Bioactive ceramicsBioactive ceramics

Bioactive ceramicsBioactive ceramics

• Bioactive ceramics: calcium phosphates, Bioactive ceramics: calcium phosphates,

bioactive glasses, and bioactive glass bioactive glasses, and bioactive glass

ceramicsceramics

• Common property: ability to bond to Common property: ability to bond to

bone and enhance bone tissue formationbone and enhance bone tissue formation

• Structural and compositional variations Structural and compositional variations

rate of bone bonding, the stimulatory rate of bone bonding, the stimulatory

effect on cell function, and the effect on cell function, and the

resorbability vary resorbability vary

Chemical composition of selected bioactive ceramics

Bioactivity *Bioactivity *

• Bioactivity property: ability of the materials to bond directly Bioactivity property: ability of the materials to bond directly to bone and enhance bone formationto bone and enhance bone formation

• Bioactive ceramics are characterized by a dynamic surfaceBioactive ceramics are characterized by a dynamic surface

• Ionic dissolution of the material surface precipitation of Ionic dissolution of the material surface precipitation of a calcium phosphate (Ca-P) layera calcium phosphate (Ca-P) layer

• Dissolution property:Dissolution property:

» Bioactive glass > Hydroxyapatite > Bioactive glass ceramicBioactive glass > Hydroxyapatite > Bioactive glass ceramic

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

• Deposited Ca-P mimic those of the mineral phase of bone in Deposited Ca-P mimic those of the mineral phase of bone in many aspectsmany aspects

• Bone deposition is enhanced by the high pool of calcium ionsBone deposition is enhanced by the high pool of calcium ions

* more in next chapter* more in next chapter

Bone formationBone formation• Similarity between the mineral phase of bone and the surface chemistry Similarity between the mineral phase of bone and the surface chemistry

of bioactive materials no fibrous capsule formed around the implantof bioactive materials no fibrous capsule formed around the implant• Bone cells attach deposit extensive bone matrix directly on the Bone cells attach deposit extensive bone matrix directly on the

material surfacematerial surface

Histomicrograph of rabbit femoral bone defect grafted with bioactive glass granules for 3 weeks. The spaces between thebioactive 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..*Bone formation..*

• Bioactive ceramic stimulation of the Bioactive ceramic stimulation of the activity of bone cells in contact activity of bone cells in contact also stimulation away from the also stimulation away from the material surfacematerial surface

• Surface of the granules of bioactive Surface of the granules of bioactive ceramic new bone formation starts ceramic new bone formation starts fills the space between the fills the space between the granulesgranules

• Bone growth inside pores begins at Bone growth inside pores begins at the wall of the pores grows until it the wall of the pores grows until it fills the poresfills the pores

• Resorbable bioactive ceramics Resorbable bioactive ceramics graft material resorbs space for graft material resorbs space for bone cells to deposit new bone bone cells to deposit new bone allows complete tissue regenerationallows complete tissue regeneration

Histomicrograph of a critical size bone defect created in the rabbit femur and grafted with granules of silica–calcium phosphate nanocomposite (SCPC75) for 3 weeks. The grafted defect wasextensively filled with new bone.( : vascular cavities; * : new bone)

* more in next chapter* more in next chapter

Testing bioactivity in vitroTesting bioactivity in vitro• Study of the formation of the hydroxyapatite (HA):Study of the formation of the hydroxyapatite (HA):

» immersing the material in physiological solution (SFB)immersing the material in physiological solution (SFB)

» analyzing the material surfaceanalyzing the material surface

» analyzing analyzing the composition of the solutionthe composition of the solution

• Bioactive ceramic in SBF a HA layer on the material surface very Bioactive ceramic in SBF a HA layer on the material surface very similar to that of biological apatitesimilar to that of biological apatite

