Kolspon Sterile Collagen Sponge Exporter

Ever wondered, what dentistry will be like in the future? Will the traditional "drill and fill" dentistry disappear? Will
dentists and other members of the dental team be replaced by robots? Will we be able replace a broken down tooth
with a "custom-grown" tooth?
Stem cells regeneration holds a lot of potential for modern day medicine and dentistry. It's exhilarating just
Imagining the possibilities! Yet, the obstacles researchers have to solve before the possibilities translate from
research to every day clinical practice are many. Growing our own teeth for dental treatment will take many more
years of research and validation yet.
Something that may take a little less time than growing an entire tooth but with equally exciting potentials, is the
increased regeneration of a layer of the tooth structure – dentine – for repair of tooth cavity or fractured tooth.
We already use dental materials, such as calcium, calcium-phosphate and calcium silicate-based medicaments(1-3),
to stimulate dentine repair at present. However the amount of reparative dentine generated is only very little -
adequate as a protective barrier or a “biological seal” to prevent damage to the dental pulp but not enough to repair
an entire cavity.
The activation of stem cells via low level laser to stimulate growth factors such as transforming growth factor beta-1
(TGF-B1) for dentine regeneration has also been reported.(4) Again, a potentially good idea but so far, the amount
of reparative dentine generated in experimental studies have not been adequate to repair the entire tooth cavity.
In January 2017, King's College London published in Scientific Reports, the possibility of growing new dentine,
enough to fill an entire tooth cavity.(5) The process relies on the use of Tideglusib – a GSK inhibiting drug
that is being tested for treatment of Alzheimer’s disease.(6)
The new approach currently being tested by King’s College London Dental Institute’s Head of Craniofacial
Development and Stem Cell Biology, Prof Paul Sharpe and co-workers, involves placing biodegradable collagen
sponge soaked with a low dose of Tideglusib (glycogen synthase kinase (GSK-3) inhbitors) to the tooth
cavity.(5,7) The collagen sponge biodegrades over time and new dentine is formed in its place, to the point
where the entire cavity is repaired by dentine.(5,7) The mechanism of action appears to be related to Tideglusib’s
ability to stimulate the activity of stem cells in the dental pulp via Wnt signalling pathway activation.(5,7)
While the research certainly sounds exciting, it will be some time yet before research translates to clinical practice.
The King's College London study was performed using the teeth of mice and cavities that were cut into the teeth
deliberately.(5) The regeneration to fill the entire cavity took at least 4 weeks.(5) Human cavities, will pose a bigger
challenge in every sense of the word. In addition to a big size difference, human cavities, with all the inflammatory
and infective processes going on, will likely affect stem cell responses and add further complications to the
challenge. Moreover, Tideglusib is still undergoing clinical trials and safety testing for its intended uses in
medicine…so translating its use to dentistry, is unlikely to happen in the near future.(8)
Sharpe suspected he could dramatically boost teeth’s natural healing ability by mobilizing stem cells in the dental
pulp. Earlier research had demonstrated the Wnt signaling pathway—a particular cascade of molecules involved in
cell-to-cell communication—is essential for tissue repair and stem cell development in many parts of the body such
as the skin, intestines and brain. Sharpe wondered: Could this signaling pathway also be important for self-repair
processes in teeth? If so, maybe exposing damaged teeth to drugs that stimulate Wnt signaling would similarly
encourage the activity of stem cells in the dental pulp—giving teeth the kind of regenerative superpowers usually
seen only in plants, salamanders and starfish.
To test this idea, Sharpe and his fellow researchers drilled holes into the molars of mice, mimicking cavities. They
then soaked tiny collagen sponges (which are made from the same protein found in dentin) in various drugs
known to stimulate Wnt signaling, including tideglusib, a compound that has been investigated in clinical
trials for its potential to treat Alzheimer's and other neurological disorders. The scientists then placed these
drug-soaked sponges in the drilled mouse molars, sealed them up and left them for four to six weeks . The
teeth treated with these drugs produced significantly more dentin than ones untreated or stuffed with an unsoaked
sponge or typical dental fillers. In most cases the technique restored the rodents’ pearly whites to their former intact
state. “It was essentially a complete repair,” Sharpe says. “You can barely see the joint where the old and new dentin
meet. This could eventually be the first routine pharmaceutical treatment in dentistry.”
David Mooney, a professor or bioengineering at Harvard University who has also investigated new ways to heal
teeth but was not involved in the study, says he is “very impressed” by these findings. “This is not just scientifically
important, but has significant practical advantages," he says. Adam Celiz, an assistant professor of bioengineering at
Imperial College London who was also not involved in the recent research, says this is an important advance in the
emerging field of regenerative dentistry. “The materials dentists use could soon be revolutionized,” he says.
Any treatment that recruits the body's native stem cells or adds new stems cells to the body, however, poses a risk of
uncontrolled tissue growth. Experimental and unregulated stem cell therapies have resulted in brain tumors, for
example, as well as bones growing in eyelids. But in this case, Sharpe says, the amounts of drug used are so tiny that
the risk of unwanted growth is minimal. Celiz agrees the danger is small but he says rigorous testing in lab animals
and clinical trials should be done to rule out potential side effects.
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Since publishing their initial study Sharpe and his colleagues have tested their regenerative technique on rats.
(Because those rodents have larger teeth than mice, a drilled rat molar better approximates human tooth decay.) The
treatment worked just as well on the rats as it had on the mice, Sharpe says, but the data has not yet been published.
Now Sharpe’s team is investigating a larger group of candidate drugs in order to determine whether another
medication works better than those already tested, and to determine the optimal dose. They are also developing an
alternative delivery system that is more amenable to modern dental practices: The chosen drug will be dissolved in a
gel that is injected into a cavity and bathed with ultraviolet light to solidify it—a quick and easy procedure similar to
one dentists already use to seal and repair teeth.
In order to formally introduce this treatment to modern dentistry, however, the researchers will need to perform
clinical trials with human patients. Such work is at least several years away, Sharpe says. But some of the drugs he
might consider are already approved for other uses in humans, which he hopes could expedite the process for
eventual approval. "A lot of dental treatments are still in the dark ages," Sharpe says. "It's time to move on."

To test the induction of Axin2 in vivo, experimental tooth damage was created, by drilling and making 0.13 mm
holes in mouse maxillary first molars to expose the pulp (Fig. 2). Pieces of Kolspon were cut to size and soaked in
solutions of the three inhibitors before being physically placed into the holes, in contact with the pulp. A glass
ionomer cement was used to cover the sponge and protect the tooth (Fig. 2G). Treated teeth were removed after 24 
h along with controls consisting of untreated teeth, MTA only and collagen sponge with no inhibitor. Pulp cells were
extracted and tested for expression of Axin2 by qPCR (Fig. 1E). Expression of Axin2 was found to be 3 fold higher
in inhibitor treated pulp cells when compared to controls (Fig. 1E). Significantly MTA showed no effect on Axin2
expression over controls suggesting current protocols do not lead to enhanced activation of Wnt signalling. After 5
days post treatment, Axin 2 expression levels were the same in with MTA and agonist treatments but these results
were compounded by the fact that newly forming odotonblast-like cells express high levels of Axin 2 (Figs S1–2).