Transcribed by Joseph Schwimmer

Craniofacial Biology Lecture #38 CCP Periodontal Regeneration 5/8/14

Slide 1 Introduction
Dr. Ronald Craig: Okay so good morning, we might as well get started. So today, so you can understand that
this course is loosely organized and for this unit - well for all the units - we try to end with a clinical case
presentation and so Im gonna do a case presentation and I am going to try to do it differently today.
This is a case that was actually seen in the PG program and what Id like you to be able to do at the end of this
CCP is Id like you to be able to define whats going to be present after when healing, if youre given a cell
population that can repopulate that wound healing site. And also given that information on inductive factors
and signaling molecules that will be present. But that kind of a high, a high standard to have, believe me my
perio residents in the first year have a hard time trying to figure out. But you have enough information from
this unit you should be able to do that, and to radically change the outcome of wound healing, to age your
patient is a remarkable thing, and patients love that, and gives you a feeling of empowerment. So let kind of
go through that thing. So thats one of objective.
The second objective is this will give me a chance to present some of the material that was an important in
these six or seven lectures but from a more clinical orientation, youre beginning to make the bridge now from
the basic science part of your curriculum to more pathology and treatment association part of your curriculum
so this is kind of timely to do at this point.
So anyways, lets talk about this gentleman.
Slide 2 Presentation
So he presented to the emergency clinic, bad things to present to emergency clinics, 42-year-old male, chief
complained my teeth are becoming loose, and we have a new patient, and they are aware that their teeth are
loose, that means that you are already trying to play catch-up football, because you have to lose at least 50%
depending upon the tooth type, but as a rough rule of thumb, you have to lose about 50% of the periodontal
connective tissue attachment apparatus to actually clinically start to see significant mobility, especially that a
patient is aware of because it doesnt occur overnight usually, it happens over a period of years. History of the
chief complaint, that he had a past emergency visit to our college, they diagnose something called a
periodontal abscess on tooth 23, and this is why you dont want to go to the emergency room because they
extracted it, and that was done four months previously. His only med is Prozac you will see a lot of folks on the
battery of serotonin type inhibitors youll get to that in pharmacology, social history middle-class, youve got a
high school diploma, is a plumber, which means he is independently wealthy. So when you start to think about
your own career odyssey, you have to go through college you have to go through dental school, most of you
will have some residency experience and then you go out into private practice and you got to set up your
private practice, or buy into someone elses. And youre way down the road before youre actually making a
profit. And when we had the house in Philadelphia, we did most of the stuff, but I refused to do the plumbing,
because its difficult because you have to have all of these special tools and stuff, so I called up a plumber for
an estimate on my house, and it was a Sunday afternoon you know Ill never forget it, and he shows up in my
slum neighborhood in western Philadelphia with his beautiful Jaguar, and he comes out of his Jaguar, and I
realized that there is perhaps some problem with my life choice as far as finances were concerned. So hes
probably, if he owns his own plumbing business hes probably independently wealthy.
Smoke cigarettes which is too bad, and family history both parents were diseased, both where he sensualist.
Dental history, episodic care, most people who come to you with severe dental disease, theyll sit in the chair
and tell you that they brush their teeth and they use floss and I believe them but I can also see what
happening, so education in oral healthcare is really really important.
He does say that when he brushes his teeth, his team bleed, but we can talk about that another time. Medical
history, chronic depressive disorder, no prior hospitalizations.
Slide 3 Presenstation
So lets get on, and youll learn or perhaps have already learned how to do this, youll do this in the clinic. Hes
already hypertensive at this point in time perhaps, poll is elevated, he doesnt like seeing you, its kind of
amazing, I wake up on Tuesdays, clinical days, and I realized that the next 25 people that I am going to meet in
the operatory hate my guts, they dont want to be there, its kind of weird, but anyways you get over that.
Chronic depressive disorder, under treatment, endocrine, renal, gastrointestinal, integument, osteoarticular,
all within normal limits, so we are going to focus in on this gentlemans periodontal problems. A head and
neck exam is within normal limits. Intraoral hes got lots of inflammation that will see, and inflammation
seems to be associated with microbial biofilm accumulation, hes got areas of recession, each got teeth that
are mobile, we are not going to go through the restorative and, well just do a visual clinical on him, not a real
perio exam, and Ill show you some radiographs.