The ionic concentration of simulated body fluid and human blood plasma

Testing bioactivity in vitroTesting bioactivity in vitro

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

vivovivo

• Rate of formation of the HA surface layer in SBF correlates well with the 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 rate of bone bonding in vivo a measure of the degree of bioactivity

of bone implant materialsof bone implant materials

• Two components involved in deposition of HA layer Two components involved in deposition of HA layer in-vitro:in-vitro:

» Dissolution of the material surfaceDissolution of the material surface

» Precipitation of a Ca-P layerPrecipitation of a Ca-P layer

• Dissolution of Ca and P ions increase in the local ionic Dissolution of Ca and P ions increase in the local ionic

concentration at the implant interface the precipitation of concentration at the implant interface the precipitation of

amorphous calcium phosphate layer matures by time to the more amorphous calcium phosphate layer matures by time to the more

thermodynamically stable HAthermodynamically stable HA

Bioactive GlassesBioactive GlassesComposition of Bioactive Glasses:Composition of Bioactive Glasses:• Most common components of bioactive glass Most common components of bioactive glass

are SiOare SiO22, CaO,Na, CaO,Na22O, and PO, and P22OO55

• SiOSiO22 content determines the chemical content determines the chemical

stability and bioactivity of the glassstability and bioactivity of the glass

• SiOSiO22 content larger than 60 wt% is chemically content larger than 60 wt% is chemically

stable not bioactive (region B)stable not bioactive (region B)

• Glass with 45wt% SiOGlass with 45wt% SiO22 is highly bioactive (A) is highly bioactive (A)

A ternary phase diagram for silicate glass in the system SiO2–Na2O–CaO. The composition of a bioactive glass containing 24.5% Na2O, 24.5% CaO, and 45% SiO2 in weight percent

Phase diagrams for Na2O–CaO–SiO2 showing fourcomposition regions A, B, C, D, and the corresponding bone-bioactivity property (C: resorbable – D: devitrification)

Bioactive Glasses..Bioactive Glasses..

Structure of Bioactive Glass:Structure of Bioactive Glass:

• An amorphous material with short range An amorphous material with short range

atomic orderatomic order

• SiOSiO22 serves as a network former, responsible serves as a network former, responsible

for chemical stabilityfor chemical stability

• CaO and NaCaO and Na22O serve as O serve as network modifiersnetwork modifiers

• Two types of oxygen, bridging and non-Two types of oxygen, bridging and non-

bridgingbridging

• Ratio of bridging oxygen to non bridging Ratio of bridging oxygen to non bridging

oxygen controls the rate of bioactivity oxygen controls the rate of bioactivity

reaction in vitro and the resorbabilityreaction in vitro and the resorbability

• Decrease in concentration of the SiODecrease in concentration of the SiO2 2

Increase in NaIncrease in Na22O or CaO Increase in the O or CaO Increase in the

rate of reactivityrate of reactivity

schematic showing the silicate structure of bioactive glass. The bridging oxygen in the Si–O–Si bond stabilizes the material.Non-bridging oxygen in the -Si–O–Na and -Si–O–Ca- enhances thedissolution in physiological solutions.

In Vitro BioactivityIn Vitro Bioactivity

Ion exchange and dissolutionIon exchange and dissolution

precipitation reaction:precipitation reaction:• Ionic character in Na–O bond is high Ionic character in Na–O bond is high

(85%) Na ions can easily exchange (85%) Na ions can easily exchange with Hwith H++ ion of the H ion of the H22O of tissue fluidO of tissue fluid

• 45% of Si-O bond is covalent limits 45% of Si-O bond is covalent limits the dissolution of silicathe dissolution of silica

• Dual effects of enhanced release of Na Dual effects of enhanced release of Na ions:ions:

» material surface rich on Si–Omaterial surface rich on Si–O--. . .. . .++H H groupsgroups

» Increase in the pH of the interfacial Increase in the pH of the interfacial fluidsfluids

• Surface Si–OH and the alkaline pH Surface Si–OH and the alkaline pH synergistically enhance the precipitation synergistically enhance the precipitation of a Ca-Pof a Ca-P

