Reactivity or yield for solution-phase catalysis in nanoporous materials with inhibited transport can exhibit a strong dependence on effective pore diameter or width, W. For example, the yield for PNB conversion to an aldol product in mesoporous silica nanoparticles is strongly enhanced upon increasing W from around 1 to 2 nm. To provide a high-fidelity description of such behavior, a multiscale modeling framework is developed incorporating three coupled levels of analysis: (i) Molecular Dynamics (MD) simulation with Effective Fragment Potentials (EFP) on the time scale of tens of ps to assess diffusion coefficients for the reactant and product species, where simulation explicitly incorporates the solvent utilized in experiment; (ii) strongly damped Langevin simulations describing the Brownian dynamics of a reactant and product pair inside the pore in an implicit solvent to assess the propensity, P, for the passing on longer time scales of these species as a function of W; EFP-MD diffusion coefficients provide input to the Langevin simulations; we emphasize that P is shown to be a key parameter controlling overall reactivity; (iii) spatially discrete coarse-grained (CG) stochastic modeling which captures the overall catalytic reaction-diffusion process on the appropriate time- and length-scales. P provides key input to these CG simulations. Kinetic Monte Carlo (KMC) simulation of this CG stochastic model allows assessment of, e.g., reactivity versus pore diameter, thereby connecting with experiment.

Light-modulated artificial neurons are vital for clinical optic nerve repair and bionic robotics. Light-sensitive ambipolar organic mixed ionic-electronic conductors (OMIECs) allow for homogeneously integrated artificial neurons, free from issues such as voltage/resistance mismatch or digital-to-analog conversion. However, their development is constrained by a trade-off between ion and electron transport, which results in low figure-of-merit (μC*) values and P/N-mode imbalance. Here, through precise molecular weight tailoring, we develop an ambipolar OMIEC with a high face-on orientation ratio of 85.5% and a 4-fold enhancement in backbone crystallinity. This approach simultaneously enhances vertical ionic transport and electron transport, enabling the synergetic optimization of electronic mobility and volumetric capacitance. The optimized material achieves high μC* values of 423.3 ± 17.3 F cm-1 V-1 s-1 (N-type) and 359.8 ± 42.6 F cm-1 V-1 s-1 (P-type). Using this OMIEC, we construct a homogeneous artificial neuron whose excitation/inhibition behaviors can be dually modulated by light and chemical environment, paving new paths for high-performance OMIECs in biological neural prosthetics and bionic machine vision systems.

Understanding the atomic-scale structure and stability of intercalated two-dimensional (2D) metals requires precise theoretical insight. Here, we present an extensive first-principles density functional theory (DFT) investigation of Pb monolayers intercalated beneath a buffer-layer graphene on a SiC(0001) substrate. To minimize lattice-mismatch strain between graphene and SiC, we employ a slightly rotated 61 × 61 SiC supercell, 3.67° off the commonly used 3 × 3 model. This approach resolves key interfacial motifs, most notably a 10 × 10 hexagonal-like phase with alternating compressive and tensile regions, that cannot be captured with smaller or unrotated models. Systematic exploration over a Pb coverage range of 0.4 < θ ≤ 1.0 reveals a chemical potential landscape featuring diverse thermodynamically stable phases, including periodic 10 × 10 hexagonal, distorted hexagonal, elongated hexagonal, and stripe-like motifs, each associated with distinct out-of-plane corrugations in the decoupled graphene layer. At θ ≈ 0.79, multiple nearly degenerate hexagonal configurations emerge, differing only in Pb arrangements within the intercalated layer, consistent with recent scanning tunneling microscopy (STM) observations. In the intermediate coverage range 0.49 < θ < 0.71, stripe-like motifs exhibit small energy differences (< 20 meV) among themselves and lie only 5-11 meV above the hexagonal phases, explaining the coexistence of multiple patterns in experiments. These findings provide theoretical support for the observed coexistence of distinct interfacial phases and highlight the intricate, atomically precise, coverage-dependent phase stability of Pb-intercalated graphene on SiC(0001).