Slide 4 Clinical Presentation
So this gentleman, a front view. So we kind of went through in this section that its the cementoenamel
junction that in general determine where the alveolar crest is going to be. And with this gentleman here is his
cementoenamel Junction nicely stained with nicotine, and here is his gingival. So obviously there has been a
breakdown in the function of the gingival. So the gingival provide a biologic seal that protects the underlying
periodontal connective tissue attachment apparatus, and that is broken down, so the integrity of that
junctional epithelium, the integrity of the underlying connective tissue is such that it allowed bacteria and
bacterial products allowed to come in. and hes got this wonderful inflammatory response look at how this
marginal gingiva is kind of red, and multiple areas of periodontal connective tissue attachment loss. This was
the tooth that was extracted several months prior, and lets make-believe that this individual was aesthetically
concerned, and this person isnt, but you will have many patients that are aesthetically concerned, and
remember I said they will come to see you and say after I would like to have an implant here, and what you
will hear is that I want a tooth here, and so there is no buccal plate here, remember most teeth are in buccal
version in relation to their alveolar process, and when that tooth was extracted. Nothing was put in place. And
so all of this area resorbed, and now you have this defect, this concavity, and furthermore here is the
cementoenamel junction, again, nicely outlined by nicotine, and bacterial products. And if you put an implant
in there, you may not even have enough bone to hold an implant, but youre certainly not gonna to have
enough bone to mimic a root eminence, like you have on the adjacent sites, and youre not going to have
these wonderful interdental papilla. So to a patient its a simple thing, they want an implant placed, but you
when you talk to them, kind of have to get their expectations, and if this person is very aesthetically
demanding, you kind of have to see that area, and alert them that there is going to be some potential
problems with their case.
Slide 5 Clinical Presentation
So lets take a look around his mouth, and maybe I can point out some other things. So here is his central
incisors, and if you didnt pick up a periodontal probe and it didnt take a radiograph, it doesnt look too bad
here, right? In fact, if I kind of look at the attached gingiva, here is the new coach and general junction up
here, and here is the attached gingiva. The way the flash caught this area, you can see this dimpling, in some
text books theyll tell you, this dimpling is a sign of health. No its not, not necessarily right, and we will show
you what kind of destruction is in that area, these teeth are mobile, this tooth is extruding because of
inflammation thats present in this site. There is our canine, thats a lateral, I guess, and now you can kind of
see the biofilm, more clearly, and you can also see the surrounding reaction of this gentlemans immune
system in the presence of that bacteria and bacterial products.
Slide 6 Clinical Presentation
And here is the lingual, you know he is a smoker, because every little orifice of those minor salivary glands our
kind of inflamed, you look in there and thats nicotine stomatitis, and lots of tar and nicotine stains.
Slide 7 Clinical Presentation
Lower incisors.
Slide 8 Clinical Presentation
And well go through this quickly.
Slide 9 Clinical Presentation
So I use a toothbrush every day, Dr. Craig.
Slide 10 Clinical Presentation
Update dont know how to use a toothbrush or use interdental cleaners effectively.
Slide 11 Clinical Presentation
So we spend a lot of time with our patients in our practice going through oral hygiene, because its really the
most effective therapy we have.
Slide 12 Clinical Presentation
I am just going to run through these really quickly.
Slide 13-17 Clinical Presentation
So this tooth is going to be the tooth that we are going to talk about as far as treatment options. Well try to
review some of the stuff that were presented in this unit, so hes got a lot of inflammation and a lot of loss of
periodontal connective tissue attachment apparatus.
Slide 18 Clinical Presentation
So this is a little light, so this is radiograph, so we said that its the cementoenamel Junction, that determined
especially the height of the alveolar crest, so you kind of draw one line here and one line here and here is the
parallel line. Here is crest, so this is obviously a big area of attachment loss.
