Calcium Orthophosphates: Applications in Nature, Biology, and Medicine Sergey Dorozhkin Copyright © 2012 Pan Stanford Publishing Pte. Ltd. ISBN 978-981-4316-62-0 (Hardcover), 978-981-4364-17-1 (eBook) www.panstanford.com

PHBHV poly(hydroxybutyrate-co-hydroxyvalerate) PHEMA polyhydroxyethyl methacrylatePHV polyhydroxyvalerate PLA polylactic acidPLGA poly(lactic-co-glycolic) acidPLGC co-polyester lactide-co-glycolide-co-ε-caprolactonePLLA poly(L-lactic acid)PMMA polymethylmethacrylatePP polypropylenePPF poly(propylene-co-fumarate)PS polysulfonePSZ partially stabilized zirconiaPTFE polytetrafluoroethylenePVA polyvinyl alcoholPVAP polyvinyl alcohol phosphateSEVA-C a blend of EVOH with starchUHMWPE ultrahigh molecular weight polyethylene 6.1 IntroductionThe fracture of bones due to various traumas or natural aging is a typical type of a tissue failure. An operative treatment frequently requires implantation of a temporary or a permanent prosthesis, which still is a challenge for orthopedic surgeons, especially in the cases of large bone defects. A fast aging of the population and serious drawbacks of natural bone grafts make the situation even worse; therefore, there is a high clinical demand for bone substitutes. Unfortunately, a medical application of xenografts (e.g., bovine bone) is generally associated with potential viral infections. In addition, xenografts have a low osteogenicity, an increased immunogenicity and, usually, resorb more rapidly than autogenous bone. Similar limitations are also valid for human allografts (i.e., tissue transplantation between individuals of the same species but of non-identical genetic composition), where the concerns about potential risks of transmitting tumor cells, a variety of bacterial

and viral infections, as well as immunological and blood group incompatibility are even stronger [1-3]. Moreover, harvesting and conservation of allografts (exogenous bones) are additional limiting factors. Autografts (endogenous bones) are still the “golden standard” among any substitution materials because they are osteogenic, osteoinductive, osteoconductive, completely biocompatible, nontoxic and do not cause any immunological problems (non-allergic). They contain viable osteogenic cells, bone matrix proteins and support bone growth. Usually, autografts are well accepted by the body and rapidly integrated into the surrounding bone tissues. Due to these reasons, they are used routinely for a long period with good clinical results [3-6]; however, it is fair to say on complication cases, those frequently happened in the past [7, 8]. Unfortunately, a limited number of donor sites restrict the quantity of autografts harvested from the iliac crest or other locations of the patient’s own body. In addition, their medical application is always associated with additional traumas and scars resulting from the extraction of a donor tissue during a superfluous surgical operation, which requires further healing at the donation site and can involve long-term postoperative pain [1, 8-11]. Thus, any types of biologically derived transplants appear to be imperfect solutions, mainly due to a restricted quantity of donor tissues, donor site morbidity, as well as potential risks of an immunological incompatibility and disease transfer [9, 11, 12]. In this light, manmade materials (alloplastic or synthetic bone grafts) stand out as a reasonable option because they are easily available, might be processed and modified to suit the specific needs of a given application [13-15]. What’s more, there are no concerns about potential infections, immunological incompatibility, sterility and donor site morbidity. Therefore, investigations on artificial materials for bone tissue repair appear to be one of the key subjects in the field of biomaterials research for clinical applications [16]. Currently, there are several classes of synthetic bone grafting biomaterials for in vivo applications [17-21]. The examples include natural coral, coral-derived materials, bovine porous demineralized bone, human demineralized bone matrix, bioactive glasses, glass-ceramics and calcium orthophosphates [11]. All of these biomaterials are biocompatible and osteoconductive, guiding bone tissue from the edges toward the center of the defect, and aim to provide a scaffold of interconnected pores with pore dimensions ranging from 200 µm [22, 23] to 2 mm [24], to facilitate tissue and vessel ingrowths. Among

them, porous bioceramics made of calcium orthophosphates appear to be very prominent due to both the excellent biocompatibility and bonding ability to living bone in the body. This is directly related to the fact that the inorganic material of mammalian calcified tissues, i.e. of bone and teeth, consists of calcium orthophosphates [25-27]. Due to this reason, other artificial materials are normally encapsulated by fibrous tissue, when implanted in body defects, while calcium orthophosphates are not [28]. Many types of calcium orthophosphatebased bioceramics with different chemical composition are already on the market (Tables 4.2 and 5.2). Unfortunately, as for any ceramic material, calcium orthophosphate bioceramics by itself lack the mechanical and elastic properties of the calcified tissues. Namely, scaffolds made of calcium orthophosphates only suffer from a low elasticity, a high brittleness, a poor tensile strength, a low mechanical reliability and fracture toughness, which leads to various concerns about their mechanical performance after implantation [29-31]. Besides, in many cases, it is difficult to form calcium orthophosphate bioceramics into the desired shapes. The superior strength and partial elasticity of biological calcified tissues (e.g., bones) are due to the presence of bioorganic polymers (mainly, collagen type I fibers [32]) rather than to a natural ceramic (mainly, a poorly crystalline ion-substituted CDHA, often referred to as “biological apatite”) phase [34, 35]. The elastic collagen fibers are aligned in bone along the main stress directions. The biochemical composition of bones is given in Table 6.1 [36]. A decalcified bone becomes very flexible being easily twisted, whereas a bone without collagen is very brittle; thus, the inorganic nano-sized crystals of biological apatite provide with the hardness and stiffness, while the bioorganic fibers are responsible for the elasticity and toughness [26, 37]. In bones, both types of materials integrate each other into a nanometric scale in such a way that the crystallite size, fibers orientation, short-range order between the components, etc., determine its nanostructure and therefore the function and mechanical properties of the entire composite [33, 38-42]. From the mechanical point of view, bone is a tough material at low strain rates but fractures more like a brittle material at high strain rates; generally, it is rather weak in tension and shear, particularly along the longitudinal plane. Besides, bone is an anisotropic material because its properties are directionally dependent [25, 26, 31]. For further details, see section 1.4 of this book.