Topics In Biomaterials: 8

Front 1

What are 6 requirements of natural biomaterials?

Back 1

1. Non-toxic

2. Non-inflammatory

3. Non-allergenic

4. Good mechanical properties

5. Induces cell attachment and differentiation (if needed)

6. Low cost

Front 2

What is the most abundant protein in the human body?

Back 2

Collagen at 30% of the total proteins in the body

Front 3

What is collagen used for in the body?

Back 3

Used for maintenance of structural integrity

Front 4

What can collagen do at a certain temperature? Why?

Back 4

At the shrinkage temperature, collagen can shrink to less than 33% of its original length due to the collapse of the triple helical structure.

Front 5

Collagen is referred to as what?

Back 5

Fibrous protein

Front 6

TRUE OR FALSE: Collagen is found in animals and plants.

Back 6

FALSE. Collagen is found exclusively in animals.

Front 7

Collagen is the primary protein of what 4 tissues?

Back 7

1. Skin

2. Bone

3. Tendon

4. Ligaments

Front 8

Collagen possesses what 3 desirable properties?

Back 8

1. Can be resorbed into the body

2. Non-toxic

3. Minimal immune response, even between different species

Front 9

Collagen exists in what 5 forms?

Back 9

1. Gel form (like in the ECM and eye)

2. Tight bundles of tendons

3. Stacked in the cornea

4. Fibers in the bones

5. Loose fibril network in the skin

Front 10

Collagen form is dictated by what?

Back 10

Their structural role in a particular organ

Front 11

Collagen fibrils are produced by what?

Back 11

Fibroblasts in which collagen is synthesized in the ER.

Front 12

What is the basic unit of collagen?

Back 12

Topocollagen which is made up of amino acids

Front 13

In order from smallest to largest, list the four steps of the hierarchy of collagen structures

Back 13

Amino acids --> Tropocollagen --> Fibrils --> Fibers

Front 14

In the ER, procollagen is known as what?

Back 14

pre-procollagen

Front 15

What is the first event that takes place in post-translational modification of collagen?

Back 15

Alpha peptide chains of glycine + Proline + hydroxyproline are formed

Front 16

What is the second event that takes place in post-translational modification of collagen?

Back 16

Hydroxylation and glycolysation takes place on the peptide chains:

Hydroxylation of proline and lysine

Glycolysation of hydroxyproline

Front 17

What is the third event that takes place in post-translational modification of collagen?

Back 17

Alpha chains are twisted around the central axis to form a triple-stranded left-handed helix

Front 18

Of the three alpha chains in each collagen molecule, two of the chains have how many amino acid residues? What are they called?

Back 18

1056 residues and are called alpha1-chains

Front 19

Of the three alpha chains in each collagen molecule, one chain has how many amino acid residues? What is it called?

Back 19

1029 residues and is called alpha2-chain

Front 20

Together, the triple helix of collagen is called what?

Back 20

A gamma-structure

Front 21

What is found in the interior of the helical structure of collagen? What are found on the outside?

Back 21

Glycine is found in the interior

Proline and hydroxyproline are pointed outward

Front 22

What 4 things further stabilize the triple helix structure of collagen?

Back 22

1. tight fit of amino acids in helix

2. Inter-H bonding between carbonyl O atom of proline (X residues) and adjacent amide H atom of glycine

3. Inter-H bonding between hydroxyl group of hydroxyproline and amide H atom of glycine

4. H20 presence to form inter-chain H bonding

Front 23

What is the difference between the polypeptide chains within the collagen molecule?

Back 23

The positions of the X and Y amino acids in the triple helix

Front 24

Once procollagen is packaged into transport vesicles, where does it go and why?

Back 24

It goes to the Golgi apparatus where oligosaccharides are added and secreted into the ECM

Front 25

How is tropocollagen formed?

Back 25

The trimeric globular C-propeptide and trimeric N-propeptide domains are cleave forming tropocollagen.

Front 26

What is the typical length and diameter of tropocollagen?

Back 26

300 nm long and 1.5 nm in diameter

Front 27

Tropocollagen self-assembles into what how?

Back 27

Self-assembles into fibrils by oxidative deamination of lysine and hydroxylysine using lysyl oxidase which forms aldol cross-linking

Front 28

Which types of collagen are fibril-forming?

Back 28

Types I, II, and III

Front 29

Which types of collagen are network-forming?

Back 29

Types IV and VII

Front 30

Which types of collagen are fibril-associated?

