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Composite biomaterial as a carrier for bone-Active substances for metaphyseal tibial bone defect reconstruction in rats

Horstmann, Peter Frederik ; Raina, Deepak Bushan LU ; Isaksson, Hanna LU orcid ; Hettwer, Werner ; Lidgren, Lars LU ; Petersen, Michael Mørk and Tägil, Magnus LU (2017) In Tissue Engineering - Part A 23(23-24). p.1403-1412
Abstract

Restoring lost bone is a major challenge in orthopedic surgery. Currently available treatment strategies have shortcomings, such as risk of infection, nonunion, and excessive resorption. Our primary aim was to study if a commercially available gentamicin-containing composite calcium sulfate/hydroxyapatite biomaterial (GBM) could serve as a carrier for local delivery of bone morphogenic protein-2 (BMP-2) and zoledronic acid (ZA) in a tibia defect model in rats. Empty and allograft-filled defects were used as controls. A 3 × 4-mm metaphyseal bone defect was created in the proximal tibia, and the rats were grouped according to defect filling: (1) Empty, (2) Allograft, (3) GBM, (4) GBM + ZA, and (5) GBM + ZA + BMP-2. In vivo microcomputed... (More)

Restoring lost bone is a major challenge in orthopedic surgery. Currently available treatment strategies have shortcomings, such as risk of infection, nonunion, and excessive resorption. Our primary aim was to study if a commercially available gentamicin-containing composite calcium sulfate/hydroxyapatite biomaterial (GBM) could serve as a carrier for local delivery of bone morphogenic protein-2 (BMP-2) and zoledronic acid (ZA) in a tibia defect model in rats. Empty and allograft-filled defects were used as controls. A 3 × 4-mm metaphyseal bone defect was created in the proximal tibia, and the rats were grouped according to defect filling: (1) Empty, (2) Allograft, (3) GBM, (4) GBM + ZA, and (5) GBM + ZA + BMP-2. In vivo microcomputed tomography (micro-CT) images at 4 weeks showed significantly higher mineralized tissue volume (MV) in the intramedullary defect region and the neocortical/callus region in all GBM-Treated groups. After euthanization at 8 weeks, ex vivo micro-CT showed that addition of ZA (GBM + ZA) and BMP-2 (GBM + ZA + BMP-2) mainly increased the neocortical and callus formation, with the highest MV in the combined ZA and BMP-2-Treated group. Qualitative histological analysis, verifying the increased neocortical/callus thickness and finding of trabecular bone in all GBM-Treated groups, supported that the differences in MV measured with micro-CT in fact represented bone tissue. In conclusion, GBM can serve as a carrier for ZA and BMP-2 leading to increased MV in the neocortex and callus of a metaphyseal bone defect in rats.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomaterial, Bone morphogenic protein, Bone regeneration, Bone substitute, Ceramic, Collagen, Zoledronic acid
in
Tissue Engineering - Part A
volume
23
issue
23-24
pages
10 pages
publisher
Mary Ann Liebert, Inc.
external identifiers
  • scopus:85027056048
ISSN
1937-3341
DOI
10.1089/ten.tea.2017.0040
language
English
LU publication?
yes
id
89c71a07-2a3c-41af-8777-16e74420ea20
date added to LUP
2018-01-25 06:56:32
date last changed
2023-09-07 20:01:03
@article{89c71a07-2a3c-41af-8777-16e74420ea20,
  abstract     = {{<p>Restoring lost bone is a major challenge in orthopedic surgery. Currently available treatment strategies have shortcomings, such as risk of infection, nonunion, and excessive resorption. Our primary aim was to study if a commercially available gentamicin-containing composite calcium sulfate/hydroxyapatite biomaterial (GBM) could serve as a carrier for local delivery of bone morphogenic protein-2 (BMP-2) and zoledronic acid (ZA) in a tibia defect model in rats. Empty and allograft-filled defects were used as controls. A 3 × 4-mm metaphyseal bone defect was created in the proximal tibia, and the rats were grouped according to defect filling: (1) Empty, (2) Allograft, (3) GBM, (4) GBM + ZA, and (5) GBM + ZA + BMP-2. In vivo microcomputed tomography (micro-CT) images at 4 weeks showed significantly higher mineralized tissue volume (MV) in the intramedullary defect region and the neocortical/callus region in all GBM-Treated groups. After euthanization at 8 weeks, ex vivo micro-CT showed that addition of ZA (GBM + ZA) and BMP-2 (GBM + ZA + BMP-2) mainly increased the neocortical and callus formation, with the highest MV in the combined ZA and BMP-2-Treated group. Qualitative histological analysis, verifying the increased neocortical/callus thickness and finding of trabecular bone in all GBM-Treated groups, supported that the differences in MV measured with micro-CT in fact represented bone tissue. In conclusion, GBM can serve as a carrier for ZA and BMP-2 leading to increased MV in the neocortex and callus of a metaphyseal bone defect in rats.</p>}},
  author       = {{Horstmann, Peter Frederik and Raina, Deepak Bushan and Isaksson, Hanna and Hettwer, Werner and Lidgren, Lars and Petersen, Michael Mørk and Tägil, Magnus}},
  issn         = {{1937-3341}},
  keywords     = {{Biomaterial; Bone morphogenic protein; Bone regeneration; Bone substitute; Ceramic; Collagen; Zoledronic acid}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{23-24}},
  pages        = {{1403--1412}},
  publisher    = {{Mary Ann Liebert, Inc.}},
  series       = {{Tissue Engineering - Part A}},
  title        = {{Composite biomaterial as a carrier for bone-Active substances for metaphyseal tibial bone defect reconstruction in rats}},
  url          = {{http://dx.doi.org/10.1089/ten.tea.2017.0040}},
  doi          = {{10.1089/ten.tea.2017.0040}},
  volume       = {{23}},
  year         = {{2017}},
}