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Tissue Engineering 1 > Test 4 > Flashcards

Test 4 Flashcards

1
Q

Heart Pathway

A

Superior vena cava > right atrium > tricuspid valve > right ventricle > pulmonary valve > pulmonary artery > lungs > pulmonary veins > left atrium > mitral valve > left ventricle > aortic valve > aorta

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2
Q

Current Cardiac Regenerative Therapies

A

1) Multipotent stem cells
2) Pluripotent stem cells
3) Non-cell strategies

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3
Q

Cardiac Multipotent Stem Cells

A

Benefits: vascularization, immunoprivileged, improved cardiac function

Limitations: low cardiomyogenic potential, poor cell engraftment, limited proliferation potential

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4
Q

Cardiac Pluripotent Stem Cells

A

Benefits: high cardiomyogenic potential, good cell engraftment, unlimited proliferation

Limitations: slow, electrical instability, teratoma formation

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5
Q

Cardiac Non-Cell Strategies

A
  • Stimulation of endogenous cardiac repair (growth factors)
  • Direct reprogramming of fibroblasts into functional cardiomyocytes
  • Tissue Engineering
  • Exosomes derived from stem cells
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6
Q

Main Targets for Tissue Engineering in Heart

A

1) Blood vessels
2) Heart muscle - myocardium
3) Heart valves

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7
Q

4 Potential Cardiac TE Cells

A

1) Multipotent Adult Germline Stem Cells
2) Endothelial Progenitor Stem Cells
3) Very Small Embryonic-like Stem Cells
4) Endogenous Cardiac Stem Cells

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8
Q

FGF Biomolecule

A

-promotes proliferation and differentiation

of endothelial cells, smooth muscle cells, fibroblasts

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9
Q

Ang1, Ang2 Biomolecules

A

-stabilize blood vessels

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10
Q

PDGF, PDGFR Biomolecules

A

-recruit smooth muscle cells

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11
Q

VE-Cadherin, CD31 Biomolecule

A

-promote endothelial junction

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12
Q

Ehprin Biomolecule

A

-formation of veins and arteries

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13
Q

Plasminogen activator inhibit -1 Biomolecule

A

-stabilizes nearby vessels

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14
Q

TE Product Requirements: Biocompatibility

A
  • Minimize inflammatory/immunological response
  • Growth and healing capabilities
  • Tissue strength, stiffness, cellularity, composition, should be simillar to native tissue
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15
Q

TE Product Requirements: Functionality

A
  • Appropriate mechanical and hemodynamic functionality

- Must be durable

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16
Q

TE Product Requirements: Blood Vessels

A

-Must be able to withstand high-pressure fluid

dynamics, turbulence

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17
Q

TE Product Requirements: Valves

A

-Must be able to operate in a very dynamic and severe
environment
-Open and close at 1 Hz, exposed to
mechanical stresses, high-pressure fluid dynamics,
turbulence, etc

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18
Q

TE Product Requirements: Myocardium Patch

A
  • High vascularity is critical

- Mechanical and electrical anisotropy

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19
Q

3 Cardiac Biomaterials

A

1) Biodegradable polymers (PGA)
2) Hydrogels (collagen, fibrin, alginate)
3) Decellularized tissue (collagen, elastin, fibronecting)

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20
Q

Valve Replacement

A

1) Valves have complex architecture
2) TEHVs require complex molds
3) Cellularize with myofibroblasts to obtain a
functional valve

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21
Q

4 Limitations of Mechanical valves

A

1) Infections
2) Thromboembolism
3) Cannot grow
4) No self-repair capability

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22
Q

Limitation of Tissue-Engineered Valves

A

-Calcification of tissue

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23
Q

3 Main Approaches to Biological Heart Valves

A

1) Cell seeding of biodegradable valve matrices
2) Cell seeding of decellularized allograft or xenograft valves
3) Promote repopulation and adaptive remodeling of decellularized allograft valves

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24
Q

Bypass Vascular Grafts

A
  • Walls cellularized with smooth muscle cells
  • Lumen cellularized with endothelial cells
  • Typical use is for coronary bypass surgery
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25
Q

