In Vivo Validation of Spray-Dried Mesoporous Bioactive Glass Microspheres Acting as Prolonged Local Release Systems for BMP-2 to Support Bone Regeneration
Julia C. Berkmann,
Aaron X. Herrera Martin,
Carlotta Pontremoli,
Kai Zheng,
Christian H. Bucher,
Agnes Ellinghaus,
Aldo R. Boccaccini,
Sonia Fiorilli,
Chiara Vitale Brovarone,
Georg N. Duda,
Katharina Schmidt-Bleek
Affiliations
Julia C. Berkmann
Julius-Wolff-Institut, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, 13353 Berlin, Germany
Aaron X. Herrera Martin
Julius-Wolff-Institut, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, 13353 Berlin, Germany
Carlotta Pontremoli
Department of Applied Science and Technology, Politecnico di Torino, 10129 Turin, Italy
Kai Zheng
Institute of Biomaterials, University of Erlangen-Nuremberg, 91058 Erlangen, Germany
Christian H. Bucher
Julius-Wolff-Institut, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, 13353 Berlin, Germany
Agnes Ellinghaus
BIH Center for Regenerative Therapies, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, 13353 Berlin, Germany
Aldo R. Boccaccini
Institute of Biomaterials, University of Erlangen-Nuremberg, 91058 Erlangen, Germany
Sonia Fiorilli
Department of Applied Science and Technology, Politecnico di Torino, 10129 Turin, Italy
Chiara Vitale Brovarone
Department of Applied Science and Technology, Politecnico di Torino, 10129 Turin, Italy
Georg N. Duda
Julius-Wolff-Institut, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, 13353 Berlin, Germany
Katharina Schmidt-Bleek
Julius-Wolff-Institut, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, 13353 Berlin, Germany
Bone morphogenetic protein-2 (BMP-2) is a known key mediator of physiological bone regeneration and is clinically approved for selected musculoskeletal interventions. Yet, broad usage of this growth factor is impeded due to side effects that are majorly evoked by high dosages and burst release kinetics. In this study, mesoporous bioactive glass microspheres (MBGs), produced by an aerosol-assisted spray-drying scalable process, were loaded with BMP-2 resulting in prolonged, low-dose BMP-2 release without affecting the material characteristics. In vitro, MBGs were found to be cytocompatible and to induce a pro-osteogenic response in primary human mesenchymal stromal cells (MSCs). In a pre-clinical rodent model, BMP-2 loaded MBGs significantly enhanced bone formation and influenced the microarchitecture of newly formed bone. The MBG carriers alone performed equal to the untreated (empty) control in most parameters tested, while additionally exerting mild pro-angiogenic effects. Using MBGs as a biocompatible, pro-regenerative carrier for local and sustained low dose BMP-2 release could limit side effects, thus enabling a safer usage of BMP-2 as a potent pro-osteogenic growth factor.