Biomaterials in repairing rat femoral defects: In vivo insights from small animal positron emission tomography/computed tomography (PET/CT) studies

Issue title: Selected papers of the 38th Conference of the German Society for Clinical Microcirculation and Hemorheology, 21-23 November 2019, Braunschweig, Germany

Guest editors: P. Wiggermann, A. Krüger-Genge and F. Jung

Article type: Research Article

Authors: Neuber, Christin^a | Schulze, Sabine^{b; c} | Förster, Yvonne^{b; c} | Hofheinz, Frank^d | Wodke, Johanna^a | Möller, Stephanie^e | Schnabelrauch, Matthias^e | Hintze, Vera^f | Scharnweber, Dieter^{f; g} | Rammelt, Stefan^{b; c; g} | Pietzsch, Jens^{a; h; *}

Affiliations: [a] Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department Radiopharmaceutical and Chemical Biology, Dresden, Germany | [b] Technische Universität Dresden, University Hospital Carl Gustav Carus, University Center for Orthopaedics and Traumatology, Dresden, Germany | [c] Technische Universität Dresden, Faculty of Medicine, Centre for Translational Bone, Joint and Soft Tissue Research, Dresden, Germany | [d] Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department Positron Emission Tomography, Dresden, Germany | [e] Biomaterials Department, INNOVENT e.V., Jena, Germany | [f] Technische Universität Dresden, Max Bergmann Center of Biomaterials, Institute of Materials Science, Dresden, Germany | [g] Center of Regenerative Therapies Dresden (CRTD), Dresden, Germany | [h] Technische Universität Dresden, School of Science, Faculty of Chemistry and Food Chemistry, Dresden, Germany

Correspondence: [*] Corresponding author: Prof. Jens Pietzsch, Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department Radiopharmaceutical and Chemical Biology, Bautzner Landstrasse 400, 01328 Dresden, Germany. [email protected].

Abstract: Biomaterials coated with artificial extracellular matrices (aECM) are intended to support the healing of critical size bone defects. This pilot study investigated (i) the feasibility of dual-tracer PET/CT imaging for functional characterization of biomaterial-assisted bone healing in a rat femoral defect model and (ii) the bone healing ability of polycaprolactone-co-lactide (PCL) scaffolds, coated with various aECM consisting of collagen type I (Col) and glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) or polysulfated hyaluronan (sHA3). [18F]FDG and [18F]fluoride PET 4 and 8 weeks after implantation of aECM-coated PCL scaffolds, which provide an in vivo measure of cellular activation and bone mineralization, respectively, combined with CT imaging (in vivo/ex vivo) and histological/immunohistochemical investigations (ex vivo) showed that coating with CS in particular is beneficial for bone healing. The possible involvement of COX-2 and TGase 2, key enzymes of inflammation and ECM remodeling, in these processes offers starting points for targeted adjuvant therapy in the course of various bone healing phases. Our investigations show the feasibility of the selected dual-tracer approach for PET/CT imaging. In principle, this approach can be extended by further PET tracers for the functional characterization of physiological processes such as hypoxia/reperfusion or selected molecular players.

Keywords: Artificial extracellular matrices, bone healing, [¹⁸F]fluorodeoxyglucose, [¹⁸F]fluoride, glycosaminoglycans, inflammation, metabolism, molecular imaging, revascularization

DOI: 10.3233/CH-199208

Journal: Clinical Hemorheology and Microcirculation, vol. 73, no. 1, pp. 177-194, 2019