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
2
Q
Current Cardiac Regenerative Therapies
A
1) Multipotent stem cells
2) Pluripotent stem cells
3) Non-cell strategies
3
Q
Cardiac Multipotent Stem Cells
A
Benefits: vascularization, immunoprivileged, improved cardiac function
Limitations: low cardiomyogenic potential, poor cell engraftment, limited proliferation potential
4
Q
Cardiac Pluripotent Stem Cells
A
Benefits: high cardiomyogenic potential, good cell engraftment, unlimited proliferation
Limitations: slow, electrical instability, teratoma formation
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
6
Q
Main Targets for Tissue Engineering in Heart
A
1) Blood vessels
2) Heart muscle - myocardium
3) Heart valves
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
8
Q
FGF Biomolecule
A
-promotes proliferation and differentiation
of endothelial cells, smooth muscle cells, fibroblasts
9
Q
Ang1, Ang2 Biomolecules
A
-stabilize blood vessels
10
Q
PDGF, PDGFR Biomolecules
A
-recruit smooth muscle cells
11
Q
VE-Cadherin, CD31 Biomolecule
A
-promote endothelial junction
12
Q
Ehprin Biomolecule
A
-formation of veins and arteries
13
Q
Plasminogen activator inhibit -1 Biomolecule
A
-stabilizes nearby vessels
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
15
Q
TE Product Requirements: Functionality
A
- Appropriate mechanical and hemodynamic functionality
- Must be durable
16
Q
TE Product Requirements: Blood Vessels
A
-Must be able to withstand high-pressure fluid
dynamics, turbulence
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
18
Q
TE Product Requirements: Myocardium Patch
A
- High vascularity is critical
- Mechanical and electrical anisotropy
19
Q
3 Cardiac Biomaterials
A
1) Biodegradable polymers (PGA)
2) Hydrogels (collagen, fibrin, alginate)
3) Decellularized tissue (collagen, elastin, fibronecting)
20
Q
Valve Replacement
A
1) Valves have complex architecture
2) TEHVs require complex molds
3) Cellularize with myofibroblasts to obtain a
functional valve
21
Q
4 Limitations of Mechanical valves
A
1) Infections
2) Thromboembolism
3) Cannot grow
4) No self-repair capability
22
Q
Limitation of Tissue-Engineered Valves
A
-Calcification of tissue
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
24
Q
Bypass Vascular Grafts
A
- Walls cellularized with smooth muscle cells
- Lumen cellularized with endothelial cells
- Typical use is for coronary bypass surgery
25
Arteries and Veins
-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)
26
Myocardium Patch
- Tissue-engineered cardiac patches can be used to treat acute myocardial infarction
- Augment contractile function
- Promote revascularization
27
Myocardial Infarction
- Heart Attack
| - Decrease in oxygen supply to part of heart, causes necrosis
28
Cell-Based cardiac pump
- Hollow structure with cardiac cells
- Contract in sync with host heart
- Proposed for chronic heart failure
29
Emphysema
Gradual damage of lung tissue, specifically thinning and destruction of the alveoli or air sacs
30
Lung Transplant Patient Survival
-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
31
Three Eye Layers
1) Sclera - fibrous tunic
2) Choroid - vascular tunic
3) Retina - nervous tunic
32
Retina
- Sensory layer, innermost
- Contains photoreceptors
- Fovea centralis (macula lutae): center of retina, sharpest vision
- Blind spot where optic nerve leaves the eye
33
Rods
- Ability to see grey tones
- Sensitive to light
- Excited in dim light
- Provide peripheral vision
- LOW RES
34
Cones
- Found in central areas
- Need bright light to be excited
- 3 types respond to either green, red, blue
35
Vitreous chamber
* Posterior segment
* Large chamber behind lens
* Filled with clear gel: vitreous humor
* Transmits light
* Supports back of lens
* Holds layers of retina in place
36
Anterior chamber
•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.
