TY - JOUR
T1 - Bone morphogenetic protein-2 release profile modulates bone formation in phosphorylated hydrogel
AU - Olthof, Maurits G L
AU - Kempen, Diederik H R
AU - Liu, Xifeng
AU - Dadsetan, Mahrokh
AU - Tryfonidou, Marianna A
AU - Yaszemski, Michael J
AU - Dhert, Wouter J A
AU - Lu, Lichun
N1 - This article is protected by copyright. All rights reserved.
PY - 2018/3/31
Y1 - 2018/3/31
N2 - The optimal release profile of locally delivered BMP-2 for safe and effective clinical application is unknown. In this work, the effect of differential BMP-2 release on bone formation was investigated using a novel biomaterial oligo[(polyethylene glycol) fumarate] bis[2-(methacryloyloxy) ethyl] phosphate hydrogel (OPF-BP) containing poly(lactic-co-glycolic acid) microspheres. Three composite implants with same biomaterial chemistry and structure but different BMP-loading methods were created: BMP-2 encapsulated in microspheres (OPF-BP-Msp), BMP-2 encapsulated in microspheres and adsorbed on the phosphorylated hydrogel (OPF-BP-Cmb), and BMP-2 adsorbed on the phosphorylated hydrogel (OPF-BP-Ads). These composites were compared to the clinically used BMP-2 carrier, Infuse® absorbable collagen sponge (ACS). Differential release profiles of bioactive BMP-2 were achieved by these composites. In a rat subcutaneous implantation model, OPF-BP-Ads and ACS generated a large BMP-2 burst release (>75%), while a more sustained release was seen for OPF-BP-Msp and OPF-BP-Cmb (~25% and 50% burst, respectively). OPF-BP-Ads generated significantly more bone compared to all other composites, and the bone formation was 12-fold higher than the clinically used ACS. Overall, this study clearly shows that BMP-2 burst release generates more subcutaneous bone compared to sustained release in OPF-BP-microsphere composites. Furthermore, composites should not only function as a delivery vehicle but also provide a proper framework to achieve appropriate bone formation.
AB - The optimal release profile of locally delivered BMP-2 for safe and effective clinical application is unknown. In this work, the effect of differential BMP-2 release on bone formation was investigated using a novel biomaterial oligo[(polyethylene glycol) fumarate] bis[2-(methacryloyloxy) ethyl] phosphate hydrogel (OPF-BP) containing poly(lactic-co-glycolic acid) microspheres. Three composite implants with same biomaterial chemistry and structure but different BMP-loading methods were created: BMP-2 encapsulated in microspheres (OPF-BP-Msp), BMP-2 encapsulated in microspheres and adsorbed on the phosphorylated hydrogel (OPF-BP-Cmb), and BMP-2 adsorbed on the phosphorylated hydrogel (OPF-BP-Ads). These composites were compared to the clinically used BMP-2 carrier, Infuse® absorbable collagen sponge (ACS). Differential release profiles of bioactive BMP-2 were achieved by these composites. In a rat subcutaneous implantation model, OPF-BP-Ads and ACS generated a large BMP-2 burst release (>75%), while a more sustained release was seen for OPF-BP-Msp and OPF-BP-Cmb (~25% and 50% burst, respectively). OPF-BP-Ads generated significantly more bone compared to all other composites, and the bone formation was 12-fold higher than the clinically used ACS. Overall, this study clearly shows that BMP-2 burst release generates more subcutaneous bone compared to sustained release in OPF-BP-microsphere composites. Furthermore, composites should not only function as a delivery vehicle but also provide a proper framework to achieve appropriate bone formation.
KW - biomaterials
KW - bone morphogenetic protein-2 release
KW - bone tissue engineering
KW - oligo[(polyethylene glycol) fumarate]
KW - poly(lactic- co-glycolic acid)
U2 - 10.1002/term.2664
DO - 10.1002/term.2664
M3 - Article
C2 - 29603878
SN - 1932-6254
VL - 12
SP - 1339
EP - 1351
JO - Journal of Tissue Engineering and Regenerative Medicine
JF - Journal of Tissue Engineering and Regenerative Medicine
IS - 6
ER -