Tissue Engineering Regenerative Medicine 2010
Olympic Biomedical Challenge
Esteemed Colleagues,
Thank you for agreeing to donate your expertise to a unique, cutting-edge
biomedical problem. As you have probably heard, LeBron James of the Cleveland
Cavaliers and Olympic Gold Medal USA Basketball Team, has suffered a careerthreatening injury to his right leg. After many consultations with medical experts,
it was decided that there is no traditional therapy that is likely to return this
dazzling athlete to current performance levels. After lengthy consideration,
LeBron has decided to aggressively pursue a risky, yet possibly rewarding, course
of action. That is why you have been invited to Pittsburgh Pennsylvania, a world
leader in the rapidly unfolding regenerative medicine revolution.
Although your specialties and inherent training vary, we recognize that only
a team of interdisciplinary professionals are equipped to answer this challenge.
Your diverse skills encompassing surgery, physiology, immunology, anatomy,
chemistry, molecular biology, physics, materials science, and engineering will be
tested as never before. As tissue engineers, you have an appreciation for the
multifaceted nature of this field, and the need to integrate a variety of science skills
to formulate solutions to the complex problem of human health. We welcome you
and thank you again. The eyes of the sports world and the world biomedical
community are now focused on your efforts in our fair city. Now to the challenge!
The supremely talented LeBron James has incurred a devastating trauma to
his right lower leg. Although the most important nerves escaped permanent
damage, there was much damage done to the dermis, the gastrocnemius muscle,
the tibia bone, and a critically important artery. It appears extremely unlikely that
standard therapies could quickly restore functionality, and there is even a chance
that permanent loss of function could abort his career. However, your relatively
untested new tissue engineering technologies appear to offer one last hope.
In the spirit of innovation and stimulating competition, your TERM (Tissue
Engineering/Regenerative Medicine) Teams will compete to develop viable
therapeutic strategies for this brave patient. It is obvious that great fame, possible
fortune, and personal satisfaction will forever touch the lives of any successful
team. Good luck, and Let the Games Begin!!
I.
Overview of Structure + Performance- Leg Model + Tissue Model
A. Tissue Model
1. What type of general tissue did you create?
2. What structural feature allows rapid identification of the general tissue type?
3. A liquid extract from a bodily tissue was tested. What was its’ density? What
common life substance has a similar density?
B. Chicken Leg Model
Identification of key tissues, their properties, and functions:
1.
2.
3.
4.
5.
How is force transmitted throughout the tissues of the leg, resulting in a leap or sprint?
Based upon the model wound, what process must we be careful to minimize in our attempts at
restoring full function to LeBron’s leg?
II.
SKIN TERM
1. Besides trauma, what other environmental factor can damage skin? What was the result
of your study?
2. What material might protect human skin from just such an insult? What evidence did
you gather to support this conclusion?
A. Skin Restoration
1. What was the purpose of the ‘Scratch Plate’ assay?
2. What critical process was revealed in your study?
3. What cellular processes led to a successful outcome?
4. What process, an unwanted type of solution, appeared to be minimized?
III.
BONE TERM
A. TE Triangle
1. What three components make up the Tissue Engineering Triangle?
2. What are the roles of these components?
3. What was the colored material that was imprinted onto the scaffolds?
4. The behavior of what living component was the subject of this experiment?
5. From where were these living components derived?
6. From your data, would any of these TE constructs likely yield a successful outcome?
Explain.
7. What was your measured GF concentration of the tissue extract taken from LeBron’s
implanted TE Bone? Is this result promising?
8. What is the desired fate (outcome) of an implanted scaffold?
9. Does your experimental data indicate that this outcome will occur in the desired time
frame? Explain.
10. What critical process that accompanies the above process was evident in the scaffold
extract taken from the TE implant used in LeBron? What cells are responsible for this
process? Why is this process so critical to bone function?
B. Bone Scaffold Synthesis and Characterization
1. Did you create a porous, organic scaffold? Why must it possess this property?
2. Was the scaffold osteo-conductive? What evidence was obtained?
3. List three required physical properties of scaffolds and explain their importance to
TERM.
4. Were you able to generate a new alloy to potentially serve as a bone scaffold?
Explain.
5. What is the significance of scaffold degradation products? Why might they be a
concern to TERM professionals?
