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Background <p>Osteoporotic bone defects (OP-BDs) present a significant clinical challenge because of a pathological microenvironment characterized by severe oxidative stress, persistent inflammation, and disrupted metabolic coupling between osteoblasts and osteoclasts. To overcome these barriers, we developed a microenvironment-remodeling nanocomposite hydrogel for re-establishing osteoimmunological and angiogenic homeostasis.</p> Results <p>Manganese dioxide (MnO<sub>2</sub>) nanozymes were first deposited onto layered double hydroxides (LDHs) via an in situ redox reaction to fabricate MnO<sub>2</sub>@LDHs nanocomposites, which were subsequently integrated into a gelatin methacryloyl (GelMA) network through interfacial hydrogen bonding to form the final hydrogel (MnO<sub>2</sub>@LDHs/GelMA). In vitro assays confirmed that the MnO<sub>2</sub> coating exhibited catalase-like activity, decomposing pathological hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) into water and oxygen (O<sub>2</sub>), thereby alleviating oxidative stress and protecting the LDH framework from acid-induced degradation. The resulting ROS depletion modulated macrophage polarization toward a pro-regenerative phenotype, thereby attenuating the inflammatory microenvironment and promoting endothelial cell migration and microvascular tube formation via paracrine signaling. Furthermore, the preserved LDH nanoplatform synergized with the ROS-depleted microenvironment to regulate bone metabolism, enhancing the osteogenic differentiation and matrix mineralization of bone marrow mesenchymal stem cells (BMSCs) while suppressing RANKL-induced osteoclastogenesis in bone marrow-derived macrophages (BMDMs). In vivo evaluations in an ovariectomized (OVX) rat critical-sized femoral defect model demonstrated that the MnO<sub>2</sub>@LDHs/GelMA hydrogel significantly attenuated inflammatory infiltration, re-established bone remodeling homeostasis, and accelerated vascularized bone regeneration.</p> Conclusion <p>This microenvironment-remodeling strategy highlights the therapeutic potential of integrating nanozymes with two-dimensional (2D) nanoplatforms, offering a promising nanobiomaterial-based approach for osteoporotic bone repair.</p> Graphical Abstract <p></p>

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Layered double hydroxide-based ROS-scavenging nanozyme hydrogels re-establish osteoimmune-angiogenic coupling for osteoporotic bone repair

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月1日

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  • Bangguo Wei,
  • Hong Wang,
  • Yi Gao,
  • Huichao Wang,
  • Jiale Gao,
  • Lining Wang,
  • Jiaying Wu,
  • Xijin Wang,
  • Guoxin Jing,
  • Shilong Wang

摘要

Background

Osteoporotic bone defects (OP-BDs) present a significant clinical challenge because of a pathological microenvironment characterized by severe oxidative stress, persistent inflammation, and disrupted metabolic coupling between osteoblasts and osteoclasts. To overcome these barriers, we developed a microenvironment-remodeling nanocomposite hydrogel for re-establishing osteoimmunological and angiogenic homeostasis.

Results

Manganese dioxide (MnO2) nanozymes were first deposited onto layered double hydroxides (LDHs) via an in situ redox reaction to fabricate MnO2@LDHs nanocomposites, which were subsequently integrated into a gelatin methacryloyl (GelMA) network through interfacial hydrogen bonding to form the final hydrogel (MnO2@LDHs/GelMA). In vitro assays confirmed that the MnO2 coating exhibited catalase-like activity, decomposing pathological hydrogen peroxide (H2O2) into water and oxygen (O2), thereby alleviating oxidative stress and protecting the LDH framework from acid-induced degradation. The resulting ROS depletion modulated macrophage polarization toward a pro-regenerative phenotype, thereby attenuating the inflammatory microenvironment and promoting endothelial cell migration and microvascular tube formation via paracrine signaling. Furthermore, the preserved LDH nanoplatform synergized with the ROS-depleted microenvironment to regulate bone metabolism, enhancing the osteogenic differentiation and matrix mineralization of bone marrow mesenchymal stem cells (BMSCs) while suppressing RANKL-induced osteoclastogenesis in bone marrow-derived macrophages (BMDMs). In vivo evaluations in an ovariectomized (OVX) rat critical-sized femoral defect model demonstrated that the MnO2@LDHs/GelMA hydrogel significantly attenuated inflammatory infiltration, re-established bone remodeling homeostasis, and accelerated vascularized bone regeneration.

Conclusion

This microenvironment-remodeling strategy highlights the therapeutic potential of integrating nanozymes with two-dimensional (2D) nanoplatforms, offering a promising nanobiomaterial-based approach for osteoporotic bone repair.

Graphical Abstract