Designing Bioactive Materials
for Tissue Repair & Regeneration

Kristyn S. Masters
Assistant Professor
Department of Biomedical Engineering
UW-Madison
6/15/2006

00:00
Hello, my name is Kristyn Masters. I'm an Assistant Professor of 
Biomedical Engineering here at the University of Wisconsin in Madison,
and today I'm going to talk about my research, which involves the
design of bioactive materials for tissue repair and regeneration.

00:20
First, a little bit about myself: I have a background in chemical engineering, 
although I have performed research in biomaterials
and tissue engineering since my undergraduate career, and I have been an 
assistant professor here at the UW-Madison since August of 2004, 
and have continued to research the areas of biomaterials tissue engineering
with a specific focus on cardiovascular tissue engineering and cell-material interactions.

00:47
So, my general research and applications of my research are the
elucidation of in vivo disease mechanisms; the identification of
potential disease treatments or preventive measures against diseases;*
synthesis and testing of novel biomaterials, so that includes
synthesizing my own biomaterials or testing existing biomaterials;*
using the information we get from cell-material interaction studies
to predict or model cell-material interactions; and, ultimately,
the development of engineered tissues.*
And I've put stars next to, actually, these are directly translational research.

01:25
So, first a little background about the basic tissue engineering concept: 
In tissue engineering, cells are isolated from an autologous donor or 
from another person or animal. These cells are then expanded
outside the body, combined with a biomaterial scaffold, and then
implanted back into the patient or cultured for a longer time 
outside the body and then implanted into the patient, in order to repair or
regenerate diseased or disfunctional tissue within that patient.

01:55
Now the motivation for my work in cell-material interactions stems from 
the progress that has so far been made in the field of tissue engineering, 
namely, that tissue engineering has in fact strayed a bit from engineering 
tissues, and this has been evidenced by many
comments by several renowned people within the field, in that tissue
engineering has had an Edisonian approach characterized by some
ad hoc tinkering.
And so my goal is to look more closely at what goes on between the
interactions of cells with materials. In order to enable the
creation of functional engineered tissues, I believe that we must
design biomaterials that actively regulate or control cell function.
And that in fact it's a lack of understanding of some of these 
cell-material interactions that leads to our inability to rationally 
engineer biomaterials.

02:46
To sort of summarize these goals, the previous goal 
of tissue engineering was really to design biomaterials that support
cell adhesion and viability. However, we are progressing from
that goal to a new goal of designing biomaterials to actually
regulate cell function that control the cell behavior, and instruct
the cells on what to do.
So, we must design material properties based upon the needs of the cells, 
and in order to do this we will start by investigating how 
controlled, systematic changes in the biomaterials scaffold environment
impact cell function. In other words, we want to address the question, 
Can we gain precise control over cell function just by changing the 
biomaterial environment in which the cells are cultured?

03:30
To summarize the cell-material interaction work, other people have shown
that material properties do regulate multiple cell functions, 
such as differentiation, cell phenotype, apoptosis, and proliferation.
So, again, we want to see, Can we gain control over cell function
by changing material properties?
We are going to make very small changes in the material composition and then assess 
how cells respond to those changes, thereby telling us about how cells are interacting 
with the materials, possibly predicting how they will interact with future materials 
that we are making, helping us design new and optimized biomaterials for many different 
applications. And this work really applies to almost any tissue engineering or biomaterial 
application within the body, and, further, as I noted on one of my earlier slides, 
this work can also help us elucidate in vivo disease mechanisms, so seeing how cells 
are interacting with an environment can help us learn how they become diseased in vivo.

04:34
I'm going to give two examples of how we're applying this work in cell-material interactions in our lab. 
Both of these examples focus upon cardiovascular tissue engineering and a diseased 
cell phenotype; however, the other work in my lab does extend to many other 
applications for many other tissues and healthy tissues as well as diseased tissues.
So, this first example is how we are using biomaterials to control cell function and 
phenotype, specifically with respect to disease phenotype.
And this is some really interesting work that has generated some very intriguing results 
in that we are looking at whether we can intentionally modulate cell behavior between 
diseased and healthy states by changing the scaffold that we culture the cells on, or in.

05:23
So, on those top pictures you see a healthy, native heart valve, and, next to it, to the 
right of that, a calcified native heart valve, or stenotic heart valve, that needs to be replaced.
Similarly, we can produce very similar cultures in our lab. These are just in vitro cultures. 
On the bottom left, we see valvular interstitial cells, which are the main component 
of heart valves, and they are cultured on a scaffold where they exhibit a very healthy 
phenotype very similar to that seen in the native healthy valve.
Now on the bottom right, we see that, when in fact we culture these same cells on a 
different scaffold, they assume a very diseased phenotype and start forming calcified 
nodules, just like we see on a calcified heart valve. 
So, in fact, what we're taking away from this is that our biomaterial environment 
is extremely important in regulating how our cells function.
We can create diseased tissues, perhaps accidentally, by using incorrect or inappropriate biomaterials.
Furthermore, we can use this information to see, How is this native ve disease occurring naturally, and how can we block it?
How can we incorporate things into our biomaterials to make sure that they are not more susceptible to this valve disease.

06:43
And the second and last example I will present today is focussing upon how diseased 
tissue implants in scaffolds behave once implanted in vivo.
When scaffolds are implanted in vivo, they will not always be implanted into a 
healthy native environment.
Frequently, they will be implanted into an environment that is very full of 
disease-promoting factors.
And so, we want to look at how cells in two, or many, different scaffolds 
are going to respond to these native disease-inducing factors.
In other words, does a 3-D biomaterial environment control how cells respond 
to growth factors or cytokinds, and there is a lot of evidence that, indeed, 
it does control that response.
So, specifically, we're looking at heart muscle.
Following a heart attack or myocardial infarction, you end up with some dead 
tissue in your heart, into which we plan on putting a myocardial patch.
However, when that myocardial patch is implanted it will be exposed to a 
lot of disease-inducing factors.
And so we're looking at, and have some preliminary evidence to show, that, 
in fact, when cells are grown in different scaffolds, but then exposed to 
native disease-inducing factors, they will respond differently to those factors, 
depending upon the scaffold composition, even if they respond identically to a healthy environment.
So this is extremely important because it really highlights the importance 
of testing our engineered tissues in a physiologically relevant environment 
to the one in which we are going to be implanting the tissue, not just a healthy environment.
In addition, it can help us, again, better understand how heart disease 
is occurring and help us optimize the tissue engineering environment 
for many types of tissue engineering applications, not just limited to cardiovascular.
So that is an overview of some of the work that is going on in my lab, 
and if you have any questions, please feel free to contact me.