Titanium (Ti)-based implants often exhibit poor osseointegration in osteoporotic bone defects, primarily due to osteoporosis frequently accompanied by excessive reactive oxygen species (ROS), which induce mitochondrial oxidative stress within osteoblasts, leading to dysfunctional mitochondria. To address this challenge, a piezo-metastructured array composed of BaTiO3 nanorods decorated with hydroxyapatite (HA) nanoparticles (termed as BTH array) was constructed on Ti, which can significantly enhance piezoelectric potential (PP) under low-intensity pulsed ultrasound (LIPUS) treatment. Based on the simulation results, the enhanced PP of BTH array under LIPUS arises from the effects of nanorod pattern induced acoustic impedance matching and the overlapping built-in electric field at BaTiO3/HA interface. The elevated PP activates voltage-gated calcium channels in osteoblasts under osteoporosis mimicking conditions, allowing Ca2+ released from degraded HA to flux into cells and appropriately elevate mitochondrial calcium levels, thereby promoting ATP synthesis. The enhanced ATP synthesis supports cytoskeletal remodeling of cells, thereby triggering migrasome formation to eliminate damaged mitochondria and promote the fission of healthy ones. This process restores mitochondrial quality control, leading to the mitigation of mitochondrial oxidative stress and ultimately enhancing osseointegration of Ti-based implants in osteoporosis bone. Thus, piezo-metastructured array coating mediated ATP synthesis in osteoblasts under LIPUS represents a promising strategy to improve implant osseointegration under osteoporosis conditions.

When tissue injury exceeds its intrinsic regenerative capacity, artificial interventions are required. Endogenous electric fields (EEFs) have been shown to regulate cell and tissue behavior, providing a physiological basis for using electrical stimulation (ES) to mimic or amplify these cues with precise, low-amplitude, continuous signaling that tunes membrane potential, Ca2+ influx, and downstream pathways. Replicating EEFs via biomaterials featuring self-generated electric fields (SGEF biomaterials) enables wireless, conformal delivery in tissues without wired power or bulky hardware, improving safety, comfort, and integration. This review focuses on polymer-based SGEF biomaterials to deliver ES without wired external power sources or batteries. We summarize the mechanisms by which ES modulates tissue repair and regeneration, and then survey polymer-based SGEF biomaterials, including piezoelectric polymers, polymer-based triboelectric nanogenerators, thermoelectric polymers, photoelectric polymers, and polymer-based magnetoelectric composites, highlighting their historical development, working principles and recent advances. The effects of polymer chemistry, structure and fabrication strategies on electrical output and stability are discussed. Representative applications in varying kinds of tissues are analyzed in terms of tissue-specific requirements. Finally, the prospects and future directions of polymer-based SGEF biomaterials are envisioned. This review presents a comprehensive summary and classifies polymer-based SGEF strategies according to their transduction mechanisms to facilitate comparison and future materials design.

Rheumatoid arthritis (RA) is driven by the breakdown of immune tolerance, arising from the coordinated actions of synovial inflammation, oxidative stress, and dysregulated cytokine production. To address this challenge, we report pH-responsive core-shell nanoparticles composed of a CaO2 core and a Ce ion-tannic acid phenolic network shell to restore immune tolerance by reprogramming innate and adaptive immune responses. Under acidic conditions, the nanoparticles undergo structural disassembly, releasing catalytic Ce ions and bioactive Ca2+. Through the Ce3+/Ce4+ redox cycle, the nanoparticles efficiently scavenge reactive oxygen species and enable sustained O2 generation, while O2 release enhances nanoparticle motility. By alleviating oxidative stress and hypoxia, these nanoparticles restore mitochondrial structure and function in macrophages, promoting anti-inflammatory M2 polarization. Concurrently, improved redox and oxygenation states in dendritic cells suppress glycolysis and inflammatory signaling, resulting in attenuated activation, reduced antigen presentation, and the induction of a tolerogenic phenotype that favors regulatory T cell differentiation. Consequently, immune tolerance is reestablished, leading to effective attenuation of synovitis and, in synergy with released Ca2+, significant protection against articular bone and cartilage destruction in a RA mouse model. This work highlights immune metabolic reprogramming as a nanomaterial enabled strategy for durable and comprehensive RA alleviation.

