| Autor: |
Siverino C; Department of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, 97070 Wuerzburg, Germany., Fahmy-Garcia S; Department of Orthopaedics and Sports Medicine, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands.; Department of Internal Medicine, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands.; Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands., Mumcuoglu D; Department of Orthopaedics and Sports Medicine, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands.; Fujifilm Manufacturing Europe B.V., 5047 TK Tilburg, The Netherlands., Oberwinkler H; Department of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, 97070 Wuerzburg, Germany., Muehlemann M; Department of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, 97070 Wuerzburg, Germany., Mueller T; Department for Molecular Plant Physiology and Biophysics, Julius-von-Sachs Institute of the University Wuerzburg, 97082 Wuerzburg, Germany., Farrell E; Department of Oral and Maxillofacial Surgery, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands., van Osch GJVM; Department of Orthopaedics and Sports Medicine, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands.; Department of Otorhinolaryngology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands., Nickel J; Department of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, 97070 Wuerzburg, Germany.; Fraunhofer ISC, Translational Center RT, 97070 Wuerzburg, Germany. |
| Abstrakt: |
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. |
