Bioactive ceramics

Bioactive ceramics
Bioactive ceramics: calcium phosphates, bioactive glasses, and bioactive glass ceramics Common property: ability to bond to bone and enhance bone tissue formation Structural and compositional variations rate of bone bonding,
Chemical composition of selected bioactive ceramics

the stimulatory effect on cell function, and the resorbability vary

Bioactivity *
Bioactivity property: ability of the materials to bond directly to bone and enhance bone formation Bioactive ceramics are characterized by a dynamic surface Ionic dissolution of the material surface calcium phosphate (Ca-P) layer Dissolution property: precipitation of a

Bioactive glass > Hydroxyapatite > Bioactive glass ceramic

Dissolution of the surface integration precipitation of a Ca-P layer bone

Deposited Ca-P mimic those of the mineral phase of bone in many aspects Bone deposition is enhanced by the high pool of calcium ions

* more in next chapter

Bone formation
Similarity between the mineral phase of bone and the surface chemistry of bioactive materials no fibrous capsule formed around the implant Bone cells attach deposit extensive bone matrix directly on the material surface

Histomicrograph of rabbit femoral bone defect grafted with bioactive glass granules for 3 weeks. The spaces between the bioactive glass particles (G) are filled with new mature bone tissue (B) containing Haversian systems and blood vessels.

The interface between PMMA bone cement and bone after 2 weeks of implantation in the cortical bone of the tibial diaphysis in goats. A thin fibrous layer (arrow heads) was always present at the interface between bone and PMMA implant

Bone formation..*
Bioactive ceramic stimulation of the activity of bone cells in contact also stimulation away from the material surface Surface of the granules of bioactive ceramic new bone formation starts fills the space between the granules Bone growth inside pores begins at the wall of the pores grows until it fills the pores Resorbable bioactive ceramics graft material resorbs space for bone cells to deposit new bone allows complete tissue regeneration

Histomicrograph of a critical size bone defect created in the rabbit femur and grafted with granules of silicacalcium phosphate nanocomposite (SCPC75) for 3 weeks. The grafted defect was extensively filled with new bone. ( : vascular cavities; * : new bone) * more in next chapter

Testing bioactivity in vitro

Study of the formation of the hydroxyapatite (HA):
immersing the material in physiological solution (SFB) analyzing the material surface analyzing the composition of the solution

Bioactive ceramic in SBF a HA layer on the material surface similar to that of biological apatite
The ionic concentration of simulated body fluid and human blood plasma

very

Testing bioactivity in vitro

HA surface layer in SBF vivo ability of the material to bond to bone in

Rate of formation of the HA surface layer in SBF correlates well with the rate of bone bonding in vivo a measure of the degree of bioactivity of bone implant materials Two components involved in deposition of HA layer in-vitro: Dissolution of the material surface Precipitation of a Ca-P layer Dissolution of Ca and P ions increase in the local ionic concentration at the implant interface the precipitation of amorphous calcium phosphate layer matures by time to the more thermodynamically stable HA

Bioactive Glasses
Composition of Bioactive Glasses:
Most common components of bioactive glass are SiO2, CaO,Na2O, and P2O5 SiO2 content determines the chemical stability and bioactivity of the glass SiO2 content larger than 60 wt% is chemically stable not bioactive (region B) Glass with 45wt% SiO2 is highly bioactive (A)
A ternary phase diagram for silicate glass in the system SiO2Na2OCaO. The composition of a bioactive glass containing 24.5% Na2O, 24.5% CaO, and 45% SiO2 in weight percent Phase diagrams for Na2OCaOSiO2 showing four composition regions A, B, C, D, and the corresponding bone-bioactivity property (C: resorbable D: devitrification)

Bioactive Glasses..
Structure of Bioactive Glass:
An amorphous material with short range atomic order SiO2 serves as a network former, responsible for chemical stability CaO and Na2O serve as network modifiers Two types of oxygen, bridging and nonbridging Ratio of bridging oxygen to non bridging oxygen controls the rate of bioactivity reaction in vitro and the resorbability
schematic showing the silicate structure of bioactive glass. The bridging oxygen in the SiOSi bond stabilizes the material. Non-bridging oxygen in the -SiONa and -SiOCa- enhances the dissolution in physiological solutions.

