Site-Directed Immobilization of an Engineered Bone Morphogenetic Protein 2 (BMP2) Variant to Collagen-Based Microspheres Induces Bone Formation In Vivo

Claudia Siverino, Shorouk Fahmy-Garcia, Didem Mumcuoglu, Heike Oberwinkler, Markus Muehlemann, Thomas Mueller, Eric Farrell, Gerjo J.V.M. van Osch, Joachim Nickel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
15 Downloads (Pure)

Abstract

For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2 s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induced the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs.

Original languageEnglish
Article number3928
JournalInternational Journal of Molecular Sciences
Volume23
Issue number7
DOIs
Publication statusPublished - 1 Apr 2022

Bibliographical note

Funding: The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union Seventh Framework Programme FP7/2007-2013/ under REA grant agreement no. 607051 and by the University of Wuerzburg (funding program OpenAccess Publishing).

Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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