Oxygen-defect bismuth oxychloride nanosheets for ultrasonic cavitation effect enhanced sonodynamic and second near-infrared photo-induced therapy of breast cancer.

Sonodynamic therapy (SDT) relies heavily on the presence of oxygen to induce cell death. Its effectiveness is thus diminished in the hypoxic regions of tumor tissue. To address this issue, the exploration of ultrasound-based synergistic treatment modalities has become a significant research focus. Here, we report an ultrasonic cavitation effect enhanced sonodynamic and 1208 nm photo-induced cancer treatment strategy based on thermoelectric/piezoelectric oxygen-defect bismuth oxychloride nanosheets (BNs) to realize the high-performance eradication of tumors. Upon ultrasonic irradiation, the local high temperature and high pressure generated by the ultrasonic cavitation effect combined with the thermoelectric and piezoelectric effects of BNs create a built-in electric field. This facilitates the separation of carriers, increasing their mobility and extending their lifetimes, thereby greatly improving the effectiveness of SDT and NIR-Ⅱ phototherapy on hypoxia. The Tween-20 modified BNs (TBNs) demonstrate ∼88.6 % elimination rate against deep-seated tumor cells under hypoxic conditions. In vivo experiments confirm the excellent antitumor efficacy of TBNs, achieving complete tumor elimination within 10 days with no recurrences. Furthermore, due to the high X-ray attenuation of Bi and excellent NIR-Ⅱ absorption, TBNs enable precise cancer diagnosis through photoacoustic (PA) imaging and computed tomography (CT).

NIR responsive scaffold with multistep shape memory and photothermal-chemodynamic properties for complex tissue defects repair and antibacterial therapy.

Complex tissue damage accompanying with bacterial infection challenges healthcare systems globally. Conventional tissue engineering scaffolds normally generate secondary implantation trauma, mismatched regeneration and infection risks. Herein, we developed an easily implanted scaffold with multistep shape memory and photothermal-chemodynamic properties to exactly match repair requirements of each part from the tissue defect by adjusting its morphology as needed meanwhile inhibiting bacterial infection on demand. Specifically, a thermal-induced shape memory scaffold was prepared using hydroxyethyl methacrylate and polyethylene glycol diacrylate, which was further combined with the photothermal agent iron tannate (FeTA) to produce NIR light-induced shape memory property. By varying ingredients ratios in each segment, this scaffold could perform a stepwise recovery under different NIR periods. This process facilitated implantation after shape fixing to avoid trauma caused by conventional methods and gradually filled irregular defects under NIR to perform suitable tissue regeneration. Moreover, FeTA also catalyzed Fenton reaction at bacterial infections with abundant H2O2, which produced excess ROS for chemodynamic antibacterial therapy. As expected, bacteriostatic rate was further enhanced by additional photothermal therapy under NIR. The in vitro and vivo results showed that our scaffold was able to perform high efficacy in both antibiosis, inflammation reduction and wound healing acceleration, indicating a promising candidate for the regeneration of complex tissue damage with bacterial infection.

NIR-activatable nitric oxide generator based on nanoparticles loaded small-molecule photosensitizers for synergetic photodynamic/gas therapy.

BACKGROUND: Therapeutic approaches that combine conventional photodynamic therapy (PDT) with gas therapy (GT) to sensitize PDT are an attractive strategy, but the molecular structure design of the complex lacks effective guiding strategies. RESULTS: Herein, we have developed a nanoplatforms Cy-NMNO@SiO2 based on mesoporous silica materials loaded NIR-activatable small-molecule fluorescent probe Cy-NMNO for the synergistic treatment of photodynamic therapy/gas therapy (PDT/GT) in antibacterial and skin cancer. The theoretical calculation results showed that the low dissociation of N-NO in Cy-NMNO enabled it to dissociate effectively under NIR light irradiation, which is conducive to produce Cy and NO. Cy showed better 1O2 generation performance than Cy-NMNO. The cytotoxicity of Cy-NMNO obtained via the synergistic effect of GT and PDT synergistically enhances the effect of photodynamic therapy, thus achieving more effective tumor treatment and sterilization than conventional PDT. Moreover, the nanoplatforms Cy-NMNO@SiO2 realized efficient drug loading and drug delivery. CONCLUSIONS: This work not only offers a promising approach for PDT-GT synergistic drug delivery system, but also provides a valuable reference for the design of its drug molecules.