Back 30

Types IX and XII

Front 31

Depending on age and tissue, the diameter of Type I collagen is within what range?

Back 31

50 to 500 nm

Front 32

Where is Type I collagen found?

Back 32

Skin, dentin, cornea, blood vessels, bone, tendon, ligament, and fibrocartilage

Front 33

Which type of collagen is the most abundant collagen and the most predominant form used in biomedical applications?

Back 33

Type I

Front 34

TRUE OR FALSE: Telopeptides do not possess the triple-helical structure nor made up of repeating glycine-X-Y structures.

Back 34

TRUE

Front 35

Where is Type II collagen found?

Back 35

Articular cartilaginous tissues and inter-vertebral disks

Front 36

Type II collagen forms what structure?

Back 36

Dense network arrays of individual thin fibrils with an interfibrillar matrix made of proteoglycans, glycoproteins, non-collagenous proteins, and water.

Front 37

Type II collagen acts as what?

Back 37

Shock absorbers

Front 38

What does Type III collagen consist of?

Back 38

3 identical polypeptide alpha1 chains

Front 39

The elastic properties of type III collagen may be due to what?

Back 39

Disulfide bonds

Front 40

Where is Type III collagen found?

Back 40

Distensible tissues, fetal skin, blood vessels

Front 41

What is the second most abundant collagen found in humans?

Back 41

Type III

Front 42

Where is Type IV collagen found?

Back 42

In the basement membranes of the eye lens, walls of blood vessels, kidneys, and skin (beneath stratified squamous epithelia)

Front 43

Type IV collagen interacts with non-collagenous components to form what? What does this allow?

Back 43

Form meshes or networks allowing a filtration system for cells, molecules, and light.

Front 44

Type IV collagen consists of what?

Back 44

Polypeptide chains of dissimilar size

Front 45

What are the 2 disadvantages of using collagen?

Back 45

1. Unpredictable degradation rate

2. No adequate mechanical properties

Front 46

What are 4 biomedical uses of collagen?

Back 46

1. Artificial skin

2. Guided tissue regeneration membranes

3. Tube allographs for peripheral nerve regeneration

4. Carriers for BMP-2 in INFUSE

Front 47

What is Elastin?

Back 47

It is an insoluble, fibrous protein composed of fibrillin and soluble tropoelastin monomers containing about 786 amino acids.

Front 48

Elastin is found in organs requiring what 3 properties?

Back 48

1. Elasticity

2. Flexibility

3. Strength

Front 49

Elastin has resistance to what 3 things?

Back 49

1. Acid

2. Alkalis

3. Most proteolytic enzymes (except elastase)

Front 50

In Elastin, the elasticity of fibers is dependent on what?

Back 50

The entropy of the relaxation of elastin

Front 51

Where is Elastin found?

Back 51

Lungs, blood vessels, elastic ligaments and in small amounts in the ear and skin

Front 52

The presence of elastin allows organs to do what?

Back 52

Retain their shape after stretching or contracting

Front 53

Flexibility allows the organs to do what 3 things?

Back 53

1. Undergo repetitive strain and deformation without rupture

2. To store energy involved in deformation

3. to recover to their original state when stress is removed

Front 54

Tropoelastin is produced by what 4 things?

Back 54

1. Endothelial cells

2. Smooth muscle cells

3. Fibroblasts

4. Chondrocytes

Front 55

Is tropoelastin soluble or insoluble?

Back 55

Soluble

Front 56

Tropoelastin is rich in what 5 amino acids?

Back 56

Glycine, proline, lysine, valine, and alanine

Front 57

Is the tropoelastin amino acid sequence structured or unstructured?

Back 57

Unstructured

Front 58

Catalyzed by lysyl oxidases, elastin is stabilized how?

Back 58

By inter-chain cross-linking the side chains of lysine residues

Front 59

In tropoelastin, oxidative deamination converts the amine groups of lysine into what?

Back 59

Reactive aldehydes or allysine residues by lysyl oxidase

Front 60

In tropoelastin, what form a desmosine cross-link?

Back 60

3 allysyl side chains and 1 unaltered lysyl side chain

Front 61

Tropoelastin becomes highly what as a result of cross-linking?

Back 61

INSOLUBLE

Front 62

What aspect of elastin allows it to stretch and bend in any direction when stressed?

Back 62

It's relatively loose, highly interconnected, and rubbery network

Front 63

What are 5 similarities between collagen and elastin?

