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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

Raina, Deepak Bushan LU ; Matuszewski, Lucas Maximilian ; Vater, Corina ; Bolte, Julia ; Isaksson, Hanna LU orcid ; Lidgren, Lars LU ; Tägil, Magnus LU and Zwingenberger, Stefan (2020) In Science Advances 6(48).
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... (More)

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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Advances
volume
6
issue
48
article number
abc1779
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85096949355
  • pmid:33246951
ISSN
2375-2548
DOI
10.1126/sciadv.abc1779
language
English
LU publication?
yes
id
122fc3a8-da37-4621-8509-d1169bfbb7e0
date added to LUP
2020-12-11 09:23:44
date last changed
2024-04-17 21:31:58
@article{122fc3a8-da37-4621-8509-d1169bfbb7e0,
  abstract     = {{<p>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.</p>}},
  author       = {{Raina, Deepak Bushan and Matuszewski, Lucas Maximilian and Vater, Corina and Bolte, Julia and Isaksson, Hanna and Lidgren, Lars and Tägil, Magnus and Zwingenberger, Stefan}},
  issn         = {{2375-2548}},
  language     = {{eng}},
  number       = {{48}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Advances}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1126/sciadv.abc1779}},
  doi          = {{10.1126/sciadv.abc1779}},
  volume       = {{6}},
  year         = {{2020}},
}