6. Why was yeast chosen as a model for testing the effects of degradation products?
7. Based upon you data, what conclusions can you draw regarding the TERM utility of
this scaffold? What was the approximate LD50?
8. Assuming that the concentration of bone scaffold degradation product was 0.2% in
LeBron’s leg tissue, does this indicate a positive outcome? Should this scaffold
material be used? Explain.
C. Bone’s Precarious Balance
1. Why are bones considered to be dynamic tissues? How does this relate to the terms
“turnover” or “remodeling?”
2. What 2 bone cell types are vital to “turnover?”
3. Which of these cells types is most valued by bone tissue engineers and why?
4. Which of these cell types appears to lose functionality with age? What problem may
result from this decreased function?
5. Why are bone tissue engineers so concerned with bone remodeling timing? What two
processes do they try to balance when utilizing a scaffold to heal critical bone defects?
6. What did the precipitate simulate in your bone remodeling activity? What molecules
would this consist of if extracted from living bone?
D. Joint and Bone Biomechanics
1. How would you define a joint? What mechanical properties must it possess to
perform its’ function?
2. What tests did you conduct to test an important property of joints? How did living
joint material compare to the other tested materials?
3. What type of forces do bones have to withstand (list 3)?
4. What forces were tested in the Bone Strength Competition? Did your TE bone
construct perform successfully? Explain.
IV.
BLOOD VESSEL TERM
A. TEBV Scaffold Construction
1. What special physical requirements must a TEBV scaffold possess? Why?
2. How do TERM researchers often prepare TEBV scaffolds prior to implantation?
3. Did your TEBV scaffold possess features that would indicate a positive outcome?
Explain.
B. Blood Substitute Characterization
1. List 3 vital properties of blood.
2. What are the three common cell populations in blood?
3. What are some of the challenges in creating a blood substitute?
4. What property of blood substitutes did you analyze?
5. Why might this property be crucial to its’ use in humans?
C. Computer Simulation
1. What critical phenomenon to TERM success is modeled in this computer simulation?
Why is this so important?
2. Why does interest in this phenomenon often overlap with oncology?
3. Was your simulation a success? Explain.
D. Genetic Manipulation
1. Manipulating the Central Dogma of Life in humans is referred to as
____________________.
2. What type of molecule did you attempt to insert into the TEBV construct?
3. What was the intended outcome of this manipulation of life instruction?
4. What evidence would indicate a successful experiment? Did your attempt succeed?
V.
MUSCLE TERM
A. Stem Cell Extraction
1. The computer model reveals attempts at isolating and extracting what type of cells?
2. From what tissue are these cells being extracted? Relating to medical history, why was
this site chosen?
3. Based upon your extraction score, have enough cells been extracted to attempt a scaffold
seeding trial? Explain.
B. Seeding Efficiency
1. What does the term seeding efficiency mean? What type of cells are usually the subject
of this type of analysis?
2. What was your seeding efficiency for this TERM construct? Assuming that 1% is a
lower successful limit, did you obtain a positive result?
C. Stem Cell Manipulation
1. What conditions must be regulated to successfully grow stem cells in vitro? List 4.
2. How do researchers control the development of stem cells in TERM?
3. List 3 behaviors of seeded stem cells that researchers attempt to influence? Which of
these is the focus of this experiment?
4. What evidence did you find indicating a successful experiment?
Counselors:
Students are reminded that they and their TE colleagues represent PTEI biotech companies that
are competing for biomedical research and business dollars, in addition to the scientific fame that
should accompany a success in such a bold venture. Team (company) sizes are recommended to
be 4 students in size, though 3 or 5 might also work.
Instructors are to serve the roles of NIH science advisor, surgeon, and physical therapist/trainer.
After presenting this unusual case to the TE teams, the teams are provided with a pamphlet
containing an overview of the challenge, a few key questions to guide their strategies, a data
collection sheet, and an outcome assessment. After the teams watch a segment of “Tissue
Engineering for Life,” they are directed to answer the following questions from their pamphlet:
Why are experts from so many different field of science utilized in TERM? Explain the possible
role of each discipline in TERM
1. What are the two major components of a living tissue? Cells and ECM
2. What tissue in the body is designed to resist the most powerful forces? bone
3. What type of tissue interfaces (connects) to the above tissue and permits movement of the
body? muscle
4. What type of cells are thought to be most useful in attempts to regenerate a living tissue?
Where can these cells be found? Stem cells, embryo and post embryo (adult: bone marrow, skin,
muscle, nerve system, umbilical cord, fat, etc.)