Back 63

1. Protein-based

2. Contains proline and lysine

3. Stable after cross-linking

4. Monomer secreted into EC space

5. Self-assembly and cross-linking occur in the EC space

Front 64

Is carbohydrates present in elastin? What about collagen?

Back 64

Elastin - NO

Collagin - YES

Front 65

How many types of elastin are there?

Back 65

1

Front 66

What are the types of cross links found in collagen and elastin?

Back 66

Collagen - Intramolecular aldol cross-links

Elastin - Intramolecular desmosine cross-links

Front 67

What are the 2 advantages of elastin?

Back 67

1. Ability to stretch and relax

2. High stability with half-life of 70 years

Front 68

What are 3 uses of elastin?

Back 68

1. Vascular stents

2. Skin repair

3. Cosmetic implantation

Front 69

What becomes a problem of elastin-based biomaterials in vivo? Why?

Back 69

Calcification because elastin serves as a nucleation site for mineralization

Front 70

Precipitation in synthetic elastin-like polypeptides as a result of a change in phase occurs when?

Back 70

When the mixture is heated above the lower critical solution temperature

Front 71

What is silk used for?

Back 71

Maintenance of structural integrity

Front 72

How is silk made?

Back 72

Made by silkworms, spiders, scorpions, mites, and flies

Front 73

Silk is composed of what 2 things?

Back 73

Sericin and fibroin

Front 74

Composition of sericin and fibrion is dependent on what?

Back 74

The location of the silk:

Outer layer of silk contains more sericin

Front 75

Silk may contain what 4 impurities?

Back 75

1. Carbohydrates

2. Waxes

3. Inorganic salts

4. Pigment

Front 76

Which is more soluble: sericin or fibroin?

Back 76

Sericin (but sericin is not soluble in cold water)

Front 77

What does Sericin do?

Back 77

It acts as a gum binder to surround the fibroin and for maintenance of structure

Front 78

What are 5 properties of sericin?

Back 78

1. Easily hydrolyzed

2. Resists oxidation

3. Antimicrobial

4. Easily absorbs and releases moisture

5. UV resistant

Front 79

Fibroin is made up of what 3 primary peptides?

Back 79

1. Heavy chain

2. Light chain

3. Fibrohexamerin

Front 80

What is fibrohexamerin?

Back 80

A glycoprotein linked by disulfide bonds

Front 81

What are the four regions of fibroin?

Back 81

3 Crystalline regions and 1 amorphous region

Front 82

What are the three crystalline regions of fibroin made of?

Back 82

Anti-parallel beta-sheet structures, primarily with Gly, Ala, Ser sequences

Front 83

Fibroin is considered to be what kind of polymer? Why?

Back 83

A block co-polymer because fibroin contains crystalline regions with amorphous regions.

Front 84

What allows silk to stretch?

Back 84

Bulky regions with valine and tyrosine that interrupt the beta-sheet

Front 85

The crystalline regions of fibroin are responsible for what 2 things?

Back 85

1. Tensile strength

2. Toughness

Front 86

Silk has what 7 properties?

Back 86

1. Insoluble in water, dilute acids, alkalis, and most organic solvents

2. Resistant to degradation

3. Hydrolyzable in concentrated sulfuric acid

4. Hygroscopic

5. Tensile strength of 650 MPa and modulus of 15 GPa (higher than steel)

6. Elastic

7. Poor conductor of electricity

Front 87

What does Region 1 of fibroin consist of?

Back 87

Highly crystalline region with repetative Gly-Ala-Gly-Ala-Gly-Ser sequence (GAGAGS)

Front 88

What does Region 2 of fibroin consist of?

Back 88

Less crystalline than region 1 but contains repetative GAGAGT or GAGAGVGT sequences

Front 89

What does Region 3 of fibroin consist of?

Back 89

Highly crystalline and contains AAS sequences

Front 90

What is Region 4 of Fibroin?

Back 90

Amorphous region with amino acid residues that are negatively charged, polar, hydrophobic and aromatic.

Front 91

Region 4 of Fibroin exhibits what?

Back 91

Helical, spring-like properties allowing the fibers to be elastic or extended

Front 92

Spider silk is composed of what?

Back 92

Long amino acid chains that form beta-pleated sheet crystals and amorphous or semi-amorphous regions or network chains

Front 93

What are beta-pleated sheet crystals?