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

Effect of glass processing on bioactivityEffect of glass processing on bioactivity

Melting method:Melting method:

• Bioactive glass is usually prepared by meltingBioactive glass is usually prepared by melting

• Source: 99.9% pure sand for SiOSource: 99.9% pure sand for SiO2, 2, Corresponding Corresponding

carbonate compound for Nacarbonate compound for Na22O and CaOO and CaO

CaCOCaCO33 CaO + CO CaO + CO22

Na2CO3 Na2O +CO2Na2CO3 Na2O +CO2

• Byproduct CO2 diffuses as bubbles through the Byproduct CO2 diffuses as bubbles through the glass melt help to mix meltglass melt help to mix melt

• Prepared Bioactive glass is dense and free of Prepared Bioactive glass is dense and free of organic components and waterorganic components and water

• Granules have better bioactivity than bulk Granules have better bioactivity than bulk

Processing steps

Chemical composition and selected raw materials

Effect of preparation methods…. Effect of preparation methods….

Sol–gel method:Sol–gel method:

• Precursors: tetraethoxysilane (TEOS, Si(O–CPrecursors: tetraethoxysilane (TEOS, Si(O–C22HH55))44) which is usually reacted with ) which is usually reacted with

soluble salts of sodium (NaCl) and calcium (Casoluble salts of sodium (NaCl) and calcium (Ca22NONO33))

• Various forms of hydrolysis and polycondensation reactions take placeVarious forms of hydrolysis and polycondensation reactions take place

• Hydrolyzation: Si(O - CHydrolyzation: Si(O - C22HH55))44 + 4H + 4H22O Si(OH)O Si(OH)44 + 4C + 4C22HH55OH (ethanol)OH (ethanol)

• Condensation: (OH)Condensation: (OH)33Si – OH + HO – Si(OH)Si – OH + HO – Si(OH)33 (OH) (OH)33Si – (O – Si-O)Si – (O – Si-O)nn- Si(OH)- Si(OH)33

• Na and Ca ions are added slowly during the hydrolysis stepNa and Ca ions are added slowly during the hydrolysis step

• Particles in the sol form long polymersParticles in the sol form long polymers

• Ageing process to allow for complete cross-linking of the silicateAgeing process to allow for complete cross-linking of the silicate

• Gel is typically heated to 110 Gel is typically heated to 110 ooC in order to remove water and alcoholC in order to remove water and alcohol

• Annealed in temperature range 350-700 Annealed in temperature range 350-700 ooC to obtain glassC to obtain glass

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

Bioactive Glass CeramicsBioactive Glass Ceramics

• Thermal treatment of bioactive glass transformation from amorphous to Thermal treatment of bioactive glass transformation from amorphous to crystalline Bioactive Glass Ceramicscrystalline Bioactive Glass Ceramics

• Significant improvement in the mechanical strength used in load bearing Significant improvement in the mechanical strength used in load bearing applications; however, there is typically a reduction in reactivity.applications; however, there is typically a reduction in reactivity.

Mechanical properties of A/W and bioverit bioactive glass ceramics

Bioactive Glass CeramicsBioactive Glass Ceramics

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

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

Calcium Phosphate CeramicsCalcium Phosphate Ceramics

• Calcium phosphates are crystalline; Chemical composition similar to mineral Calcium phosphates are crystalline; Chemical composition similar to mineral phase of bone capable of inducing a direct bond with bonephase of bone capable of inducing a direct bond with bone

• A variety of calcium phosphate ceramics exist hydroxyapatite (HA) and A variety of calcium phosphate ceramics exist hydroxyapatite (HA) and tricalcium phosphate (TCP) most used tricalcium phosphate (TCP) most used

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

Composition of HydroxyapatiteComposition of Hydroxyapatite

• Stoichiometric HA has a rigid hexagonal di -pyramidal crystalline structureStoichiometric HA has a rigid hexagonal di -pyramidal crystalline structure

