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Comparison of synthetic ceramic products formulated with autologous blood coagulum containing rhBMP6 for induction of bone formation

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Abstract

Purpose

Osteogrow, an osteoinductive device containing recombinant human Bone Morphogenetic Protein 6 (rhBMP6) in autologous blood coagulum, is a novel therapeutic solution for bone regeneration. This study aimed to evaluate different commercially available calcium phosphate synthetic ceramic particles as a compression-resistant matrix (CRM) added to Osteogrow implants to enhance their biomechanical properties.

Methods

Osteogrow implants with the addition of Vitoss, ChronOs, BAM, and Dongbo ceramics (Osteogrow-C, where C stands for ceramics) were evaluated in the rodent subcutaneous ectopic bone formation assay. Osteogrow-C device was prepared as follows: rhBMP6 was added to blood, and blood was mixed with ceramics and left to coagulate. Osteogrow-C was implanted subcutaneously in the axillary region of Sprague–Dawley rats and the outcome was analyzed 21 days following implantation using microCT, histology, morphometric analyses, and immunohistochemistry.

Results

Osteogrow-C implants with all tested ceramic particles induced the formation of the bone-ceramic structure containing cortical bone, the bone between the particles, and bone at the ceramic surfaces. The amount of newly formed bone was significant in all experimental groups; however, the highest bone volume was measured in Osteogrow-C implants with highly porous Vitoss ceramics. The trabecular number was highest in Osteogrow-C implants with Vitoss and ChronOs ceramics while trabeculae were thicker in implants containing BAM and Dongbo ceramics. The immunological response and inflammation were comparable among ceramic particles evaluated in this study.

Conclusion

Osteogrow-C bone regenerative device was effective with a broad range of commercially available synthetic ceramics providing a promising therapeutic solution for the regeneration of long bone fracture nonunion, large segmental defects, and spinal fusion surgeries.

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Data availability

Raw data were generated at the Laboratory for Mineralized Tissues. Derived data supporting the findings of this study are available from the corresponding author, S.V., upon request.

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Acknowledgements

We are grateful to Stryker Corporation (Kalamazoo, Minessota, USA) for providing Vitoss ceramic particles evaluated in this study. We thank to Mirjana Marija Renic and Djurdjica Car for their excellent technical assistance in animal experiments and excellent preparation of histology sections.

Funding

This research was funded by the FP7 Health Program (FP7/2007–2013) under grant agreement HEALTH-F4-2011–279239 (Osteogrow), H2020 Health GA 779340 (OSTEOproSPINE), and European Regional Development Fund—Scientific Center of Excellence for Reproductive and Regenerative Medicine (project “Reproductive and regenerative medicine—exploration of new platforms and potentials,” GA KK.01.1.1.01.0008 funded by the EU through the ERDF).

Author information

Authors and Affiliations

  1. Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Zagreb, Croatia

    Nikola Stokovic, Natalia Ivanjko, Viktorija Rumenovic & Slobodan Vukicevic

  2. Scientific Center of Excellence for Reproductive and Regenerative Medicine, Zagreb, Croatia

    Nikola Stokovic, Natalia Ivanjko, Viktorija Rumenovic, Mihaela Peric & Slobodan Vukicevic

  3. Department of Pathology and Cytology, University Hospital Centre Zagreb, Zagreb, Croatia

    Anita Breski

  4. perForm Biologics Inc, Holliston, MA, USA

    Kuber T. Sampath

  5. Department for Intracellular Communication, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, Zagreb, Croatia

    Mihaela Peric

  6. Department of Orthopaedic Surgery, School of Medicine, University of Zagreb, Zagreb, Croatia

    Marko Pecina

Authors
  1. Nikola Stokovic
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  2. Natalia Ivanjko
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  3. Viktorija Rumenovic
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  4. Anita Breski
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  8. Slobodan Vukicevic
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by NI, NS, VR, and AB. The first draft of the manuscript was written by NS and SV, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Slobodan Vukicevic.

Ethics declarations

Ethics approval

Study has received ethics approval from the Ethics Committee at School of Medicine, University of Zagreb and the Croatian National Ethics Committee (EP 191/2019 and EP 296/2020).

Animal care complied with the SOPs of the Animal Facility and the European conventions for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS 123). The ethical principles of the study ensured compliance with European Directive 010/63/E, the Law on Amendments to Animal Protection Act (Official Gazette 37/13, the Animal Protection Act (Official Gazette 102/17), the Ordinance on the Protection of Animals used for Scientific Purposes (Official Gazette 55/13), and FELASA recommendations.

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Not applicable.

Competing interests

Slobodan Vukicevic is a founder of Genera Research and a coordinator of the EU HORIZON 2020 grant OSTEOproSPINE, funding clinical studies for new bone repair drugs (patent WO2019076484A1).

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Stokovic, N., Ivanjko, N., Rumenovic, V. et al. Comparison of synthetic ceramic products formulated with autologous blood coagulum containing rhBMP6 for induction of bone formation. International Orthopaedics (SICOT) 46, 2693–2704 (2022). https://doi.org/10.1007/s00264-022-05546-3

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