Department of Regenerative Musculoskeletal Medicine, Institute for Musculoskeletal Medicine, University Hospital Muenster, Westfaelische Wilhelms University Muenster, Albert-Schweitzer-Campus 1, Building D3, 48149 Muenster, Germany
Richard Stange
Department of Regenerative Musculoskeletal Medicine, Institute for Musculoskeletal Medicine, University Hospital Muenster, Westfaelische Wilhelms University Muenster, Albert-Schweitzer-Campus 1, Building D3, 48149 Muenster, Germany
Günther Wittenberg
Protestant Hospital of Bethel Foundation, Department of Diagnostic and Interventional Radiology, Burgsteig 13, 33617 Bielefeld, Germany
Johannes FW Greiner
Department of Cell Biology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany
Andreas Hütten
Thin Films & Physics of Nanostructures, Universitätsstrasse 25, 33615 Bielefeld, Germany
Christian Kaltschmidt
Department of Cell Biology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany
Scaffold materials for bone regeneration are crucial for supporting endogenous healing after accidents, infections, or tumor resection. Although beneficial impacts of microtopological or nanotopological cues in scaffold topography are commonly acknowledged, less consideration is given to the interplay between the microscale and nanoscale. Here, micropores with a 60.66 ± 24.48 µm diameter ordered by closely packed collagen fibers are identified in pre-wetted Spongostan, a clinically-approved collagen sponge. On a nanoscale level, a corrugated surface of the collagen sponge is observable, leading to the presence of 32.97 ± 1.41 nm pores. This distinct micro- and nanotopography is shown to be solely sufficient for guiding osteogenic differentiation of human stem cells in vitro. Transplantation of Spongostan into a critical-size calvarial rat bone defect further leads to fast regeneration of the lesion. However, masking the micro- and nanotopographical cues using SiO2 nanoparticles prevents bone regeneration in vivo. Therefore, we demonstrate that the identified micropores allow migration of stem cells, which are further driven towards osteogenic differentiation by scaffold nanotopography. The present findings emphasize the necessity of considering both micro- and nanotopographical cues to guide intramembranous ossification, and might provide an optimal cell- and growth-factor-free scaffold for bone regeneration in clinical settings.
