Explaining blue biotechnology with the example of using corals as bones.

1. Blue Biotechnology
Bone from Coral
Malvi Prakash
01/11/2017

2. Introduction
Blue biotechnology is a field that uses applications from molecular
biology, biotechnology and genetic engineering on freshwater and
marine organisms.
The role of blue biotechnology is mainly, to:
1. Provide tools for diagnosis
2. Provide and understanding of the genetics, physiology, biochemistry
and ecology
3. Recognize bioactive compounds and their modes of action

3. Ongoing Research Fields
Research Area Source Goals
Health Industry Algae, microbes, sponges Novel bioactives; pharmaceutical
and therapeutic uses
Industrial Products Algae Biopolymers for health, cosmetics
and food
Environmental
Studies
Marine organisms Biosensing technologies, non-
toxic antifouling technology
Energy Industry Algae Biofuels, biorefineries
Food Industry Invertebrates, algae, other fish Aquaculture, zero waste
recirculation system
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4. Corals as Bone Substitutes
Bone graft is a bone tissue sample that is used in surgical processes to
help regrow new bones (like a knee).
It is also used to heal damaged bones or problematic joints. They are
used in orthopedics, dentistry (cavities, etc.), spinal surgeries, etc.
Commonly, there are three sources of obtaining the graft:
1. animal (bovine)
2. human (donor)
3. synthetic or mineral
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5. Why do we need this substitute?
Usually, grafts are from animal or human sources:
1. Human sources have the risk of being rejected in the body
2. Animal sources have a disease risk, like mad cow disease
-Also, bovine sources need to heated upto 1000 degrees and that
makes the material very hard which doesn’t dissolve inside the
body and doesn’t get replaced by the new bone.

6. Corals as Bone Substitutes
For a long time, scientists have searched for biomaterials that can mimic
human bones in structure and function.
Corals caught the eye due to their porosity and composition of calcium
carbonate
-They way its exoskeleton is interconnected seem to be
supportive of new bone and blood vessel growth.
To put them into use, they must be converted to coralline hydroxyapatite
(HAp).
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7. Corals as Bone Substitutes
Mineral phase in corals consists of calcium carbonate majorly which is
in a structural form of aragonite.
-Impurities present are strontium, magnesium and fluoride ions
along with an organic matrix.
Though, not particularly osteoinductive or osteogenic, corals promote
cell attachment, growth factors passage, growth spreading and
differentiation.
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8. Corals as Bone Substitutes
A study conducted in Kolkata, India suggests a way of how this could
be done. It consists mostly hydrothermal process with many other
stages.
Repeated washing of coral
discs with chemicals and
alternative heating
Treatment with two
different solutions with
growth factors IGF 1 and
BMP 2
3, 4

9. Corals as Bone Substitutes
Results
Slow Good Better
Differentiated into 3 groups
Control BMP 2 IGF 1
Dents in tibia of 18 rabbit subjects
Inserted with converted coral implants
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10. Corals as Bone Substitutes
Corals also support growth of bone marrow.
-When coral supplemented bone marrow cells were infused in
defects, the surface area of the bone increased significantly as
compared to the ones in which only corals were not used.
The reabsorption of corals in the system made the grafting procedure
last much longer than traditional grafting techniques.
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11. Corals as Bone Substitutes
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Fig. 1: Human osteoblasts Fig. 2: Colonization of Isididae sps

12. Corals as Bone Substitutes
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Fig. 3: Interspace mineralization with coral (SEM imaging); transverse view of distal node; organic matrix on
which mineralization takes place

13. Corals as Bone Substitutes
8Fig. 4: Bone formation through coral tissues

14. Corals as Bone Substitutes
Today, the company “COREBONE” develops these grafts from corals.
They grow their corals in laboratories with a special diet of bioactive
materials that get embedded in their skeleton after ingestion.
These corals give similar texture and porosity as a bone would require
to regrow blood vessels through them.
-The pore size is usually 100-500µm, which is large enough for
tissue ingrowth.
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15. How do they do it?
• Drinking water through
reverse osmosis process
• added sea salts and
minerals
Closed systems/
Controlled conditions
• Cleaned and sterilized
with gamma radiation
• Further treatments
Branches cut off
• Used for surgeries and
other procedures
Shipped to customers

16. How do they do it?
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Fig. 5: Corals growing in controlled environment Fig. 6: Corals that were fed with bioactive compounds

