Adjuvant drug-assisted bone healing: Part II – Modulation of angiogenesis

Issue title: Bone Healing

Guest editors: J. Pietzsch and F. Jung

Article type: Research Article

Authors: Rothe, Rebecca^a | Schulze, Sabine^{b; c} | Neuber, Christin^a | Hauser, Sandra^a | Rammelt, Stefan^{b; c; d; 1; *} | Pietzsch, Jens^{a; e; 1; *}

Affiliations: [a] Department of Radiopharmaceutical and Chemical Biology, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany | [b] University Center of Orthopaedics and Traumatology (OUC), University Hospital Carl Gustav Carus, Dresden, Germany | [c] Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany | [d] Center for Regenerative Therapies Dresden (CRTD), Tatzberg 4, Dresden, Germany | [e] Technische Universität Dresden, School of Science, Faculty of Chemistry and Food Chemistry, Dresden, Germany

Correspondence: [*] Corresponding authors: Prof. Dr. Stefan Rammelt, University Center for Orthopaedics and Traumatology, University Hospital Carl Gustav Carus, Fetscherstrasse 74, 01307, Dresden, Germany. Tel.: +49 351 4583211; Fax: +49 351 4584307; E-mail: stefan.rammelt@uniklinikum-dresden.de and Prof. Dr. Jens Pietzsch, Department of Radiopharmaceutical and Chemical Biology, Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstraße 400, 01328, Dresden, Germany. Tel.: +49 351 2602622; Fax: +49 351 26012622; E-mail: j.pietzsch@hzdr.de.

Note: [1] SR and JP share senior authorship.

Abstract:  The treatment of critical-size bone defects following complicated fractures, infections or tumor resections is a major challenge. The same applies to fractures in patients with impaired bone healing due to systemic inflammatory and metabolic diseases. Despite considerable progress in development and establishment of new surgical techniques, design of bone graft substitutes and imaging techniques, these scenarios still represent unresolved clinical problems. However, the development of new active substances offers novel potential solutions for these issues. This work discusses therapeutic approaches that influence angiogenesis or hypoxic situations in healing bone and surrounding tissue. In particular, literature on sphingosine-1-phosphate receptor modulators and nitric oxide (NO•) donors, including bi-functional (hybrid) compounds like NO•-releasing cyclooxygenase-2 inhibitors, was critically reviewed with regard to their local and systemic mode of action.

Keywords: Critical-size bone defects, neovascularization, nitric oxide donors, signaling, small molecules, sphingosine-1-phosphate receptor

DOI: 10.3233/CH-199103

Journal: Clinical Hemorheology and Microcirculation, vol. 73, no. 3, pp. 409-438, 2019