Calcium Orthophosphate-Based Bioceramics

Abstract

Various types of grafts have been traditionally used to restore damaged bones. In the late 1960s, a strong interest was raised in studying ceramics as potential bone grafts due to their biomechanical properties. A bit later, such synthetic biomaterials were called bioceramics. In principle, bioceramics can be prepared from diverse materials but this review is limited to calcium orthophosphate-based formulations only, which possess the specific advantages due to the chemical similarity to mammalian bones and teeth. During the past 40 years, there have been a number of important achievements in this field. Namely, after the initial development of bioceramics that was just tolerated in the physiological environment, an emphasis was shifted towards the formulations able to form direct chemical bonds with the adjacent bones. Afterwards, by the structural and compositional controls, it became possible to choose whether the calcium orthophosphate-based implants remain biologically stable once incorporated into the skeletal structure or whether they were resorbed over time. At the turn of the millennium, a new concept of regenerative bioceramics was developed and such formulations became an integrated part of the tissue engineering approach. Now calcium orthophosphate scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous and harbor different biomolecules and/or cells. Therefore, current biomedical applications of calcium orthophosphate bioceramics include bone augmentations, artificial bone grafts, maxillofacial reconstruction, spinal fusion, periodontal disease repairs and bone fillers after tumor surgery. Perspective future applications comprise drug delivery and tissue engineering purposes because calcium orthophosphates appear to be promising carriers of growth factors, bioactive peptides and various types of cells.

Keywords: bioceramics; biomaterials; biomedical applications; calcium orthophosphates; grafts; hydroxyapatite; tissue engineering; tricalcium phosphate.

Figure 1

Several examples of the commercial calcium orthophosphate-based bioceramics.

Figure 2

Soft X-ray photographs of the operated portion of the rabbit femur. (a) Four weeks; (b) 12 weeks; (c) 24 weeks; and (d) 72 weeks after implantation of CDHA. (e) Four weeks; (f) 12 weeks; (g)24 weeks; and (h) 72 weeks after implantation of sintered HA. Reprinted from Reference [141] with permission.

Figure 3

A schematic of 3D printing and some 3D printed parts (fabricated at Washington State University) showing the versatility of 3D printing technology for ceramic scaffolds fabrication with complex architectural features. Reprinted from Reference [74] with permission.

Figure 4

A schematic diagram representing the changes occurring with particles under sintering. Shrinkage is noticeable.

Figure 5

Linear shrinkage of the compacted ACP powders that were converted into β-TCP, BCP (50% HA + 50% β-TCP) and HA upon heating. According to the authors: “At 1300 °C, the shrinkage reached a maximum of approximately ~25%, ~30% and ~35% for the compacted ACP powders that converted into HA, BCP 50/50 and β-TCP, respectively” [261]. Reprinted from Reference [261] with permission.

Figure 6

Transparent HA bioceramics prepared by spark plasma sintering at 900 °C from nano-sized HA single crystals. Reprinted from Reference [414] with permission.

Figure 7

Photographs of a commercially available porous calcium orthophosphate bioceramics with (a,b) different porosity; and (c) a method of their production. For photos, the horizontal field width is 20 mm. The picture (c) is reprinted from Reference [457] with permission.

Figure 8

β-TCP porous ceramics with different pore sizes prepared using polymethylmethacrylate balls with diameter equal to: (a) 100–200 μm; (b) 300–400 μm; (c) 500–600 μm; and (d) 700–800 μm. Horizontal field width is 45 mm. Reprinted from Reference [92] with permission.

Figure 9

SEM pictures of HA bioceramics sintered at (A) 1050 °C; and (B) 1200 °C. Note the presence of microporosity in (A) and not in (B). Scale bar is 1 μm. Reprinted from Reference [563] with permission.

Figure 10

Different types of biomedical applications of calcium orthophosphate bioceramics. Reprinted from Reference [623] with permission.

Figure 11

A typical microstructure of calcium orthophosphate cement after hardening. The mechanical stability is provided by the physical entanglement of crystals. Reprinted from Reference [629] with permission.

Figure 12

Shows how a plasma-sprayed HA coating on a porous titanium (dark bars) dependent on the implantation time will improve the interfacial bond strength compared to uncoated porous titanium (light bars). Reprinted from Reference [66] with permission.

Figure 13

A schematic diagram showing the arrangement of the FA/β-TCP biocomposite layers. (a) A non-symmetric functionally gradient material (FGM); and (b) symmetric FGM. Reprinted from Reference [636] with permission.

Figure 14

Schematic illustrations of fabrication of pore-graded bioceramics: (a) lamination of individual tapes, manufactured by tape casting; and (b) a compression molding process. Reprinted from Reference [429] with permission.

Figure 15

Rounded β-TCP granules of 2.6–4.8 mm in size, providing no sharp edges for combination with bone cement. Reprinted from Reference [665] with permission.

Figure 16

A sequence of interfacial reactions involved in forming a bond between tissue and bioactive ceramics. Reprinted from References [66,67,68,69] with permission.

Figure 17

A schematic diagram representing the events, which take place at the interface between bioceramics and the surrounding biological environment: (1) dissolution of bioceramics; (2) precipitation from solution onto bioceramics; (3) ion exchange and structural rearrangement at the bioceramic/tissue interface; (4) interdiffusion from the surface boundary layer into the bioceramics; (5) solution-mediated effects on cellular activity; (6) deposition of either the mineral phase (a) or the organic phase (b) without integration into the bioceramic surface; (7) deposition with integration into the bioceramics; (8) chemotaxis to the bioceramic surface; (9) cell attachment and proliferation; (10) cell differentiation; and (11) extracellular matrix formation. All phenomena, collectively, lead to the gradual incorporation of a bioceramic implant into developing bone tissue. Reprinted from Reference [76] with permission.

Figure 18

A schematic diagram representing the phenomena that occur on HA surface after implantation: (1) beginning of the implant procedure, where a solubilization of the HA surface starts; (2) continuation of the solubilization of the HA surface; (3) the equilibrium between the physiological solutions and the modified surface of HA has been achieved (changes in the surface composition of HA does not mean that a new phase of DCPA or DCPD forms on the surface); (4) adsorption of proteins and/or other bioorganic compounds; (5) cell adhesion; (6) cell proliferation; (7) beginning of a new bone formation; and (8) new bone has been formed. Reprinted from Reference [707] with permission.

Figure 19

A schematic view of a third generation biomaterial, in which porous calcium orthophosphate bioceramics acts as a scaffold or a template for cells, growth factors, etc. Reprinted from Reference [62] with permission.

Figure 20

A schematic drawing presenting the potential usage of HA with various degrees of porosity. Reprinted from Reference [542] with permission.