MSE/BioE C118 - Biological Performance of Materials

Prof. K. E. Healy
370 HMMB

Final Exam: December 14, 2006 5-8PM Closed Book Exam/One sheet of notes
Please answer all of the questions clearly and box your final answer. Useful equations, data, and
physical constants appear at the end of the exam.

NAME:__________________________________________________
ID NUMBER:_____________________________________________

Prob. 1 Prob. 2 Prob. 3 Prob. 4 Prob. 5 Total

Max = 20 Max = 20 Max = 20 Max = 20 Max=20 Max = 100

Extra Credit (2 pts.)

What decision did the FDA make last week regarding drug eluting stents?
MSE/BioE C118 Name:
1. The current blood-compatibility problems with drug eluting stents has prompted your company to
investigate alternative coatings. (20 pts.)
a. Surfaces that resist protein adsorption should have three common characteristics. What are
they?
b. You create a new coating from poly(sponge bob) [pSB], a polymer having these three
common characteristics. Derive an expression for pSB surface density (molec./area) in terms
of the degree of polymerization (5,000) and bond length (l=0.27 nm) that would optimize
blood-compatibility. Assume an ideal solvent. What is this optimal surface density?
c. Assuming your material can be modeled by the exponential approximation to the Alexander-
de Gennes equation, calculate the interaction free energy per unit area, W(D), at Rg. Is this
energy sufficient to repel protein adsorption and platelet adhesion?
MSE/BioE C118 Name:
2. Answer the following questions regarding controlled drug delivery.(20 pts.)
a. One type of drug delivery system is a monolithic device. In a monolithic device, the drug is
dispersed in a polymer matrix and its release is controlled by diffusion from the matrix. Assume
the concentration of the drug is less than the solubility limit of the drug in the matrix. Based on
Ficks first law, will this device have a constant flux? (Please state Ficks first law and explain,
each variable, listing appropriate units).
b. For a membrane controlled drug delivery device, what is the flux when the membrane is non-
porous? What is the flux when the membrane is porous?
c. The flux in these systems is expected to be constant. Assuming the membrane does not
change (i.e. it does not degrade or change shape), what parameter from your equation must be
kept constant in order to guarantee a constant flux? Why might this be hard to ensure?
Sometimes, membrane controlled devices show an initial burst release that is nonlinear. What
causes this burst effect?
d. Draw the release rate of a protein encapsulated in a PLGA microsphere. Will the microsphere
undergo homogenous or heterogeneous degradation? Please justify. What is the effect of size
dispersity of microspheres on the release rate? What processing technique can be used to
create more uniform sized spheres?
MSE/BioE C118 Name:
3. You would like to design a scaffold (i.e., porous body) for engineering the regeneration of tissue in
the body. (20 pts.)
a. What are the three key components of tissue engineering?
b. After considering the materials available commercially, you decide to use biodegradable
polymers for the scaffold. What are the advantages of using a biodegradable polymer for this
application?
c. For your biodegradable polymers you are considering using poly(L-lactide), poly(D,L-lactide-co-
glycolide), or poly(sebacic acid-hexadecandioic acid anhydride) [poly(SA-HAD anhydride)].
Discuss the degradation mechanisms and rates for each in an aqueous environment.
d. You decide to make the scaffold out of 25:75 poly(D,L-lactide-co-glycolide), how would you
make a scaffold out of this material? How fast would you expect it to degrade and why? What
kind of processing could you perform to extend the lifetime of the scaffold?
e. How would you enhance the growth of cells within the scaffold?
MSE/BioE C118 Name:
4. Current synthetic vascular grafts are made of ePTFE [e-poly(tetrafluoroethylene)]. You are
considering developing an alternative material and start the design process. Please answer the
following questions. (20pts.)
a. Give 5 design criteria a successful vascular graft must meet.
b. What is the meaning of the e in ePTFE?
c. What is the current limitation of ePTFE vascular grafts?
d. When the graft is placed into service it is rapidly exposed to blood and its components.
Describe the intrinsic, extrinsic, and common pathways of the blood-clotting cascade.
What are the most important molecules for the common pathway and what are their
biochemical roles.
e. You consider using either the critical surface tension (c) or the minimum SL hypothesis
to help you determine whether ePTFE will resist protein adsorption. Using
poly(tetrafluoroethylene) as an example, demonstrate that the theories contradict one
another. Can you rely on these theories to predict protein adsorption behavior?
MSE/BioE C118 Name:
5. Select one presentation topic given by a different group in class [you cannot select your own].
Identify the topic, address the materials used for the application from the standpoint of the general
biological performance. Critically evaluate the design modification presented in class, and suggest
possible alternatives. (20 pts.)
 MSE/BioE C118 Name:
Dupre equation: W12= 1 + 2 - 12
W12= 2(1 2)1/2

Girifalco-Good-Fowkes: 12= 1 + 2 -2i(1i 2i)1/2

i dispersive, polar, ionic, metallic, acid-base,

Lifshitz-van der Waals, etc.
i
H2O H2O = 72.8 ergs/cm , H2O = 21.8 ergs/cm2 , H2Op = 51 ergs/cm2
2 d

Young equation: SV= LV COS + SL

Van der Waals interaction free energy between a plate and a sphere
A123 R
WA (D) =
6D
Van der Waals interaction free energy between a plate and a plate
A123
WA (D) =
12D 2
Electrostatic interaction free energy between a plate and a sphere
- ' 1+ eD * 0
W E ( D) = o R2 (132 2
+ 23 ) 2 + 2 )( 1 eD ,+ (
/2 13 23
ln + ln 1 e 2D
)2
. 13 23 1

Where 1= polymer surface

2= sphere (e.g., cell, protein)
3= medium

Electrostatic interaction free energy between a plate and a plate

# &
W E ( D) = (64kT u 2 )eD Where u = tanh% ze13 4kT (
$ '

100L
Alexander-de Gennes equation: W( D) kT exp D L
( ) for D < 2L
s

Surface density =1/s2

MSE/BioE C118 Name:
Alexander (1977) L = nl5/3/s2/3

Radius of gyration Rg=ln1/2/61/2

Equations governing flux (g/cm2-sec) through a membrane

EDKC DKC
J= J=
l l