The intercalation of rare-earth metals into the galleries of epitaxial graphene layer(s) grown on SiC(0001) substrate offers a unique synthesis approach to form functional two-dimensional (2D) heterostructures with properties controlled by atomically defined graphene-metal interfaces. The most stable position for the intercalated atoms is found beneath the buffer layer, where they form bonds with the silicon-terminated SiC substrate. Here, we systematically studied the thermally assisted intercalation of gadolinium (Gd) under epitaxial bilayer graphene (BLG) as a function of coverage and annealing temperatures. We identified kinetic conditions to form a non-equilibrium phase, where the intercalants populate the gallery between the top BLG layers. The more energetically favorable structure is also observed, in which Gd atoms diffuse beneath the buffer layer, forming a quasi-ordered “triangular” phase at the SiC interface. Scanning tunneling microscopy and spectroscopy reveal the coexistence of Gd atoms at different subsurface locations in adjacent regions. Density functional theory is employed to model Gd intercalation at various sites and to assess their stability, in agreement with experimental observations. Nano-infrared imaging unambiguously identifies the Gd-intercalated regions at the mesoscale. The successful synthesis of metastable phases in BLG highlights the importance of fine-tuning the kinetic parameters for the precise synthesis of 2D metal-graphene heterostructures.

Electroporation can inhibit bacteria through membrane damage; however, its application against implant-related infections remains exploration. Herein, a piezo-assemblage (BM) was developed on Ti by growing octahedral Mn-MIL-100 onto BaTiO3 nanotubes. The piezoelectric properties of Mn-MIL-100 and its enhancing effect on those of BM are demonstrated. Under ultrasound (US), Mn-MIL-100 and BaTiO3 become polarized; the piezoelectric and built-in electric fields synergistically separate US-induced hot charges, and accumulate positive ones at Mn-MIL-100 tips to further generate a high local electric field. The efficient charge separation coupled with charge accumulation promotes ROS generation. When bacteria invade, the local electric field at Mn-MIL-100 tips induces bacterial electroporation, which synergizes with ROS to kill bacteria efficiently. After sterilization, Mn-MIL-100 endows BM with nanozyme-like properties in ROS scavenging, which promotes M2 phenotype of M1 macrophages to facilitate anti-inflammation and tissue regeneration. This electroporation-based antibacterial therapy provides a unique perspective for treating infected implants.

A corrosion-resistant coating for Mg alloys applied in marine environments is developed, integrating self-healing and antibacterial functions. It comprises an inner microporous MgO layer and an outer layer of layered-doublehydroxides (LDH) co-doped with MoO42- and deprotonated 2-mercaptobenzothiazolium (MBT-), forming Mo-S bonds. This dual-ion doping strategy enhances corrosion resistance by accelerating ion release, promoting self-healing through weakened bonding between the doped ions and LDH octahedra due to the formed Mo-S bonds. Released MBT- also provides high antibacterial rate against Staphylococcus aureus (93.76 %) and mitigate biocorrosion. This approach offers an effective strategy for a protective coating construction on Mg in marine applications.

[This corrects the article DOI: 10.1016/j.bioactmat.2025.09.001.].

The ever-growing antibiotic resistance in bacteria poses an enormous threat to public health and the environment. The horizontal transfer of antibiotic resistance genes (ARGs) is a major pathway for disseminating antibiotic resistance. As an inexpensive, nontoxic, and biocompatible material, ZnO with diverse sizes and surface properties have been prepared for widespread use. However, the effects and mechanisms of ZnO particles with different structural properties on the horizontal transfer of ARGs are not comprehensively understood. In this study, two groups of ZnO particles, one with the same size (93 nm) and different charge types (-9.5 and + 17.4 mV), and the other homogeneously positively charged but of different sizes (93, 215, and 2381 nm), were prepared. Their impacts on the horizontal transformation of ARGs mediated by plasmid pUC19 into E coli DH5α were investigated. In the positively charged group, the smallest ZnO nanoparticles at concentrations of 0.1-100 μg/mL induced 1.04-1.35 and 1.37-1.71-fold increases in transformation frequency when compared with that of the medium-sized and largest particles, respectively. In the similar-sized groups, positive ZnO promoted 1.06-1.32-fold increases than negative ZnO. Further investigation suggested that smaller and positive ZnO adsorbed more plasmids and correspondingly increased the uptake by recipient bacteria than that of larger and/or negative ZnO. In addition, the enhanced bacterial membrane permeability, ATP synthesis, and DNA replication were also accounted for the increased transformation. These results suggest that smaller-sized and positive ZnO poses a high environmental risk of spreading antibiotic resistance.

