolution along with better understanding of bone-healing biology, however, have lead to the development of several bone graft substitutes that are currently available to the orthopaedic surgeons.62, 66
Section snippets
Bone graft characteristics
Osteogenesis, osteoinduction, and osteoconduction are the three essential elements of bone regeneration along with the final bonding between host bone and grafting material which is called osteointegration. Osteoprogenitor cells living within the donor graft, may survive during transplantation, could potentially proliferate and differentiate to osteblasts and eventually to osteocytes. These cells represent the “osteogenic” potential of the graft.20 “Osteoinduction” on the other hand is the
Autograft
Autologous bone, the golden standard of bone grafting, provides optimal osteoconductive, osteoconductive, and osteogenic properties.20 Iliac crest is the most frequently chosen donor site as it provides easy access to good quality and quantity cancellous autograft. Harvesting autologous bone from the iliac crest has, however, several downsides as it lengthens the overall surgical procedure and is usually complicated by residual pain and cosmetic disadvantages.1, 22, 62, 66 Furthermore, it may
Allograft
Allograft is the most frequently chosen bone substitute and is regarded as the surgeon's second option.14 Its use has increased 15-fold the past decade and accounts for about one-third of bone grafts performed in the United States.7 The current increasing availability of allograft tissue has made it possible to manufacture customised types, such as dowels, strips, and chips.55 Allograft bone has more limitations in the essential bone graft characteristics described earlier and yields more
Bone-graft substitutes
A bone-graft substitute should be: osteoconductive, osteoinductive, biocompatible, bio-resorbable, structurally similar to bone, easy to use, and cost-effective.
A large number of bone-graft alternatives are currently commercially available for orthopaedic use. They vary in composition, mechanism of action, and special characteristics. Table 3 shows a variety of bone-graft-substitute materials. It is important to note that they all are osteoconductive, offer various levels of structural support,
Demineralised bone matrix
Demineralised bone matrix can be produced through decalcification of cortical bone. Then, is processed in order to reduce the potential for infection and immunogenic host response. The material produced, the DBM, retains the trabecular collagenous structure of the original tissue and can serve as a biologic osteoconductive scaffold despite the loss of structural strength once contributed by the pre-existing bone mineral.43 Bone demineralisation does not eliminate all bone growth factors, which
Synthetic bone substitutes
Considerable advances have been made with synthetic alternatives over the past decade. These materials may soon provide results comparable to autograft (Table 3). Until recently, synthetics were not in favour compared to autograft and allograft. Synthetic bone grafts at most possess only two of the four characteristics of an ideal bone graft material (osteointegration, osteoconduction). Ideally synthetic bone graft substitutes should be biocompatible, show minimal fibrotic reaction, undergo
Ceramics
Ceramics are synthetic scaffolds made from calcium phosphate that have been used in dentistry and in orthopaedics since the 1980s.3, 32, 64 Tricalcium phosphate ceramic has a stoichiometry similar to amorphous bone precursors, whereas hydroxyapatite has a stoichiometry similar to bone mineral. Ceramics do not exist naturally, but they have been shown to induce a biologic response similar to that of bone. Alone, synthetic ceramics posses no osteogenic or osteoinductive properties, and
Bioactive glasses
Bioactive glasses are hard, solid (non-porous), materials consisting of, calcium, phosphorus, and silicon-dioxide (silicate, the main component). By varying the proportions of sodium oxide, calcium oxide, and silicon dioxide, all range of forms can be produced from soluble to non-resorbable. They possess both osteointegrative and osteoconductive properties. A mechanically strong bond between bioactive glass and bone forms eventually through hydroxyapatite crystals similar to that of bone.30
Biologic/synthetic composite grafts
One of the most promising emerging surgical options may be the use of a “composite graft” that contains osteogenic cells and osteoinductive growth factors along with a synthetic osteoconductive matrix. Composite materials being tested in preclinical and clinical trials may exhibit functionality comparable to autograft and allograft. Composite synthetic grafts offer an alternative that can potentially unite the three essential bone-forming properties in more controlled and effective combinations
Conclusion
Fresh autogenous cancellous and, to a lesser degree, cortical bone are the gold standard graft materials that, ideally, all other bone substitutes should compare their performances. Bone defects bring the dilemma of graft choice to the orthopaedic surgeon. It is sensible to assume that not all bone graft substitutes will perform the same way. The variety of the available scaffolds in industry and their combinations (composite grafts), represent not only the different clinical needs and
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