Overuse Bone and Tendon Injuries - Science and Theories of Tomorrow

Overuse Bone & Tendon Injury
Theories of Tomorrow
Stephen M. Pribut, D.P.M., FAAPSM, FACFAS
Past President, AAPSM
Clinical Assistant Professor of Surgery
George Washington University Medical School

drpribut.com dr.pribut@gmail.com

Friday, August 17, 12

Hang On Tight


Thoughts

• “If in the last few years you haven’t discarded a
major opinion or acquired a new one, your critical
thinking capacity may be broken.”

• “All models are wrong, but some are
useful.” (George Box)


Where We Are Going

• Introduction 15%

• Old Theories and New (tissue theory) 10%

• Cell Mechanics and Mechanotransduction 40%

• Bone 25%

• Tendons 10%


And now for something completely different...


Dive Deep & Think Hard
• Does it all stop with Newton & Root or McPoil &
Kirby? Should we look in the frontal plane or the
sagittal? Or should we look deeper?

• Let’s explore general concepts to solve speciﬁc
problems.

• Go deeper: Cellular Biomechanics and Signaling

• Cellular Concepts

• Structure creates function

• Mechanics or enzyme cascade or both?

Dive In, Dive Deep

4 Questions To Answer

• Does eccentric stretching work?

• Why didn’t PRP work better than saline for
Achilles tendinopathy?

• How does ultrasound stimulate bone healing?

• Does mechanics play a role in healing?


More thinkers, theorists
and researchers are
needed!


How and from where do
scientists get ideas?

And where do comedians get
their jokes? Ones like Lenny
Bruce, George Carlin?


Dreams

• Kekule - 1865 theory of resonance of Benzene.
Inspired by day dream.


Literature
• Quark - named from Joyce’s
Finnegan’s Wake

• Murray Gell-Mann chose name in
1963

• Admitted to “perusing” the
book, but not reading it

• Feels beauty and elegance plays
role in theory


Architecture
• Donald Ingber, M.D., PhD.

• Tensegrity as cellular feature inspired
by Kenneth Snelson’s “Needle” and
Buckminster Fuller

• Cytoskeleton works through
tensional regulation

• Cell shape regulation (via matrix
ﬁrmness) alters genetic expression
and affects stem cell and cancer cell
growth


Einstein

• “As Newton once said, ‘If I have seen further
than others, it is because I have stood on the
shoulders of giants’. ”

• Special relativity built on the work of Maxwell
and Lorentz among others.


One View:
You didn’t build that alone.


The joke was not approved by Einstein.


Break Down the Barriers

• Basic Science
• Chemistry, Physics, Mathematics, Engineering
• Architecture, Psychology, Environmental Science
• Exercise Physiology, Nutrition Science,
Pharmacological Sciences


Interdisciplinary Convergence
Biological Engineering Physical
Sciences Science Sciences
Biochemistry
Molecular Biology

Donald Ingber: “the boundaries between the living and
non-living systems are beginning to break down.”

Podiatric Medicine
• Divisions

• Surgery

• Biomechanics

• Wound Care

• Other areas

• Barriers

• intra-disciplinary

• interdisciplinary


Bone & Tendon
Maintenance and Healing
Things we know: inﬂuencing factors

• Exercise • Diet

• Aging • Genetics

• Sleep • Psychiatric Disorders -
(some evidence)


Mind & Gait


Gait Revealer of Aging
& Alzheimer's
• Mayo Clinic: N= 1341, followed over 15
months

• Lower cadence, velocity and length of
stride correlated with significantly larger
declines in global cognition, memory and
executive function.

• Basel, Switzerland: N= 1153, mean age of 78

• gait became "slower and more variable as
cognition decline progressed."

• Cognitively healthy, mild cognitive
impairment or Alzheimer's dementia.

• Those with Alzheimer's walked slower than
those with MCI, who walked slower than
those who were cognitively healthy.


