Synthetic Calcium Phosphate Ceramics for Treatment of Bone Fractures

Bone is a complex natural material with outstanding mechanical properties and remarkable self-healing capabilities. The mechanical strength is achieved by a complex structure of a mineral part comprising apatitic calcium phosphate crystals embedded in an organic matrix. Bone also contains several types of cells constantly replacing mature bone with new bone. These cells are able to seal fractures and fill gaps with new bone in case of structural damage. However, if a defect exceeds a critical size, surgery is necessary to fill the void with a spacer in order to prevent soft tissue from growing into the defect and delaying the healing process. The spacers, also known as bone grafts, can either be made of fresh bone from the patient, of processed bone from donor organisms, or of synthetic materials chemically similar to the mineral part of bone. Synthetic bone void fillers are also known as bone graft substitutes. This review aims at explaining the biological and chemical background that lead to the development of synthetic bone graft substitutes and gives an overview of the current state of development. It also highlights the multidisciplinary nature of biomaterials research, which combines cell biology and medicine with chemistry, mineralogy, crystallography, and mechanical engineering

Bone Substitutes

In daily clinical practise we frequently encounter situations in which the bone volume is insufficient for an ideal dental implant placement. Bone regeneration can provide the structural support necessary in these cases. Procedures such as sinus lifting and alveolar ridge augmentation have reached high levels of predictability and already are of major importance in implant practise. Interest for bone substitutes for alveolar ridge augmentation or preservation appears in the early 1980 ¿s alongside the development of endoosseous dental implants. Although first studies regarding bone substitutes dates from 1920 by Albee (Albee, 1920), until 1980 ¿s there are very few studies in reference this issue. From 1980 ¿s until nowadays an exponential number of studies about bone substitutes have been made. The reason for this increasing interest in bone substitutes stems from the fact that about 10- 20% of the patients that need treatments with dental implants, require bone regeneration procedures before implant placement. Moreover, more than 60% of the population in industrialized countries need dental prosthetic replacements (Peterson, 2006), ideally with implants. This is the reason why the market of dental implants is experiencing an increase of approximately 15% every year. Bone regeneration procedures are becoming an almost daily practice in dentistry all around the world as a result of the wide acceptance of dental implants as the ¿ideal ¿ option for oral rehabilitation. Bone regeneration procedures are critical for the success of dental implant treatments in cases where there is a deficiency in bone width and/or height. The cornerstone in these treatments is the use of bone substitutes to create a bone mantle that covers the screw to enhance implant stability and treatment outcome. In this chapter, we will discuss the different types of bone substitutes and recent developments achieved to enhance the outcomes of bone regeneration procedures with the newest available biomaterials. The term ¿bone graft ¿ was defined by Muschler (Bauer, 2000) as: ¿any implanted material that alone or in combination with other materials promotes a bone healing response by providing oteogenic, osteoinductive or osteoconductive properties ¿. An osteogenic material can be defined as one that has inherent capacity to form bone, which implies to contain living cells that are capable of differentiation into bone cells. An osteoinductive material 92 Implant Dentistry ¿ The Most Promising Discipline of Dentistry provides biologic signals capable to induce local cells to enter a pathway of differentiation leading to mature osteoblasts. An osteoconductive biomaterial provides a three-dimensional interconnected scaffold where local bone tissue may regenerate new living bone. However, osteoconductive biomaterials are unable to form bone or to induce its formation. Another property that is interesting to find especially in bone substitutes is biodegradability. This is defined as the capacity of degradation of a particle by two mechanisms principally; through a passive chemical degradation or dissolution, and through active cellular activity mediated by osteoclast and/or macrophages. Moreover, the biological properties of bone substitute biomaterials are also influenced by their porosity, surface geometry and surface chemistry. The events leading to bone healing and regeneration are influenced by all the variables mentioned above. These properties are related to the biomaterial itself, however, host factors such as bone quality, vascularity of the graft bed and tobacco addiction may also influence the final outcome of a bone regeneration procedure with a bone substitute.Estomatologí

Osteoclast differentiation from human blood precursors on biomimetic calcium-phosphate substrates