• Molecular formula: CaMolecular formula: Ca55(PO(PO44))33OHOH

• Unit cell: ten Ca ions (10 CaUnit cell: ten Ca ions (10 Ca+2+2) Chemical formula: Ca) Chemical formula: Ca1010(PO(PO44))66(OH)(OH)22

• Stoichiometry of HA exact atomic ratio of Ca/P (10/6 or 1.67) in the unit cellStoichiometry of HA exact atomic ratio of Ca/P (10/6 or 1.67) in the unit cell

• Non-stoichiometric HA destabilization of the crystal enhanced Non-stoichiometric HA destabilization of the crystal enhanced dissolutiondissolution

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

Structure of hydroxyapatiteStructure 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 HydroxyapatitePreparation of Hydroxyapatite

• Solid state reaction between Ca(OH)Solid state reaction between Ca(OH)22 or CaCO or CaCO33 and CaHPO and CaHPO44.2H2O or β-.2H2O or β-

CaCa33(PO4)(PO4)22 above 950 above 950 ooC forms HAC forms HA

• Wet precipitation method: Wet precipitation method: 10Ca(OH)10Ca(OH)2 2 + 6H+ 6H33POPO44 Ca Ca1010(PO(PO44))66(OH)(OH)2 2 + 18H+ 18H22OO

• An alternate method (pH~11):An alternate method (pH~11):» 10Ca(NO10Ca(NO33))22.4H2O + 6NH.4H2O + 6NH44.2HPO.2HPO44 + 8NH + 8NH44OH CaOH Ca1010(PO(PO44))66(OH)(OH)2 2 + 20NH+ 20NH44NONO33 + 6H + 6H22OO

• Precipitate is dried and calcined at 400 Precipitate is dried and calcined at 400 ooC for 1 h to obtain HAC for 1 h to obtain HA

• The nature and crystallinity depends on processing parameters, temperature, The nature and crystallinity depends on processing parameters, temperature, pH, and reaction durations pH, and reaction durations

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

Composition and Structure of β-TCPComposition and Structure of β-TCP

• Three polymorphic structures of TCP: β-TCP, α-TCP, and α’-TCPThree polymorphic structures of TCP: β-TCP, α-TCP, and α’-TCP

• All have higher resorption rate than most other calcium phosphate ceramicsAll have higher resorption rate than most other calcium phosphate ceramics

• β-TCP and to a lesser extent α-TCP are widely used as bone graftsβ-TCP and to a lesser extent α-TCP are widely used as bone grafts

• Stoichiometric formula of β-TCP is CaStoichiometric formula of β-TCP is Ca33(PO4)(PO4)22; Ca/P ratio 1.5; Ca/P ratio 1.5

Bioactivity of TCPBioactivity of TCP

• Dissolution, precipitation, and ion exchange in physiological Dissolution, precipitation, and ion exchange in physiological media Calcium phosphate ceramics can be transformed media Calcium phosphate ceramics can be transformed into biological apatiteinto biological apatite

• Substitution of Ca by Mg, Zn, Si, and Y enhance the solubility Substitution of Ca by Mg, Zn, Si, and Y enhance the solubility and bioactivityand bioactivity

• Dissolution rate of calcium:Dissolution rate of calcium:

» TTCP > α-TCP > OHA > β-TCP > CDHA > s-HATTCP > α-TCP > OHA > β-TCP > CDHA > s-HA

• Dissolution rate of phosphate:Dissolution rate of phosphate:

» TTCP > OHA > s-HA > CDHA > α-TCP > β-TCPTTCP > OHA > s-HA > CDHA > α-TCP > β-TCP

• The degradation of HA composition, crystal size, The degradation of HA composition, crystal size, porosity, and preparation methodsporosity, and preparation methods

• Amorphous HA: gradual surface degradation; crystalline HA: Amorphous HA: gradual surface degradation; crystalline HA: negligible degradation negligible degradation

Apatite Formation and Bone Bioactivity of β-TCPApatite Formation and Bone Bioactivity of β-TCP

