Biomedical E ngineer ing
Gene Expression
•  PCR was used to
investigate the expression
of ECM and myogenesis
(MyoD) genes.
•  RNA extracted from normal
and repair tissue.
•  Un-repaired and DSM
treated muscle.
ECM genes up
MyoD gene down
•  DSM + Minced Muscle
ECM genes way up
MyoD gene up
Expression Ra5o (Col1/MyoD) Biomedical E ngineer ing
Gene Expression
•  Expression ratio of
MyoD to various ECM
related genes calculated
•  Expression ratio
elevated for VML and
DSM treatment groups
•  Gene ratio similar to
normal muscle for DSM
+MM treatment groups
•  TA Plug = defect muscle
plug inserted back into
defect
45 VML
30 DSM
15 DSM+MM
TA
TA Plug
0 1.25 1.5 1.75 2 2.25 Peak Contrac5le Force (N/kg) TA
VML
DSM
DSM+MM
TGF-β1 /
MyoD
13.7±6.8
41.9±18.0 34.6±12.3
3.6±1.7
Col 1 /
MyoD
9.8±5.3
32.9±10.5 30.3±15.5
10.6±4.5
Col 3 /
MyoD
15.6±7.8
47.1±15.8 38.1±15.3
9.4±4.2
CTGF /
MyoD
12.4±5.7
51.5±37.0
4.4±2.1
Timp-1 /
MyoD
14.6±8.3
45.9±25.2 30.8±12.5
28.6±7.3
4.9±1.6
Biomedical E ngineer ing
Conclusions
•
ECM by itself appears incapable of
regenerating damaged muscle
•
Supplementation with muscle cells
improved contractile force
•
The balance between myogenesis
and fibrosis also appears to play a
role
What Next
•  Engineered ECM scaffolds
•  Aligned fiber bundle scaffold
•  Aged animal repair
Biomedical E ngineer ing
Traumatic Brain Injury
1.7 Traumatic brain injuries each
year
Approximately ¾ are closed head
injuries
Caused by falls, sport injuries,
vehicular accidents
Blow to head causes brain to collide
with skull interior
The loads and strains affect CNS
cell homeostasis
Biomedical E ngineer ing
Astrocyte Mechanobiology
•  Astrocytes are ubiquitous cells
throughout brain tissue.
•  Play a key role in neuron survival
•  Regulate the ECM environment (glial
scarring)
•  Role of force in glial scar formation is
unclear
Rat astrocytes stained for GFAP and DAPI
Hypothesis: Mechanical stimuli triggers the production of a neurodegenerative ECM environment by astrocytes
Biomedical E ngineer ing
Cellular Crash Test
To explore astrocyte mechanobiology
we have developed a novel cellular
crash test bioreactor.
1.
2.
3.
4.
Shuttle with cell culture inserts
Accelerometer
Guide rod
Spring dampened impact base
Integrated with a PC computer and
LabView)
Impacts up to 300g with
Durations up to 20ms