17. Types of Corals used
Fig. 7: Different corals that are used (white coral; phylum; madrepora group; deep-sea Bamboo coral (Anthozoa:
Gorgonacea: Isididae))

18. Corals as Bone Substitutes
In some experiments conducted by scientists, corals are prepared for
bone materials in two ways:
1. Low temperature or hydrothermal method: a known volume of
hydrofluoric acid was added
2. High temperature or solid state reaction method: the coral is reacted
with chemicals at 900℃
Hydroxyapatite is a compound widely used for dental and orthopedic
purposes. Due to the lack of mechanical properties it is usually
associated with zirconia.
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19. Corals as Bone Substitutes
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Graph 1: Peaks of human bone, corals with high
temperature and low temperature technique
Graph 2: Peaks of human bone, corals with high
temperature and low temperature technique (with
Zirconia)

20. What is the current problem?
The problem now is to find a way to make these coral bone grafts
bioactive.
-when they are bioactive, they get the ability to communicate with
the human body cells.
Why do we need the coral cells to talk to our cells?
-“biological” bone graft which
will further help in reducing
rejection of the graft
-with communication the risk
of disease like mad cow
disease, can be reduced
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21. What is the focus?
The coral bone grafts being produced today need to have four qualities:
strength, biocompatibility, remodeling and bioactivity:
1. Strength: so it doesn’t get rejected
2. Biocompatibility: so growth can be stimulated on graft surface
3. Remodeling: so the new bone can grow while the graft degrades
4. Bioactivity: so it can communicate with human cells
CORE BONE says they are the first company to achieve all four
qualities with the costing lesser than usual grafting techniques which is
up to $5,000 (including hospitalization).
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23. References
1. McGrury, Dennis. Medicines of the Ocean. https://www.imms.org/downloads/brochure/IMMS_MedicineOfTheSea_Brochure_quadfold-
final.pdf (2012).
2. Hamza, S., Slimane, N., Azari, Z., Pluvinage, G. Structural and mechanical properties of the coral and nacre and the potentiality of their
use as bone substitutes. (2013).
3. Herlekar, I. Bone grafting using corals. Health and Medicine. https://indiabioscience.org/news/2015/bone-grafting-using-corals. (2015).
4. Ige, O., Umoru, L., Aribo, S. Natural Products: A Minefield of Biomaterials. ISRN Materials Science.
http://dx.doi.org/10.5402/2012/983062. (2012).
5. Marchac, D., Sándor, G. Experience with the use of biocoral in the craniofacial skeleton. Journal of Craniofacial Surgery.
https://www.researchgate.net/publication/231169840_Experience_with_the_use_of_Biocoral_in_the_craniofacial_skeleton. (1994).
6. Zhang, X., Vecchio, K. Conversion of natural marine skeletons as scaffolds for bone tissue engineering. Frontier of Material Science.
(2013).
7. Ehrlich, H., Etnoyer, P., Litvinov, S., et al. Biomaterial structure in deep-sea bamboo coral (Anthozoa: Gorgonacea: Isididae):
perspectives for the development of bone implants and templates for tissue engineering. Materials science and materials engineering.
(2006).
8. Binderman, I., Yaffe, A. Engineered coral, an optimal scaffold for tissue engineering of bone. http://core-bone.com/wp-
content/uploads/2016/08/Davos-publication.pdf . (2013).
9. Sivakumar, M., Manjubala, I. Preparation of hydroxyapatite/fluoroapatite-zirconia composites using Indian corals for biomedical
applications. Materials Letters. https://doi.org/10.1016/S0167-577X(01)00225-7. (2001).
10. Barkan, Y. Sci-Fi Medicine Sees Corals Turned Into Bone Grafts. NoCamles. http://nocamels.com/2015/02/corebone-okcoral-bone-
grafts-coral/. (2015).

24. The future of grafting is in the oceans!!
The patent of coral diet and coral growth for this specific purpose was
gained by CORE BONE in 2011
-since then the company has been testing the product successfully
with results of bone marrow formation similar to what it would be
in an actual human bone in a more efficient way
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25. Corals as Bone Substitutes
Corals have been converted to hydroxyapatite since 1974 when it was
first performed by Roy and Linnehan.
Coral granules have been used in craniofacial surgeries.
-in many cases there has been reported reabsorption and
augmentation of the material.
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