The interaction between biomaterials and immune system is a critical area of research, especially in tissue engineering and regenerative medicine. A fascinating and less explored aspect involves the immunomodulatory behaviors of macrophage (MΦ)-derived exosomes induced by biomaterial surfaces. Herein, untreated surface, nanostructured surface, and type I collagen (Col-I)-decorated nanostructured surface of titanium implants are chosen to culture MΦs, followed by extraction of MΦ-derived exosomes and investigation of their immunomodulatory functions and mechanisms. The results show that the exosomes in the untreated group carried plenty of inflammatory cytokines, predominantly C─C motif chemokine ligand 2 (CCL2). After targeting recipient cells, the CCL2 on the exosomes can specifically bind to its receptor C─C motif chemokine receptor 2, triggering downstream signaling pathways to induce internalization of membrane integrin β1 and targeted lysosomal degradation, consequently suppressing the functions of recipient cells. In contrast, the exosomes in the nanostructured group, especially Col-I-decorated nanostructured group carried few CCL2, moderating their inhibition on the functions of recipient cells. These findings not only clearly show that CCL2 is a key constituent of exosomes involved in the interaction between biomaterials and host immune system, but also potentially a key target for designing advanced biomaterials to promote tissue repair and regeneration.

Traditional cotton gauze remains a primary wound dressing for initial wound protection and exudate control. However, it lacks antibacterial property and fails to support angiogenesis and epithelial regeneration. To address these limitations, a one-step solvent-based strategy was developed to uniformly integrate ZIF-8 nanoparticles onto gauze with good interfacial stability. The functionalized gauze shows pH-responsive Zn2+ releasing behavior. When bacteria invade the wound, pathogen-secreted organic acids trigger rapidly degradation of ZIF-8, resulting in a burst release of Zn2+, which increases bacterial membrane permeability, induces intracellular ROS production and protein leakage, and ultimately leads to bacterial death. Simultaneously, the gauze rapidly concentrates plasma components and red blood cells at the wound interface due to the high specific surface area of ZIF-8 and sustained release of Zn2+. During proliferation and remodeling phases of wound repair, Zn2+ further promotes tissue regeneration by stimulating the migration, adhesion, proliferation and differentiation of HUVECs and L929, enhancing angiogenesis and epithelial remodeling. In infected skin wound models, this functionalized gauze exhibits on-demand antibacterial activity, inflammation suppression, and accelerated collagen deposition and wound healing, demonstrating great clinical application potential.

Pathological microenvironment of diabetes including hyperglycemia, excessive reactive oxygen species (ROS), and accumulation of advanced glycation end products leads to high risk of infection and persistent inflammatory reaction, retarding biointegration of implants. To address this issue, a dual‐catalysis system consisting of Na 2 TiO 3 nanotubes with CeO 2 nanodots and polydopamine (PDA) cover is constructed on Ti implant to manipulate ROS generation and scavenging for antibiosis and tissue regeneration. Na 2 TiO 3 and CeO 2 form heterojunction, in which oxygen vacancies (VOs) contribute to the separation of electron‐hole pairs under near‐infrared light (NIR) irradiation. In NIR mode, the photocatalysis‐induced ROS and photothermal‐induced hyperthermia by Na 2 TiO 3 ‐CeO 2 heterojunction and PDA cover synergistically kill bacteria efficiently. In non‐NIR mode, CeO 2 nanodots and PDA cover show excellent superoxide dismutase (SOD) and catalases (CAT) like enzyme activities, and they catalyze ROS (e.g., ·O 2 − and H 2 O 2 ) thoroughly into benign O 2 and H 2 O, relieving the oxidative stress of microenvironment and accelerating M2 macrophage phenotype. It helps biofunctional recovery of endothelial cells and fibroblasts, promoting tissue regeneration around implants in diabetic models. This work proposes a promising approach of manipulating ROS generation and scavenging to treat infection and regulate inflammatory reaction, thereby improving biointegration and performance of implants in diabetic microenvironment.