Arteries and Veins

A

-Arteries carry oxygenated blood from the heart to the body (expect the
pulmonary artery)
-Veins carry deoxygenated blood used by the body back to the heart (except the pulmonary vein)

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26
Q

Myocardium Patch

A
  • Tissue-engineered cardiac patches can be used to treat acute myocardial infarction
  • Augment contractile function
  • Promote revascularization
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27
Q

Myocardial Infarction

A
  • Heart Attack

- Decrease in oxygen supply to part of heart, causes necrosis

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28
Q

Cell-Based cardiac pump

A
  • Hollow structure with cardiac cells
  • Contract in sync with host heart
  • Proposed for chronic heart failure
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29
Q

Emphysema

A

Gradual damage of lung tissue, specifically thinning and destruction of the alveoli or air sacs

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30
Q

Lung Transplant Patient Survival

A

-Survival depends on many factors, including the
pre-transplant diagnosis, recipient age, weight
and overall health, type of transplant, various
donor characteristics and other factors.
-90% of those who pass away from complications from their lung transplant do so because
of acute cellular rejections.
-In first year, bacterial infection leading cause of mortality

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31
Q

Three Eye Layers

A

1) Sclera - fibrous tunic
2) Choroid - vascular tunic
3) Retina - nervous tunic

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32
Q

Retina

A
  • Sensory layer, innermost
  • Contains photoreceptors
  • Fovea centralis (macula lutae): center of retina, sharpest vision
  • Blind spot where optic nerve leaves the eye
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33
Q

Rods

A
  • Ability to see grey tones
  • Sensitive to light
  • Excited in dim light
  • Provide peripheral vision
  • LOW RES
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34
Q

Cones

A
  • Found in central areas
  • Need bright light to be excited
  • 3 types respond to either green, red, blue
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35
Q

Vitreous chamber

A
  • Posterior segment
  • Large chamber behind lens
  • Filled with clear gel: vitreous humor
  • Transmits light
  • Supports back of lens
  • Holds layers of retina in place
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36
Q

Anterior chamber

A

•Smaller chamber between lens and cornea
• Filled with aqueous humor
• Nourishes lens and cornea (90 minutes!)
• Focuses incoming light
• Held in place by ligaments attached to ciliary
body.

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37
Q

Choroid Coat

A
  • Vascular, nutritive layer
  • Contains melanin (prevents light from scattering inside the eye)
  • Anterior portion contains ciliary body and iris
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38
Q

Ciliary body

A
  • Processes that secrete aqueous humor

- Muscle changes shape of lens to adapt near/far vision

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39
Q

Iris

A
  • Made of pigmented smooth muscle

- Controls size of the pupil by dilation and constriction

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40
Q

Sclera

A
  • Fibrous tunic
  • Dense white fibrous connective tissue
  • Contains sclera, cornea, conjunctiva
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41
Q

Sclera

A
  • White of the eye
  • Gives eye shape
  • Protects inside of eye
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42
Q

Cornea

A
  • Transparent epithelium protects front of eye

- Where light enters

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43
Q

Conjunctiva

A

Clear mucous membrane that covers sclera

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44
Q

Lens

A
  • Posterior to pupil and iris
  • Avascular transparent structure
  • Consists of crystallin protein arranged in layers
  • Attaches to ciliary body by ligaments that fine tune focusing of light on retina
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45
Q

Eye Protection

A
  • Eyebrows
  • Eyelids
  • Eyelashes
  • Conjunctiva
  • Meibomian glands (oily lubricant)
  • Lacrimal apparatus (tears, antibodies and antibacterial agents)
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46
Q

Refraction

A
  • Both cornea and lens refract light rays

- To focus light, lens must change shape

47
Q

Myopia

A
  • Nearsightedness
  • Only close objects can be seen
  • Requires concave (negative) lenses
  • Light rays focused in front of retina
48
Q

Hyperopia

A
  • Farsightedness
  • Only distant objects can be seen clearly
  • Convex (positive) leens
  • Light rays focused behind retina
49
Q