• Bone-bonding ability of β-TCP is well documentedBone-bonding ability of β-TCP is well documented

• Considerable debate on the apatite forming ability of β-TCP upon immersion in Considerable debate on the apatite forming ability of β-TCP upon immersion in SBFSBF

• Differences in the experimental design, conditions discrepancies in the Differences in the experimental design, conditions discrepancies in the results related to the in vitro deposition of the HA surface layerresults related to the in vitro deposition of the HA surface layer

• Degradation of TCP is solution-mediated and cell-mediated Degradation of TCP is solution-mediated and cell-mediated

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

Apatite Formation….. Apatite Formation…..

• Doping with metal ions (Mg, Zn, Sr, Si): stabilization of β-TCP structureDoping with metal ions (Mg, Zn, Sr, Si): stabilization of β-TCP structure

• The ability of calcium phosphate ceramics to adsorb proteins is an important The ability of calcium phosphate ceramics to adsorb proteins is an important factor that mediates initial cell response to the materialfactor that mediates initial cell response to the material

Decrease in the dissolution rate of β-TCP upon substitution of Ca with 0.1–1.0 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% β-TCP; (3) 25%β-TCP/70% α-TCP/5% Ca2P2O7; (4) 30%β-TCP, 70%α-TCP; (5) 90%β-TCP/ 10% HA, and (6) 85%β-TCP/15%HA

Silica-Calcium Phosphate NanocompositeSilica-Calcium Phosphate Nanocomposite

CompositionComposition• SCPC is a family name for a series of compositions in a multi-phase bioactive SCPC is a family name for a series of compositions in a multi-phase bioactive

ceramic systemceramic system

• Excellent bioactivity of Si rich SCPC are due to physicochemical properties of Excellent bioactivity of Si rich SCPC are due to physicochemical properties of its phases and the controlled release of Si from the substrateits phases and the controlled release of Si from the substrate

Crystalline StructureCrystalline Structure• The crystalline structure of SCPC is complex, as it contains solid solutions The crystalline structure of SCPC is complex, as it contains solid solutions

instead of pure phasesinstead of pure phases

• Highly defective and immature phases; poor crystallization at low temperature Highly defective and immature phases; poor crystallization at low temperature synthesissynthesis

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

Structure and Bioactivity RelationshipStructure and Bioactivity Relationship

• The grain size of the SCPC75 is 50nm high density of grain boundaries The grain size of the SCPC75 is 50nm high density of grain boundaries preferential sites for protein adsorption and cell adhesionpreferential sites for protein adsorption and cell adhesion

• Maximum counts for Ca, Na, and P at grain boundaries ; maximum Si in bulkMaximum 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 RelationshipStructure and Bioactivity Relationship

Effect on bone cell function and tissue formation:Effect on bone cell function and tissue formation:• Two crystalline phases: β-NaCaPOTwo crystalline phases: β-NaCaPO44 ss and α-cristobalite (SiO2) ss relayed to ss and α-cristobalite (SiO2) ss relayed to

the effect on bone cell function and tissue formationthe effect on bone cell function and tissue formation

• β-NaCaPOβ-NaCaPO44 ss phase: enhanced bioactivity due to Na stimulatory effect on ss phase: enhanced bioactivity due to Na stimulatory effect on

the differentiation of human bone-derived cells, inducing mRNA and protein the differentiation of human bone-derived cells, inducing mRNA and protein expression osteoblast differentiationexpression osteoblast differentiation

• SCPC has high porosity high protein adsorption and cell adhesionSCPC has high porosity high protein adsorption and cell adhesion

(a) SEM micrographs of the SCPC at different magnifications: a- two pores 100 m 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 m in diameter (arrows). d- single hexagonal calcium phosphate crystals (0.7 m) (white arrows) and round-shaped silica crystals (0.2 m)(black arrows) are in close contact. (b) TEM micrograph of the porous structure of SCPC showing nanopores in the size range 50–100 nm