lecture 17: tissue engineering - understanding tissue mechanics Flashcards
1
Q
What is the easiest way to understand a material?
A
- try to break it
- when you try to/do break a material you can understand its structure
- e.g. stretching a rubber band → it elongates → try to measure force being exerted on the material
- plot a graph of force vs displacement
- can convert force into stress, displacement into strain
- yungst blah?
- if steeper line than material is stiffer
- relates to ligaments/tendonds
- tissue engineering is about replacing parts → need to understand the biological tissue
2
Q
How does the ACL get injured?
A
- ACL injuries occur when bones of the leg twist in opposite directions under full body weight
- ACL stabilises the knee
- very susceptible to injury
3
Q
What is functional tissue engineering?
A
- functional tissue engineering: the role of biomechanics
- Butler DL, Goldstein SA, Gulak F
- tissue engineerng uses implanted cells, scaffolds, DNA, protein and/or protein fragments to replace or repair injured or diseased tissues and organs
- despite its early success, tissue engineers have faced challenges in repairing or replacing tissues that serve a predominantly biomechanical function
- an evolving discipline called “functional tissue engineering” (FTE) seeks to address these challenges
- replacements for load-bearing structures
- in vivo stress/strain histories need to be measured for a variety of activities
- provide mechanical thresholds that tissue repairs/replacements will likely encounter after surgery
- mechanical properties of the native tissues must be established for subfailure and failure conditions
- these “baseline data” probide parameters within the expected thresholds for different in vivo activities and beyond these levels if safety factors are to be incorporated
- a subset of these mechanical properties must be selected and prioritised
- standards must be set when evaluating the repairs/replacements after surgery so as to determine “how good is good enough?”
- some aspects of the repair outcome may be inferior, but other mechanical characteristics of the repairs and replacements might by suitable
- new and improved methods must also be developed for assessing the function of engineered tissues
- the effects of physical factors on cellular activity must be determined in engineered tissues
- knowing these signals may shorten the iterations required to replace a tissue successfully and direct cellular activity and phenotype toward a desired end goal
- to effect a better repair outcome, cell-matrix implants may benefit from being mechanically stimulated using in vitro “bioreactors” prior to implantation
- increasing evidence suggests that mechanical stress, as well as other physical factors, may significantly increase the biosynthetic activity of cells in bioartificial matrices
- incorporating each of these principles of functional tissue engineering should result in safer and more efficacious repairs and replacements for the surgeon and patient
4
Q
What is a multi scale approach?
A
- to research methods
- gross level → whole body measurements
- macro level → joints
- micro level → cellular level
5
Q
What about cartilage and bone?
A
- ligament failing but articulating surface is also being damaged
6
Q
What is micro-damage in the osteochondral explants following a single impact load?
A
- adult equine stifle
- diamond saw
- embedded explant
- microscope
- compression indenter
- light
- embedded specimen
- high speed camera 1000 fps
- can see the cartilage and bone with impactor coming
- when you apply a high speed load the material stiffens
7
Q
What is planar measurement of deformation?
A
- tracking the points 2D in motion studio
- can measure how much strain is on the cartilage and how much strain is on the bone
- without failing and when it fails
- the maximum slope of the tangent to loading curves - maximum Young’s modulus
- the grey area under the loading curve was calculated as the maximum absorbed energy per unit volume
8
Q
What is seen in µCT scanning of impact-induced injury?
A
9
Q
What is finite element modelling?
A
10
Q
What is seen when comparing locations of fracture and lines of high strain and stress?
A
11
Q
What is the structure of bone?
A
- complex structure
- hard bone
- spongy bone
- cells in it
- canals
- blood vessels
- composite
- not homogeneous material
- what type of data would i get out of it?
- trabecula bone
- composed of a network of branching, interconnected sheets and bars called trabeculae
- this internal structure creates a series of interconnected spaces that are filled with vascular tissue called marrow, a functional part of the circulatory system producing both red and certain white blood cells
12
Q
What do you do to understand the mechanical properties of bone?
A
- quasi static tensile/compression tests conducted using Instron Micro-tester
- take a bone
- apply load to creation compression
- pull it apart to test tension
- tissue samples from C0-C7 were extracted from 5 male cadavers
- shape it nicely → want to have a dimension that can be measured
- camera to see what happens
13
Q
What is a stress-strain plot of cortical bone?
