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A facile one-stage treatment of critical bone defects using a calcium sulfate/hydroxyapatite biomaterial providing spatiotemporal delivery of bone morphogenic protein-2 and zoledronic acid.

Authors
  • Raina, Deepak Bushan1
  • Matuszewski, Lucas-Maximilian2
  • Vater, Corina2
  • Bolte, Julia2
  • Isaksson, Hanna3, 4
  • Lidgren, Lars3
  • Tägil, Magnus3
  • Zwingenberger, Stefan2
  • 1 Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund 22185, Sweden. [email protected] , (Sweden)
  • 2 University Hospital Carl Gustav Carus at Technische Universität Dresden, University Center of Orthopedic, Trauma and Plastic Surgery, Dresden 01307, Germany. , (Germany)
  • 3 Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund 22185, Sweden. , (Sweden)
  • 4 Lund University, Department of Biomedical Engineering, Lund 22100, Sweden. , (Sweden)
Type
Published Article
Journal
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Publication Date
Nov 01, 2020
Volume
6
Issue
48
Identifiers
DOI: 10.1126/sciadv.abc1779
PMID: 33246951
Source
Medline
Language
English
License
Unknown

Abstract

Bone morphogenic proteins (BMPs) are the only true osteoinductive molecules. Despite being tremendously potent, their clinical use has been limited for reasons including supraphysiological doses, suboptimal delivery systems, and the pro-osteoclast effect of BMPs. Efforts to achieve spatially controlled bone formation using BMPs are being made. We demonstrate that a carrier consisting of a powder of calcium sulfate/hydroxyapatite (CaS/HA) mixed with bone active molecules provides an efficient drug delivery platform for critical femoral defect healing in rats. The bone-active molecules were composed of osteoinductive rhBMP-2 and the bisphosphonate, and zoledronic acid (ZA) was chosen to overcome BMP-2-induced bone resorption. It was demonstrated that delivery of rhBMP-2 was necessary for critical defect healing and restoration of mechanical properties, but codelivery of BMP-2 and ZA led to denser and stronger fracture calluses. Together, the CaS/HA biomaterial with rhBMP-2 and/or ZA can potentially be used as an off-the-shelf alternative to autograft bone. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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