The impaired healing of diabetic wounds is largely attributable to the pathological microenvironment, which promotes susceptibility to bacterial infection, hyperinflammation, vasculopathy, and neuropathy. To address these issues, a bimetallic catalyst core-shell nanoplatform ((Cu@Ce)HM) with Cu-bonded Ce-MOF as core and HHC36-loaded hyaluronic acid (HA) as shell is constructed. (Cu@Ce)HM demonstrates potent antibacterial efficacy (eliminating 97.01 % of Staphylococcus aureus (S. aureus) and 99.55 % of Escherichia coli (E. coli)) through the responsive release of Cu ions and HHC36 in infected diabetic microenvironment. Furthermore, (Cu@Ce)HM effectively scavenges excessive reactive oxygen species (ROS) via its superoxide dismutase (SOD)- and catalase (CAT)-mimicking enzymatic activities. Density functional theory (DFT) calculations reveals that Cu bonding induces electron rearrangement within the Ce-MOF, stabilizing the coexistence of Cu+/Cu2+ and Ce3+/Ce4+ redox couples. This bimetallic synergy enables efficient catalysis, improving ROS scavenging performance of (Cu@Ce)HM. (Cu@Ce)HM improves the pathological microenvironment by scavenging ROS and supplying low-dose Cu ions, and thus promotes the recovery and M2 phenotype of M1 macrophages, enhancing anti-inflammatory cytokine secretion. This immunomodulation further augments the biofunctions of endothelial cells (HUVECs) and neural cells (PC12). Transcriptome sequencing analysis indicates that the antioxidant properties and Cu supplementation provided by (Cu@Ce)HM promotes the recovery and differentiation of damaged PC12 cells by upregulating key signaling pathways, including PI3K/Akt/CREB, Ras/ERK/CREB, and Ras/ERK/MAPK. This study presents a promising "all-stage" management strategy for infected diabetic wound regeneration, integrating infection elimination, immunoregulation, and the facilitation of neuroangiogenesis and extracellular matrix (ECM) remodeling.

Conventional titanium (Ti)-based implants often fail to achieve osseointegration in bone defects accompanied by rheumatoid arthritis (RA), primarily due to the RA pathological microenvironment, characterized by elevated reactive oxygen species (ROS) levels and hypoxia. This microenvironment induces mitochondria dysfunction and intracellular Ca2+ overload, facilitating macrophage polarization toward the M1 phenotype and thus impairing osteoimmunomodulatory osseointegration. To address this challenge, a nanozyme-inspired coating, featuring the deposition of MnFe2O4 nanoparticles onto a polydopamine (PDA)-decorated surface of microporous TiO2, is constructed on Ti (known as MFO coating). The osteoimmunomodulatory osseointegration of the coating, both in vitro and in vivo, accompanied by RA was assessed, and the underlying mechanisms were also investigated. Due to the efficient conversion of H2O2 into O2 and robust ROS-scavenging capabilities, the coating mitigates mitochondria ROS accumulation and intracellular Ca2+ overload induced by the pathological microenvironment, while simultaneously elevating intracellular O2 levels, thereby preventing macrophage apoptosis. Meanwhile, by improving the microenvironment, the coating activates moderate mitophagy through the Ca2+-AMPK-mTOR signaling pathway, facilitating the removal of dysfunctional mitochondria and the preservation of mitochondrial dynamics and integrity. As a result, the restored mitochondria reprogram their metabolic pathway from relying on anaerobic to relying on aerobic oxidative phosphorylation, facilitating macrophage polarization toward the M2 phenotype, which not only inhibits osteoclastogenesis but also accelerates osseointegration in rats with RA. The coating presents a transformative approach to Ti-based implant design for bone defects associated with inflammatory diseases, potentially reducing the risk of revision surgery and offering a long-lasting lifespan for patients.

Current modifications of Ti-based materials with porous scaffolds for achieving biological fixation often decrease corrosion fatigue strength ( sigma cf ) of the resultant implants, thereby shortening their service lifespan. To resolve this issue, in the present, a step-wise graded porous Ti-6Al-7Nb scaffold was additively manufactured on optimally surface mechanical attrition treated (SMATed) Ti-6Al-7Nb (specifically denoted as S-Ti6Al7Nb) using laser powder bed fusion (PBF) technology. The microstructure, bond strength, residual stress distribution, and corrosion fatigue behavior of porous scaffolds modified S-Ti6Al7Nb were investigated and compared with those of mechanically polished Ti-6Al-7Nb (P-Ti6Al7Nb), S-Ti6Al7Nb, and porous scaffolds modified P-Ti6Al7Nb. Results showed that corrosion fatigue of porous scaffolds modified Ti-6Al-7Nb was propagation controlled. Moreover, the crack propagation behavior in the PBF scaffold's fusion zone (FZ) and heat-affected zone (HAZ), exhibiting insensitivity to the microstructural configurations characterized by columnar prior- beta grain (PBG) boundaries and acicular alpha' martensites, coupled with the PBF-induced residual tensile stresses in these regions, resulted in a considerable decrease in sigma cf for porous scaffolds modified P-Ti6Al7Nb compared to P-Ti6Al7Nb. In contrast, step-wise graded porous scaffold-modified S-Ti6Al7Nb demonstrated an improved sigma cf which was even higher than that of P-Ti6Al7Nb. Such an advancement in corrosion fatigue strength is primarily attributed to the presence of residual compressive stresses within the underlying S-Ti6Al7Nb substrate, extending beyond FZ and HAZ. These stresses increased the crack propagation threshold, leading to crack deflection/branching and increased crack-path tortuosity, thereby synergistically markedly enhancing the crack propagation resistance of porous scaffolds modified S-Ti6Al7Nb. (c) 2024 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science & Technology.