Mind & Bone


Depression & Bone
Risk
• Affects 16% of population
• Meta-analysis - lower BMD
• Percentage decrease in BMD was 5.9% for the lumbar
spine and 6% for the hip
• 4 of 5 prospective studies on fracture risk concluded
that depression was associated with an increase in
fracture risk
• Many patients were taking SSRI drugs
• Exercise regimen not taken into account


Possible Factors Involved
in BMD and Depression
• Animal data suggest a relationship between a hyperactive
efferent autonomic nervous system and bone resorption.
• Impairment of the immune system in depression has been
documented. Proinﬂammatory cytokines interleukins (IL) 1
and 6 and tumor necrosis factor are high.
• Cytokines are stimulants of the hypothalamic-pituitary-
adrenal axis, which may account for the
hyperadrenocorticism observed in depression. Eskandari et al
reported a reduction in anti-inﬂammatory cytokine IL-13.
• SSRI’s - have shown increased bone loss in post-menopausal
women, increased risk of fracture, and increased rate of falling
Richards JB, Papaioannou A, Adachi JD, Joseph L, Whitson HE, Prior JC, Goltzman D; Canadian Multicentre
Osteoporosis Study Research Group. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch
Intern Med. 2007 January 167(2):188-94.

Ziere G, Dieleman JP, van der Cammen TJ, Hofman A, Pols HA, Stricker BH. Selective serotonin reuptake inhibiting
antidepressants are associated with an increased risk of nonvertebral fractures. J Clin Psychopharmacol. 2008 August
28(4):411-7.

Exercise, Mind & Bone

• Reduces risk of depression
• Lowers risk of osteoporosis
• Seems to lessen risk of hip osteoarthropathy
• Mechanics - forces, vibration, pulses of exercise and
weight bearing impacts cognition and bone formation

Will we kiss tissue
stress theory goodbye?


What should we look at?

• The 28 types of collagen?
• Cells?
• Bacterial ﬂora?
• Structural mechanics and biomechanics?
Where will this lead us?


Levels Of Concern:
Getting Small

Scanning electron micrograph: bone callus of healed complete trabecular fractures in an osteopenic
vertebra probably caused by excessive local microdamage. Frost HM. The Microdamage (MDx)
Connection. In: Frost HM. The Utah Paradigm of Skeletal Physiology Vol 1. Athens, Greece: ISMNI;
2004;4:208-219. Copyright © 2004, ISMNI.


Looking Back


Thinking Too Narrow

• “lower extremity”speciﬁc theories
• Root Biomechanics
• Nigg proprioception-vibration
“new paradigm”
• Sagittal plane biomechanics
• STJ-axis position


Less narrow: Tissue Stress

• McPoil, Hunt (1995) JOST
• Did not consider their theory original
• McPoil: “while the tissue stress model is
by no means a novel idea”
• Meant to replace STJ neutral and Root
“compensation” theories for injuries


Tenets of Tissue Stress
Theory
1. Accurately identify the anatomical structure which is
injured or symptomatic.
2. Determine the structural and functional characteristics of
the individual's foot and lower extremity.
3. Determine the most likely type of abnormal tissue stress
which is causing the pathology within the injured anatomical
structure (i.e. compression, tension or shearing stress).
4. Design a treatment protocol to reduce the abnormal tissue
stresses on the injured structure and reduce the local
inﬂammatory response so that more normal gait and
weightbearing function can occur.


Tissue Stress

• Empirical observations
• Not an explanation
• Let’s look deeper!


Conceptual Limitations
and Impact of Theories
• Humors
• Bleeding, leeches & poultices
• Bleeding - is good for hemochromatosis
• Leeches are good for Dr. Armstrong but nano-worms are on the way
• Geocentric vs. Heliocentric
• Ptolomaic
• Copernican
• Galileo - house arrest
• Giordano Bruno - staked & burned by Cardinal Belarmine
• Evolution v. 7000 year old world
• Pierre Teillard de Chardin


Out of Many - One:
Uniﬁed Theory
• Cellular mechanics Nature doesn’t separate disciplines!
• Mechanobiology
• Tensegrity
• Cell surface strain, activation of integrins
• Physics
• Newton, Hook,Young
• Biomechanics
• Spring theory
• Pulsed forces
• Biological systems theory
• Enzyme cascade
• Receptors (surface)


Other possibilities (to tissue
stress)

• Systems biology
• Genomics
• Cellular Mechanobiology and Energetics
(CME) (Cellular Mechanics)


Cells vs. Tissue

• All tissues derive from cells, so it is at the cellular
level we are likely to ﬁnd our ultimate solutions.
(Pribut 2009)


Let’s Not Forget
Wound Care
• It isn’t a magic soup you are pouring into
the wound
• It isn’t chef’s special sauce
• There is more too it
• Cellular Mechanics plays a large role


Why look at the cell?

