Co-delivery of rhBMP-2 and zoledronic acid using calcium sulfate/hydroxyapatite carrier as a bioactive bone substitute to enhance and accelerate spinal fusion

Xinggui Tian; Corina Vater; Deepak Bushan Raina; Lisa Findeisen; Lucas-Maximilian Matuszewski; Magnus Tägil; Lars Lidgren; Anja Winkler; Robert Gottwald; Niels Modler; Klaus-Dieter Schaser; Alexander C. Disch; Stefan Zwingenberger

Bioactive Materials (Jun 2024)

Co-delivery of rhBMP-2 and zoledronic acid using calcium sulfate/hydroxyapatite carrier as a bioactive bone substitute to enhance and accelerate spinal fusion

Xinggui Tian,
Corina Vater,
Deepak Bushan Raina,
Lisa Findeisen,
Lucas-Maximilian Matuszewski,
Magnus Tägil,
Lars Lidgren,
Anja Winkler,
Robert Gottwald,
Niels Modler,
Klaus-Dieter Schaser,
Alexander C. Disch,
Stefan Zwingenberger

Affiliations

Xinggui Tian: University Center of Orthopaedic, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany; Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany; Corresponding author. University Center of Orthopedic, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at TU Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
Corina Vater: University Center of Orthopaedic, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany; Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany
Deepak Bushan Raina: Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund, 22185, Sweden
Lisa Findeisen: University Center of Orthopaedic, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany; Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany
Lucas-Maximilian Matuszewski: University Center of Orthopaedic, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany; Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany
Magnus Tägil: Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund, 22185, Sweden
Lars Lidgren: Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund, 22185, Sweden
Anja Winkler: Institute of Lightweight Engineering and Polymer Technology at TUD Dresden University of Technology, 01062, Dresden, Germany
Robert Gottwald: Institute of Lightweight Engineering and Polymer Technology at TUD Dresden University of Technology, 01062, Dresden, Germany
Niels Modler: Institute of Lightweight Engineering and Polymer Technology at TUD Dresden University of Technology, 01062, Dresden, Germany
Klaus-Dieter Schaser: University Center of Orthopaedic, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany
Alexander C. Disch: University Center of Orthopaedic, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany
Stefan Zwingenberger: University Center of Orthopaedic, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany; Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany

Journal volume & issue: Vol. 36
pp. 256 – 271

Abstract

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Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been FDA-approved for lumbar fusion, but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage. One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is to give systemic bisphosphonates, but it presents challenges with systemic side effects and low local bioavailability. The aim of this in vivo study was to analyze if posterolateral spinal fusion (PLF) could be improved by utilizing a calcium sulfate/hydroxyapatite (CaS/HA) carrier co-delivering rhBMP-2 and zoledronic acid (ZA). Six groups were allocated (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, and CaS/HA + BMP-2 + local ZA). 10-week-old male Wistar rats, were randomly assigned to undergo L4-L5 PLF with implantation of group-dependent scaffolds. At 3 and 6 weeks, the animals were euthanized for radiography, μCT, histological staining, or biomechanical testing to evaluate spinal fusion. The results demonstrated that the CaS/HA biomaterial alone or in combination with local or systemic ZA didn't support PLF. However, the delivery of rhBMP-2 significantly promoted PLF. Combining systemic ZA with BMP-2 didn't enhance spinal fusion. Notably, the co-delivery of rhBMP-2 and ZA using the CaS/HA carrier significantly enhanced and accelerated PLF, without inhibiting systemic bone turnover, and potentially reduced the dose of rhBMP-2. Together, the treatment regimen of CaS/HA biomaterial co-delivering rhBMP-2 and ZA could potentially be a safe and cost-effective off-the-shelf bioactive bone substitute to enhance spinal fusion.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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