Plumbene, a two-dimensional (2D) material consisting of a single layer of lead (Pb) atoms in a honeycomb lattice, stands as a pioneering addition to the elemental 2D material family. This comprehensive review encapsulates the theoretical predictions and experimental advancements that underscore its potential. With properties shaped by significant spin-orbit coupling and structural buckling, plumbene offers a playground for phenomena like the quantum spin Hall effect, superconductivity, and topological phase transitions. Despite promising theoretical insights, experimental realization has encountered challenges, primarily due to high reactivity of Pb and the need for precise fabrication conditions. This paper critically examines the electronic, thermal, mechanical, and topological attributes of plumbene, alongside synthesis methods, functionalization techniques, and substrate effects. It further proposes directions for addressing synthesis challenges and integrating plumbene into advanced technologies, particularly in electronic, spintronic, and quantum computing applications. This review aims to bridge the gap between theoretical potential and experimental progress, fostering a deeper understanding of this intriguing material.

Recently realized high-mobility semiconducting epitaxial graphene on silicon carbide (SiC) [Zhao, J. Nature 2024, 625 (7993), 60-65, 10.1038/s41586-023-06811-0] provided an important step toward integration of the graphene-based system into active components in postsilicon micro- and nanoelectronics. However, the exact atomic-scale structure and complex bonding configurations of the first epitaxial graphene carbon layer (Cbuffer) remain an open problem. Our recent report [Kolmer, M. Communications Physics 2024, 7 (1), 16, 10.1038/s42005-023-01515-3] has shed new light on understanding this interface, where the external transverse electric field-dependent dynamic switching behavior of the Cbuffer-SiC bonds was observed. Here, using scanning tunneling microscopy and spectroscopy (STM and STS), we present direct evidence of silicon (Si) vacancies at the interface and provide their distribution at the topmost reconstructed SiC(0001) layer. Bias voltage and epitaxial graphene thickness-dependent characterization of the collective Cbuffer-SiC interface showed that "Si" vacancy sites beneath Cbuffer are stable under STM electric fields. Moreover, the vacancies introduce localized electronic states below the Fermi level, thereby enhancing the charge-transfer phenomenon across the interface.

Carbon monoxide (CO) has multi-biofunctions, including antibiosis and immunoregulation, promising great therapeutic potential. However, poor controllability of releasing, unbalanced dose for antibiosis and cytocompatibility, and unexplored antibacterial mechanism, limit its practical application. To address these issues, a photo-responsive COT nanocontainer is designed on Ti by loading thermosensitive CO donors in PDA-modified TiO2 nanotubes. The nanocontainer shows outstanding photothermal properties, so as to break the Mn-CO bonds of CO donors under near-infrared (NIR) irradiation, generating thermal CO bubbles on-demand by regulating NIR power, and thus realizing different therapy modes. At antibacterial mode of COT with high-power NIR irradiation (e.g., 0.7 W cm-2), abundant hyperthermal CO bubbles from COT kill bacteria efficiently by inducing bacterial ferroptosis, which is demonstrated by hallmarks of overloaded Fe ions, lipid peroxidation, glutathione depletion, etc. At immunoregulation mode with low-power NIR irradiation (e.g., 0.3 W cm-2), mild thermal CO bubbles help macrophages to polarize into anti-inflammatory M2 phenotype, and they combine with cytokines from M2 macrophages to promote fibroblast response. These dual therapy modes of COT are verified to kill bacteria, modulate immunoreaction, and accelerate tissue repair in infected models. This study provides a controllable therapy strategy for using CO in treating infection and improving tissue regeneration.