Bone substitutes in orthopaedic surgery: from basic science to clinical practice

Abstract

Bone substitutes are being increasingly used in surgery as over two millions bone grafting procedures are performed worldwide per year. Autografts still represent the gold standard for bone substitution, though the morbidity and the inherent limited availability are the main limitations. Allografts, i.e. banked bone, are osteoconductive and weakly osteoinductive, though there are still concerns about the residual infective risks, costs and donor availability issues. As an alternative, xenograft substitutes are cheap, but their use provided contrasting results, so far. Ceramic-based synthetic bone substitutes are alternatively based on hydroxyapatite (HA) and tricalcium phosphates, and are widely used in the clinical practice. Indeed, despite being completely resorbable and weaker than cortical bone, they have exhaustively proved to be effective. Biomimetic HAs are the evolution of traditional HA and contains ions (carbonates, Si, Sr, Fl, Mg) that mimic natural HA (biomimetic HA). Injectable cements represent another evolution, enabling mininvasive techniques. Bone morphogenetic proteins (namely BMP2 and 7) are the only bone inducing growth factors approved for human use in spine surgery and for the treatment of tibial nonunion. Demineralized bone matrix and platelet rich plasma did not prove to be effective and their use as bone substitutes remains controversial. Experimental cell-based approaches are considered the best suitable emerging strategies in several regenerative medicine application, including bone regeneration. In some cases, cells have been used as bioactive vehicles delivering osteoinductive genes locally to achieve bone regeneration. In particular, mesenchymal stem cells have been widely exploited for this purpose, being multipotent cells capable of efficient osteogenic potential. Here we intend to review and update the alternative available techniques used for bone fusion, along with some hints on the advancements achieved through the experimental research in this field.

Fig. 1

a Cortical strut autograft from fibula in a proximal humeral non union treated by ORIF. b One year X-ray control show bone healing and the persistence of the autograft

Fig. 2

a, b Morcelized homologous bone graft obtained from a banked femoral head. c Severe acetabular bone loss in a mobilized hip revision cup. d X-ray control at 2 years with evidence of bony stable osseointegration of the new cup in the remodeled bone graft

Fig. 3

a, b Bovine bone substitute (Xenograft) in chips and blocks shape. c The xenograft is clearly visible and not resorbed in a well bone healed proximal humeral fracture at 1 year of follow up. d Acetabular bone defect filled with the same material

Fig. 4

HA-TCP bone substitutes in proximal humeral and tibial traumatic bone loss. a Intraoperatory implant of the material in the proximal humerus. b X-ray control at 1 year show the substitute inside the humeral head. c–f X ray and CT scan at 3 year of follow up in the proximal tibia. The HA-TCP material resulted well osseointegrated, but without any sign of resorption or bone substitution

Fig. 5

Injectable TCP cement bone substitutes: a–b injectable cements have the advantage to be mouldable and contourable to the bone loss in mininvasive or open surgery; c bone loss in a distal tibial open fracture delayed union (CT scan); d 1 year X-ray control, showed bone consolidation and osseointegration of the TCP cement

Fig. 6

Calcium sulphate (CS): a Pellets fill the residual gap after DHS explant in a healed intertrochanteric fracture. b Two months after the CS was totally resorbed. c Antibiotic loaded CS pellets in a tibial osteomyelitis. d Three years CT scan control do not show any evidence of bone regeneration. No signs of CS were founded while the infection was healed

Fig. 7

Demineralized Bone Matrix (DBM): a–c Complex proximal humeral fracture treated by ORIF, DBM and calcium sulphate (Allomatrix-Wright); d One year follow up demonstrate good consolidation of the fracture

Fig. 8

Platelet Rich Plasma (PRP): a–d autologous blood is obtained in the operating room. After centrifugation the different components are differentiate. e, f A platelet concentrate is obtained for injection or deposition into the bone gap or wound