Site-directed immobilization of an engineered bone morphogenetic protein 2 (BMP2) variant to collagen-based microspheres induces bone formation in vivo

Please always quote using this URN: urn:nbn:de:bvb:20-opus-284572
  • 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 toFor 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.show moreshow less

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Metadaten
Author: Claudia Siverino, Shorouk Fahmy-Garcia, Didem Mumcuoglu, Heike Oberwinkler, Markus Muehlemann, Thomas Mueller, Eric Farrell, Gerjo J. V. M. van Osch, Joachim Nickel
URN:urn:nbn:de:bvb:20-opus-284572
Document Type:Journal article
Faculties:Fakultät für Biologie / Julius-von-Sachs-Institut für Biowissenschaften
Medizinische Fakultät / Lehrstuhl für Tissue Engineering und Regenerative Medizin
Language:English
Parent Title (English):International Journal of Molecular Sciences
ISSN:1422-0067
Year of Completion:2022
Volume:23
Issue:7
Article Number:3928
Source:International Journal of Molecular Sciences (2022) 23:7, 3928. DOI:10.3390/ijms23073928
DOI:https://doi.org/10.3390/ijms23073928
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:bone morphogenetic protein 2 (BMP2); bone regeneration; covalent coupling; subcutaneous animal model
Release Date:2023/04/13
Date of first Publication:2022/04/01
EU-Project number / Contract (GA) number:607051
OpenAIRE:OpenAIRE
Open-Access-Publikationsfonds / Förderzeitraum 2022
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International