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01-04-2021 | Original Paper

Synthetic ceramic macroporous blocks as a scaffold in ectopic bone formation induced by recombinant human bone morphogenetic protein 6 within autologous blood coagulum in rats

Authors: Nikola Stokovic, Natalia Ivanjko, Marina Milesevic, Ivona Matic Jelic, Kristian Bakic, Viktorija Rumenovic, Hermann Oppermann, Larry Shimp, T. Kuber Sampath, Marko Pecina, Slobodan Vukicevic

Published in: International Orthopaedics | Issue 4/2021

Abstract

Purpose

We have recently developed an autologous bone graft substitute (ABGS) containing recombinant human bone morphogenetic protein 6 (rhBMP6) in autologous blood coagulum (ABC) that induces new bone formation in vivo. In order to improve biomechanical properties of the implant, compression resistant matrix (CRM) consisting of synthetic ceramics in the form of macroporous cylinders was added to the ABGS and we evaluated the biomechanical properties and the quantity and quality of bone formation following subcutaneous implantation in rats.

Methods

ABGS implants containing rhBMP6 in ABC with cylindrical ceramic blocks were implanted subcutaneously (n = 6 per time point) in the axillary region of Sprague-Dawley rats and removed at specified time points (7, 14, 21, 35, and 50 days). The quantity and quality of newly formed bone were analyzed by microCT, histology, and histomorphometric analyses. Biomechanical properties of ABGS formulations were determined by employing the cut test.

Results

MicroCT analyses revealed that ABGS implants induced formation of new bone within ceramic blocks. Histological analysis revealed that on day seven following implantation, the endochondral ossification occupied the peripheral part of implants. On days 14 and 21, newly formed bone was present both around the ceramic block and through the pores inside the block. On both days 35 and 50, cortical bone encircled the ceramic block while inside the block, bone covered the ceramic surface surrounding the pores. Within the osseous circles, there were few trabeculae and bone marrow containing adipocytes. ABGS containing cylindrical ceramic blocks were more rigid and had significantly increased stiffness compared with implants containing ceramic particles as CRM.

Conclusion

We demonstrated that macroporous ceramic blocks in a form of cylinders are promising CRMs with good handling and enhanced biomechanical properties, supporting bone formation with ABGS containing rhBMP6 within autologous blood coagulum. Hence, ABGS containing ceramic blocks should be tested in preclinical models including diaphyseal segmental defects and non-unions in larger animals.

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Title: Synthetic ceramic macroporous blocks as a scaffold in ectopic bone formation induced by recombinant human bone morphogenetic protein 6 within autologous blood coagulum in rats
Authors: Nikola Stokovic
Natalia Ivanjko
Marina Milesevic
Ivona Matic Jelic
Kristian Bakic
Viktorija Rumenovic
Hermann Oppermann
Larry Shimp
T. Kuber Sampath
Marko Pecina
Slobodan Vukicevic
Publication date: 01-04-2021
Publisher: Springer Berlin Heidelberg
Published in: International Orthopaedics / Issue 4/2021
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI: https://doi.org/10.1007/s00264-020-04847-9

At a glance: The STEP trials

Springer Medicine

Synthetic ceramic macroporous blocks as a scaffold in ectopic bone formation induced by recombinant human bone morphogenetic protein 6 within autologous blood coagulum in rats

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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