“But which is the stone that supports the bridge?” Kublai
Khan asks.

“The bridge is not supported by one stone or another,” Marco
answers, “but by the line of the arch they form.”

“Why do you speak to me of stones? It is only the arch that
matters to me.”

Polo answers: “Without stones there is no arch.”

- Italo Calvino (Invisible Cities, 82)


The Cell:
Basic Unit of Life


Cells > Tissues
• The cell is to biology what the atom is to
chemistry and physics. - after Niels Bohr

• “with the cell, biology discovered its atom” -
paraphrase of George Henry Lewes
(1817-1878)


Cell Doctrine
(1838,1839-1859)

• All organisms are composed of one or
more cells
• The cell is the basic unit of organization
• All cells come from preexisting ones
Virchow and others


Old Model of Cell
Structure
• Blob - like a balloon ﬁlled with ﬂuid
• Alteration in cell membrane shape via external forces
have little effect across entirety of cell


New Model of
Cellular Structure
• Tensegrity object
• Tensional integrity (Kenneth Snelson
creator/Buckminster Fuller applellation)
• Microtubules (tubulin)
• Microﬁlaments (actin)
• Tension in ﬁlaments, compression in struts
Bendix image: Oxford


Tensegrity
• Buckminster Fuller - named it
• Kenneth Snelson - made it
• Donald Ingber - nailed it -
brought it to a theory of the
cell

The Needle


Built Like A Tent


(A) A high magnification view of a Snelson sculpture with sample compression and tension
elements labeled to visualize the tensegrity force balance based on local compression and
continuous tension.

Ingber D E J Cell Sci 2003;116:1157-1173

©2003 by The Company of Biologists Ltd


He la cells -
Cytoskeleton


HeLa


Cellular & Molecular
Mechanics

• Mechanobiology
• Nanotechnology
• Chemical Biology
• Cellular biomechanics


Course Study
NSF-GEM Summer School 2012
• Introduction to Cell and Molecular Biology

• Introduction to Physiology

• Cell & Molecular Biomechanics: Basic Mechanics

• Introduction to Continuum, Fluid and Solid Mechanics

• Continuum & Statistical Mechanics

• Molecular Biomechanics

• Cell Biomechanics

• Tissue and Muscle Biomechanics

• Computational Biomechanics

• Mechanosensing and Transduction

• Musculoskeletal System

• Immune System

• Cellular/Subcellular Levels


• Polymerizes into ﬁlaments (crosslinks)
• Found in all eukaryote cells
• Interact with microtubules and
intermediate ﬁlaments
• Polar - point in one direction
• First found with myosin in muscles

Spatial Cell Biology: Location, Location, Location

• Vectors of reaction
• Field effect of gradients, reactions,movements,
forces
• Interconnectivity and connectivity
• A place for everything and everything in the right
place
• Directionality of transmembrane proteins
• Hox genes

56


Fig. 1 The genome as a GPS device.

H Y Chang Science 2009;326:1206-1207

Published by AAAS


New Cell Theory

• Not only genes - but physics and chemistry
• Dynamic patterns generated by physical and biological
systems can yield a “field effect”
• Similarities to fields of force (electrical, magnetic,
gravitational)
• Cell fields sustained by concentration gradient or patterns
of dynamic mechanical stress and strain
• Field concept: creates discomfort among many biologists
The Way of The Cell, 2002

58


Cells as Adaptive Architecture:
Intelligent Building Materials
• Resilient and adequately strong
• Multifunctional
• optic, taste, touch, otic, neuro, mechanical
• Learn, adapt, self-organize
• Move, grow, recover from stresses
• Include self-organizing materials (protein
conformation, microtubules,)
After Ingber, 2011


ECM
• More dynamic & versatile than previously thought

• Biomechanical properties range from soft and compliant to stiff and
rigid

• Elasticity & biomechanical properties affect how a cell senses and
detects external forces

• Focal adhesion complex (FAC) (integrins and signaling proteins) act as
a mechanosensor