5. What do researchers use to guide the 3-dimensional organization of these newly added cells?
Once this structure is implanted within the body, what is its ultimate fate? (clue: is it meant to be
a permanent implant, like a metal plate) scaffolds, it is meant to biodegrade
6. Regarding the implanted cells, what three major cell processes must researchers successfully
direct? Proliferation, migration, and differentiation
7. What molecules do researchers utilize to influence these cell processes? (Hint: what
molecules does your body use to control cell, and thus, tissue behavior?) growth factors, a type
of signaling molecule/hormones
8. In summary, it appears that three components are required to build an implantable TE
construct: cells, scaffolds, and signals.
9. The above three components can be referred to as the TE triangle. However, to achieve
successful regeneration, another component must be assured. What is it? (Hint: What body
component must all cells and tissues have to ensure adequate health?) blood supply
10. What are the two major processes used by the body to repair damaged tissue? Which of
these must be avoided in tissue engineering therapy? Why? scarring and regeneration.
Scarring must be avoided because it does not provide the same functionality as the target tissue
Assessment Report
TERM Team Company Name:
Professional Members and Specialties:
*Each yes is scored as 5 points
SKIN:
1. Did the epidermis regenerate within the allotted time period? (scale = 1-5) ___
BONE
1. Did your imprinted scaffold successfully influence stem cells to develop into osteoblasts?
(scale = 1-5) ___
2. Did your scaffold biodegrade in the desired time frame? (scale = 1-5) ___
3. Was their evidence of ossification in the scaffold? (scale = 1-5) ___
4. Did your TE bone successfully resist bending forces? (2.5Kg = 1, 3.0Kg = 2, 3.5Kg = 3,
4.0Kg = 4, 4.5Kg-above = 5)
5. Did you create a new alloy for use as a scaffold? (yes or no)___
6. Were the scaffold degradation products biocompatible at a concentration of 1%? (90-100%
survival = 5, 80-89% = 4, 70-79% = 3, 60-69% =2, below 60% = 1)
7. Was your tested allograft joint material effective at resisting friction? (scale = 1-5) ___
BLOOD VESSEL
1. Was your scaffold compressible and elastic? (scale = 1-5) ___
3. Was your scaffold resistant to shock forces? (scale = 1-5) ___
4. Did you successfully incorporate an angiogenesis promoting gene? (yes or no)
5. Did the scaffold achieve sufficient angiogenesis? (95-100% = 5, 90-94% = 4, 85-89% = 3,
75-84% = 2, 60-74% = 1)
MUSCLE
1. Did you successfully extract a sufficient population of stem cells for therapeutic use?
(5,500 – above = 5; 5,000-5499 = 4; 4,500-4999 = 3; 4,000-4499 = 2, under 4,000 = 1)
2. Did you seed your target tissue construct with a sufficient number of cells? (above 5% =
10, above 4% = 8, above 3% = 6, above 1% = 4, less than 1% =2)
3. Did your TE construct result in the formation of new myofibers? (scale refers to
myofibers/visual field; average of 4 fields – above 50 = 10, above 40 = 8, above 30 = 6,
above 20 = 4, less than 20 = 2)
Muscle: ___
_________
___________
____
Blood Vessel: ___
_____
Bone: ___
__________
______
Skin: ___
Total Points:_____
Points
_____ (91- 100) GOLD complete regeneration! Return to Olympic Champion Form
_____ (81-90) SILVER excellent regeneration, minimal scarring, Olympic Contender
_____ (71-80) Bronze very good regeneration, minimal scarring, Olympic Contender
_____ (61-70) Highly functional , amateur athlete status
_____ (51-60) functional, non-competitive athletics
_____(41-50) functional, performance restricted
_____ (40 –less) non-functional, candidate for new TE attempt
PTEI
CELLS
BLOOD
SIGNALS
SCAFFOLDS
2010 Biomedical
Olympic Challenge
Tissue Engineering Regenerative Medicine 2010