What is biological material? Is natural coral a biomaterial?

Very briefly, a biological material is a product which, inserted into the body, is not rejected. It does not generate immune reactions. It is "accepted" by the body.

What are the characteristics of natural coral?

Jean André PEYSONNEL, an 18th century French surgeon, determined the fact that corals were animals: coral polyps. In their tissues they maintain single-celled algae, zooxanthellae, which use photosynthesis to produce the elements which are essential to the corals. They also remove toxic residues. Chlorophyll, combined with various pigments thus helps give corals their different colours.

For further information: a Natural coral production unit

Physical characteristics of coral:
This material, of natural origin, is a Calcium carbonate compound in its crystalline phase: aragonite. It displays great architectural regularity, with open pores allowing fluids to circulate freely inside the skeleton.

Cross-section of human spongy bone

Cross-section of coral – porites – displaying
50% porosity
Here you can see the similarity between the two structures

This porosity varies according to the species of coral under consideration. The volume of porosity, pore interconnection, regularity and diameter (150 µm on average) all mean that, once implanted in the bone tissue, there is total and rapid invasion of the graft by blood or bone marrow cells, vascularisation is established (insert here calculations of pore areas and volumes). The coral architecture provides an exceptional surface for exchanges between the biomaterial and the bone..

Biomechanical characteristics of coral:
The mechanical characteristics of coral depend on the haemodynamic constraints it is under and the organisation and volume of its porosity. They therefore differ according to the type and species under consideration.

For further information on the mechanical characteristics of coral

Chemical characteristics of coral :
In the book: Les coraux, B. Robin, C. Petron and C. Rives and coll. have shown that the primary phase in the development of the coral skeleton resembles mammalian osteogenesis in its fundamental mechanisms. Corals are essentially composed of mineral elements but also several appropriate amino acids – which should be eliminated, or at least reduced as much as possible - using specific purification processes such as supercritical fluids – to avoid, minimise and/or remove any harmful immune reactions.

There are differences between coral and fresh bone. The mineral phase in particular – 2/3 of bone composition – which is essentially in the form of calcium phosphate. Although the organic phase is important in bone – 1/3 of its composition – it is reduced to a very small proportion of amino acids in coral. However these should be eliminated to avoid any risk of immune reaction.

There are analogies: Two have specific action. Strontium is involved in the growth of bone crystal. Fluorine increases bone formation in spongy bone, in small doses and has the opposite effect on the bone walls at high concentration. It acts by stimulating osteoblast precursor cells.

For further information on the chemical characteristics of coral

Biocompatibility :

Tests were performed on rats, rabbits, sheep, pigs and dogs. They concerned the behaviour of tissues coming into contact with the material in various implantation sites: subcutaneous, intramuscular, intraosseous, subperiosteal and alveolodental.

No acute or chronic inflammatory reactions were observed, nor any granulocytic infectious reaction, nor any rejection with proliferation of round cells or fibrous encapsulation. No tissue concerned showed any immune reaction against the biomaterial. Very good tolerance was observed in all cases.

Coral in skin

Coral in muscle

Coral in bone

Coral in bone

Coral in neoformed bone

Coral in neoformed bone

Bioresorbability and coral in animals :

Filling a collapsed spongy bone in dogs – with a fragment of coral implanted in one end of the bone – shows almost total resorption of the biomaterial in six weeks and its replacement by bone tissue.

Histological studies have shown, particularly in dogs and pigs, the presence of numerous osteoclasts in contact with the coral during resorption. Carbonic anhydrase was revealed in the osteoclasts. The involvement of carbonic anhydrase in the destruction of carbonate substrates has been studied since 1969 and the demonstration of this role proved by the slowing of destruction after administration of acetazolamide, a specific carbonic anhydrase inhibitor .

To verify the hypothesis of this enzyme's role in the destruction of coral carbonate skeletons, 10 femoral transcortical resections involving replacement by this biomaterial have been performed on animals treated with acetazolamide.
In comparison with untreated subjects, a definite slowing in the resorption of implanted coral was noted. This was accompanied by bone necrosis on the edge of the graft, which tended to spread to the entire bone. These resections were not consolidated, even one year later and all led to pseudarthrosis. The resorption of coral carbonate skeleton is, at least partly, due to the carbonic anhydrase in osteoclasts.

The transformation of coral into bone takes place in several successive phases. These are embedded as the calcification front advances.

Experiments led, histologically, to the revelation of five phases, recorded consistently, which are successive and embedded as the resorption front and calcification fronts advance.

Group "Formation et Destruction des Tissus calcifiés"
(Formation and destruction of calcified tissues)
University Paris VII Biology and Genetics research unit

Phase 1 (Image 1) :
The coral is invaded by blood cell and bone marrow elements:

x 200 PAS colouring. Preparation as demineralised tissue. The coral is partly demineralised and appears to be translucid. The entire porosity is invaded by the coral implanted in the femoral diaphysis of a dog.

Phase 2 (Image 2) :
Establishment of a vascularisation.

x 160 Masson trichrome stain. Preparation as demineralised tissue, but the coral is only partly demineralised. In this image, two arterioles can clearly be seen (arrows) and the shells of their walls can be clearly differentiated.

Phase 3 (Image 3) :
Resorption of coral by osteoclasts.

x 1200 Haematoxylin-eosin stain. Preparation as demineralised tissue. The coral is only partly decalcified and appears as a whitish area. Two osteoclasts are on the edge of the coral, their brush-like edges directed towards the material to be resorbed (arrows) .

Phase 4 (Image 4) :
Osteoblastic apposition responsible for bone neoformation. It is concomitant with the resorption phase.

x 180 Haematoxylin-eosin stain. Preparation as decalcified tissue, with the coral only partly decalcified. The neoformed bone is displayed as deep pink, with the first osteoblastic layer laid directly on the coral: successive layers will gradually thicken the new trabeculae (arrows).

Phase 5 (Image 5) :
Remodelling of neoformed tissue according to the architecture of the implantation site.

x 200 Masson's trichrome stain. Preparation as demineralised tissue. Cortical bone site of implantation of a fragment of CORAL in a dog's femur, after 18 months.

At the end of the process, BIOCORAL© has been totally resorbed, the neoformed bone tissue which initially formed the coral architecture has been remodelled as haversian tissue.

Group"Formation et Destruction des tissus calcifiés" (Formation and destruction of calcified tissues)
Université Paris VII U.F.R. de Biologie et Génétique - Paris FRANCE

The resorption process has been studied in dogs and pigs.

Image 1 x 1000 - Paragon stain
Preparation as non-demineralised tissue.

Implantation in a pig's metaphysis, 4 weeks after surgery. The coral is dark brown, the edges fringed with osteoclastic action (arrows). The non-demineralised preparation technique does not allow accurate identification of cells. This is done on decalcified preparation.

Iconography: L.R.O. U.A. CNRS 1161 Paris FRANCE

Image 2 x 1000 - Haematoxylin-eosin stain
Preparation as demineralised tissue. The coral is only partly decalcified and appears as a translucid area.

The osteoclast, with its brush-like border, is clearly visible, directly against the coral and hollowing a resorption lacuna (arrow).

Group"Formation et Destruction des tissus calcifiés" (Formation and destruction of calcified tissues)
University Paris VII Biology and Genetics research unit - Paris FRANCE

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