37
Choroid Coat
- Vascular, nutritive layer
- Contains melanin (prevents light from scattering inside the eye)
- Anterior portion contains ciliary body and iris
38
Ciliary body
- Processes that secrete aqueous humor
| - Muscle changes shape of lens to adapt near/far vision
39
Iris
- Made of pigmented smooth muscle
| - Controls size of the pupil by dilation and constriction
40
Sclera
- Fibrous tunic
- Dense white fibrous connective tissue
- Contains sclera, cornea, conjunctiva
41
Sclera
- White of the eye
- Gives eye shape
- Protects inside of eye
42
Cornea
- Transparent epithelium protects front of eye
| - Where light enters
43
Conjunctiva
Clear mucous membrane that covers sclera
44
Lens
- 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
45
Eye Protection
- Eyebrows
- Eyelids
- Eyelashes
- Conjunctiva
- Meibomian glands (oily lubricant)
- Lacrimal apparatus (tears, antibodies and antibacterial agents)
46
Refraction
- Both cornea and lens refract light rays
| - To focus light, lens must change shape
47
Myopia
- Nearsightedness
- Only close objects can be seen
- Requires concave (negative) lenses
- Light rays focused in front of retina
48
Hyperopia
- Farsightedness
- Only distant objects can be seen clearly
- Convex (positive) leens
- Light rays focused behind retina
49
Astigmatism
- Two focal planes
| - Horizontal and vertical light rays have different focal points
50
Retinal Detachment
-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
Macular Degeneration
- 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
Cataracts
- Opaque defect in cornea or lens
| - Caused by injury, medication, diabetes
53
Conjunctivitis
- 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
Glaucoma
- Blockage to aqueous humor flow
- Increase of pressure inside eye
- Can lead to degeneration of eye function
55
Diabetic retinopathy
- most common cause of vision loss among people with diabetes
- swelling of macula
56
Cornea Tissue Engineering
Cells: mucosal epithelial cells, limbal stem cells
Tissues: amniotic membrane
57
Lens Tissue Engineering
Currently, cataracts removed surgically and replaced with artificial intraocular lense
58
PCO
-Posterior capsule opacification
-lens epithelial cells remaining after cataract
surgery have grown on the capsule causing it to
become hazy and opaque
59
Retina Tissue Engineering
Cells: retinal pigment epithelium, ESC, iPSC
Biomaterial: thinner than 50 um, porous, biodegradable, correct Young's modulus
Biomaterial Examples: PLGA, PLLA, PGS, PCL
60
Two Approaches for Bionic Eye
1) Artificial Silicon Retina - ASR
| 2) Multi-unit Artificial Retina Chipset
61
ASR
- 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
MARC
- Multi-unit Artificial retina chipset
| - uses CCD camera input and laser beam to transmit image into chip present in retina
63
Neuroglia in PNS
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
Neuroglia in CNS
Oligodendrocytes:
-myelinate CNS axxons
Astrocytes:
-Maintain blood-barrier
Microglia:
-remove cell waste
Ependymal cells:
- line ventricals/spinal cord
- make cerebrospinal fluid
65
Dendrites
Conduct impulses towards the cell body
66
Soma
Control center of neuron
67
Axon
- Conduct impulses away from cell body
- Only one axon per neuron
- Trigger zone: site where action potentials are generated
68
Sensory neurons
- afferent = conduct signals to CNS
| - specialize to detect stimuli
69
Interneurons
- within CNS
| - interconnect incoming sensory pathways to outgoing motor pathways
70
Motor neurons
-efferent = from CNS to muscles/effectors
71
Myelination in CNS
- 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
Myelination in PNS
- By Schwann cell (myelinate only one axon)
| - Assists in nerve fiber regeneration
73
White Matter
- Aggregation of myelinated axons from many neurons
| - Brain and spinal cord
74
Grey Matter
- Lacks myelin
| - Formed from neuronal cell bodies and dendrites
75
PNS Division
- Somatic
- Autonomic
- Enteric
76
Cranial Nerves
- 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
Spinal Nerves (PNS)
-31 pairs of left-right spinal nerves
78
Rate of nerve signal travel depends on 2 factors
1) Fiber diameter
| 2) Presence or absence of myelin