Back 93

Stacks of amino acids rich in alternating G and Ala or Ala blocks

Front 94

What is the problem with spider silk?

Back 94

It's difficult to harvest thus cannot be produced large scale

Front 95

What are 5 uses of silk?

Back 95

1. Artificial tendons, ligaments

2. Tissue repair

3. Wound healing

4. Sutures for eye or neurosurgery

5. Substitute for kevlar fibre

Front 96

How does polymerization occur in chitosan?

Back 96

Linking monosaccharides together via O-glycosidic bonds between hydroxyl groups

Front 97

Chitosan is derived from what?

Back 97

Chitin

Front 98

What is a major tensile element of the exoskeleton?

Back 98

Chitin

Front 99

Chitin is made up of what?

Back 99

Long linear polymeric chains of N-acetyl-D-glucosamine

Front 100

Deacetylation of chitosan allows for what 4 things?

Back 100

1. Tighter packaging

2. Increased crystallinity

3. Different biodegradation rates

4. Different levels of osteogenesis

Front 101

What is the chemical difference between cellulose and chitosan?

Back 101

Chitosan has an amine group

Cellulose has a hydroxyl group

Front 102

What is the difference between cellulose and chitin?

Back 102

Cellulose has an hydroxyl group

Chitin has an acetyl group

Front 103

What are the 2 differences between chitin and chitosan?

Back 103

Chitosan has an amine group and no oxygen double bond

Chitin has an acetyl group and has an oxygen double bond

Front 104

Chitosan is made up of what?

Back 104

Linear polysaccharide chains of beta-1,4,D-glucosamine and N-acetyl-d-glucosamine.

Front 105

What is the degree of deacetylation?

Back 105

Is the measure of molar fraction of glucosamines to N-acetyl glucosamines in Chitosan.

Front 106

Chitosan possesses what 4 favorable properties for use as a biomaterial?

Back 106

1. Elicits minimal foreign body reaction

2. Can be dissolved in water, depending on pH

3. Has available side groups for attachment of growth factors

4. Controllable mechanical and biodegradation properties

Front 107

Although tougher and more flexible than ceramics, chitosan tends to be what?

Back 107

Tends to swell when immersed in physiologic solution and is mechanically weak.

Front 108

Degradation of chitosan is dependent on what?

Back 108

Its crystallinity and the degree of deacetylation.

Front 109

An increase in the degree of deacetylation causes what to crystallinity and rate of degradation?

Back 109

Increases crystallinity and decreases rate of degradation.

Front 110

Does cell viability improve on chitosan with higher degrees of deacetylation or lower degrees of deacetylation?

Back 110

Higher degrees!

Front 111

What is the formula for cellulose?

Back 111

(C6H10 O5)n

Front 112

Cellulose is what kind of compound?

Back 112

Beta-glucan

Front 113

Why is cellulose rigid and rod-like?

Back 113

Due to orientation of the glycosidic bond

Front 114

What is Cellulose?

Back 114

Highly abundant organic polymer found in cell walls of plants that is comprised of glucose units linked beta-1,4-glycosidic bonds

Front 115

Why does cellulose possess hygroscopic properties?

Back 115

Because of less crystalline regions that allow for swelling when immersed in water

Front 116

Extensive hydrogen bonding between cellulose chains causes native cellulose to be what?

Back 116

Roughly 70% crystalline

Front 117

What are three off label properties of cellulose?

Back 117

1. Tasteless

2. Odorless

3. Hydrophilic

Front 118

Where is Cellulose I found?

Back 118

Plants

Front 119

Cellulose I contains more of what kind of structure?

Back 119

More beta sheets than alpha helix

Front 120

Cellulose I consists of what kind of glucan chains?

Back 120

Parallel beta-1,4-linked

Front 121

Where is Cellulose II found?

Back 121

Algae, mold, and bacteria

Front 122

Cellulose II contains more of what kind of structure?

Back 122

More alpha helix than beta sheets

Front 123

Cellulose II consists of what kind of glucan chains?

Back 123

Anti-parallel beta-1,4 linked

Front 124

Why is Cellulose II thermodynamically stable?

Back 124

High hydrogen bonding

Front 125

Cellulose II can be converted from Cellulose I via what?

Back 125

Alkali treatment

Front 126

How is cellulose III formed?

Back 126

By treating Cellulose I and II with liquid ammonia

Front 127

How is cellulose IV formed?

Back 127

By heat treating Cellulose III.