• links cytoskeleton with the ECM

• Change in mechanical force alters TGF-β signaling in mouse tendon
(Maeda et al., 2011) indicating other signals may also be activated


ECM Components

• Collagen & Elastic
Fibers

• Glycoproteins
• Fluid


Cells in ECM

• Produce and maintain
extracellular matrix
• Fibroblasts: form ﬁbers
• Migratory: reactionary
(immune response)
• macrophages (red,
orange)
• mast cells

• Lymphocytes

The extracellular matrix: A dynamic niche

February 20, 2012 // JCB vol. 196 no. 4 395-406
The Rockefeller University Press, doi: 10.1083/jcb.201102147
© 2012 Lu et al.


ECM Biomechanics
• Major factor in cell fate determination
• Impact cell differentiation
• Affect cell and tissue function
• Matrix stiffening affects cell migration
• Dynamic and remodels - interacting with cells and
cell functions


Stem Cell Mechanobiology:
ECM and the Stem Cell
• Impact of matrix stiffness
– Hard - bone cell
– Soft - fat cell
– Medium - muscle cells
• Stiffness of ECM
– Youngs modulus
– Impacts genetic expression

65


Integrins
• Transmembrane
• Cell attachment to other cells or ECM
(celll-cell / cell-ECM)
• Stabilize cells and tissues
• Remodeling of focal adhesions affects cell
shape, gene expression and tissue
organisation.


Conformational changes

• Alter binding affinity
• Possibly force
dependent
• Enzymes/Proteins linked
to cytoskeleton
• Mechanics plays large


• Integrins play a role in cell stiffness detection
• Alteration of conformation of cytoskeleton
Wang et al (2009)

Summary: Integrins

• Connect in 2 directions: the ECM to the cytoskeleton
and cell membrane to the nucleus
• Signal both outside-in and from the inside-out
• Detect forces in their environment
• Affects the movement of cells
• Functional changes: conformation and clustering
• Activate tyrosine kinases


Cell Mechanics
• Challenges the “central dogma” which is
followed by disease based researchers
(biologists, physicians)(DNA-RNA-Protein)
• Cell/molecular mechanics is a new concept
to researchers and clinicians
• Young and developing ﬁeld
• Georgia Tech, Emory, MIT, Harvard - Leaders
& Lecturers


Cells and fluid
shear stress
Kamkin A, Kiseleva I, editors. Mechanosensitivity in Cells and Tissues.
Moscow: Academia; 2005. Appendix. Available from: http://

•
www.ncbi.nlm.nih.gov/books/NBK7500/

Almost all cells respond to fluid shear stress

• Most endothelial cells orient in direction of fluid shear
(except heart valve endothelial cells and vascular smooth
muscle)

• Lower cells: dinoflagellates (red tide) - produce
phospholuminescence to mild fluid shear

• Single cell grouping to form multicellular organisms - cell
connectivity (surface receptors) response to shear


Molecular mechanisms for integration of mechanical/adhesive signals.

Weber G F et al. J Cell Sci 2011;124:1183-1193

©2011 by The Company of Biologists Ltd


Mechanotransduction: Recent Theories
(after Roger D. Kamm of MIT)

• Changes in membrane ﬂuidity and the diffusivity of
transmembrane receptors --> receptor clustering (Butler,
2002, Wang, 2004)
• Direct mechanical effects on the nuclear membrane, DNA,
and gene expression (Ingber)
• Stretch-activated ion channels (Gullinsgrud, 2003, 2004)
• Force-induced changes in the conformation of load-
bearing
proteins (Schwartz, 2001, Jiang, 2003, Bao, 2002)


Another -ome
• Ominomics - spreading widely and not happily (WSJ Aug 15, 2012)

• One more: The “Mechanome” (M. Lang, MIT):

• The complete state of stress existing from tissues to cells to
molecules

• The biological state that results from the distribution of forces

• Knowledge of the mechanome requires:

• the distribution of force throughout the cell/organ/body

• the functional interactions between these stresses and the
fundamental biological processes

• “Mechanomics” is then the study of how forces are transmitted and the inﬂuence
they have on biological function


Bone
• Julius Wolff (1892)

• First recognized ability of tissue to adapt to mechanical
stresses

• Observed trabeculae matched the principal stress lines of
bone

• How does a force become a cascade of biological signals?

