Bone is not composed of hydroxyapatite (HAp), but of carbonate apatite (CO3Ap). Although the decomposition of CO3Ap begins at around 400°C, and thus, the fabrication of CO3Ap blocks by sintering is ...difficult, CO3Ap blocks have recently been fabricated via a dissolution–precipitation reaction in Na2HPO4 solution using a CaCO3 block as a precursor. Compared to sintered HAp, which is not resorbed by osteoclasts, CO3Ap is resorbed by osteoclasts. Furthermore, CO3Ap upregulates the differentiation of osteoblasts. Therefore, CO3Ap can be used as a replacement for bones with regards to the so-called bone remodeling process. Clinical trials have confirmed the safety and usefulness of CO3Ap granules, including the replacement of CO3Ap granules to new bone. In Dec 2017, CO3Ap was approved as an artificial bone substitute by the Pharmaceuticals and Medical Devices Agency. CO3Ap granules can be used for all dental and maxillofacial surgeries, including the bone reconstruction aimed for dental implantation.
Carbonate apatite artificial bone Ishikawa, Kunio; Hayashi, Koichiro
Science and technology of advanced materials,
12/2021, Letnik:
22, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Bone apatite is not hydroxyapatite (HAp), it is carbonate apatite (CO
3
Ap), which contains 6-9 mass% carbonate in an apatitic structure. The CO
3
Ap block cannot be fabricated by sintering because ...of its thermal decomposition at the sintering temperature. Chemically pure (100%) CO
3
Ap artificial bone was recently fabricated through a dissolution-precipitation reaction in an aqueous solution using a precursor, such as a calcium carbonate block. In this paper, methods of fabricating CO
3
Ap artificial bone are reviewed along with their clinical and animal results. CO
3
Ap artificial bone is resorbed by osteoclasts and upregulates the differentiation of osteoblasts. As a result, CO
3
Ap demonstrates much higher osteoconductivity than HAp and is replaced by new bone via bone remodeling. Granular-type CO
3
Ap artificial bone was approved for clinical use in Japan in 2017. Honeycomb-type CO
3
Ap artificial bone is fabricated using an extruder and a CaCO
3
honeycomb block as a precursor. Honeycomb CO
3
Ap artificial bone allows vertical bone augmentation. A CO
3
Ap-coated titanium plate has also been fabricated using a CaCO
3
-coated titanium plate as a precursor. The adhesive strength is as high as 76.8 MPa, with excellent tissue response and high osteoconductivity.
In this review article the available results about application of sol–gel synthesis method for the preparation of different calcium phosphates and composite materials are summarized. The attention is ...paid to calcium phosphate-containing compounds which show the biological properties and could be used as potential phosphate bioceramics in medicine. It was demonstrated that the sol–gel synthesis method is a powerful tool for the synthesis of calcium hydroxyapatite and other phosphates, and different calcium phosphate-based composites at mild synthetic conditions resulted in high reproducibility, high phase purity, and desired morphology. Thus, the sol–gel synthesis method enables the researchers to develop biomaterials with superior features in terms of biomedical applications.
For the synthesis of calcium phosphate biomaterials an effective sol–gel chemistry approaches have been developed. KI, EG, and AK. “Sol–gel synthesis of calcium phosphate-based biomaterials—A review of environmentally benign, simple, and effective synthesis routes”.
Highlights
The sol-gel chemistry approaches for synthesis of calcium phosphate biomaterials were observed.
Calcium hydroxyapatite, different calcium phosphates, and composites are discussed.
These CP biomaterials show a high biocompatibility and increased biological behaviour.
The sol-gel synthesis method is a powerful tool for the synthesis of CP biomaterials.
High reproducibility, high phase purity and desired morphology could be achieved.
Although block- or granular-type sintered hydroxyapatite are known to show excellent tissue responses and good osteoconductivity, apatite powder elicits inflammatory response. For the fabrication of ...hydroxyapatite block or granules, sintering is commonly employed. However, the inorganic component of bone and tooth is not high crystalline hydroxyapatite but low crystalline B-type carbonate apatite. Unfortunately, carbonate apatite powder cannot be sintered due to its instability at high temperature. Another method to fabricate apatite block and/or granule is through phase transformation based on dissolution-precipitation reactions using a precursor phase. This reaction basically is the same as a setting and hardening reaction of calcium sulfate or plaster. In this paper, apatite block fabrication methods by phase transformation based on dissolution-precipitation reactions will be discussed, with a focus on the similarity of the setting and hardening reaction of calcium sulfate.
