TY - JOUR
T1 - The Osteoinductive Effect of Controlled Bone Morphogenic Protein 2 Release Is Location Dependent
AU - Olthof, Maurits G.L.
AU - Lu, Lichun
AU - Tryfonidou, Marianna A.
AU - Loozen, Loek D.
AU - Pouran, Behdad
AU - Yaszemski, Michael J.
AU - Meij, Björn P.
AU - Dhert, Wouter J.A.
AU - Alblas, Jacqueline
AU - Kempen, Diederik H.R.
N1 - Funding Information:
The authors acknowledge the financial support from the National Institutes of Health (R01 AR45871 and R01 EB03060), the AO Foundation (AO startup grant S-15-46K), the Dutch Arthritis Foundation (LLP12 and LLP22), and Anna-NOREF foundation. Furthermore, the authors thank Nynke Ankringa from the Department of Veterinary Pathology of the University of Utrecht for analyzing histology, and Michiel Croes and Marianne K.E. Koolen from the Department of Orthopedic Surgery of the University Medical Center Utrecht for assisting with the surgery.
Publisher Copyright:
© Copyright 2019, Mary Ann Liebert, Inc., publishers 2019.
PY - 2019/2
Y1 - 2019/2
N2 - The main challenge in bone morphogenic protein 2 (BMP-2)-based application lies in finding strategies that prolong its effective period as it has a short biological half-life. Several BMP-2 release profiles have shown to enhance bone formation at various application sites. However, it remains to be determined which BMP-2 release profile best augments bone formation and whether this effect is location dependent. Therefore, the aim of this study was to investigate the effect of BMP-2 release from oligo[(polyethylene glycol) fumarate] bis(2-(methacryloyloxy)ethyl) phosphate (OPF-BP) composites on the osteoinductive efficacy at ectopic versus orthotopic application. By varying the BMP-2 loading method, three different OPF-BP composites were created with varied release profiles. The composites were compared with unloaded OPF-BP as negative control, and to the clinically used Infuse ® absorbable collagen sponge (ACS) as positive control. Bone formation was assessed by microcomputed tomography after 9 weeks of subcutaneous implantation and 3, 6, and 9 weeks of orthotopic implantation in rats (n = 48). Whereas a BMP-2 burst release of >49% generated significantly more bone compared with sustained release (burst release <30%) at the subcutaneous implantation site, differential release did not affect bone formation at the orthotopic site. Furthermore, all BMP-2 containing OPF-BP composites showed significantly more bone formation compared with ACS in the orthotopic implantation site. In conclusion, this study clearly shows that the osteoinductive effect of different BMP-2 release profiles is location dependent. In addition, more bone formation in OPF-BP compared with ACS at both application sites emphasizes the role of biomaterials as a scaffold to achieve proper bone tissue formation. The main challenge in bone morphogenic protein 2 (BMP-2)-based application lies in finding strategies to prolong its biologic activity as it has a short biological half-life. The present study uses a phosphate-modified oligo[(polyethylene glycol) fumarate] hydrogel that can be tuned to achieve differential release profiles of biologically active BMP-2 release. We demonstrate that this platform outperforms Infuse ® , currently used in the clinic and that the osteoinductive effect of BMP-2 is location dependent. Altogether, this study stresses the importance of evaluating efficacy of bone tissue engineering strategies at an orthotopic location rather than subcutaneously. Even more so, it emphasizes the role of biomaterials as a scaffold to achieve proper bone tissue engineering.
AB - The main challenge in bone morphogenic protein 2 (BMP-2)-based application lies in finding strategies that prolong its effective period as it has a short biological half-life. Several BMP-2 release profiles have shown to enhance bone formation at various application sites. However, it remains to be determined which BMP-2 release profile best augments bone formation and whether this effect is location dependent. Therefore, the aim of this study was to investigate the effect of BMP-2 release from oligo[(polyethylene glycol) fumarate] bis(2-(methacryloyloxy)ethyl) phosphate (OPF-BP) composites on the osteoinductive efficacy at ectopic versus orthotopic application. By varying the BMP-2 loading method, three different OPF-BP composites were created with varied release profiles. The composites were compared with unloaded OPF-BP as negative control, and to the clinically used Infuse ® absorbable collagen sponge (ACS) as positive control. Bone formation was assessed by microcomputed tomography after 9 weeks of subcutaneous implantation and 3, 6, and 9 weeks of orthotopic implantation in rats (n = 48). Whereas a BMP-2 burst release of >49% generated significantly more bone compared with sustained release (burst release <30%) at the subcutaneous implantation site, differential release did not affect bone formation at the orthotopic site. Furthermore, all BMP-2 containing OPF-BP composites showed significantly more bone formation compared with ACS in the orthotopic implantation site. In conclusion, this study clearly shows that the osteoinductive effect of different BMP-2 release profiles is location dependent. In addition, more bone formation in OPF-BP compared with ACS at both application sites emphasizes the role of biomaterials as a scaffold to achieve proper bone tissue formation. The main challenge in bone morphogenic protein 2 (BMP-2)-based application lies in finding strategies to prolong its biologic activity as it has a short biological half-life. The present study uses a phosphate-modified oligo[(polyethylene glycol) fumarate] hydrogel that can be tuned to achieve differential release profiles of biologically active BMP-2 release. We demonstrate that this platform outperforms Infuse ® , currently used in the clinic and that the osteoinductive effect of BMP-2 is location dependent. Altogether, this study stresses the importance of evaluating efficacy of bone tissue engineering strategies at an orthotopic location rather than subcutaneously. Even more so, it emphasizes the role of biomaterials as a scaffold to achieve proper bone tissue engineering.
KW - application sites
KW - bone morphogenetic protein 2
KW - bone tissue engineering
KW - oligo[(polyethylene glycol) fumarate]
UR - http://www.scopus.com/inward/record.url?scp=85061478946&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061478946&partnerID=8YFLogxK
U2 - 10.1089/ten.tea.2017.0427
DO - 10.1089/ten.tea.2017.0427
M3 - Article
C2 - 30101676
AN - SCOPUS:85061478946
SN - 1937-3341
VL - 25
SP - 193
EP - 202
JO - Tissue Engineering - Part A
JF - Tissue Engineering - Part A
IS - 3-4
ER -