3D-printed manganese dioxide incorporated scaffold promotes osteogenic-angiogenic coupling for refractory bone defect by remodeling osteo-regenerative microenvironment

作者：Yipei Yang, Zhenyu Yao, Yuanyi Sun, Yangyi Nie, Yuanchi Zhang, Z. J. Li, Zhiheng Luo, Wenjing Zhang, Xiao Wang, Yuhan Du, Wei Zhang, Ling Qin, Hongxun Sang, Yuxiao Lai · 发表于：Bioactive Materials · 年份：2024 · DOI：10.1016/j.bioactmat.2024.10.019 · 被引用次数：35 · 研究领域：Bone Tissue Engineering Materials、Periodontal Regeneration and Treatments、Mesenchymal stem cell research

The treatment of refractory bone defects is a major clinical challenge, especially in steroid-associated osteonecrosis (SAON), which is characterized by insufficient osteogenesis and angiogenesis. Herin, a microenvironment responsiveness scaffold composed of poly-L-lactide (PLLA), and manganese dioxide (MnO 2 ) nanoparticles is designed to enhance bone regeneration by scavenging endogenous reactive oxygen species (ROS) and modulating immune microenvironment in situ. A catalase-like catalytic reaction between MnO 2 and endogenous hydrogen peroxide (H 2 O 2 ) generated at the bone defect area, which typically becomes acidic and ROS-rich, triggers on-demand release of oxygen and Mn 2+ , significantly ameliorating inflammatory response by promoting M2-type polarization of macrophages, reprograming osteoimmune microenvironment conducive to angiogenesis and osteogenesis. Furthermore, the fundamental mechanisms were explored through transcriptome sequencing analysis, revealing that PLLA/MnO 2 scaffolds (PMns) promote osteogenic differentiation by upregulating the TGF-β/Smad signaling pathway in human bone marrow mesenchymal stem cells (hBMSCs). Overall, the PMns exhibit superior immunomodulatory, excellent osteogenic-angiogenic properties and promising candidates as bone graft substitutes for therapy clinical refractory bone defects. • A multifunctional composite scaffold fabricated by an innovative low-temperature rapid prototyping 3D-printing technology. • The study emphasizes the...