• Wolff’s law - old & simpliﬁed & narrow but not wrong

• Mechanotransduction - new & can be generalized


Osteocyte:
The Mechanosensor

• Dynamic fluid flow with higher peak shear stress amplitudes, faster
oscillating frequencies, and longer loading durations are optimal for
promoting bone formation.

• “Structural adaptation of the bone is mediated by loading-induced
interstitial fluid flow within the bone microstructure.”

• Osteocytes are the central mechanotransducer and mechanosensor

• demonstrated that COX-2 mRNA levels are elevated in osteocytes
subjected to higher peak shear stress and longer flow durations

• RANKL/OPG mRNA levels decreased in response to higher peak shear
stress amplitudes, faster oscillating frequencies, and longer flow durations.

Biomechanics
• Where does what we know ﬁt in?
• Does foot strike and running
mechanics play a role?

• How do orthotics impact the signal
to bone?

• What exactly is the signal and how
does the signaling work?


Gait Analysis Treadmill:
Dream Machine

h/p/cosmos Quasar Treadmill
about $24,000


Good Vibrations
• Just the right amount helps

• Too much hurts

• Complex signal

• Alterations in running cadence, speed, shoe, terrain will alter
the input into the musculoskeletal system

• Standing waves - augmented wave forms

• As Paul Langer mentioned: Barefoot: more variability in step
rate, length. Possibly helpful for certain injuries.


Complex Functions:
Body & Vibration
• Shoe, Surface, Body - have an impact on vibration. In phase and out of
phase qualities factor in.

• Benno Nigg’s - muscle tuning + bonus

• Bessel Functions - wavelike oscillatory behavior or a combination of
oscillation & exponential decay or growth

• Fourier Transformation - potential ﬁlter via soft tissue.


Schematic diagram of how forces applied through the ECM (A) or directly to the cell surface (B) travel to integrin-
anchored focal adhesions through matrix attachments or cytoskeletal filaments, respectively

F. J. Alenghat et al., Sci. STKE 2002, pe6 (2002)
Published by AAAS


Relationship Status: “It’s Complicated”

Schematic diagram of how forces applied
through the ECM or directly to the cell
surface travel to integrin-anchored focal
adhesions through matrix attachments or
cytoskeletal filaments


Cytokines are a part of
the soup many of us
are looking for.


Cytokines and Growth Factors
Affecting Bone:
Stimulators of Resorption


Affecting Bone:
Inhibitors of Resorption


Affecting Bone:
Stimulator of Formation


“Look for something that inhibits
destruction and enhances formation”

“Then you may ﬁnd the MSG of cell
making soup.”


• Mouse study
• Stimulates osteoblast differentiation
• Inhibits osteoclast activity (anti-osteoclastogenic)
• Osteoprotective
• Contrast with alendronate (only inhibits resorption)


SEM3a:
Coupling bone synthesis and degradation.

Translational medicine: Double protection for weakened bones
• Mone Zaidi & Jameel Iqbal
Nature 485, 47–48 (03 May 2012) doi:10.1038/485047a


Osteoporosis
• Primary
– Type I - Post-menopausal (estrogen-induced)
• trabecular bone loss > cortical
– Type II - Age related
• both trabecular and cortical bone loss
• Secondary
–pharmaceuticals, endocrine disorder, chronic
renal disease, immobilization, nutritional,
connective tissue disorders

91


Cortical Bone and Aging

• Trabecular bone fairs worse
• With a decrease in BMD the cortex
becomes thinner making for higher fracture
risk


Medication: Impact On
Injury
• Prilosec, Protonix - increase risk of fracture
and stress fracture
• Fluoroquinones - increase risk of tendon
and ligament injury
• NSAIDs - questionable connection


Nutrients, Aging and Bone

• Decreased protein
intake leads to
sarcopenia
• Sarcopenia leads to
decreased skeletal
loading and decreased
IGF-1
• Decrease hormones
• Vitamin deﬁciencies
• Bone Weakens

from Nutrition, Bone and Aging


Bone Healing Stimulators

• Utility
• Cost
• Evolution


Principles and First Attempts in
Stimulating Bone Healing

• Pizeoelectric crystal theory
• Basset and Becker, Science 1962
• Led to implantable electrodes
• Anode/Cathode - tissue destruction