Slide 19 Clinical Presentation
The anteriors, bone level way up here, should be up here, lost about 50%, so these teeth our real loose, Again,
this is the tooth that we are going to be treatment planning for, very very deep, this is called the infrabony
vertical defect, some people get periodontal disease equally on all teeth, and so there is connective tissue
attachment destruction, that goes equally, sort of like the tide going out at a wharf, you know all the pilings
equally affected. And folks that have a much more severe and hard to treat case tend to have these vertical
kinds of defects that are site-specific rather than tooth specific, and these types tend to be much more
aggressive, and you need to be more aggressive in your treatment.
Slide 20 Clinical Presentation
Here is that tooth that was extracted, prior to extraction, again, more vertical defects. When you
radiographically see two of the three components of the alveolar process, so you can see this kind of radio
dense area so thats the bundle bone of the alveolus proper, and thats being supported by this spongy looking
material, so thats trabecular bone of the alveolus. And you can see the buccal and lingual cortical plates but
the cortical plate is the third component.
Slide 22 Clinical Presentation
And youll have to have odontogenesis in order to have those components of the maxilla and in the
mandibular arches, really deep defects. So a lot of these teeth are not really treatable, but we are gone to try
to treat one of them.
Slide 23 Diagnosis
So the first thing you want to do is to come up with a diagnosis. You dont need to know this stuff now. But
next year I will give you some lectures on gingivitis and periodontitis, but for now, this is a moderate to severe
periodontitis patient, so the function of the gingiva is broken down and has allowed bacterial antigens,
perhaps even bacteria to get deep into the periodontal connective tissue attachment apparatus. That ensues
and immune response which well learn about in general pathology, an innate & adaptive immune response.
And what actually destroying the patients tissues is his own immune response. We talked a little bit about
MMPs, so most of this tissue is type I collagen so youll have to have MMPs that will break down this collagen.
Any idea why you would want to do that from an evolutionary standpoint? Why would you want to have
mostly the neutrophils are the guys who come in and snarf down bacteria, and phagocytose them and kill
them, but those PMNs also bring in MMP 8 which destroys fibrillar collagen. Why would you want to do that?
First one this disease was studied in the last century, people thought that they were collagenases in the bugs,
so collagenases in the bugs were doing the destruction. But it was actually been MMPs that the patient brings
in doing the destruction. Why would you want to do that? Any ideas?
(student: can it help the breakdown of the bone because the bone has some collagen?)
Dr. Craig: well the bone is being destroyed, the bone is being resorbed, and but connective tissue is being
resorbed, the periodontal ligament is being destroyed, the gingiva is being destroyed, thats why when you
put your probe in, it goes further down.
(student: what it have to be due to breaking down fiber clots during bone?)
Dr. Craig: we are getting closer.
(student: do you need to open up the area so that still can get rid of the bacteria?)
Dr. Craig. Bingo! So if you make yourself kind of small, and become like a neutrophil, so the neutrophil is
targeted to that area, and the endothelial cells and we will learn about this in general pathology- actually
have receptors that recruit out of a stream of cells that come through, target out neutrophils, and the
neutrophils get out of the vasculature into the extra vascular space and we will learn about all different kinds
of signaling molecule neutrophils use to hone in where the infection is. But if you think of a neutrophil, its
really big, and if you think of a bacteria, thats a really tiny, like two or three orders of magnitude. So its really
easy for the bacteria to get into that collagen meshwork, the extracellular matrix brushwork, if you will. And
how does that big old cell get in and phagocytose if that little bacterial cell or bacterial colony this are
embedded in that meshwork, or that extracellular meshwork. So what has allowed is, the PMNs bring in the
MMPs, the MMPs breakdown that extracellular matrix, exposing the bacteria, allowing the polymorph
neutrophils to phagocytose or kill the bacteria, but doing so you destroy your own tissues. And if this
continues, in a chronic kind of situation, you end up with is that look like periodontitis. And thats good, so you
kind of have to think a little teliologically, giving the powers of human thought to inanimate objects.
