Fabrication of 3D printed trabecular bone-templated scaffolds modified with rare earth europium (III)-based complex for enhancing mitochondrial function in bone regeneration

Bone defects have been a tough clinical challenge. The natural trabecular tissue reflects a balance between the minimal metabolic cost of maintenance and maximal network stability, with mitochondria being the energy suppliers for osteogenesis. Herein, a 3D printed trabecular bone-templated scaffold composed of polylactide (PLA) modified with europium (III)-organic ligands (polydopamine and chitooligosaccharide, PDA/COS@Eu) was fabricated (denoted as Tra-PLA/PDA/COS@Eu) to augment bone repair by facilitating mitochondrial function. First, the trabecular bone templated-scaffold provides superior mechanical performance and permeability in contrast to a computer aided designed (CAD) scaffold under a same volume fraction. Tra-PLA/PDA/COS@Eu scaffold up regulated PI3K/AKT/S6K/HIF-1α pathway and significantly promoted BMSCs proliferation and osteogenic differentiation. In addition, Tra-PLA/PDA/COS@Eu scaffold provided anti-inflammatory environment by promoting macrophages M2 polarization through COS, and significantly stimulated BMSCs osteogenesis with enhanced mitochondrial function and biosynthesis. Remarkably, Eu ions are the key ingredient in enhancing mitochondrial function and biosynthesis in BMSCs. Further studies showed that the above-mentioned facilitations in a rabbit bone defect model were found to be more significant with trabecular bone-templated scaffolds, as opposed to CAD scaffolds. In summary, this novel trabecular bone-templated scaffold targeting mitochondrial function has the potential to become an effective method in the treatment of large bone defects.