JOM • March 2008 38 www.tms.org/jom.html Overview Biological Materials Science Hydroxyapatite (HA)-reinforced poly- mer biocomposites offer a robust system to engineer synthetic bone substitutes with tailored mechanical, biological, and surgical functions. The basic design rationale has been to reinforce a tough, biocompatible polymer matrix with a bioactive HA filler. A large number of studies have investigated modifications to the biocomposite structure and com- position, aimed at improving the me- chanical properties, often through modi- fied or novel processing methods. In this article, the effects of the polymer com- position and molecular orientation; the HA/polymer interface; and the HA-re- inforcement content, morphology, pre- ferred orientation, and size are reviewed with respect to mechanical properties, drawing frequent comparisons between various HA-reinforced polymer compos- ites and bone tissue. INTRODUCTION Hydroxyapatite (HA)-reinforced poly- mer biocomposites were first conceived by W. Bonfield and colleagues 1–6 as a bone analog biomaterial enabling me- chanical properties to be tailored to mim- ic those of bone tissue. Bone tissue ex- hibits a complex, hierarchical structure over several length scales, 7,8 beginning with a distinction between the more dense cortical bone in the diaphysis and less dense trabecular bone in the epiphy- ses of long bones, such as a human femur (Figure 1). However, regardless of differ- ences in intermediate levels of structure, the extracellular matrix (ECM) of all bone tissue is essentially constructed by mineralized collagen fibrils, which can be accurately represented as a two-phase composite comprising a collagen matrix reinforced with 40–50 vol.% (50–60 wt.%) apatite crystals (Figure 1). The apatite crystals are nanoscale, plate-like, Hydroxyapatite-Reinforced Polymer Biocomposites for Synthetic Bone Substitutes Ryan K. Roeder, Gabriel L. Converse, Robert J. Kane, and Weimin Yue How would you… …describe the overall significance of this paper? Through progress over the last quarter century, hydroxyapatite reinforced polymers have been engineered to mimic important aspects of the structure and properties of human bone tissue. …describe this work to a materials science and engineering professional with no experience in your technical specialty? This review demonstrates how the basic elements of composite materials design—namely, the polymer matrix composition and molecular orientation; the matrix/ reinforcement interface; and the reinforcement content, morphology, preferred orientation and size— have been used to engineer synthetic bone substitutes with tailored mechanical, biological, and surgical function. …describe this work to a layperson? Synthetic biomaterials that promote integration with bone tissue are an enabling technology in the devel- opment of improved orthopaedic implants, bone grafts, and tissue engineering approaches to treat diseased, malformed, or injured bone tissue. and elongated with a c-axis preferred orientation in directions of principal stress, such as the longitudinal anatom- ic axis of long bones. 7–9 Thus, bone tis- sue exhibits anisotropic and inhomoge- neous mechanical properties. 10–12 Human cortical bone exhibits elastic moduli of 16–23 GPa and 6–13 GPa, tensile strengths of 80–150 MPa and 50–60 MPa, and fracture toughness of 4–6 MPa·m 1/2 and 2–4 MPa·m 1/2 for load applied along the longitudinal and transverse axes, respectively. 7,10,13–16 Trabecular bone has an effective elas- tic modulus and tensile strength in the range of 0.05–0.5 GPa and 1–6 MPa, respectively, depending on the apparent tissue density. 7,14,17 While the apparent properties of trabecular bone (75–95% porosity) are significantly lower than those for cortical bone (5–10% poros- ity) due to the highly porous structure, the properties of the ECM are rela- tively similar. 7,14,18 Therefore, cortical bone mechanical properties should be used as the benchmark for the design of new biomaterials prior to the introduc- tion of the porosity requisite for bone ingrowth. This review will focus on the mate- rial design without porosity, recogniz- ing that porosity is ultimately essential for the vascularization and growth of bone into an implant. The justifica- tion for this approach is two-fold: first, comparing the mechanical properties of porous materials is complicated by the complexity of the pore architec- ture, and second, porosity can always be added, though perhaps not easily, by removal of material. The majority of all commercialized and FDA-approved orthopaedic im- plants utilize relatively few biomate- rials, with mechanical properties that typically deviate from the ECM of bone by an order of magnitude (Figure 2). Metals include stainless steel, cobalt- chrome, and titanium alloys. Ceram- ics include alumina, zirconia, HA, and other calcium phosphates. Polymers include ultra-high molecular weight polyethylene (UHMWPE), polymethyl methacrylate (PMMA), and polyaryle- therketone (PAEK). Most metals and ceramics are much stiffer than bone tissue, which can re- sult in mechanical mismatch (“stress shielding”) between the implant and the