ROS-Scavenging Nanoengineered Bioactive Glass Interfaces Reprogram Macrophage Immunity for Tendon-Bone Regeneration

TY - JOUR

T1 - ROS-Scavenging Nanoengineered Bioactive Glass Interfaces Reprogram Macrophage Immunity for Tendon-Bone Regeneration

AU - Cai, Bowen

AU - Zeng, Fanrui

AU - Xue, Kaixiao

AU - Shen, Zhi

AU - Qiao, Chang

AU - Wu, Han

AU - Wang, Qunyi

AU - Zhang, Jue

AU - Homaeigohar, Shahin

AU - Zheng, Kai

AU - Zhu, Bin

AU - Fang, Jiahu

N1 - © The Author(s) 2026.

PY - 2026/6/9

Y1 - 2026/6/9

N2 - Failure of rotator cuff repair largely stems from ineffective regeneration of the tendon–bone interface (TBI), driven by persistent inflammation and excessive reactive oxygen species (ROS) accumulation at the biomaterial tissue interface. Here, we engineer an immunoregulatory suture interface by incorporating cerium-doped mesoporous bioactive glass nanoparticles (Ce-MBGNs) into a gelatin/tannic acid (Gel/TA) coating on polyethylene terephthalate (PET) sutures. The hierarchical Gel/TA/Ce-MBGN coating displays uniform morphology, robust adhesion, and superior ROS-scavenging activity. In vitro, Ce-MBGN-functionalized surfaces markedly promote osteogenic and chondrogenic differentiation of bone marrow mesenchymal stem cells, while polarizing macrophages toward an anti-inflammatory M2 phenotype and substantially reducing intracellular ROS. In a rat rotator cuff repair model, high Ce-MBGN-loaded sutures significantly enhance fibrocartilaginous enthesis regeneration, increase bone mineral density, and elevate M2 macrophage infiltration at the TBI. These regenerative effects correlate with suppressed HIF-1α expression in vivo, suggesting that localized redox modulation drives macrophage immunometabolic reprogramming to foster a pro-regenerative microenvironment. This Ce-MBGN-enabled interface engineering strategy simultaneously scavenges ROS, modulates immunity, and supports multi-lineage tissue regeneration at the TBI, offering a promising, clinically translatable approach for immunomodulatory suture design to improve rotator cuff repair outcomes.

AB - Failure of rotator cuff repair largely stems from ineffective regeneration of the tendon–bone interface (TBI), driven by persistent inflammation and excessive reactive oxygen species (ROS) accumulation at the biomaterial tissue interface. Here, we engineer an immunoregulatory suture interface by incorporating cerium-doped mesoporous bioactive glass nanoparticles (Ce-MBGNs) into a gelatin/tannic acid (Gel/TA) coating on polyethylene terephthalate (PET) sutures. The hierarchical Gel/TA/Ce-MBGN coating displays uniform morphology, robust adhesion, and superior ROS-scavenging activity. In vitro, Ce-MBGN-functionalized surfaces markedly promote osteogenic and chondrogenic differentiation of bone marrow mesenchymal stem cells, while polarizing macrophages toward an anti-inflammatory M2 phenotype and substantially reducing intracellular ROS. In a rat rotator cuff repair model, high Ce-MBGN-loaded sutures significantly enhance fibrocartilaginous enthesis regeneration, increase bone mineral density, and elevate M2 macrophage infiltration at the TBI. These regenerative effects correlate with suppressed HIF-1α expression in vivo, suggesting that localized redox modulation drives macrophage immunometabolic reprogramming to foster a pro-regenerative microenvironment. This Ce-MBGN-enabled interface engineering strategy simultaneously scavenges ROS, modulates immunity, and supports multi-lineage tissue regeneration at the TBI, offering a promising, clinically translatable approach for immunomodulatory suture design to improve rotator cuff repair outcomes.

KW - Tendon-bone interface

KW - Rotator cuff repair

KW - Surface modification

KW - Macrophage polarization

KW - Cerium-doped bioactive glass nanoparticles

KW - Immunomodulation

KW - tendon–bone interface

KW - immunomodulation

KW - surface modification

KW - macrophage polarization

KW - rotator cuff repair

KW - cerium-doped bioactive glass nanoparticles

UR - https://www.scopus.com/pages/publications/105043861745

U2 - 10.1093/rb/rbag121

DO - 10.1093/rb/rbag121

M3 - Article

C2 - 42404410

SN - 2056-3418

VL - 13

JO - Regenerative biomaterials

JF - Regenerative biomaterials

M1 - rbag121

ER -