Bone Stimulator:
Ultrasound Based
• Based on observation and thought that stress was
helpful

• Actions appear to be based on mechanotransduction
• Cannalicular ﬂuid ﬂow stimulates osteocytes (shear
forces)

• 30 minutes per day


Problems & Solutions in
Bone Healing
• Pricing - $3000
• Distribution
• Company representatives
• eBay
• Disposable with built in obsolescence - “number of
charges”


US Stimulation of Bone
Healing

• Yes, it works
• Extremely useful delayed union
• Jones and other ﬁfth metatarsal base/shaft fractures


Tendon


Tendon: Function & Properties

• Attach muscle to bone
• Remember: It is a musculoskeletal system
• Relatively avascular, slow metabolism

101


Tendon Loading

• Transmits the force of contraction to bone
• High mechanical loads
– 4 times body weight (2600 N) during walking
– 8 times body weight (3100–5330 N) during
running and jumping
• Adaptable
102


Seek Optimal Loading


et. al. 2004

theoretical framework of
strain based ﬁber
reorientation


Does Tendon
Hypertrophy With Use?

http://biodidac.bio.uottawa.ca/info/regles.htm


“There was a signiﬁcant difference in CSA along the length of the
tendon in both runners (P<0.001) and non-runners (P<0.01) (Fig. 2”
(36% greater CSA at distal aspect, but not proximal)
6 male runners ~ 80 km/ week (5 years experience)
Control: 6 non runners


10 male runners
10 female runners
10 female non-runners
MRI/US examinations
(Patellar & Achilles)
Men CSA > Women
Women trained = untrained
Distal patellar and Achilles tendon CSAs were greater than the proximal part in all three groups

Women seem to exhibit less adaptive response in tendon

Mechanism of
Hypertrophy
• Possibly increased cross linking between
collagen molecules or ﬁbrils
• Slow adaptation
• Men > Women
• Impact of estrogen? Body builder and ROH Wrestler Mike Mondo

• Methodology: US v. MRI

What makes tendons
pop?
• Fluroquinolone: Increase real or illusion?

• Sex linked?

• Overload when not properly adapted?

• CSA & Genetics?


• Between 1991 - 2002 risk increased from
22.1 to 32.6/100,000 (Denmark)
• Evaluated within 90 d of use
• Fluoroquinolone use -Tripled the risk
• Sex-standardized calculation


• Long term exercise: improves mechanical
properties
• Immobilisation - weakens mechanical structure
•Applied strain affects synthesis of matrix proteins
• Set point:
• Too low or too high = catabolism
• Just right = stimulation for optimal remodeling

• 16 men
• Plantar ﬂexion isometric resistance training
• Tendon stiffness increases over 2 - 3 month period
• Adapts to resistance training slowly, but to detraining
rapidly.
• Less vigorous than Alfredson protocol
• LOWER VOLUME: Less Pain = More Gain

Achilles Tendinopathy

• Eccentric Stretching (indiscriminately applied)
• PRP
• Surgery

115


Achilles Tendinopathy

• Poultices and Plasters
• Leeches
• Bleeding

116


• Little evidence in its favor
• Researchers need to determine the optimal
protocol for preparation and injection


Is PRP like “Chef’s
Special Sauce”

• How can we get the right stuff?
• Should we throw a blender and a
centrifuge at the problem?


Biologist Analysis of
Circuit Board


• all followed at 6, 12, 24 weeks
• eccentric stretching + saline or PRP
• no signiﬁcant difference between control
and study group

Short & Intermediate term:
No Difference

Am J Sports Med 2011 39: 1623 (online May 21, 2011)

• 59.3% (16 patients of 54 randomized) were satisfied with treatment
(insignificant difference of -2.7% in treated group)
• 56.5% returned to previous sports level (difference +1.8%)
• 1 Year Follow UP: No benefit of PRP over placebo

Conclusion: A PRP injection in addition to eccentric exercises
did not result in clinical improvement or improved structural
reorganization after 1 year in chronic mid-portion Achilles
tendinopathy compared with a placebo.