Decrease in concentration of the SiO2 Increase in Na2O or CaO Increase in the rate of reactivity

In Vitro Bioactivity
Ion exchange and dissolution precipitation reaction:
Ionic character in NaO bond is high (85%) Na ions can easily exchange with H+ ion of the H2O of tissue fluid 45% of Si-O bond is covalent limits the dissolution of silica Dual effects of enhanced release of Na ions: material surface rich on SiO-. . .+H groups Increase in the pH of the interfacial fluids Surface SiOH and the alkaline pH synergistically enhance the precipitation of a Ca-P

A schematic showing the surface modifications of bioactive glass due to interaction with simulated body fluid.

Effect of glass processing on bioactivity

Melting method:

Bioactive glass is usually prepared by melting

Source: 99.9% pure sand for SiO2, Corresponding carbonate compound for Na2O and CaO CaCO3 CaO + CO2

Na2CO3

Na2O +CO2

Processing steps

Byproduct CO2 diffuses as bubbles through the glass melt help to mix melt Prepared Bioactive glass is dense and free of organic components and water Granules have better bioactivity than bulk
Chemical composition and selected raw materials

Effect of preparation methods.

Solgel method:
Precursors: tetraethoxysilane (TEOS, Si(OC2H5)4) which is usually reacted with soluble salts of sodium (NaCl) and calcium (Ca2NO3) Various forms of hydrolysis and polycondensation reactions take place Hydrolyzation: Si(O - C2H5)4 + 4H2O Si(OH)4 + 4C2H5OH (ethanol) (OH)3Si (O Si-O)n- Si(OH)3 Condensation: (OH)3Si OH + HO Si(OH)3 Particles in the sol form long polymers Ageing process to allow for complete cross-linking of the silicate Gel is typically heated to 110 oC in order to remove water and alcohol

Na and Ca ions are added slowly during the hydrolysis step

Annealed in temperature range 350-700 oC to obtain glass

Advantages over melting process: purity of the final product, tailoring of the compositional range , absence of Na (sodium)

Bioactive Glass Ceramics

Thermal treatment of bioactive glass transformation from amorphous to crystalline Bioactive Glass Ceramics Significant improvement in the mechanical strength used in load bearing applications; however, there is typically a reduction in reactivity.

Mechanical properties of A/W and bioverit bioactive glass ceramics

Bioactive Glass Ceramics

Crystallization of bioactive glass slows down the surface reactivity reduction in the dissolution rate

Significant decrease in the solubility of bioactive glass as the percentage of crystallization increased

Calcium Phosphate Ceramics

Calcium phosphates are crystalline; Chemical composition similar to mineral phase of bone capable of inducing a direct bond with bone A variety of calcium phosphate ceramics exist hydroxyapatite (HA) and tricalcium phosphate (TCP) most used

Concentration of the inorganic components of enamel, dentin, bone, and stoichiometric HA

Composition of Hydroxyapatite

Stoichiometric HA has a rigid hexagonal di -pyramidal crystalline structure Molecular formula: Ca5(PO4)3OH Unit cell: ten Ca ions (10 Ca+2) Stoichiometry of HA Non-stoichiometric HA dissolution Chemical formula: Ca10(PO4)6(OH)2 enhanced exact atomic ratio of Ca/P (10/6 or 1.67) in the unit cell destabilization of the crystal

Non-stoichiometric HA : more reactive (and thus, bioactive)

Structure of hydroxyapatite

(a) Defect-free 1 X 1 X 2 supercell of the monoclinic modification of hydroxyapatite as obtained from full geometry optimization. The phosphate ions are illustrated as transparent tetrahedra. Two types of calcium ions are discriminated, that is, Ca(1) sites which are located between the phosphate ions and Ca(2) sites which form staggered triangles (dashed lines) resulting in channels parallel to the c-axis. (b) illustrates that each Ca(2)-triangle embeds a hydroxide ion.

