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Effects of additional collagen in biphasic calcium phosphates: a study in a rabbit calvaria

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Abstract

Objectives

Biphasic calcium phosphates (BCP) are synthetic biomaterials developed as an alternative to the autogenous bone grafts and xenografts. The aim of the present study was to assess the influence of the addition of collagen onto the BCP resorption rate and bone formation.

Material and methods

Eighteen male NWZ rabbits approximately 12 weeks of age were used. Critical size defects were randomly treated with bilayered BCP materials comprising 12% HA and 88% α-TCP with and without collagen or sham-operated, respectively. All defects were covered with a resorbable collagen membrane. Animals were euthanized after 3 and 12 weeks of healing and investigated by micro-CT, histologic, and histomorphometric analysis.

Results

Woven bone formation was observed from the original bone at 3-week healing in all samples. After 3 months, mainly lamellar new bone in the peripheral area was observed. In the central region, both woven and lamellar bone were seen. Samples containing collagen showed less residual biomaterial than without collagen at both healing periods. Both types of granules were in close contact with new bone, yielding a complete defect closure at 3 months of healing. However, new bone volume and area was similar for both biomaterials.

Conclusions

Within its limitations, the study results qualify collagen as a biocompatible carrier for BCPs. The presence of collagen indicated neither significant impact on the resorption of the BCPs nor on bone formation.

Clinical relevance

The addition of collagen to BCPs might not be beneficial for the augmentation of extended bone deficiencies.

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Acknowledgments

The authors wish to thank the staff at the ESI, Surgical Unit, DBMR, University of Bern, Switzerland, for excellent handling of the animals, Mr. Mark Siegrist for his assistance during μCT evaluation and Ms. Inga Grigaitiene for the histological preparation. The synthetic bone substitutes were kindly provided by Geistlich Pharma AG (Wolhusen, Switzerland).

Funding

The study was supported by the Department of Cranio-Maxillofacial Surgery, Faculty of Medicine, University of Berne, Switzerland.

Author information

Authors and Affiliations

  1. Department of Cranio-Maxillofacial Surgery, Berne University Hospital Faculty of Medicine, University of Berne, Freiburgstrasse 10, 3010, Berne, Switzerland

    Benoit Schaller, Masako Fujioka-Kobayashi, Viola Christina Schuler, Hiroki Katagiri, Niklaus P. Lang & Nikola Saulacic

  2. Geistlich Pharma AG, Bahnhofstrasse 40, 6110, Wolhusen, Switzerland

    Claudio Zihlmann

  3. Advanced Research Center, The Nippon Dental University School of Life Dentistry at Niigata, 1‑8 Hamauracho, Chuo‑ku, Niigata 951-8580, Japan

    Hiroki Katagiri

Authors
  1. Benoit Schaller
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  2. Masako Fujioka-Kobayashi
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  3. Claudio Zihlmann
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  4. Viola Christina Schuler
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  5. Hiroki Katagiri
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  6. Niklaus P. Lang
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  7. Nikola Saulacic
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Corresponding author

Correspondence to Nikola Saulacic.

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Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved from the Committee for Animal Research, Canton of Berne, Switzerland (Nr: BE 89/17).

Informed consent

For this type of study, formal consent is not required.

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Electronic supplementary material

Suppl. Fig. 1

Surface appearance of the particles of BBCP and BBCP_C. The rough surfaces with pores are observable on each particle. Collagen matrix is further contained in BBCP_C material (PNG 3497 kb)

High resolution image (TIF 3718 kb)

Suppl. Fig. 2

Toluidine blue and fuchsin staining of BBCP and BBCP_C particles after mixed with blood during surgery. Blood cells (yellow arrowheads) are attached and kept on the surface of bone substitutes despite a lot of liquid handling. Collagen fibers (black arrows) also encapsulated blood cells (yellow arrowheads) in BBCP_C materials (PNG 5042 kb)

High resolution image (TIF 5265 kb)

Suppl. Fig. 3

Center of the defect next to the dura mater treated with BBCP (A) and the periphery of defect treated with BBCP_C granules (B) after 3 weeks of healing. Direct contact of new bone (NB) is restricted to the surface of both type of granules (*) (PNG 5176 kb)

High resolution image (TIF 5321 kb)

Suppl. Fig. 4

Higher magnification of the periphery of the defects treated with BBCP (A) and BBCP_C (B) granules after 3 weeks of healing. Apposition of new bone (NB) is observed in the large pores of both types of granules (*) (PNG 4649 kb)

High resolution image (TIF 4633 kb)

Suppl. Fig. 5

Center of the defects treated with BBCP (A) and BBCP_C (B) granules after 3 weeks of healing. Nonintegrated granules (*) are covered with a plenty of multinucleated giant cells (arrowheads) and a condensed fibrous tissue (PNG 5477 kb)

High resolution image (TIF 5703 kb)

Suppl. Fig. 6

Periphery of the defect treated with BBCP (A) and center of the defect treated with BBCP_C granules (B) after 3 months of healing. Residual granules (*) are embedded in the newly formed bone (NB). Osteons (arrowheads) are observed within the newly formed lamellar bone and perforating the granules (PNG 5033 kb)

High resolution image (TIF 5069 kb)

Suppl. Fig. 7

Higher magnification of the center of the defect treated with BBCP (A) and BBCP_C (B) granules after 3 months of healing. Residual granules (*) are almost completely surrounded by a layer of multinuclear cells (arrowheads). Cell poor and highly vascularized loose connective tissue is observed between the granules (PNG 5290 kb)

High resolution image (TIF 5516 kb)

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Schaller, B., Fujioka-Kobayashi, M., Zihlmann, C. et al. Effects of additional collagen in biphasic calcium phosphates: a study in a rabbit calvaria. Clin Oral Invest 24, 3093–3103 (2020). https://doi.org/10.1007/s00784-019-03181-8

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  • DOI: https://doi.org/10.1007/s00784-019-03181-8

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