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 - Funding Information:
We thank Dr. Nynke Ankringa, ECVP board‐eligible veterinary pathologist of the Faculty of Veterinary Medicine at the University of Utrecht, for her assistance during the histological analysis. We also thank James L. Herrick and Carl T. Gustafson of Mayo Clinic for technical support. The authors wish to acknowledge the National Institutes of Health (R01 AR45871 and R01 EB03060), the AO Foundation (AO startup Grant S‐15‐46K), the Dutch Arthritis Foundation (LLP22), and Anna‐NOREF Foundation for their financial support.
Funding Information:
We thank Dr. Nynke Ankringa, ECVP board-eligible veterinary pathologist of the Faculty of Veterinary Medicine at the University of Utrecht, for her assistance during the histological analysis. We also thank James L. Herrick and Carl T. Gustafson of Mayo Clinic for technical support. The authors wish to acknowledge the National Institutes of Health (R01 AR45871 and R01 EB03060), the AO Foundation (AO startup Grant S-15-46K), the Dutch Arthritis Foundation (LLP22), and Anna-NOREF Foundation for their financial support.
Publisher Copyright:
Copyright © 2018 John Wiley & Sons, Ltd.
PY - 2018/6
Y1 - 2018/6
N2 - The optimal release profile of locally delivered bone morphogenetic protein-2 (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 the 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 with 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%), whereas 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 than did all other composites, and the bone formation was 12-fold higher than that of the clinically used ACS. Overall, this study clearly shows that BMP-2 burst release generates more subcutaneous bone than do 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 bone morphogenetic protein-2 (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 the 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 with 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%), whereas 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 than did all other composites, and the bone formation was 12-fold higher than that of the clinically used ACS. Overall, this study clearly shows that BMP-2 burst release generates more subcutaneous bone than do 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)
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U2 - 10.1002/term.2664
DO - 10.1002/term.2664
M3 - Article
C2 - 29603878
AN - SCOPUS:85046159086
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 -