Ceramic Degradation and Calcification

Question 1

Ceramic Resistance to Corrosion

Answer 1

• Either HIGHLY corrosion resistant or highly soluble (can quickly dissolve/erode)
• Ceramics/glasses ARE corroded metals, so represent a lower energy state

Question 2

Ceramics/Bioceramics Applications and Characteristics

Answer 2

• used in orthopedics and dentistry
• high melting temperatures, low thermal/electric conductivity, high hardness and compression strength, low tensile strength/plastic deformation, wettability/low friction

Question 3

General Reactivity:

Answer 3

• Bioinert (1st generation): sintered/fused oxides, elicit an immune response and forms a fibrous capsule
• Bioactive (2nd gen): surface reactivity promotes binding to bone/soft tissues, lack fibrous scar layer
• Resorbable (3rd gen, and porous 2nd gen): ionically bonded materials that are stable in air, dissolve in bodily fluid
• chemical composition and microstructure are important at determining degradation rates (STUDY IMAGE)

Question 4

More on Degradation:

Answer 4

• in orthopedics, joint replacements use inert ceramics, while bone-contacting parts utilize bioactive or resorbable
• Effect of crystallinity: highly crystalline are more prone to inertness, while glasses have specific composition need to be bioactive
• Effect of particle size: bioactive glasses with particles < 90 micrometers are resorbable, while hydroxyapatite requires particles of < 10 micrometers
• Also, surface area and porosity

Question 5

Calcification/Mineralization

Answer 5

• occurs on both synthetic and natural biomaterials, in the circulatory system and at other sites
• causes stiffening of materials, blockage of valves/stents, and clouding of lenses
• ‘ectopic’ mineralization (outside of musculoskeletal and dental systems), causes severe consequences

Question 6

Pathologic Calcification in mature mineral phase

Answer 6

• Poorly crystalline calcium phosphate
• Dystrophic calcifications: in damaged/diseased tissues or related to biomaterials
• Metastatic: in otherwise normal tissue in individuals with elevated mineral metabolism
• rate of dystrophic calcification still accelerated in a patient with high calcium/phosphorous serum levels (elevated metabolism, like kidney failure or osteoporosis)

Question 7

Principal sites?

Answer 7

• Cells and ECM of dead tissues
• intrinsic calcification occurs within the tissue, extrinsic occurs at the surface associated with attached cells/proteins

Question 8

Heart Valves

Answer 8

• Disorders can cause stenosis (obstructing flow) or regurgitation (reverse flow)
• Bioprosthetic heart valves have three leaflets of tissues of glutaraldehyde-treated porcine/bovine material (lowers immunogenicity and kills cells)
• mounted on metal/plastic stent with three struts, and a base ring covered by sewing cuff

Question 9

Heart Valve calcification

Answer 9

• calcific degeneration of the bioprosthetic heart valves is a significant problem, usually deposits occur at “commissures” (whether branches meet)
• half of these fail within 12-15 years
• rapid in young patients, almost always failure in < 4 years
• can try using human allograft valves (difficulty finding correct size, proper donor in given time frame)
• also occurs on polymeric heart valves and flexing surface of blood pumps

Question 10

Calcification of other implants/devices

Answer 10

• Breast implants: calcified plaques at interface of fibrous capsule and implant surface (in 100% implanted for more than 23 years)
• Intrauterine contraceptive devices: could prevent release of active contraceptive agent
• Urinary Stents/Prostheses: mineral crust forms, can lead to obstruction and failure
• Soft lenses: lens opacity develops, high calcium in tear fluid

Question 11

Mechanisms of Biomaterial Calcification

Answer 11

• Determined by mechanical factors, host factors, implant structure
• NO associated role for inflammation in promoting calcification

Question 12

Mechanical factors

Answer 12

• intrinsic and extrinsic mineralization occurs at sites of intense deformations
• dynamic stresses and static deformation also promote

Question 13

Host factors?

Answer 13

• Metabolism: calcification is more rapid in immature patients
• Both inductive and inhibitory biochemical factors (inhibitors include osteopontin and phosphocitrate, inducers include inorganic phosphate, phospholipids, and cytokines)
• Initial sites are dead cells and cell membrane fragments, as phospholipids can bind calcium and mitochondria are enriched in calcium
• fixation serves as mineralization nucleation sites
• fibers of ECM, denatured proteins, fatty acids, etc.

Question 14

Calcification Prevention

Answer 14

• Agents used to treat clinical bone disease would prevent, but they also impede growth and interfere with regular physiological calcification
• EHBP inhibits growth of crystals
• modifying treated implants with metal ions, or AOATM can prevent calcification (KNOW METHODS)
• can also pre-treat with SDS/other detergents to remove phospholipids and decellularize the tissue