%0 Journal Article %1 Mumcuoglu:2018:Mater-Sci-Eng-C-Mater-Biol-Appl:29519439 %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 myown %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/29519439 %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 72μm-sized spheres showed a significant decrease in the burst release compared to 207-μm 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 (KD: 1.2nM). This study demonstrated that the presented RCP microspheres are promising versatile BMP-2 delivery vehicles.

@article{Mumcuoglu:2018:Mater-Sci-Eng-C-Mater-Biol-Appl:29519439, 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 72μm-sized spheres showed a significant decrease in the burst release compared to 207-μm 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 (KD: 1.2nM). This study demonstrated that the presented RCP microspheres are promising versatile BMP-2 delivery vehicles.}, added-at = {2018-05-18T21:11:35.000+0200}, 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/20ecfdb525ceb5d7c9b8e7530e3d7e459/tdmueller}, description = {Collagen I derived recombinant protein microspheres as novel delivery vehicles for bone morphogenetic protein-2. - PubMed - NCBI}, doi = {10.1016/j.msec.2017.11.031}, interhash = {30adca1e4ddc3ed49c8ac74c19e8970c}, intrahash = {0ecfdb525ceb5d7c9b8e7530e3d7e459}, journal = {Mater Sci Eng C Mater Biol Appl}, keywords = {myown}, month = mar, pages = {271-280}, pmid = {29519439}, timestamp = {2018-05-18T21:11:35.000+0200}, title = {Collagen I derived recombinant protein microspheres as novel delivery vehicles for bone morphogenetic protein-2}, url = {https://www.ncbi.nlm.nih.gov/pubmed/29519439}, volume = 84, year = 2018 }