Astigmatism

A
  • Two focal planes

- Horizontal and vertical light rays have different focal points

50
Q

Retinal Detachment

A

-As we age, shrinkage of the vitreous body (humor) may lead to a detachment of the
retina from the choroid
-A retinal detachment is considered a medical emergency and needs immediate repair
before vision loss becomes permanent

51
Q

Macular Degeneration

A
  • Loss of vision in the center of the visual field (the macula)
  • Damage to retina
  • Major cause for visual impairment in older adults
  • Impossible to recognize faces
52
Q

Cataracts

A
  • Opaque defect in cornea or lens

- Caused by injury, medication, diabetes

53
Q

Conjunctivitis

A
  • Inflammation of the conjunctival membrane, covers part of anterior eye
  • Caused most frequently by viral infections (pink eye) and allergy.
  • Also result from bacterial infections and many other irritants
54
Q

Glaucoma

A
  • Blockage to aqueous humor flow
  • Increase of pressure inside eye
  • Can lead to degeneration of eye function
55
Q

Diabetic retinopathy

A
  • most common cause of vision loss among people with diabetes
  • swelling of macula
56
Q

Cornea Tissue Engineering

A

Cells: mucosal epithelial cells, limbal stem cells

Tissues: amniotic membrane

57
Q

Lens Tissue Engineering

A

Currently, cataracts removed surgically and replaced with artificial intraocular lense

58
Q

PCO

A

-Posterior capsule opacification
-lens epithelial cells remaining after cataract
surgery have grown on the capsule causing it to
become hazy and opaque

59
Q

Retina Tissue Engineering

A

Cells: retinal pigment epithelium, ESC, iPSC
Biomaterial: thinner than 50 um, porous, biodegradable, correct Young’s modulus

Biomaterial Examples: PLGA, PLLA, PGS, PCL

60
Q

Two Approaches for Bionic Eye

A

1) Artificial Silicon Retina - ASR

2) Multi-unit Artificial Retina Chipset

61
Q

ASR

A
  • Artificial Silicon Retina
  • Microscopic silicon chip
  • Contains solar cells called microphotodiodes
  • Convert light energy from images into electrical impulses
  • Powered solely by incident light
62
Q

MARC

A
  • Multi-unit Artificial retina chipset

- uses CCD camera input and laser beam to transmit image into chip present in retina

63
Q

Neuroglia in PNS

A

Satellite cells:

  • surround neuron cell bodies
  • Regulate O2 and Co2 nutrient and neurotransmitter levels

Schwann cells:

  • surround axons, myelination of axon
  • Participate in repair process after injury
64
Q

Neuroglia in CNS

A

Oligodendrocytes:
-myelinate CNS axxons

Astrocytes:
-Maintain blood-barrier

Microglia:
-remove cell waste

Ependymal cells:

  • line ventricals/spinal cord
  • make cerebrospinal fluid
65
Q

Dendrites

A

Conduct impulses towards the cell body

66
Q

Soma

A

Control center of neuron

67
Q

Axon

A
  • Conduct impulses away from cell body
  • Only one axon per neuron
  • Trigger zone: site where action potentials are generated
68
Q

Sensory neurons

A
  • afferent = conduct signals to CNS

- specialize to detect stimuli

69
Q

Interneurons

A
  • within CNS

- interconnect incoming sensory pathways to outgoing motor pathways

70
Q

Motor neurons

A

-efferent = from CNS to muscles/effectors

71
Q

Myelination in CNS

A
  • By oligodendrocytes (myelinate multiple axons)
  • Myelin sheath: insulating layer around a nerve fiber
  • Newer layers of myelin must be pushed under the older ones
72
Q

Myelination in PNS

A
  • By Schwann cell (myelinate only one axon)