The prognosis, we dont really need to talk a lot about the prognosis, its going to lose a lot of teeth. Hopefully
he has a titanium deficiency that we can treat with lots of titanium implants. So this problem list, but what is
his problem as far as this disease is concerned? While the number one problem is that he is allowing this
biofilm to form, and as you will learn next year its not the massive biofilm that is important for periodontitis,
it is allowing the most apical part of that biofilm to become relatively anaerobic, and then these gram-negative
anaerobes take over, and that thats what his immune system is responding to with such veracity. So, if you
dont allow any areas of the biofilm to become anaerobic, in other words you remove it each day, then you
dont have the inciting element present to make the disease go, and then calculus is nothing more than
calcified biofilm. Thats a really great place for bugs to hang out and recolonize.
(student: something about periodontitis)
Dr. Craig: You know that bone loss is because of the immune system, so the bugs are there. In fact, some of
the bugs kind of set up the inflammation, but have a very tricky way of blunting it. Should I tell you this stuff
now? So as it turns out there is one group of bugs called the red group, and they are gram-negative
anaerobes, and what these guys have done, is they only use carbon for their energy and carbon source, and
they also need a lot of iron, so what they do is they call in more inflammation, so they got a lot of PMNs, and
PMNs are pumping out MMPs, and the MMPs is breaking down the patients protein, and allowing for
peptide, and thats what they use for their carbon and nitrogen sources, so that good. Then, you are bringing
in a lot of inflammation, so you get a lot of swelling and hemorrhage, and they love heme, thats how they get
their iron. And that theyve worked out really subtle ways of getting rid of complement and other things that
kill them off, so in many ways they are sort of parasitic, but we will talk of them next year, we are getting a
little ahead of ourselves.
Okay, so plaque, that biofilm is really important, the first thing you got to do is how to get rid of that biofilm,
right? The Tuesdays they never teach you in school is how to manage money, very few people manage money,
the second thing is how to care for your teeth, no one ever teaches you that, I never know how to take care of
my teeth until I got to dental school. Most people are not, are (???) susceptible to periodontitis. Any idea,
have they told you in the epidemiology course how many people are susceptible to periodontitis at this point
that time? If you went out on first Avenue, and we tackled 100 people, and we opened their mouths, how
many of them would have severe periodontitis like this? Like 50, over 20 (age), you dont want to tackle
children, but you can tackle adults. How many say over 50%? How many people say it more than 50%? If you
say more, it actually turns out to be about 14%. Most people are not susceptible to this disease. However 14%
of how many are in the United States, I mean thats a big enough number, however not everyone is
susceptible to this disease, so not everyone has to have this meticulous plaque and debridement. So when you
go ahead and remove that calculus with your instrument, you are removing the affected root cement them
along with the calculus, the calculus gets interdigitated with the relatively soft matrix. Its got digital
inflammation with bleeding upon probing, if youve got a site that doesnt bleed, I feel really good, I dont care
what the pocket depth is. If I have a site that looks inflamed, and when I remove my probe it bleeds, those
gram-negative anaerobic, red group, its probably there. So that upon probing, is not associated with health,
one of the things you get from probing. When you actually put a periodontal probe into a site, and youll
actually get this number, you read the number off the, what are you measuring? Are you measuring anything
anatomical? No. So its a function of the probe diameter, how hard you push, and how much inflammation is
present, associated with these MMPs destroying the extracellular matrix.
Genetics, and so as it turns out about 14% of the human population is susceptible to this type of disease.
About 50% of the variance, and we will talk about this next year in a course called diagnosis and treatment of
oral diseases, about 50% of the disease is due to genetic factors, factors they arent characterized, but there
seems to be a very big genetic component to this disease.
Smoking,at one point in time there are people that actually said that periodontitis loss caused by cigarette
smoking, the association is so tight. Thats not true. But it is a very strong modification factor, if you have the
gram-negativeanaerobes, and you are susceptible, and you throw on cigarette smoking, this disease takes off
like wildfire. So thats a problem for us, so we have to do something about smoking.
And he is depressed, depressed people are really hard to motivate. So you will find out until we actually do
some research thats a little more of a public health thing. If your total success of your therapy is dependent
on their being able to practice oral hygiene that means you have to change their human behavior, and Naslow,
you knows the human behavior specialist from Harvard, said that very few people can actually change their
behavior. So you will find, if you do Perio like I do, you will find youre trying to crawl into their heads and find
some motivating factors so they will change their behavior and they will start to have good oral hygiene. Its
kind of sad when you think about how much time has been spent training your hand to do all these wonderful
techniques, and its really about patients hands that are the important part of the equation. Perhaps youll
come up with some way that well rely on plaque control for the future.