The design of synthetic bone grafts to foster bone formation is a challenge in regenerative medicine. Understanding the interaction of bone substitutes with osteoclasts is essential, since osteoclasts not only drive a timely resorption of the biomaterial, but also trigger osteoblast activity. In this study, the adhesion and differentiation of human blood-derived osteoclast precursors (OCP) on two different micro-nanostructured biomimetic hydroxyapatite materials consisting in coarse (HA-C) and fine HA (HA-F) crystals, in comparison with sintered stoichiometric HA (sin-HA, reference material), were investigated. Osteoclasts were induced to differentiate by RANKL-containing supernatant using cell/substrate direct and indirect contact systems, and calcium (Ca++) and phosphorus (P5+) in culture medium were measured. We observed that OCP adhered to the experimental surfaces, and that osteoclast-like cells formed at a rate influenced by the micro- and nano-structure of HA, which also modulate extracellular Ca++. Qualitative differences were found between OCP on biomimetic HA-C and HA-F and their counterparts on plastic and sin-HA. On HA-C and HA-F cells shared typical features of mature osteoclasts, i.e. podosomes, multinuclearity, tartrate acid phosphatase (TRAP)-positive staining, and TRAP5b-enzyme release. However, cells were less in number compared to those on plastic or on sin-HA, and they did not express some specific osteoclast markers. In conclusion, blood-derived OCP are able to attach to biomimetic and sintered HA substrates, but their subsequent fusion and resorptive activity are hampered by surface micro-nano-structure. Indirect cultures suggest that fusion of OCP is sensitive to topography and to extracellular calcium.Preprin

Calcium carbonate-calcium phosphate mixed cement compositions for bone reconstruction

The feasibility of making calcium carbonate-calcium phosphate (CaCO3-CaP) mixed cements, comprising at least 40 % (w/w) CaCO3 in the dry powder ingredients, has been demonstrated. Several original cement compositions were obtained by mixing metastable crystalline calcium carbonate phases with metastable amorphous or crystalline calcium phosphate powders in aqueous medium. The cements set within at most 1 hour at 37°C in atmosphere saturated with water. The hardened cement is microporous and exhibits weak compressive strength. The setting reaction appeared to be essentially related to the formation of a highly carbonated nanocrystalline apatite phase by reaction of the mestastable CaP phase with part or almost all of the metastable CaCO3 phase. The recrystallization of metastable CaP varieties led to a final cement consisting of a highly carbonated poorly crystalline apatite (PCA) analogous to bone mineral associated with various amounts of vaterite and/or aragonite. The presence of controlled amounts of CaCO3 with a higher solubility than the apatite formed in the well-developed calcium phosphate cements might be of interest to increase resorption rates in biomedical cement and favor its replacement by bone tissue. Cytotoxicity testing revealed excellent cytocompatibility of CaCO3-CaP mixed cement compositions

Comparative histological and histomorphometric results of six biomaterials used in two-stage maxillary sinus augmentation model after 6-month healing

To evaluate the performances of six different bone substitute materials used as graft in maxillary sinus augmentation by means of histological and histomorphometric analysis of bone biopsies retrieved from human subjects after a 6-month healing period. Materials and Methods. Six consecutive patients (3 males, 3 females, aged 50-72 years), healthy, nonsmokers, and with good oral hygiene, presenting edentulous posterior maxilla with a residual bone crest measuring ≤ 4 mm in vertical height and 3 to 5 mm in horizontal thickness at radiographic examination, were selected to receive sinus augmentation and delayed implant placement. Under randomized conditions, sinus augmentation procedures were carried out using mineralized solvent-dehydrated bone allograft (MCBA), freeze-dried mineralized bone allograft (FDBA), anorganic bovine bone (ABB), equine-derived bone (EB), synthetic micro-macroporous biphasic calcium-phosphate block consisting of 70% beta-tricalcium phosphate and 30% hydroxyapatite (HA-β-TCP 30/70), or bioapatite-collagen (BC). After 6 months, bone core biopsies were retrieved and 13 implants were placed. Bone samples were processed for histological and histomorphometric analysis. CT scans were taken before and after surgery. After 4 months of healing, patients were restored with a provisional fixed acrylic resin prosthesis, as well as after further 2-4 months with a definitive cemented zirconia or porcelain-fused-to-metal crowns. Results. There were no postoperative complications or implant failures. The histological examination showed that all biomaterials were in close contact with newly formed bone, surrounding the graft granules with a bridge-like network. No signs of acute inflammation were observed. The histomorphometry revealed 20.1% newly formed bone for MCBA, 32.1% for FDBA, 16.1% for ABB, 22.8% for EB, 20.3% for HA-β-TCP 30/70, and 21.4% for BC. Conclusions. Within the limitations of the present investigation, all the six tested biomaterials showed good biocompatibility and osteoconductive properties when used in sinus augmentation procedures, although the FDBA seemed to have a better histomorphometric result in terms of newly formed bone and residual graft material. This trial is registered with ClinicalTrials.gov Identifier (Registration Number): NCT03496688

