Gelatin-Modified Calcium/Strontium Hydrogen Phosphates Stimulate Bone Regeneration in Osteoblast/Osteoclast Co-Culture and in Osteoporotic Rat Femur Defects—In Vitro to In Vivo Translation
Benjamin Kruppke,
Seemun Ray,
Volker Alt,
Marcus Rohnke,
Christine Kern,
Marian Kampschulte,
Christiane Heinemann,
Matthäus Budak,
Josephine Adam,
Nils Döhner,
Lucretia Franz-Forsthoffer,
Thaqif El Khassawna,
Christian Heiss,
Thomas Hanke,
Ulrich Thormann
Affiliations
Benjamin Kruppke
Institute of Materials Science, Technische Universität Dresden, Max Bergmann Center of Biomaterials, 01069 Dresden, Germany
Seemun Ray
Department of Trauma, Campus Giessen, Hand and Reconstructive Surgery, University Hospital Giessen-Marburg GmbH, Rudolf-Buchheim-Str. 7, 35385 Giessen, Germany
Volker Alt
Department of Trauma, Campus Giessen, Hand and Reconstructive Surgery, University Hospital Giessen-Marburg GmbH, Rudolf-Buchheim-Str. 7, 35385 Giessen, Germany
Marcus Rohnke
Institute of Physical Chemistry, Justus-Liebig-Universität Giessen, Heinrich-Buff-Ring 17, 35392 Gießen, Germany
Christine Kern
Institute of Physical Chemistry, Justus-Liebig-Universität Giessen, Heinrich-Buff-Ring 17, 35392 Gießen, Germany
Marian Kampschulte
Justus-Liebig-Universität Giessen, Klinik für Diagnostische und Interventionelle Radiologie, Klinikstr. 33, 35392 Gießen, Germany
Christiane Heinemann
Institute of Materials Science, Technische Universität Dresden, Max Bergmann Center of Biomaterials, 01069 Dresden, Germany
Matthäus Budak
Department of Trauma, Campus Giessen, Hand and Reconstructive Surgery, University Hospital Giessen-Marburg GmbH, Rudolf-Buchheim-Str. 7, 35385 Giessen, Germany
Josephine Adam
Institute of Materials Science, Technische Universität Dresden, Max Bergmann Center of Biomaterials, 01069 Dresden, Germany
Nils Döhner
Department of Trauma, Campus Giessen, Hand and Reconstructive Surgery, University Hospital Giessen-Marburg GmbH, Rudolf-Buchheim-Str. 7, 35385 Giessen, Germany
Lucretia Franz-Forsthoffer
Department of Trauma, Campus Giessen, Hand and Reconstructive Surgery, University Hospital Giessen-Marburg GmbH, Rudolf-Buchheim-Str. 7, 35385 Giessen, Germany
Thaqif El Khassawna
Department of Trauma, Campus Giessen, Hand and Reconstructive Surgery, University Hospital Giessen-Marburg GmbH, Rudolf-Buchheim-Str. 7, 35385 Giessen, Germany
Christian Heiss
Department of Trauma, Campus Giessen, Hand and Reconstructive Surgery, University Hospital Giessen-Marburg GmbH, Rudolf-Buchheim-Str. 7, 35385 Giessen, Germany
Thomas Hanke
Institute of Materials Science, Technische Universität Dresden, Max Bergmann Center of Biomaterials, 01069 Dresden, Germany
Ulrich Thormann
Department of Trauma, Campus Giessen, Hand and Reconstructive Surgery, University Hospital Giessen-Marburg GmbH, Rudolf-Buchheim-Str. 7, 35385 Giessen, Germany
The development and characterization of biomaterials for bone replacement in case of large defects in preconditioned bone (e.g., osteoporosis) require close cooperation of various disciplines. Of particular interest are effects observed in vitro at the cellular level and their in vivo representation in animal experiments. In the present case, the material-based alteration of the ratio of osteoblasts to osteoclasts in vitro in the context of their co-cultivation was examined and showed equivalence to the material-based stimulation of bone regeneration in a bone defect of osteoporotic rats. Gelatin-modified calcium/strontium phosphates with a Ca:Sr ratio in their precipitation solutions of 5:5 and 3:7 caused a pro-osteogenic reaction on both levels in vitro and in vivo. Stimulation of osteoblasts and inhibition of osteoclast activity were proven during culture on materials with higher strontium content. The same material caused a decrease in osteoclast activity in vitro. In vivo, a positive effect of the material with increased strontium content was observed by immunohistochemistry, e.g., by significantly increased bone volume to tissue volume ratio, increased bone morphogenetic protein-2 (BMP2) expression, and significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio. In addition, material degradation and bone regeneration were examined after 6 weeks using stage scans with ToF-SIMS and µ-CT imaging. The remaining material in the defects and strontium signals, which originate from areas exceeding the defect area, indicate the incorporation of strontium ions into the surrounding mineralized tissue. Thus, the material inherent properties (release of biologically active ions, solubility and degradability, mechanical strength) directly influenced the cellular reaction in vitro and also bone regeneration in vivo. Based on this, in the future, materials might be synthesized and specifically adapted to patient-specific needs and their bone status.