Slide 24 Diagnosis & Treatment Plan
So youll learn that most treatment plants are divided into phases, and this gentleman is only going two have
to phases, and were only going to focus in on his surgical phase. The first thing youve got to do is youve got
to teach him how to do oral hygiene, and a very high level, because he is susceptible to the disease, and you
are going to go in and do something called scaling and root planning, youre going to remove those hard
bacterial products called calculus, so-called affected cementum from the root surfaces, even if you got into
playing very well, antigens from the calculus will diffuse into the gingival connective tissue and cell their
immune system thinks that there are still live bugs there, and the disease will march on, so you gotta get in
there and remove all those deposits.
Because this patient have severe periodontitis, so I want to try to tip the scales as much as I can in his favor, so
I use something called doxycycline, very very low-levels of it, its marketed to us in a form called Periostat, we
talked about this in basic tissues. That preferentially inhibits MMP 8, tends to leave MMP 1 intact, so I use a
lot of this in my practice, get him to stop smoking cigarettes, perhaps take up another habit like heroin or
whatever. But you definitely want him to stop smoking.
And then at the end, what do you do is after you finished all your phase 1, you go back and you do all your
charting again, and you look at the sites, well first off your looking is the oral hygiene good? And if the oral
hygiene is good, and I put my probe in, and if it looks inflamed and I have bleeding upon probing, or I have
suppuration welling up out of that area, well you know maybe I have to do something, maybe this site is so
deep that he cant get in to clean all the apex, maybe the site is so deep, I couldnt get down and cleaned all
the way and clean to the apex, and so perhaps, maybe some kind of making those pockets more manageable
would be in order, but you only do that if they have a great oral hygiene. When you get into practice youll
forget that, and then you do like your surgeries and stuff, because thats what you get paid for, and your
patient doesnt get better right? You dont want to be in that position, because that a terrible position to be
in. So well only do surgical corrections at least in my practice, and thats almost the truth, then they have
really good oral hygiene. Until we come up with a better way.
Slide 25 - Outcomes
So how do I correct those deep pockets that I cant maintain and he cant maintain? So here is this lower first
molar, has this deep infrabone packet, have a little wad of I dont know what there. So clinically you look in,
and if you didnt have a periodontal probe, you didnt have a set of periapical radiographs, you wouldnt really,
you would kind of miss this, until you lost 50% of the periodontal connective tissue attachment apparatus, and
then the two could become really loose and then you wouldve lost the ballgame. So we are going to go
through a series of things that we can do for this site, and with a special eye to what is going to be the
resulting interface between this previously exposed root surface, its exposed to this periodontal pocket, and
all the sub gingival biofilm, and got connective tissue that forms there after wound healing.
As it turns out, in a historical way, so the first thing were going to talk about, is Ive already been here in a
closed procedure, so what if I kind of go in, and I make an incision from both sides, and with my elevator I
come in and I peel away the gingiva both on the lingual and the buccal, and now I can kind of like look in there,
and I can see those calculus deposits, and I have much more access, so thats called a flap for debridement.
And you will learn about this stuff in your second and third years.
And the next thing we are going to talk about his about there is a hole there. So why dont we put in a bar
graft, so that was the next thing we started to do. So we will talk about the outcomes of doing that.
And since this is a nice 3-wall infrabony, and when you get into the Perio lectures you will learn that you can
do wonders here, I love seeing these kinds of defects. You can be a hero in these kinds of defects. And thats
going to be using something called guided tissue regeneration that we touched on in this lecture series, and
then the latest thing that you can do is guided tissue regeneration, but just using enamel matrix protein, so
called Emdogain. And we will look to see what kind of interface you get with that. And if all else fails you can
extract it and put in a dental implant, and we will talk a little bit about the interface between go dental
implants and the connective tissue after wound healing. So lets do the first thing.
Flap surgery for debridement, I still do this, this is probably one of our earliest approaches, flap the area,
getting clean it out, resuture it.
