Bone repair and regeneration

At the beginning of their research work, the Doctors Camprasse focussed focused on the osseointegration properties of nacre as a bone substitute, with the aim of proposing an alternative to titanium dental implants. They then extended their research work to orthopaedic bone repair and regeneration. Look at their extensive work, backed by publications in scientific journals.

Field of application: dentistry

To test out and demonstrate the proprieties of nacre in the dental field, the Doctors Camprasse began by carrying out their first cases (on animals). First, they did so privately, then at the French National Veterinary School’s Biomedical Research Centre [Centre de Recherche Biomédicale de l’Ecole Nationale Vétérinaire] in Maisons-Alfort.

Biocompatibility of nacre


1988
 Publication in scientific journal Médecine et Thérapeutique (1) 

Substitution, in animals and human subjects, of the dental nerve with the skeletons of aquatic invertebrates [Substitution de la racine dentaire par des squelettes d’invertébrés aquatiques chez l’animal et l’homme]

The aim of this clinical study was to demonstrate perfect biocompatibility between the maxillary bone and the naturally-occurring CaCO3 in skeletons of aquatic invertebrates (coral and Pinctada maxima). The conclusion is as follows: it now appears possible to use artificial roots made of aragonite in oral implantology on a routine basis. The Doctors Camprasse noted rapid osteointegration, which seems to be produced by a chemotaxis of the material on the bone cell.

Tooth root

Mechanical properties and osseointegration of nacre

1990 Publication in scientific journal Clinical Materials (2)

Artificial dental root made of natural calcium carbonate (Bioracine)

The aim of this essay was to highlight the exceptional mechanical properties of nacre (hardness, strength, elasticity).

The conclusion reached by the Doctors Camprasse is as follows: the artificial dental root made from nacre, taken from the internal shell of the Pinctada maxima, is very close to bone tissue in terms of its composition, and presents remarkable hardness, strength, and elasticity.

A histological study of the interface between the implant and the human maxillary bone also demonstrated an extraordinary union cellular union between these two tissue types and therefore osseointegration of the nacre implant. Nacre is an exceptional tooth substitute, with biological properties answering to natural bone.

Pinctada Maxima

Regeneration of the maxillary bone (Odontostomatology)

1991

Scientific publication in Implantodonné (3)

A new biomaterial for bone regeneration – Clinical Study [Un biomatériau de régénération osseuse nouveau – Etude Clinique]

Having demonstrated in vivo that nacre was a non-toxic, bioactive and osteogenic biomaterial, the Doctors Camprasse worked on various odontostomatological pathologies, through clinical case at Hôpital Lariboisière hospital: remedying defected bone, elevating maxillary or mandibular ridges, remodeling to remedy loss of substance, augmentation of the vestibulo-palatine or vestibulo-lingual width in implantology, and extractions where decay was present.

The conclusions are as follows: four years on, the Doctors Camprasse can state that Bionacre® (in powder form used as a coagulum) is an extremely effective biomaterial for bone regeneration which opens up an array of possibilities in the field of bone surgery.

Powdered nacre used as a coagulum

Field of application: orthopaedics

Following their major discoveries concerning the properties of nacre in dental implantology, in the early 1990s the Doctors Camprasse broadened their fundamental clinical research, to gain an understanding of the mechanisms of actions of nacre on bone cells generally.

Osteoinduction in nacre

1992 Publication in scientific journal Tissue and Cell (4)

Demonstration of the capacity of nacre to induce bone formation by human osteoblasts maintained in vitro

The aim of this study was to test out the hypothesis according to which nacre may stimulate biomineralisation in human osteoblast maintained in vitro.

The conclusion is as follows: The Doctors Camprasse successfully demonstrated that when human osteoblasts were cultivated in the presence of nacre, a complete bone formation sequence was reproduced. The Doctors were the first to demonstrate that nacre contains molecular factors that induce osteoblastic differentiation, and that this osteoblastic differentiation enables the triggering of the bone’s biomineralisation mechanism. At the same time, they also demonstrated that nacre is not cytotoxic to bone cells.

Bone cell osteoblast

Osteogenic activity of nacre (orthopaedics)

1992 Publication in scientific journal Calcified Tissue International (5)

Nacre initiates biomineralization by human osteoblasts maintained in vitro

The aim of this study was to test out the hypothesis according to which there may be simultaneous presence of bone and nacre on human osteoblasts. Previously, the Doctors Camprasse had demonstrated that osteoblasts were able to differentiate themselves and thus trigger the bone’s biomineralisation mechanism.

The conclusion is as follows: The Doctors Camprasse successfully demonstrated that nacre does have a powerful osteogenic effect on human osteoblasts when they are placed near nacre. In other words, nacre has this spectacular ability to induce the formation of new, fresh bone.

Bone tissue under the microscope

Interface between bone and nacre implant

2014      Publication in scientific journal Journal of Raman Spectroscopy (6)

The interface between nacre and bone after implantation in the sheep: a nanotomographic and Raman study

The aim of this study was to analyse the interface between bone and nacre, to better ascertain biocompatibility with bone. The study was carried out on the bones of five sheep.

The conclusion is as follows: The Doctors Camprasse successfully confirmed a modification of the bone tissue around the nacre implant and the direct affixation of the bone, without a layer of organic matter, sandwiched between the calcium carbonate and the calcium phosphate. In addition, new bone formation is observed in direct contact with nacre, as previously demonstrated.

