Prof. Dr. Ansgar Petersen (Berlin, DE), Dr. Martina Tortorici (Berlin, DE), Aaron Herrera (Berlin, DE), Christoph Gayer (Aachen, DE), PD Dr. Katharina Schmidt-Bleek (Berlin, DE), Dr. Agnes Ellinghaus (Berlin, DE), Hans Leemhuis (Herzogenrath, DE), Prof. Dr. Georg Duda (Berlin, DE)
Abstract text (incl. figure legends and references)
Until today, no pure biomaterial strategy for the regeneration of large bone defect exists despite clear advantages over the use of autologous bone grafts and growth factors. We have previously shown that a soft, collagen-based biomaterial with channel-like pores is able to induce development-like healing of critical size bone defects (Petersen et al., Nat Commun 2018). Here, we report on the incorporation of a 3D printed support structure for the mechanobiological optimization of the biomaterial and its evaluation in small and large animal models. Support structures were produced from medical grade polycaprolactone (PCL) by selective laser sintering, immersed into a collagen dispersion, directionally frozen and freeze-dried to produce mechano-hybrid-scaffolds (MHS). Mechano-bioreactors were used to characterize cell recruitment into MHS and to verify stability under in vivo-like loads. MHS were first evaluated in 5mm critical size defects in the rat femur and then applied to 3cm defects in the sheep tibia. No bioactive molecules, cells or bone grafts were added. Bone defect healing was studied via x-ray, µ-CT and (immune)histology. The strong cell recruitment potential of the collagen-based guiding structure was not impaired in MHS while mechanical properties were clearly improved. Implantation of MHS into the bone defect in rats revealed a robust induction of endochondral ossification. Compared to pure collagen scaffolds, MHS further improved the linear alignment of extracellular matrix fibers and stabilized the endochondral healing process. Nine weeks after implantation, three out of six animals were in the process of bony bridging. Even in the 3cm tibia defect in sheep, MHS induced a linear alignment of collagen fibers across the entire bone defect guiding tissue mineralization. The results of this study verify the potential of the architecturally and mechanobiologically optimized MHS to induce the regeneration of critical size bone defects.