Slide 26 - Outcomes
And what happens if you do that, and so here is that little cartoon from Stuart Nymans a historic article. So
weve kind of made this, its called an inversed bevel incision, and we removed all the tissue that was sitting
there, its all chronic inflammatory tissue, just get it out of there so you can kind of see, and that gives us
access to the root surface, and then we resuture back, so now weve got this scaffold, this fibrin scaffold. So
blood is going to come in and heavy bleeding is a sign of life. Bleeding is your friend, so if you have blood
coming into the area, there is lots of exposed type I collagen, that is a really good hemostatic agent, that is
going to precipitate the clotting cascade, the end result is fibrinogen converts to the polymer fibrin, so you got
this fibrin scaffold that gets decorated with fibronectin, and under that fibronectin highway, comes all sorts of
cells. First ones in there are polymorph nuclear leukocytes, cleaning out the area getting rid of the bacteria,
and then youve got cells from the gingival epithelium, connective tissue, alveolar bone, periodontal ligament,
and what happens is the epithelium, its function is to cover connective tissue, so it goes through mitosis real
quickly, and migrate along that previous exposed root surface, and then you got something that colloquially
known as a long junctional epithelial attachment. So thats what we used to have, I still get patients this in the
right context. I cant probe it any longer, this epithelium is attached to the root by hemidesmosomes, gotta
know that. I can probe and thats fine, bacteria cant get in here, at least to the bottom of the cell because
thats as far as they can populate. So all is great with the world. But I send the patient back to the referring
dentist, and he says Dr. Craig, I cant probe him, but on the x-ray I still see this defect, I have this hole here.
And by now youve noticed that in dentistry we dont like holes, if there is a hole in the tooth you want to fill
it, if there is a hole in the dentition you want to put an artificial tooth there. If there is a hole in the bone, you
want to fill it with something. So we started putting it in bone grafts, and if youre smart, you put in a bone
graft thats not decalcified. So you fill this thing up with bone and you take a radiograph, because its not
decalcified it comes back as this stuff. And then youre referring dentist calls you up, Dr. Craig, once again
youve performed a miracle!
But if you look at that root surface, do you have cementum, periodontal ligament, alveolar bone? Or do you
have something else? What do you think you have there? You didnt stop that gingiva from migrating down
there, right? So what youll have, is youll have a whole bunch of bone particles that may or may not be
converted into the patients own bone. But you have this long junctional epithelial interface. So it looks good
on the radiograph but you still got the same results that you would have gotten with a flap & debridement.
And thats what it looks like there, so here is the sulcular epithelium, there is this long junctional epithelium
attachment, this is from a monkey experiment, a primate experiments. So here is the notch, this is depth of
the previous attachment loss. And here is some bone that is regenerating and here is a little bit of cementum,
periodontal ligament, thats regenerating.
Slide 27 - Outcomes
And so these are the kinds of observations that let Stuart Nyman to propose to use a barrier to selectively
allow cells from the periodontal ligament, to get on to that fibrin scaffold and exclude itself from gingival
connective tissue and epithelium, so you get this wonderful regeneration of alveolar bone and periodontal
ligament and cementum.
And in lecture we talked about, we said this is a wonderful thing, this is unbelievable, this is mind blowing, I
was taught that periodontitis is irreversible, well its reversible, and we also talked about the stem cell
population that lives down here, and what we did is we allowed him appropriate stem cell population to come
in here, and the stem cell population, and we dont really understand why or how, was able to identify this as
the previously exposed root surface, so some of the cells differentiated cementoblasts. And once cementum
was laid down, some of these cells came in and said whew thats cementum, so now I gotta make some
periodontal ligament, so they became periodontal ligament fibroblasts. And then finally if youre lucky you get
the third tissue which is alveolar bone exactly as it forms during development. With one caveat, if you look
carefully, I forgot high-power on this, and I should have, this is all cellular cementum, and during development,
but first cementum thats laid down on the root surface is acellular cementum. So you got part of the
equation, youve got the appropriate cell population, but you dont have to write cocktail of inductive factors
Slide 28 - Outcomes
So we talked a little bit about Lars Hammerstrum, at the Karolinska Institute in Sweden, and he was able to
show that amelogenin, and amelogenin like peptides appear to be at least one of the signaling molecules, and
that kind of makes sense, because the inner layer of HERS is directly derived from the inner layer of the
enamel organ, the enamel organ makes enamel protein amelogenin, further down it makes that crazy
intermediate matrix, that has amelogenin in it, so why not put amelogenin like peptides on previously exposed
roots. And thats what we did here, so we made a little divot, and this is a pig, and we were interested to see if
we can get periodontal connective tissue attachment apparatus things that normally dont support
regeneration like gutta-percha. So anyway I am just want to show you a control, this is an old experiment, this
is a little divot. So all this area was exposed surgically, and all this regenerated, and if before you replace the
flaps you put Emdogain, in-place, what happens is so here is the native cementum, here is the notch, and most
of this area is acellular cementum just a couple of cementocytes. You can kind of see, this area had MTA,
methyltrioxa(?) aggregate which normally doesnt support cementum formation during healing of root canals,
and you get this nice thick layer of cementum if you put Emdogain on top of that material.
