Growth factors involved in fracture repair (Table 1. OKU 5 Chapt 2 )
| Growth Factor | Location | Function |
| Transforming growth factor-· (TGF-1, TGF-2) | Platelets, osteoblasts, chondrocytes, bone matrix |
|
| Insulin-like growth factor (IGF) or somatomedin C | Found in bone and cartilage | Stimulates cartilage growth |
| Platelet-derived growth factor (PDGF) | Platelets, monocytes, endothelial cells |
|
| Fibroblast growth factor (FGF) | Inflammatory cells, osteoblasts, chondrocytes |
|
| Tumor necrosis factor (TNF) | Macrophages |
|
OKU5 Chapt 2 - Bone Graft Substitutes
Bone graft substitutes generally include inorganic osteoconductive substances as well as organic bone-derived proteins. Inorganic materials serve purely as osteoconductive matrices and include calcium phosphate ceramics and polylactic acid polymers. Bone-derived proteins can either be extracted from human or bovine sources or generated by recombinant DNA technology and are primarily osteoinductive.
Osteoconductive Materials
Osteoconduction is a process whereby surfaces provide a framework that facilitates the migration of cells used for angiogenesis, chondrogenesis, and osteogenesis.
Traditionally, two ceramics have received the most attention: tricalcium phosphate and hydroxyapatite. Structurally analogous to bone, with a pore size ranging from 100 to 300 (m, these ceramics are extremely biocompatible. The rate of resorption by the host bone is directly related to the porosity of the matrix; tricalcium phosphate is considered to be more biodegradable than hydroxyapatite. Both ceramics have been used in limited studies to reconstruct cancellous bone defects. Unfortunately, calcium phosphates are extremely brittle, making them poor substitutes for structural grafts. Collagen-based graft substitutes are also currently under study. Bovine liquid collagen combined with hydroxyapatite-tricalcium phosphate ceramic granules is considered to be primarily osteoconductive. This composite material has demonstrated promising results in multicenter Phase III clinical trials. Because they are purely osteoconductive, calcium phosphate ceramics and collagen substrates make excellent autograft expanders, with the host graft providing the necessary osteoinductive proteins.
Polylactic acid polymers have enjoyed a reliable history as a resorbable suture material that has an average degradation rate of 6 months. The degradation rate can be adjusted by altering the structure of the material and thereby altering the surface area available to the aqueous environment. In addition, the degradation rate depends strongly on the percentage of the racemic form of lactic acid found in the polymer, with L-lactic acid enjoying the longest half-life. Although promising as an osteoinductive factor delivery system, polylactic acid polymers are still largely investigational.
Osteoinductive Materials
Osteoinduction is the recruitment of mesenchymal-type cells to form cartilage and bone under the influence of a particular stimulus.
A large degree of research activity is being directed toward the study and development of osteoinductive bone graft substitutes. BMP clearly potentiates bone healing; seven individual BMPs have been identified, sequenced, and cloned. Recombinant human BMP-2 (rhBMP-2), when implanted in extraskeletal sites, has been found to induce bone formation through endochondral ossification and, therefore, has undergone the most extensive study. Initial studies have been extremely promising; in these, rhBMP-2 used in conjunction with a variety of carriers demonstrates healing of bone defects in a high percentage of animals.
However, severe practical difficulties with the initial collagen-based carriers (disease transmission, potential rejection, and supply limitations) have resulted in research directed toward the combining of rhBMPs with noncollagenous matrices. Resorbable poly L-lactic acid lattices and hydroxyapatite ceramics hold the most promise. Unfortunately, neither composite is sufficiently strong to serve as a structural graft. The clinical indications for these types of combined osteoinductive proteins and osteoconductive matrices are similar to those for current applications of cancellous bone graft or freeze-dried allograft. Frozen allografts are still considered the most versatile structural biologic implant available for long-bone reconstruction.