Front 128

What are 4 uses of cellulose?

Back 128

1. Pill tablet binders (less viscous = rapid drug release)

2. Artificial skin

3. Hemodialysis membranes

4. Control of hemorrage during surgery

Front 129

TRUE OR FALSE: Chitosan is used in bulk.

Back 129

FALSE. It's too mechanically weak.

Front 130

What are 3 uses of chitosan?

Back 130

1. Gel to repair cartilage

2. Bandages

3. Scaffolds

Front 131

What is alginate?

Back 131

Non-branched polysaccharide polymers derived from bacterial and marine algae.

Front 132

Alginate is made up of what 2 monomers?

Back 132

1. B-D-mannuronic acid (M)

2. a-L-guluronic acid (G)

Front 133

Alginate monomers are epimers with a difference where?

Back 133

C5

Front 134

TRUE OR FALSE: a-L-guluronic acid (G) cannot be modified.

Back 134

TRUE

Front 135

How can M alginate be modified?

Back 135

It can undergo acetylation at C2 and C3 hydroxyl groups and undergo epimerization forming G monomers

Front 136

What are 8 properties of Alginate monomers?

Back 136

1. Dependent on co-monomer blocks and degree of acetylation

2. Non-toxic

3. Non-inflammatory

4. Hygroscopic

5. Easily processed in water

6. Biodegradable

7. Controllable porosity

8. Able to attach biological cues

Front 137

If the pH is too low, what happens to alginate?

Back 137

It shrinks and does not release encapsulated cells or growth factors

Front 138

If the pH is too high, what happens to alginate?

Back 138

Rapid degradation of alginate

Front 139

Hyaluronic acid is found naturally in what 7 places?

Back 139

1. ECM

2. Connective tissues

3. Epithelial tissues

4. Neural tissues

5. Synovial fluid

6. Vitreous humor

7. Umbilical cord

Front 140

Hyaluronic acid is made up of what 2 things?

Back 140

1. a-1,4-D-glucuronic acid

2. b-1,3-N-acetyl-D-glucosamine

Front 141

What are the 4 roles of hyaluronic acid?

Back 141

1. Viscoelastic property and ability to swell to serve as lubricant and shock absorber

2. Resistant to compression

3. Regulates tissue and matrix water during wound repair

4. Antioxidant effect and helps mediate inflammation

Front 142

What are 3 uses for hyaluronic acid?

Back 142

1. Lubricants and mechanical support

2. Viscoelastic gel for dermal ulcers, wounds, and burns

3. Opthalmic surgical aid in cataract extraction, intraocular lens implantation, and retinal attachment surgery

Front 143

What is Chondroitin Sulfate?

Back 143

Sulfated, unbranched polysaccharide polymer found in the ECM that is used for maintaining structural integrity of tissues

Front 144

Chondroitin Sulfate is made of what two things?

Back 144

1. N-acetyl-D-galactosamine

2. D-glucoronic acids

Front 145

Sulfation of the N-acetyl-D galacosamine in Chondroitin Sulfate occurs where?

Back 145

At the OH group in the C4 (type A) or C6 (type B) position

Front 146

What are 5 properties of Chondroitin Sulfate?

Back 146

1. Bind and modulate growth factors

2. Involved with cell adhesion, migration, proliferation, and differentiation

3. Non-immunogenic

4. Degradable in water

5. By-products are oligosaccharides

Front 147

What are 3 uses of Chondroitin Sulfate?

Back 147

1. Nutritional supplements for osteoarthritic patients

2. Delivery carrier for tissue engineering

3. Opthalmic applications due to viscoelastic properties

Front 148

Corals are found naturally in coral reefs as what?

Back 148

Crystalline calcium carbonate

Front 149

Depending on species, what percentage is the open pore structure of coral?

Back 149

20 to 80% open pores

Front 150

Depending on species, what is the pore size range of coral?

Back 150

150 um to 500 um

Front 151

What are 3 issues with using corals?

Back 151

1. Unstable if untreated

2. Brittle

3. Lacks mechanical integrity for load bearing applications

Front 152

What are 2 uses of corals?

Back 152

1. Fillings of defects in orthopedics, crainofacial bones, dental, neurosurgery (spinal)

2. Bone graft substitutes

Front 153

What improves the stability of coral?

Back 153

Hydrothermal treatment improves stability by converting CaCO3 to carbonated hydroxyapatite but it still has an unstable degradation time.