So now youve kind of completed the equation, you have the correct cell population coming in, you have
pluripotential periodontal ligament stem cells are coming in, and then you also have a layer of amelogenin, or
amelogenin like peptides on that root surface, and that induces cells to become acellular cementoblasts, and
lay down acellular cementum, and notice how its attached to the surface as opposed to cellular cementum,
doesnt really have that same attachment. Whats the clinical significance? I dont know. But in this situation
youve more closely mimicked what occurs during development.
Slide 29 Outcomes
Okay, so what if all fails and you extracted tooth and put in an implant, this is a bio horizon implant, and the
person who developed that is actually here, his name is Jack Ritchie, and if you actually get a chance to hear
Jack Ritchie, and you hear about biomaterial and implants, definitely hear Jack.
Slide 30 Outcomes
So anyways, this is another study we did a few years ago, we put in implants into pigs, and we were trying to
get periodontal ligaments to form, but we did get some wonderful histology. And heres an implant in a pig,
and here is the area of the osteotomy after healing, and if you kind of look real carefully up here, there is the
gingival tissues, epithelium goes all the way down just enough to this thread and after that bone comes really
close to this titanium surface, titanium is really reactive in the atmosphere, it makes a number of oxides, and
as it turns out titanium oxide is immunologically privileged, you dont mount an immune response to titanium
oxide. And so the bone forms in this osteotomy site, and its fuses, has a very very close adaptation to the
titanium surface. So this is really an ankylosis, there really is no periodontal ligament down here, right? But
there is fusion of bone, Brandemar called this osteointegration, its really ankylosis, but everyone kind of uses
osteointegration. And its a very close adaptation of bone to the implant, so much so that the implant is
practically immobile. And one of the things that amazes me is this area here, that gingiva during the sealing
mechanism, and so you dont have any of the five principal fibers, you have ankylosis. And you only have three
of the five gingival fibers, and so what youre really counting on are these epithelial cells to attach to these
hemidesmosomes on that epithelial surface, to seal out all the bacteria and bacterial products on the site.
Slide 31 Outcomes
Okay, any questions on what you get at that interface in various scenarios, because youll be asked this on an
outcomes learning assessment, otherwise known as the final to this course. Okay let me go on to this one
more thing, so we talked about BMP, very little, we talked a lot about amelogenin, so the two inductive
signaling molecules. We talked a little bit about the gingival connective tissue somehow inducing the overlying
gingival epithelium to become keratinized or non-keratinized, depending upon the source of the underlying
connective tissue, I showed you a free gingival graft, I showed you something called Alloderm which doesnt
have any cells in it so obviously there doesnt seem to be any cell signaling involved. And Ill show you what we
actually do now.