A
- the stress-strain curve for bone in tension is as shown
- it has three distinct regions
- in the initial region, the curve is nearly a straight line → elastic zone, if you apply load and don’t go past this zone you should be able to return to normal position
- a modulus can be calculated to be about 17GPa
- in the intermediate region, the bone exhibits non-linear elastoplastic material behaviour → if you get to this point and return, you will have a permanent deformation
- yielding also occurs in this region
- the yield strength of bone is about 110MPa
- the final portion, the bone exhibit a plastic material behaviour and the stress-strain plot begins to straighten
- bone fractures at about 128 MPa, for which the tensile strain is about 0.026
- strain is the amount of elongation over the original length
- can’t stretch it a lot
- a lot of information → once you produce this curve you have information to compare to a tissue engineering construct
14
Q
What experiments demonstrate the complex structure of bone?
A
- figure shows the viscoelastic nature of bone
- the specimen of bone subjected to rapid loading (high strain rate) has a greater elastic modulus and ultimate strength than a specimen that is loaded more slowly (low strain rate)
- the stress-strain plot is also dependent upon the orientation of bone with respect to the direction of loading
- figure demonstrate the anisotropic behaviour
- the cortical bone has a larger ultimate strength and a arger elastic modulus in the longitudinal direction than the transver se direction
- viscoelastic materials cause a lot of problems for engineers
- anisotropic
15
Q
What is the ultimate strength and elastic and shear moduli for human femoral cortical bone?
A
these numbers are important because tissue engineering structures need to mimic some of these properties
16
Q
What is the stress-strain plot of cancellous bone?
A
- the compressibe stress-strain plot contain an initial linearly elastic region up to a strain of about 0.05
- the material yielding occurs as the trabeculae begin to fracture
- this initial elastic region is followed by a plateau region of almost constant stress until fracture (Ductile)
- however, cancellous bone fractures abruptly under tension, showing a brittle material behaviour
- cancellous bone is about 25 to 30% as dense, 5 to 10% as stiff and 5 times as ductile as cortical bone
- energy absorption of cancellous bone is higher under compressive than under tensile
- all of the trabecula structures start to break and fill up and as you keep going you get a sort of compact material
17
Q
What is whole bone failure?
A
- the load at failure of a whole bone will depend on
- geometry
- material properties
- rate of loading
- orientation of loading
- mode of loading
- tensile load: clean break
- compression: oblique
- rotation: somewhat combined
- bending
- bending + compression
- most bones are subject to bending
18
Q
What are two main types of fibres that could be found in connective tissues (skin, ligament, tendon…)?
A
- collagenous fibres (collagen) are unbranched, colourless fibres that are usually deposited in bundles to form wavy, parallel groups
- elastic fibres are branching, yellowish fibres that are deposited singly and stretch readily under tension. the individual fibres are straight rather than wavy
20
Q
What are stress-strain plots for collagen and elastin fibres?
A
- both collagen and elastin impart a certain amount of resilience to tissue, collagenous fibres are stronger than elastic ones and can withstand far greater tension before they break
- you can stretch elastic fibres to about 200% before it fails, stress is very low until just before it breaks
- collagen: very strong but you can’t stretch it a lot
- ligaments have high percentage of elastin therefore very elastic and can stretch
- achilles tendon has low amount of elastin therefore cannot stretch very much
- ligaments connect bone to bone, tendons connect muscle to bone
- contract muscle → force distributes to bone via tendon
- if the tendon was very elastic it would take some time for that → slap face
21
Q
What are varying morphologies of collagen and elastic fibres in soft tissue?
A
- skin
- similar percentage to tendon
- behaves something like a ligament → can be stretched quite a bit before failure
- pulling it is bascially applying force to align the collagens
- once they are aligned you get the strain
- tendon
- in tendon, the collagens are orientated in alignment with the tensile stresses that the tendon undergo physiologically, whereas skin in a relaxed state has fibres that are not in any order
- ligament
- just because they have similar composition does not mean they will have the same behaviour
- have to take morphology of the microstructure into consideration
22
Q
What are langer’s lines?
A
- these maps indicate that there are definite lines of tension or cleavage lines within the skin that are characteristic for each part of the body
- in microscopic sections cut parallel with these lines, most of the collagenous bundles are in cross section
- the cleavage lines correspond closely with the crease lines on teh surface of the skin in most parts of the body
- the pattern of cleave lines, according to Cox varies with the body configuration, but is constant for individuals of similar build regardless of age
- there are limited areas of the body in which the orientation of the bundles is irregular and confused
- the cleavage lines are of particular interest to the surgeon because an incision made parallel to the lines heals with a fine linear scar, while an incision across the lines may set up irregular tensions that result in an unsightly scar
- prestress in the body
