The osteoinductive effect of controlled bone morphogenic protein 2 release Is location dependent

Journal article (2019)

Authors

Maurits G.L. Olthof Mayo Clinic, University Medical Center Utrecht, Universiteit Utrecht, University of Zürich
Lichun Lu Mayo Clinic
Marianna A. Tryfonidou Universiteit Utrecht
Loek D. Loozen University Medical Center Utrecht
B. Pouran Biomaterials & Tissue Biomechanics - Mechanical, Maritime and Materials Engineering , University Medical Center Utrecht
Michael J. Yaszemski Mayo Clinic
Björn P. Meij Universiteit Utrecht
Wouter J.A. Dhert Universiteit Utrecht, University Medical Center Utrecht
Jacqueline Alblas University Medical Center Utrecht
Diederik H.R. Kempen Onze Lieve Vrouwe Gasthuis
Research Group
Biomaterials & Tissue Biomechanics (Mechanical, Maritime and Materials Engineering) (TU Delft)
Bone tissue engineering Application sites Bone morphogenetic protein 2 Oligo[(polyethylene glycol) fumarate]
More Info
expand_more

Published Date

2019

Language

English

Reuse Rights

Other than for strictly personal use, it is not permitted to download, forward or distribute the text or part of it, without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license such as Creative Commons.

Faculty

Mechanical, Maritime and Materials Engineering

Department

Biomechanical Engineering

Research Group

Biomaterials & Tissue Biomechanics

Abstract

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.