Nanotomography of an orthopaedic screw

in a sheep bone

In vivo assessment of bio-erosion and of the affixation of nacre screws onto the bone

2016         Publication in scientific journal Orthopaedics & Traumatology: Surgery & Research (7)

In vivo erosion of orthopaedic screws prepared from nacre (mother of pearl)

The aim of this study was to analyse the behaviour of nacre screws with the hypothesis according to which the screw would be assimilated by the bone without inflammatory effects, and without rejection occurring.

The Doctors Camprasse noted several phenomena:

  • The erosion is gradual
  • The cells do not have ragged edges (no inflammation)
  • The mineralisation rate is augmented in the vicinity of the nacre screw

In conclusion, nacre screws have the advantage of presenting in vivo partial resorbability properties thanks to the cells that originated from the macrophages, and to their osteoconductive affixation onto the material, without setting off a local inflammatory reaction.

In vivo study

on a sheep bone

Cell turnover

2019         Publication in scientific journal Journal of Materials Science: Materials in Medicine (8)

Giant cells and osteoclasts present in bone grafted with nacre differ by nuclear cytometry evaluated by texture analysis

The aim of this study was to analyse the interface between the nacre implant and the bone.

The Doctors Camprasse observed that there was partial erosion on the surface of the nacre screw, a few microns deep. This highlights the melding between the bone and the nacre screw and goes some way towards showing the osteointegration of the screw in the bone.

n : nacre, ob : old bone, nfb : newly-formed bone

In vivo osseointegration and erosion of nacre screws in an animal model

2020        Publication in scientific journal Journal of Biomedical Materials Research Part B: Applied Biomaterials (9)

The aim of this study was to compare the in vivo osseointegration and erosion of nacre screws versus titanium screws in an animal model.

Nacre is a promising biomaterial in maxillofacial surgery, it is resorbable only in contact with the bone marrow and has interesting osseointegration properties. In addition, it does not cause an inflammatory reaction and could be used as a bone graft substitute. It could also be used as a resorbable material for osteosynthesis, sparing the surgical removal of the device after bone consolidation.

Microcomputed tomography 2D images showing nacre screws implanted in the femoral condyle of the rat sacrificed at (a) T0, (b) T1 month, (c) T6 months and (d) T12 months.

Critical clinical study

15-cm femur bone loss

Surgery carried out on a human subject at Hôpital Béclère hospital, by Doctor Philippe Cottin

  1. Gunshot wound (buckshot), with a 15-cm femur bone loss.
  2. After multiple complications and two failed iliac crest autografts, decision to use the bone substitute Bionacre® to remodel the sequester.
  3. Five years on, good consolidation of the femoral core. No septic processes or fistula
  4. 20 years on, consolidation and remodelling of the medullary canal.

15-cm femur bone loss

2021 Feedback from Dr COTTIN with Drs. Serge and Georges Camprasse.

  1. Speed ​​of consolidation on an infected septic medium.
  2. Reappearance of the femur on the post-operative X-rays, in the few weeks that followed.
  3. Appearance of bone spicules on the paths of the external fixator, where the nacre was gone.
  4. Quasi-anatomical reconstruction of the bone: Reproduction of the medullary canal, perfect corticalization of the bone, very thick, on a constraint line, impressive formation of the peripheral canal.
  1. Camprasse G, Camprasse S, Gill G. Substitution de la racine dentaire par des squelettes d’invertébrés aquatiques chez l’animal et l’homme. Comptes Rend Acad Sci, Paris. 1988;307:485‑91.
  2. Camprasse S, Camprasse G, Pouzol M, Lopez E. Artificial dental root made of natural calcium carbonate (bioracine). Clinical Materials. 1990;5(2):235‑50.
  3. Lopez E, Vidal B, Berland S, Bozon C, Camprasse S, Camprasse G. Un biomatériau de régénération osseuse nouveau: étude clinique. Implantodonné. 1991;2:13‑7.
  4. Lopez E, Vidal B, Berland S, Camprasse S, Camprasse G, Silve C. Demonstration of the capacity of nacre to induce bone formation by human osteoblasts maintained in vitro. Tissue and Cell. 1992;24(5):667‑79.
  5. Silve C, Lopez E, Vidal B, Smith DC, Camprasse S, Camprasse G, et al. Nacre initiates biomineralization by human osteoblasts maintained In Vitro. Calcif Tissue Int. 1992;51(5):363‑9.
  6. Pascaretti‐Grizon F, Libouban H, Camprasse G, Camprasse S, Mallet R, Chappard D. The interface between nacre and bone after implantation in the sheep: a nanotomographic and Raman study. Journal of Raman Spectroscopy. 2014;45(7):558‑64.
  7. Libouban H, Pascaretti-Grizon F, Camprasse G, Camprasse S, Chappard D. In vivo erosion of orthopedic screws prepared from nacre (mother of pearl). Orthopaedics & Traumatology: Surgery & Research. 2016;102(7):913‑8.
  8. Chappard D, Kün-Darbois J-D, Pascaretti-Grizon F, Camprasse G, Camprasse S. Giant cells and osteoclasts present in bone grafted with nacre differ by nuclear cytometry evaluated by texture analysis. J Mater Sci: Mater Med. 2019;30(9):100.
  9. Kün‐Darbois, J. D., Libouban, H., Camprasse, G., Camprasse, S., & Chappard, D. (2021). In vivo osseointegration and erosion of nacre screws in an animal model. Journal of Biomedical Materials Research Part B: Applied Biomaterials109(6), 780-788.