Bone morphogenetic protein-2 (BMP-2) is a powerful osteoinductive protein; however, there is a need for the development of a safe and efficient BMP-2 release system for bone regeneration therapies. Recombinant extracellular matrix proteins are promising next generation biomaterials since the proteins are well-defined, reproducible and can be tailored for specific applications. In this study, we have developed a novel and versatile BMP-2 delivery system using microspheres from a recombinant protein based on human collagen I (RCP). In general, a two-phase release pattern was observed while the majority of BMP-2 was retained in the microspheres for at least two weeks. Among different parameters studied, the crosslinking and the size of the RCP microspheres changed the in vitro BMP-2 release kinetics significantly. Increasing the chemical crosslinking (hexamethylene diisocyanide) degree decreased the amount of initial burst release (24h) from 23% to 17%. Crosslinking by dehydrothermal treatment further decreased the burst release to 11%. Interestingly, the 50 and 72mum-sized spheres showed a significant decrease in the burst release compared to 207-mum sized spheres. Very importantly, using a reporter cell line, the released BMP-2 was shown to be bioactive. SPR data showed that N-terminal sequence of BMP-2 was important for the binding and retention of BMP-2 and suggested the presence of a specific binding epitope on RCP (K(D): 1.2nM). This study demonstrated that the presented RCP microspheres are promising versatile BMP-2 delivery vehicles.
Mumcuoglu, Didem
de Miguel, Laura
Jekhmane, Shehrazade
Siverino, Claudia
Nickel, Joachim
Mueller, Thomas D
van Leeuwen, Johannes P
van Osch, Gerjo J
Kluijtmans, Sebastiaan G
eng
Netherlands
2018/03/10
Mater Sci Eng C Mater Biol Appl. 2018 Mar 1;84:271-280. doi: 10.1016/j.msec.2017.11.031. Epub 2017 Dec 1.
%0 Journal Article
%1 mumcuoglu2018collagen
%A Mumcuoglu, D.
%A de Miguel, L.
%A Jekhmane, S.
%A Siverino, C.
%A Nickel, J.
%A Mueller, T. D.
%A van Leeuwen, J. P.
%A van Osch, G. J.
%A Kluijtmans, S. G.
%D 2018
%J Mater Sci Eng C Mater Biol Appl
%K Animals myOwn uni_network
%P 271-280
%R 10.1016/j.msec.2017.11.031
%T Collagen I derived recombinant protein microspheres as novel delivery vehicles for bone morphogenetic protein-2
%U https://www.ncbi.nlm.nih.gov/pubmed/29519439https://www.sciencedirect.com/science/article/pii/S0928493117317447?via%3Dihub
%V 84
%X Bone morphogenetic protein-2 (BMP-2) is a powerful osteoinductive protein; however, there is a need for the development of a safe and efficient BMP-2 release system for bone regeneration therapies. Recombinant extracellular matrix proteins are promising next generation biomaterials since the proteins are well-defined, reproducible and can be tailored for specific applications. In this study, we have developed a novel and versatile BMP-2 delivery system using microspheres from a recombinant protein based on human collagen I (RCP). In general, a two-phase release pattern was observed while the majority of BMP-2 was retained in the microspheres for at least two weeks. Among different parameters studied, the crosslinking and the size of the RCP microspheres changed the in vitro BMP-2 release kinetics significantly. Increasing the chemical crosslinking (hexamethylene diisocyanide) degree decreased the amount of initial burst release (24h) from 23% to 17%. Crosslinking by dehydrothermal treatment further decreased the burst release to 11%. Interestingly, the 50 and 72mum-sized spheres showed a significant decrease in the burst release compared to 207-mum sized spheres. Very importantly, using a reporter cell line, the released BMP-2 was shown to be bioactive. SPR data showed that N-terminal sequence of BMP-2 was important for the binding and retention of BMP-2 and suggested the presence of a specific binding epitope on RCP (K(D): 1.2nM). This study demonstrated that the presented RCP microspheres are promising versatile BMP-2 delivery vehicles.
@article{mumcuoglu2018collagen,
abstract = {Bone morphogenetic protein-2 (BMP-2) is a powerful osteoinductive protein; however, there is a need for the development of a safe and efficient BMP-2 release system for bone regeneration therapies. Recombinant extracellular matrix proteins are promising next generation biomaterials since the proteins are well-defined, reproducible and can be tailored for specific applications. In this study, we have developed a novel and versatile BMP-2 delivery system using microspheres from a recombinant protein based on human collagen I (RCP). In general, a two-phase release pattern was observed while the majority of BMP-2 was retained in the microspheres for at least two weeks. Among different parameters studied, the crosslinking and the size of the RCP microspheres changed the in vitro BMP-2 release kinetics significantly. Increasing the chemical crosslinking (hexamethylene diisocyanide) degree decreased the amount of initial burst release (24h) from 23% to 17%. Crosslinking by dehydrothermal treatment further decreased the burst release to 11%. Interestingly, the 50 and 72mum-sized spheres showed a significant decrease in the burst release compared to 207-mum sized spheres. Very importantly, using a reporter cell line, the released BMP-2 was shown to be bioactive. SPR data showed that N-terminal sequence of BMP-2 was important for the binding and retention of BMP-2 and suggested the presence of a specific binding epitope on RCP (K(D): 1.2nM). This study demonstrated that the presented RCP microspheres are promising versatile BMP-2 delivery vehicles.},
added-at = {2024-02-15T15:08:22.000+0100},
author = {Mumcuoglu, D. and de Miguel, L. and Jekhmane, S. and Siverino, C. and Nickel, J. and Mueller, T. D. and van Leeuwen, J. P. and van Osch, G. J. and Kluijtmans, S. G.},
biburl = {https://www.bibsonomy.org/bibtex/227822cfa0ca9131ec4a78a271b728e39/jvsi_all},
doi = {10.1016/j.msec.2017.11.031},
interhash = {30adca1e4ddc3ed49c8ac74c19e8970c},
intrahash = {27822cfa0ca9131ec4a78a271b728e39},
issn = {1873-0191 (Electronic)
0928-4931 (Linking)},
journal = {Mater Sci Eng C Mater Biol Appl},
keywords = {Animals myOwn uni_network},
note = {Mumcuoglu, Didem
de Miguel, Laura
Jekhmane, Shehrazade
Siverino, Claudia
Nickel, Joachim
Mueller, Thomas D
van Leeuwen, Johannes P
van Osch, Gerjo J
Kluijtmans, Sebastiaan G
eng
Netherlands
2018/03/10
Mater Sci Eng C Mater Biol Appl. 2018 Mar 1;84:271-280. doi: 10.1016/j.msec.2017.11.031. Epub 2017 Dec 1.},
pages = {271-280},
timestamp = {2024-02-15T15:11:55.000+0100},
title = {Collagen I derived recombinant protein microspheres as novel delivery vehicles for bone morphogenetic protein-2},
type = {Journal Article},
url = {https://www.ncbi.nlm.nih.gov/pubmed/29519439https://www.sciencedirect.com/science/article/pii/S0928493117317447?via%3Dihub},
volume = 84,
year = 2018
}