Slide 32 Outcomes
So this gentleman had a number of recessions, and he wasnt treated here, but this lady was, this was an
elderly lady. And I just want to briefly to describe, now you understand that if you get connective tissue from a
site that normally supports stratified squamous keratinized epithelium, thats what youll be able to induce an
effect, so this is the other lady that has these multiple recessions, and remember that you tend to get
recessions on the buccal, because most teeth are in buccal version in relationship to the alveolar bone, so she
doesnt like to look at this. Most of these are done for aesthetic reasons, not for health reasons. So you kind of
do this thing called a tunnel technique. My assistant loves these. So what you do, you have to anesthetize
them first, mind you, never forget that. And then you go in with a little micro blade, that they use for
ophthalmic surgery, it works very well, and you place the blade into the sulcus, and you make a little pouch,
and you go all the way around, all the way around, and then you go back in with little tiny elevators, and you
get into that little pouch, and you undermine, lift up the gingiva off the alveolar bone you have
communication on the other side, so you have a pouch here, a pouch here, and you go underneath this
papillary area, and you make like a little tunnel. Thats kind of neat. And then you go to the palate, you
measure out how much connective tissue you need, and you add a little bit, because the connective tissue is
going to shrink on you. You go up to the palate, you make a little trap door, so you dissect the trapdoor, so the
epithelium and some of the connective tissue stays with the trapdoor, and you climb in into that space
vacated by the trapdoor, you dissect out a big long strip of connective tissue. Then, you put it on the bracket
table, you take a picture because you are very proud, of this long piece of connective tissue youve got. And
then you go back in, and you take a suture, and you run the suture from say here, all the way through the
tunnel all the way to here. Then you take your connective tissue, then you hook it to the suture, and this is the
fun part, and can take the needle all the way back if you want. This is the fun part, so now you start pulling
over here on the suture, connected to the connective tissue, and the connected tissue goes through the
tunnel, through the tunnel, through the tunnel, through the tunnel. Out the other side, you dont even have to
put sutures in, and meanwhile youre covering these recessions with connective tissue, and if you are lucky,
the underlying alveolar bone and the overlying flap will give vascularity to the connective tissue strip you put
in there, and after wound healing this is what it looked like. Pretty amazing stuff, my assistant loves that, in
fact she wants to pull the suture in and everything, looks like a train going through the tunnel. Anyways, thats
called a tunnel procedure. It works because, they epithelium that migrates over that connective tissue bed
and its probably through the extracellular matrix molecules that are present get instructed, or induced to
form a stratified squamous epithelium.
Slide 33 Outcomes
Okay, so I think I kind of beat this to death, so what we try to kind of convey in these lectures, if you have a
pluripotential stem cell population that can still express the genes that are appropriate for the tissue you
want, and that wound healing environment, and you supply the right inductive factor, you will end up with
cells that are committed to that phenotype, and you have to set up the wound healing environment to allow
those cells to divide, and to differentiate to the phenotype that you want in that site. So there is basically
three concepts that we try to provide during this unit. First off, and Dr. Wishe also did a nice job with this
during tooth development that odontogenesis and development of the periodontal connective tissue
attachment apparatus as a component of that, can be viewed as a epithelial mesenchymal interaction. And
that wound healing recapitulates a lot of the events that occurred during development, so if you really
understand how periodontal tissues are developed, then you would be able to select the right pluripotential
stem cell population, and you will be able to supply the right inductive factors to really change the outcome of
wound healing rather dramatically.
So this has really kind of become this idea biomimetics. In fact, our Department of biomaterials is also called
the Department of biomimetics to kind of reflect this idea. So this is kind a different strategy in Perio and
implantology for the last few years. So you try to set up the wound healing environment to try to mimic what
happened during development, and you have the incredible ability to induce periodontal regeneration, which
will only a dream when I went to dental school.
No questions? Is everyone confused, or if everyone really exhausted?
(student question: can periodontitis cause the cyst/abcess?) it was directly caused by periodontitis. He had
lost so much attachment as you saw on the radiograph, these areas tend to abcess, and abcess are a collection
of bacteria and mostly neutrophils trying to warn it off. And it becomes painful. But you will learn about that in
general pathology, thats not part of this course.
Okay, so the next two hours were going to morph, the next two hours are going to be presented by Dr. Louis
Lin. Dr. Lin and I go back to many years. So hes gonna give you two hours on the biology of the dental pulp,
today and 8 oclock on Monday, and Ill come back at my clock on Monday and share with you how teeth
erupt, or more perhaps to the point of what we dont know about how teeth erupt. Turns out it is still up for
grabs, and we will see you then are you guys have a good weekend. And we will see you on Monday.