TY  - JOUR
A1  - Siverino, Claudia
A1  - Fahmy-Garcia, Shorouk
A1  - Mumcuoglu, Didem
A1  - Oberwinkler, Heike
A1  - Muehlemann, Markus
A1  - Mueller, Thomas
A1  - Farrell, Eric
A1  - van Osch, Gerjo J. V. M.
A1  - Nickel, Joachim
T1  - Site-directed immobilization of an engineered bone morphogenetic protein 2 (BMP2) variant to collagen-based microspheres induces bone formation in vivo
JF  - International Journal of Molecular Sciences
N2  - 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 induces 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.
KW  - bone morphogenetic protein 2 (BMP2)
KW  - bone regeneration
KW  - covalent coupling
KW  - subcutaneous animal model
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284572
SN  - 1422-0067
VL  - 23
IS  - 7
ER  -