79
Graded (Local) potential
- Used for short-distance communication only
- Do not travel down axon
- Depolarize the cell
80
Action potential
- Allow for communication over long distances within the body
- Requires threshold stimulus to fire
- Trigger zone is where action potential is generated
81
Resting membrane potential
- Created using ion gradients and a variety of ion channels
- Creates net negative charge inside cell
- 70 mV
82
Action Potential Graph
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
Local Potentials vs Action Potentials
Local Potential: reversible, decremental, graded
| Action Potential: irreversible, nondecremental, not graded
84
Synaptic Transmission
- 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
Regeneration of PNS Nerve Fiber
Can occur if:
- neuron soma is intact
- some neurolemma of Schwann cell remains
- Nerve growth factors
86
Steps of PNS Nerve Fiber Regeneration
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
Engineered Nervous Tissue Cells: Schwann Cells
- Autologous Schwann Cells difficult to obtain in large numbers
- Allogeneic Schwann Cells involved in immunological rejections
88
Engineered Nervous Tissue Cells: Neural Crest Related Precursors
– From skin
| – Differentiate into neurons and Schwann cells
89
Engineered Nervous Tissue Cells: Embryonic Stem cells
-Grown in spheroid
90
Engineered Nervous Tissue Cells: BMSCs, ASCs, iPS
-Differentiate into Schwann Cells
91
Engineered Nervous Tissue Biomaterials: Decellularized
– Autologous non-neural
– Allogeneic neural / non-neural
– Xenogeneic neural / non-neural
92
Engineered Nervous Tissue Biomaterials: Naturally derived polymers
– 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
Engineered Nervous Tissue Biomaterials: Biodegradable Synthetic polymers
– poly(phospoesters), polyurethanes, electrically conducting polymers
– FDA / CE (European) commerically available:
• Neurotube: PGA
• Neurolac: PLC
94
Engineered Nervous Tissue Biological Factors: Growth Factors
– 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
Engineered Nervous Tissue Biological Factors: Growth Factors Release
– 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
Engineered Nervous Tissue Electrical Factors: Electrical charges
-Stimulate cellular differentiation
– Neurite extension
– polyaniline, polypyrrole, polythiophene, and polyacetylene
– Graphene
97
Tay-Sachs Diseasee
- 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
Multiple Sclerosis
- Degenerative disorder of the Myelin Sheath
- Oligodendrocytes & myelin sheaths in the CNS deteriorate
- Myelin replaced by hardened scar tissue
- "Immue-mediated"
99
Amyotrophic Lateral Sclerosis
- Neruodegenerative Disease
| - Nerve cells break down, which reduces functionality in the muscles they supply
100
Alzheimer's Disease
-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
Parkinson Disease
- Degeneration of dopamine-releasing neurons
| - Progressive loss of motor function beginning in 50s or 60s: No recovery
102
Tissue Engineering for Neurodegenerative Diseases
- Blood Brain barrier model
- Drug Toxicity/Disease Modeling
- Neurodegeneration Model
- Neuromuscular Junction Model
- 3D Printed Nervous System on a chip
103
Brain Tumors
Arise from:
- Meninges
- Metastasis from non-neuronal tumors in other organs
- Glial cells (mitotically active)
104
Spinal Cord Injury
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
Scaffold Design for Nerve Repair
- 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
Biodegradable glass
repair facial / median
| nerve in sheep
107
ZnO ceramic
neural scaffold for PNS
| regeneration
108
```
Carbon nanostructures (nanotubes,
nanofibers, graphene)
```
used as guides
109
Al2O3 nanostructures:
biocompatibility with
| neural cells
110
Natural Materials for nerve repair
-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
Advanced Therapies for Nerve Repair
-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
Ink-Jet printing of polymers
- -Precise delivery of polymer solutions.
| - 3D structures with desired thickness, dimensions, incorporation of biomolecules possible
113
Nanostructures are the anwer
yes they are
