Infection control and bone regeneration remain critical challenges in bone defect treatment. We developed a 3D-printed scaffold incorporating copper-based metal–organic framework-74 (Cu-MOF-74) within a polycaprolactone/hydroxyapatite composite. The synthesized Cu-MOF-74 exhibited a well-defined crystalline structure and rod-like morphology, as confirmed by TEM, EDS, FTIR, and XRD analyses. The scaffolds exhibited hierarchical pores (100–200 μm) and demonstrated tunable hydrophilicity, as evidenced by the water contact angles decreasing from 103.3 ± 2.02° (0% Cu-MOF-74) to 63.60 ± 1.93° (1% Cu-MOF-74). A biphasic Cu²⁺ release profile was observed from the scaffolds, reaching cumulative concentrations of 98.97 ± 3.10 ppm by day 28. Antimicrobial assays showed concentration-dependent efficacy, with 1% Cu-MOF-74 scaffolds achieving 90.07 ± 1.94% and 80.03 ± 2.17% inhibition against Staphylococcus aureus and Escherichia coli, respectively. Biocompatibility assessments using bone marrow-derived mesenchymal stem cells revealed enhanced cell proliferation at Cu-MOF-74 concentrations ≤ 0.2%, while concentrations ≥ 0.5% induced cytotoxicity. Osteogenic differentiation studies highlighted elevated alkaline phosphatase activity and mineralization in scaffolds with 0.05–0.2% Cu-MOF-74 scaffolds, particularly at 0.05% Cu-MOF-74 scaffolds, which exhibited the highest calcium deposition and upregulation of bone sialoprotein and osteopontin expression. These findings demonstrate the dual functional efficacy of Cu-MOF-74/PCL/HAp scaffolds in promoting both infection control and bone regeneration. These optimized Cu-MOF-74 concentrations (0.05–0.2%) effectively balance antimicrobial and osteogenic properties, presenting a promising strategy for bone defect repair in clinical applications.

Repairing large bone defects effectively requires concurrent osteogenesis and angiogenesis, a significant challenge for conventional biomaterials often limited by suboptimal structural design and an inability to provide spatiotemporally controlled bioactive cues. Here, we report a novel chemophysical dual-responsive system rationally designed to address this osteogenic-angiogenic coupling challenge. This system integrates a structurally engineered bimetallic FeCu-metal-organic framework (FeCu-MOF) within a poly(lactic acid)/hydroxyapatite (PLA/HA) scaffold. The engineered FeCu-MOF architecture enables the programmed and sustained co-release of Fe³⁺ and Cu²⁺ ions, providing tailored chemical signals. Synergistic pulsed electromagnetic field (PEMF) stimulation was introduced as a physical cue to further enhance the scaffold's bioactivity. The composite scaffolds, featuring interconnected hierarchical porosity and enhanced hydrophilicity due to FeCu-MOF incorporation, demonstrated distinct Fe³⁺/Cu²⁺ release profiles. In vitro, these scaffolds exhibited excellent biocompatibility and significantly promoted bone marrow mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation. Notably, this structure-derived dual-ion release also indicated pro-angiogenic potential. Crucially, daily PEMF treatment synergistically amplified these cellular responses. In vivo evaluation in a rat cranial defect model confirmed the system's efficacy. While FeCu-MOF/PLA/HA scaffolds alone enhanced bone regeneration, their combination with PEMF yielded the most robust outcomes, characterized by markedly superior vascularized bone formation. Comprehensive analysis, including micro-CT, histology, and immunohistochemistry, confirmed these findings by demonstrating improved bone volume, density, and architecture, mature integrated tissue, and enhanced coupled expression of CD31 and osteogenic markers. In summary, the study validates a powerful synergistic strategy for enhanced bone regeneration. This strategy, integrating programmable, structure-derived bimetallic ion release with PEMF stimulation, successfully achieved synergistic angiogenic-osteogenic coupling, offering a promising approach for complex defect scenarios.

The effective healing of chronic wounds requires balancing antimicrobial activity with tissue regeneration. In this study, we developed a novel, eco-friendly synthesis method using Artemisia argyi extract to produce silver nanoparticles (AgNPs), addressing toxicity concerns associated with conventional chemical synthesis methods. Through optimization of multiple synthesis parameters, monodisperse spherical AgNPs with an average diameter of 6.76 ± 0.27 nm were successfully obtained. Plant-derived compounds from Artemisia argyi extract acted as efficient mediators for both reduction and stabilization, yielding nanoparticles with high crystallinity. The synthesized AgNPs exhibited potent antibacterial activity against both Gram-negative and Gram-positive bacteria, with minimum inhibitory concentrations of 8 μg/mL against Escherichia coli and 32 μg/mL against Staphylococcus aureus, while maintaining high biocompatibility with L929 fibroblasts at concentrations ≤ 8 μg/mL. When integrated into polylactic acid/collagen type I (PLA/Col1) nanofibrous matrices, the optimized 0.03% AgNPs/PLA/Col1 dressing significantly accelerated wound healing in a diabetic rat model, achieving 94.62 ± 2.64% wound closure by day 14 compared to 65.81 ± 1.80% observed in untreated controls. Histological analyses revealed a dual-functional mechanism wherein controlled silver ion release provided sustained antibacterial protection, while concurrently promoting tissue regeneration characterized by enhanced collagen deposition, reduced inflammation, and increased neovascularization. This innovative approach effectively addresses critical challenges in diabetic wound care by providing simultaneous antimicrobial and regenerative functions within a single biomaterial platform.

Severe endometrial injury is a leading cause of female infertility, driven by the convergence of inadequate vascularization, persistent inflammation, infection, and excessive fibrosis. Existing therapies address these pathologies in isolation, falling short of the coordinated remodeling essential for functional regeneration. Here, we report an injectable, thermally responsive composite hydrogel that embeds copper‐based metal–organic framework (HKUST‐1) nanoparticles within a porcine acellular dermal matrix (PADM) network, coupling biomimetic extracellular matrix support with sustained Cu ^{2 +} delivery. In vitro, the hydrogel promotes endothelial migration and tubular network formation, shifts macrophage polarization toward the reparative M2 phenotype, and exhibits broad‐spectrum bactericidal activity. In a rat endometrial injury model, it increases gland density and CD31 ⁺ neovascularization while suppressing fibrotic collagen deposition. Crucially, it restores hormonal responsiveness by upregulating estrogen and progesterone receptor expression. These coordinated improvements translate into meaningful fertility restoration, with implanted embryos increasing from 8 ± 2 to 14 ± 1. Transcriptomic profiling indicates coordinated changes in extracellular matrix remodeling and ion transport programs. The PADM@HKUST‐1 hydrogel demonstrates that integrating biomimetic scaffolding with sustained bioactive ion delivery achieves comprehensive uterine microenvironment remodeling, offering a translatable approach for clinical management of severe endometrial injury.