Preparation of Hydroxyapatite

Solid state reaction between Ca(OH)2 or CaCO3 and CaHPO4.2H2O or -Ca3(PO4)2 above 950 oC forms HA Wet precipitation method: 10Ca(OH)2 + 6H3PO4 Ca10(PO4)6(OH)2 + 18H2O An alternate method (pH~11):
10Ca(NO3)2.4H2O + 6NH4.2HPO4 + 8NH4OH Ca10(PO4)6(OH)2 + 20NH4NO3 + 6H2O

Precipitate is dried and calcined at 400 oC for 1 h to obtain HA The nature and crystallinity depends on processing parameters, temperature, pH, and reaction durations

X-ray diffraction pattern of hydroxyapatite prepared by wet method and sintered at 1200 C

Composition and Structure of -TCP

Three polymorphic structures of TCP: -TCP, -TCP, and -TCP All have higher resorption rate than most other calcium phosphate ceramics -TCP and to a lesser extent -TCP are widely used as bone grafts Stoichiometric formula of -TCP is Ca3(PO4)2; Ca/P ratio 1.5

Bioactivity of TCP
Dissolution, precipitation, and ion exchange in physiological media Calcium phosphate ceramics can be transformed into biological apatite Substitution of Ca by Mg, Zn, Si, and Y enhance the solubility and bioactivity Dissolution rate of calcium: TTCP > -TCP > OHA > -TCP > CDHA > s-HA Dissolution rate of phosphate: TTCP > OHA > s-HA > CDHA > -TCP > -TCP The degradation of HA composition, crystal size, porosity, and preparation methods Amorphous HA: gradual surface degradation; crystalline HA: negligible degradation

Apatite Formation and Bone Bioactivity of -TCP

Bone-bonding ability of -TCP is well documented Considerable debate on the apatite forming ability of -TCP upon immersion in SBF

SEM images of apatite growth on the surface of -TCP when soaked in SBF

Differences in the experimental design, conditions discrepancies in the results related to the in vitro deposition of the HA surface layer Degradation of TCP is solution-mediated and cell-mediated

Apatite Formation..
Doping with metal ions (Mg, Zn, Sr, Si): stabilization of -TCP structure The ability of calcium phosphate ceramics to adsorb proteins is an important factor that mediates initial cell response to the material

Decrease in the dissolution rate of -TCP upon substitution of Ca with 0.11.0 mol Zn

Histogram showing the adsorption of (a) fibronectin and (b) BMP-2 on various biphasic ceramics. The biphasic ceramics are (1) 100% HA; (2) 95% HA/5% -TCP; (3) 25%-TCP/70% TCP/5% Ca2P2O7; (4) 30%-TCP, 70%-TCP; (5) 90%-TCP/ 10% HA, and (6) 85%-TCP/15%HA

Silica-Calcium Phosphate Nanocomposite

Composition
SCPC is a family name for a series of compositions in a multi-phase bioactive ceramic system

Chemical composition in mol% of selected formulations of silica-calcium phosphate nanocomposite

Excellent bioactivity of Si rich SCPC are due to physicochemical properties of its phases and the controlled release of Si from the substrate The crystalline structure of SCPC is complex, as it contains solid solutions instead of pure phases Highly defective and immature phases; poor crystallization at low temperature synthesis

Crystalline Structure

Structure and Bioactivity Relationship

The grain size of the SCPC75 is 50nm high density of grain boundaries preferential sites for protein adsorption and cell adhesion Maximum counts for Ca, Na, and P at grain boundaries ; maximum Si in bulk

a) A grain boundary in the SCPC nanocomposite. (b) Lorentzian fitting curves of elemental distributions along the grain boundary in (a). X-ray microanalysis showed that the grain boundary had maximum counts for Ca, Na, and P, whereas the grain bulk was rich in Si.

Structure and Bioactivity Relationship

Effect on bone cell function and tissue formation:
Two crystalline phases: -NaCaPO4 ss and -cristobalite (SiO2) ss relayed to the effect on bone cell function and tissue formation -NaCaPO4 ss phase: enhanced bioactivity due to Na stimulatory effect on the differentiation of human bone-derived cells, inducing mRNA and protein expression osteoblast differentiation SCPC has high porosity high protein adsorption and cell adhesion

(a) SEM micrographs of the SCPC at different magnifications: a- two pores 100 mm in diameter on the surface of the material. b- the walls of the large pores are very porous. c- higher magnification of the wall of the pores showing homogeneously distributed interconnected pores 3 mm in diameter (arrows). d- single hexagonal calcium phosphate crystals (0.7 mm) (white arrows) and round-shaped silica crystals (0.2 mm)(black arrows) are in close contact. (b) TEM micrograph of the porous structure of SCPC showing nanopores in the size range 50100 nm