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Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial

Raina, D. B. LU ; Gupta, A; Petersen, M. M.; Hettwer, Werner; McNally, M.; Tägil, M. LU ; Zheng, M. H.; Kumar, A. LU and Lidgren, L. LU (2016) In Bone and Joint Research 5(10). p.500-511
Abstract

Objectives: We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. Materials and Methods: We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins.... (More)

Objectives: We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. Materials and Methods: We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy. Results: C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (sd) 0.8) and BMP-7 (50.6 ng/mg, sd 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage. Conclusion: Extra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomimetic material, Growth factors, Hydroxyapatite, Osteoblast, Osteopromotive
in
Bone and Joint Research
volume
5
issue
10
pages
12 pages
publisher
British Editorial Soc Bone Joint Surgery
external identifiers
  • scopus:85018423314
  • wos:000387460800008
ISSN
2046-3758
DOI
10.1302/2046-3758.510.BJR-2016-0133.R1
language
English
LU publication?
yes
id
7854eaad-4087-4155-8132-9dbb7cf175bd
date added to LUP
2017-05-19 10:58:59
date last changed
2017-09-18 11:36:31
@article{7854eaad-4087-4155-8132-9dbb7cf175bd,
  abstract     = {<p>Objectives: We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. Materials and Methods: We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy. Results: C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (sd) 0.8) and BMP-7 (50.6 ng/mg, sd 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage. Conclusion: Extra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation.</p>},
  author       = {Raina, D. B. and Gupta, A and Petersen, M. M. and Hettwer, Werner and McNally, M. and Tägil, M. and Zheng, M. H. and Kumar, A. and Lidgren, L.},
  issn         = {2046-3758},
  keyword      = {Biomimetic material,Growth factors,Hydroxyapatite,Osteoblast,Osteopromotive},
  language     = {eng},
  number       = {10},
  pages        = {500--511},
  publisher    = {British Editorial Soc Bone Joint Surgery},
  series       = {Bone and Joint Research},
  title        = {Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial},
  url          = {http://dx.doi.org/10.1302/2046-3758.510.BJR-2016-0133.R1},
  volume       = {5},
  year         = {2016},
}