- Assists in nerve fiber regeneration

73
Q

White Matter

A
  • Aggregation of myelinated axons from many neurons

- Brain and spinal cord

74
Q

Grey Matter

A
  • Lacks myelin

- Formed from neuronal cell bodies and dendrites

75
Q

PNS Division

A
  • Somatic
  • Autonomic
  • Enteric
76
Q

Cranial Nerves

A
  • On: olfactory
  • Old: optic
  • Olympus: oculomotor
  • Towering: trochlear
  • Top: trigeminal
  • A: abducens
  • Fin: facial
  • And: auditory
  • German: glossopharyngeal
  • Viewed: vagus
  • Some: skeletal/accessory
  • Hop” hypoglossal
77
Q

Spinal Nerves (PNS)

A

-31 pairs of left-right spinal nerves

78
Q

Rate of nerve signal travel depends on 2 factors

A

1) Fiber diameter

2) Presence or absence of myelin

79
Q

Graded (Local) potential

A
  • Used for short-distance communication only
  • Do not travel down axon
  • Depolarize the cell
80
Q

Action potential

A
  • Allow for communication over long distances within the body
  • Requires threshold stimulus to fire
  • Trigger zone is where action potential is generated
81
Q

Resting membrane potential

A
  • Created using ion gradients and a variety of ion channels
  • Creates net negative charge inside cell
  • 70 mV
82
Q

Action Potential Graph

A

1) Local potential rises: Na+ ion arrive at axon hillock, depolarizing membrane
2) Threshold: potential reaches -55 mV, voltage-gated Na+ channels open
3) Neuron fires: membrane depolarizes, producing a spike as it passes past 0 mV, K+ gates slowly open
4) Peak: usually around +35 mVV
5) Repolarization K+ leaves neuron to drop membrane back to RMP
6) Hyperpolarization: K+ gates stay open long enough to drop 1-2 mV below RMP
7) Return to RMP

83
Q

Local Potentials vs Action Potentials

A

Local Potential: reversible, decremental, graded

Action Potential: irreversible, nondecremental, not graded

84
Q

Synaptic Transmission

A
  • action potential causes voltage-gated Ca 2+ channel to open in synaptic end bulb
  • Causes a release of neurotransmitter across synaptic cleft to bind to postsynaptic ligand-gated channels
85
Q

Regeneration of PNS Nerve Fiber

A

Can occur if:

  • neuron soma is intact
  • some neurolemma of Schwann cell remains
  • Nerve growth factors
86
Q

Steps of PNS Nerve Fiber Regeneration

A

1) Fiber is cut: macrophages clean up debris
2) Degeneration of schwann cell and axon
3) Regeneration: form regeneration tube, require NGFs
4) Regenerated fiber: fiber contacts target, soma shrinks to its original size

87
Q

Engineered Nervous Tissue Cells: Schwann Cells

A
  • Autologous Schwann Cells difficult to obtain in large numbers
  • Allogeneic Schwann Cells involved in immunological rejections
88
Q

Engineered Nervous Tissue Cells: Neural Crest Related Precursors

A

– From skin

– Differentiate into neurons and Schwann cells

89
Q

Engineered Nervous Tissue Cells: Embryonic Stem cells

A

-Grown in spheroid

90
Q

Engineered Nervous Tissue Cells: BMSCs, ASCs, iPS

A

-Differentiate into Schwann Cells

91
Q

Engineered Nervous Tissue Biomaterials: Decellularized

A

– Autologous non-neural
– Allogeneic neural / non-neural
– Xenogeneic neural / non-neural

92
Q

Engineered Nervous Tissue Biomaterials: Naturally derived polymers

A

– ECM proteins: collagen, laminin, fibrin, fibronectin, hyaluronan
– Polysaccharides: chitosan, alginate, agarose
– Proteins: silk, keratin
– FDA approved: NeuroGen
– CFDA (China’s FDA) approved: Chitosan based TENG

93
Q

Engineered Nervous Tissue Biomaterials: Biodegradable Synthetic polymers

A

– poly(phospoesters), polyurethanes, electrically conducting polymers
– FDA / CE (European) commerically available:
• Neurotube: PGA
• Neurolac: PLC