Development of 3D PCL microsphere/TiO\u3csub\u3e2\u3c/sub\u3e nanotube composite scaffolds for bone tissue engineering

In this research, the three dimensional porous scaffolds made of a polycaprolactone (PCL) microsphere/TiO2 nanotube (TNT) composite was fabricated and evaluated for potential bone substitute applications. We used a microsphere sintering method to produce three dimensional PCL microsphere/TNT composite scaffolds. The mechanical properties of composite scaffolds were regulated by varying parameters, such as sintering time, microsphere diameter range size and PCL/TNT ratio. The obtained results ascertained that the PCL/TNT (0.5 wt%) scaffold sintered at 60 °C for 90 min had the most optimal mechanical properties and an appropriate pore structure for bone tissue engineering applications. The average pore size and total porosity percentage increased after increasing the microsphere diameter range for PCL and PCL/TNT (0.5 wt%) scaffolds. The degradation rate was relatively high in PCL/TNT (0.5 wt%) composites compared to pure PCL when the samples were placed in the simulated body fluid (SBF) for 6 weeks. Also, the compressive strength and modulus of PCL and PCL/TNT (0.5 wt%) composite scaffolds decreased during the 6 weeks of storage in SBF. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay and alkaline phosphates (ALP) activity results demonstrated that a generally increasing trend in cell viability was observed for PCL/TNT (0.5 wt%) scaffold sintered at 60 °C for 90 min compared to the control group. Eventually, the quantitative RT-PCR data provided the evidence that the PCL scaffold containing TiO2 nanotube constitutes a good substrate for cell differentiation leading to ECM mineralization

Biomedicals from Bone

The realm of biomaterials, under which biomedical materials can be categorised, has a broad definition base and recognises materials that are synthesized or naturally sourced. Biomaterials are normally those that come into contact with live tissue and physiological fluids. They have applications as prostheses to replace lost function of joints or to replace bone tissue, for diagnosing medical conditions, as a form of therapy, or as a storage unit. The diversity and scope of biomaterials science research, and especially its application to the improvement of trauma, disease, and congenital defects in the human condition, are making this branch of science increasingly dominant and topical in many countries. An exciting aspect is that such research is interdisciplinary. The varied problems of the human condition that biomaterials research addresses occupy the efforts not only of medical doctors who act as the end users of such technology, but also those of chemists, physicists, engineers, and biologists in creating the technological advances. Chemistry, in particular, plays a major role in such research, after all it is the foundation stone on which biomaterials polymer science and biomedical scaffold materials are built

Preparation, physical-chemical characterisation and cytocompatibility of calcium carbonate cements

The feasibility of calcium carbonate cements involving the recrystallisation of metastable calcium carbonate varieties has been demonstrated. Calcium carbonate cement compositions presented in this paper can be prepared straightforwardly by simply mixing water (liquid phase) with two calcium carbonate phases (solid phase) which can be easily obtained by precipitation. An original cement composition was obtained by mixing amorphous calcium carbonate and vaterite with an aqueous medium. The cement set and hardened within 2 hours at 37°C in an atmosphere saturated with water and the final composition of the cement consisted mostly of aragonite. The hardened cement was microporous and showed poor mechanical properties. Cytotoxicity tests revealed excellent cytocompatibility of calcium carbonate cement compositions. Calcium carbonates with a higher solubility than the marketed calcium phosphate cements might be of interest to increase biomedical cement resorption rates and to favour its replacement by bone tissue