Although studies on scaffolds for tissue generation have mainly focused on the chemical composition and pore structure, the effects of scaffold shape have been overlooked. Scaffold shape determines ...the scaffold surface area (SA) at the single-scaffold level (i.e., microscopic effects), although it also affects the amount of interscaffold space in the tissue defect at the whole-system level (i.e., macroscopic effects). To clarify these microscopic and macroscopic effects, this study reports the osteogenesis abilities of three types of carbonate apatite granular scaffolds with different shapes, namely, irregularly shaped dense granules (DGs) and two types of honeycomb granules (HCGs) with seven hexagonal channels (∼255 μm in length between opposite sides). The HCGs possessed either 12 protuberances (∼75 μm in length) or no protuberances. Protuberances increased the SA of each granule by 3.24 mm
while also widening interscaffold spaces and increasing the space percentage in the defect by ∼7.6%. Interscaffold spaces were lower in DGs than HCGs. On DGs, new bone formed only on the surface, whereas on HCGs, bone simultaneously formed on the surface and in intrascaffold channels. Interestingly, HCGs without protuberances formed approximately 30% more new bone than those with protuberances. Thus, even tiny protuberances on the scaffold surface can affect the percentage of interscaffold space, thereby exerting dominant effects on osteogenesis. Our findings demonstrate that bone regeneration can be improved by considering macroscopic shape effects beyond the microscopic effects of the scaffold.
The scaffold chemical composition and pore architecture are critical for successful bone regeneration. Although the effects of chemical composition, micron-scale pores, and macropores (≥100 μm) are ...known, those of nanometer-scale pores (nanopores) are unknown. Here, honeycomb scaffolds (HCSs) composed of carbonate apatite and bone mineral, were fabricated with three distinct nanopore volumes, while other parameters were comparable between HCSs. Their compressive strengths and nanopore volumes linearly correlated. The HCSs were implanted into critical-sized bone defects (CSDs) in the rabbit femur distal epiphyses. The nanopore volume affected both osteoclastogenesis and osteogenesis. HCSs with nanopore volumes of ≥0.15 cm3 g-1 promoted osteoclastogenesis, contributing to bone maturation and bone formation within 4 weeks. However, HCSs with nanopore volumes of 0.07 cm3 g-1 promoted significantly less bone maturation and neoformation. Nevertheless, HCSs with nanopore volumes of ≥0.18 cm3 g-1 did not undergo continuous bone regeneration throughout the 12 week period due to excessive osteoclastogenesis, which favored HCS resorption over bone neoformation. When the nanopore volume was 0.15 cm3 g-1, osteoclastogenesis and osteogenesis progressed harmonically, resulting in HCS replacement with new bone. Our results demonstrate that the nanopore volume is critical for controlling osteoclastogenesis and osteogenesis. These insights may help establish a coherent strategy for developing scaffolds for different applications.
Surgical site infection (SSI) is a severe complication associated with orthopedic bone reconstruction. For both infection prevention and bone regeneration, the framework surface of osteoconductive ...and bioresorbable scaffolds must be locally modified by minimum antibacterial substances, without sacrificing the osteoconductivity of the scaffold framework. In this study, we fabricated antibacterial honeycomb scaffolds by replacing carbonate apatite, which is the main component of the scaffold, with silver phosphate locally on the scaffold surface via dissolution-precipitation reactions. When the silver content was 9.9 × 10
wt %, the honeycomb scaffolds showed antibacterial activity without cytotoxicity and allowed cell proliferation, differentiation, and mineralization. Furthermore, the antibacterial honeycomb scaffolds perfectly prevented bacterial infection
in the presence of methicillin-resistant
, formed new bone at 2 weeks after surgery, and were gradually replaced with a new bone. Thus, the antibacterial honeycomb scaffolds achieved both infection prevention and bone regeneration. In contrast, severe infection symptoms, including abscess formation, osteolytic lesions, and inflammation, occurred 2 weeks after surgery when honeycomb scaffolds without silver phosphate modification were implanted. Nevertheless, the unmodified honeycomb scaffolds eliminated bacteria and necrotic bone through their scaffold channels, resulting in symptom improvement and bone formation. These results suggest that the honeycomb structure is inherently effective in hindering bacterial growth. This novel insight may contribute to the development of antibacterial scaffolds. Moreover, our modification method is useful for providing antibacterial activity to various biomaterials.