94
Q

Engineered Nervous Tissue Biological Factors: Growth Factors

A

– Nerve Growth Factor (NGF)
– Brain-Derived Neurotrophic Factor (BDNF)
– Neurotrophin-3 (NT-3)
– Glial Derived Neurotrophic Factor (GDNF)
– Ciliary Neurotrophic Factor (CNTF)
– Fibroblast Growth Factors (FGF)

95
Q

Engineered Nervous Tissue Biological Factors: Growth Factors Release

A

– Adsorption of growth factors into scaffold during fabrication
– Entrapment of growth factor-loaded microspheres into scaffold
– Immobilization of factors onto scaffold
– Installation of osmotic mini-pump or injection device
– Gene Therapy

96
Q

Engineered Nervous Tissue Electrical Factors: Electrical charges

A

-Stimulate cellular differentiation
– Neurite extension
– polyaniline, polypyrrole, polythiophene, and polyacetylene
– Graphene

97
Q

Tay-Sachs Diseasee

A
  • Degenerative disorder of the Myelin Sheath
  • Hereditary disorder of infants of Eastern European Jewish ancestry
  • Abnormal accumulation of glycolipid GM2 in myelin sheath disrupts conduction of nerve signals
98
Q

Multiple Sclerosis

A
  • Degenerative disorder of the Myelin Sheath
  • Oligodendrocytes & myelin sheaths in the CNS deteriorate
  • Myelin replaced by hardened scar tissue
  • “Immue-mediated”
99
Q

Amyotrophic Lateral Sclerosis

A
  • Neruodegenerative Disease

- Nerve cells break down, which reduces functionality in the muscles they supply

100
Q

Alzheimer’s Disease

A

-Neurodegenerative Disease
-Memory loss for recent events, moody, combative, lose ability to talk, walk & eat
-Show deficiencies of ACh & NGF
-Neurofibrillay tangles (microtubules): insoluble
twisted fibers found inside the brain’s nerve
cells. Cannot transport nutrients
-Formation of β-amyloid protein from breakdown product of PMs

101
Q

Parkinson Disease

A
  • Degeneration of dopamine-releasing neurons

- Progressive loss of motor function beginning in 50s or 60s: No recovery

102
Q

Tissue Engineering for Neurodegenerative Diseases

A
  • Blood Brain barrier model
  • Drug Toxicity/Disease Modeling
  • Neurodegeneration Model
  • Neuromuscular Junction Model
  • 3D Printed Nervous System on a chip
103
Q

Brain Tumors

A

Arise from:

  • Meninges
  • Metastasis from non-neuronal tumors in other organs
  • Glial cells (mitotically active)
104
Q

Spinal Cord Injury

A

1) Less/no sensation
2) Can’t sweat
3) Less body hair
4) Can’t cough (respiratory failure #1 cause of death among SCI patients)

105
Q

Scaffold Design for Nerve Repair

A
  • Nerve Guidance Conduit/Channel (NGC); cylindrical tube with empty lumen
    -After implantation, neural scaffold should act as a substrate for adhesion,
    proliferation, migration, and function of neural cells
106
Q

Biodegradable glass

A

repair facial / median

nerve in sheep

107
Q

ZnO ceramic

A

neural scaffold for PNS

regeneration

108
Q 
Carbon nanostructures (nanotubes,
nanofibers, graphene)
A

used as guides

109
Q

Al2O3 nanostructures:

A

biocompatibility with

neural cells

110
Q

Natural Materials for nerve repair

A

-PGA,PLA,PLGA -processed into foams and seeded
with Schwann cells
- cross-linked PEG hydrogels + growth factors to mimic
the ECM are under development

111
Q

Advanced Therapies for Nerve Repair

A

-PLGA- Collagen conduits filled with collagen
fibres showed 80mm nerve defects to be treated in dogs.
-Not well controlled because of handmade
fabrication techniques and no scale up possible.

112
Q

Ink-Jet printing of polymers

A
  • -Precise delivery of polymer solutions.

- 3D structures with desired thickness, dimensions, incorporation of biomolecules possible

113
Q

Nanostructures are the anwer

A

yes they are

Tissue Engineering 1 (4 decks)

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