Plane of Progression


Tendinopathy

• Achilles
• Posterior tibial (+ deltoid ligament)
• Peroneus longus or peroneus brevis
• Flexor hallucis longus


FHL Tendinopathy

• Causes
• Dorsiflexion exercises for plantar fasciitis
• Lack of flexion stability in shoe
• Flip-flop or open heel shoe


FHL Tendinopathy:
Treatment
• Stop offending exercises
• Toss bad shoes
• Strengthening exercises
• Use stability shoes
• Orthotic to reduce load on tendon


Mechanobiology:
What Else Can Be Done?

• Nano-delivery of drugs
• Biological nano-robotics
• Nano-worms/leeches


Synthetic Platelets

Model for improved handling of clot in
tendon healing?

Who you gonna call? Clot Busters!

UC Santa Barbara, via Science Daily 2012


Liquid Plumr® for capillaries

•Nanoparticles
•Biodegradable
•Deliver low dose tPA
•New method of drug
delivery
•Could help in
diagnosis of location by
scanning
•Designed to break
apart at speciﬁc shear
level

nanoparticles release tPA - shear force trigger (Ingber, 2012) (Wyss Institute of Harvard)


Casts

• Plaster
• Polymer resin
• Cam Walkers / Pneumatic Cast Boot


Plaster
• Gypsum (Calcium sulfate)

• Gives off heat when mixed
with water forming a
dihydrate: 2CaSO4.½H2O(s) +
3H2O(l) = 2CaSO4.2H2O(s)

• Easily decorated

• Not stable when wet. Not
very strong

• Smells, skin irritation, muscle
atrophy, itchy, panic attacks

Heather Tomkins, anatomical drawing on a plaster cast. via boingboing


Plastic Resin Polymers
• “Fiberglass” - reinforced
polymers for improved
strength

• Lighter, stronger, water
resistant

• Decorator colors
• Similar problems to Plaster
re: hygiene


Pneumatic Walking Cast
• Previous materials
• Plaster
• Plastic polymer resin
(ﬁberglass)

• Solved - much of “Cast
Disease”

• Allows exercise

Pneumatic Cast Boot:
Problems
• Occlusive

• Over-inﬂated too often

• Skin rashes - allergy to materials, ﬁbers

• Nerve damage from compression

• Affects balance

• Limb length related problems - back, other joints

• axis alignment not correct: other pains


Fixing The Boot
• Breathable material

• Feedback system to prevent over-inﬂation

• Material testing to avoid ﬁber shards. (Breathability
improvement less moisture and leaching of materials from
lining)

• Limb length equalizers to be dispensed with boot

• Find a better way to align with ankle axis

• Production facility - stability, compliance with standards


Answers to 4 Questions

• Does eccentric
• Sometimes
stretching work?
• Why didn’t PRP work • Eccentric
better than saline for stretching
Achilles tendinopathy?
• Mechanics
• How does ultrasound and ﬂuid
stimulate bone healing? shear
• Does mechanics play a
• Yes, indeed
role in healing?


After Lecture:


Ingber: View of Modern
Biomechanics
• “we still have no conceptual framework that
embraces basic paradigms of biology together with
physical principles such as conservation of mass,
momentum and energy”

• “we lack a comprehensive theory that permits
prediction of the many shapes, material properties,
motions, and ﬂuxes that are encountered in the
living world”
Fredberg, Discher, Ingber et. al.. Biomechanics: cell research and applications for the next decade. Ann
Biomed Eng. 2009 May, 37(5) 847-859


New Rules for Orthotics

● Problem speciﬁc planning
● Conform well or appropriately to the foot
● Be made over a 3D image or model of the foot
● Alter the application of forces as determined to
be appropriate for the clinical problem.
● Be based on an examination of both the static and
dynamic biomechanics, kinetics and kinematics (as
much as is possible.)
● Take into account the requirements of the
individual, sport, environment, and foot wear.

Cell Rules
• Mechanotransduction Unit - Cell + ECM
• Reset cellular activity by alteration of
biomechanical forces

• Impact via
– Mechanics
– Diet
– Genetics
– Hormonal considerations
– Cell signaling biochemistry 142


Mechanics and Mechanotransduction

Encyclopedia of Biomaterials and Biomedical Engineering, 2008, p.1783-1793, Taylor & Francis)


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