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•Scaffolds with channels directed differently are fabricated by 3D printing.•Channel direction is a critical parameter for bone regeneration.•Channel connection to the periosteum is ...important for a smooth replacement by bone.•Biaxial channels result in too rapid scaffold resorption and bone disappearance.•Micro/nanopores are insufficient, and channels are necessary for bone regeneration.
Although the channel architecture of a scaffold is critical for bone regeneration, little is known for the channel direction. In this study, four types of carbonate apatite cylindrical scaffolds; scaffolds with biaxial channels (VH-scaffold), with uniaxial vertical channels (V-scaffold), with uniaxial horizontal channels (H-scaffold), and without channels (N-scaffold), were implanted in a rabbit femur defect for 4 and 12 weeks. Although the largest bone was formed 4 weeks post-implantation in the VH-scaffold, newly formed bone disappeared with the scaffold after 12 weeks. Thus, biaxial channels resulted in the rapid dissolution of the scaffold and were counterproductive in long-term bone regeneration. The V-scaffold that had channels connected to the periosteum was gradually resorbed throughout 12 weeks post-implantation. The percentage of mineralized bone in the V-scaffolds was equal to that in the natural bone. The resorption and bone percentage of H-scaffolds that had no channels connected to the periosteum were slower and lower, respectively, than those of V-scaffolds. Thus, channels should be connected to the periosteum to achieve smooth replacement by the new bone. In the N-scaffold, much less bone was formed inside the scaffold. This study contributes to providing a design guide for scaffold development in bone engineering.
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•Three-dimensional multiscale porous scaffolds are constructed from interconnecting honeycomb granules.•In an early stage, macropores play a crucial role in promoting new bone ...formation.•In the medium term, micropores rather than macropores were the dominant factor affecting the replacement of scaffolds with new bone.•Pore size distribution, rather than porosity, is crucial for osteogenesis in the early to medium term.•Optimizing the pore size distribution of the scaffold is an effective strategy to improve osteogenic ability without sacrificing mechanical strength.
The use of scaffolds with pores ranging from macroscale to nanoscale (i.e., multiscale pores), is an effective strategy to achieve favorable bone regeneration. Here, we report the fabrication of multiscale porous scaffolds (MPSs) and evaluate the effects of macropores (>100 μm) and micropores (<10 μm) on bone regeneration in the early to medium term. MPSs were constructed from interconnecting carbonate apatite honeycomb granules. The uniaxial macropores penetrating the honeycomb granules linked the gaps among the granules, creating an interconnected macroporous architecture. MPSs with different proportions of macropores and micropores were implanted into rabbit femurs. In an early stage, macropores played a crucial role in promoting new bone formation. In the medium term, micropores, rather than macropores, were the dominant factor affecting the replacement of MPSs with new bone. Notably, micropores of 100 nm to 10 μm primarily promoted MPS resorption by osteoclasts, stimulating secondary osteogenesis. Our findings demonstrated that pore size distribution, rather than porosity, was crucial for osteogenesis in the early-to-medium term. Although conventional scaffold development sacrifices mechanical strength to improve bone formation, our findings indicate that optimizing the pore size distribution is a promising strategy to develop scaffolds that satisfy the requirements of both osteogenesis and mechanical strength.
•High-purity OCP blocks could be fabricated from DCPD blocks.•Weak basic high-PO4-containing solution induced OCP formation from DCPD.•The mechanical strength of this OCP block is higher than that ...from CaSO4 block.
Octacalcium phosphate (OCP) blocks are attractive as bone substitutes because of their excellent biocompatibility. They can be fabricated from precursor ceramic blocks via a compositional conversion process. Herein, high-purity OCP blocks were fabricated through a dissolution–precipitation reaction from precursor blocks of dicalcium hydrogen phosphate dihydrate (DCPD) immersed in a 1.00-mol/L basic phosphate solution of disodium hydrogen phosphate (NaAP; pH ∼ 9) at 70 °C for 2 days. The results showed that they were completely converted to OCP blocks comprising interlocking ribbon-like crystals while maintaining their shape. The diametral tensile strength of the obtained OCP blocks was ∼6 MPa, which was significantly higher than that of OCP blocks fabricated from calcium sulfate as the precursor.
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