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

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

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 diox...

Full description

Saved in:
Bibliographic Details
Main Authors: Yipei Yang, Zhenyu Yao, Yuanyi Sun, Yangyi Nie, Yuanchi Zhang, Ziyue Li, Zhiheng Luo, Wenjing Zhang, Xiao Wang, Yuhan Du, Wei Zhang, Ling Qin, Hongxun Sang, Yuxiao Lai
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-02-01
Series:Bioactive Materials
Subjects:
Osteogenic-angiogenic coupling
Steroid-associated osteonecrosis
Manganese dioxide
Refractory bone defect
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X2400464X
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 (MnO2) 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 MnO2 and endogenous hydrogen peroxide (H2O2) generated at the bone defect area, which typically becomes acidic and ROS-rich, triggers on-demand release of oxygen and Mn2+, 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/MnO2 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.
ISSN:2452-199X

Similar Items