EGFR-Targeted and NIR-Triggered Lipid-Polymer Hybrid Nanoparticles for Chemo-Photothermal Colorectal Tumor Therapy.

Background: Epidermal growth factor receptor (EGFR) is a major target for the treatment of colorectal cancer. Thus, anti-EGFR antibody conjugated lipid-polymer hybrid nanoparticles can offer a potential means of enhancing the efficacy of chemotherapeutics in EGFR overexpressing cancers. In addition, the combination of chemotherapy and photothermal therapy is a promising strategy for cancer treatment. Hence, it is highly desirable to develop a safe and effective delivery system for colorectal tumor therapy. Methods: In this study, EGFR-targeted and NIR-triggered lipid-polymer hybrid nanoparticles (abbreviated as Cet-Iri-NPs) were prepared with copolymer PPG-PEG, lipids DSPE-PEG-Mal and lecithin as carriers, CPT-11 as an anticancer chemotherapeutic agent, indocyanine green (ICG) as a photothermal agent, and cetuximab as a surface-targeting ligand. Results: In vitro analyses revealed that Cet-Iri-NPs were spherical with size of 99.88 nm, charge of 29.17 mV, drug entrapment efficiency of 51.72%, and antibody conjugation efficiency of 41.70%. Meanwhile, Cet-Iri-NPs exhibited a remarkable photothermal effect, and pH/NIR-triggered faster release of CPT-11 with near infrared (NIR) laser irradiation, which induced enhanced cytotoxicity against SW480 cells. Furthermore, the promoted tumor-growth suppression effect of Cet-Iri-NPs on SW480 tumor xenograft nude mice was achieved under NIR laser irradiation. Conclusion: These results indicate that the well-defined Cet-Iri-NPs are a promising platform for targeted colorectal cancer treatment with chemo-photothermal therapy.

Predictive models for heat stress assessment in Holstein dairy heifers using infrared thermography and machine learning.

Heat stress is a condition that impairs the animal's productive and reproductive performance, and can be monitored by physiological and environmental variables, including body surface temperature, through infrared thermography. The objective of this work is to develop computational models for classification of heat stress from respiratory rate variable in dairy cattle using infrared thermography. The database used for the construction of the models was obtained from 10 weaned heifers, housed in a climate chamber with temperature control, and submitted to thermal comfort and heat wave treatments. Physiological and environmental data were collected, as well as thermographic images. The machine learning modeling environment used was IBM Watson, IBM's cognitive computing services platform, which has several data processing and mining tools. Classifier models for heat stress were evaluated using the confusion matrix metrics and compared to the traditional method based on Temperature and Humidity Index. The best accuracy obtained for classification of the heat stress level was 86.8%, which is comparable to previous works. The authors conclude that it was possible to develop accurate and practical models for real-time monitoring of dairy cattle heat stress.

Fluorine Doping Mediated Epitaxial Growth of NaREF4 on TiO2 for Boosting NIR Light Utilization in Bioimaging and Photodynamic Therapy.

By integrating TiO2 with rare earth upconversion nanocrystals (NaREF4), efficient energy transfer can be achieved between the two subunits under near-infrared (NIR) excitation, which hold tremendous potential in the fields of photocatalysis, photodynamic therapy (PDT), etc. However, in the previous studies, the combination of TiO2 with NaREF4 is a non-epitaxial random blending mode, resulting in a diminished energy transfer efficiency between the NaREF4 and TiO2. Herein, we present a fluorine doping-mediated epitaxial growth strategy for the synthesis of TiO2-NaREF4 heteronanocrystals (HNCs). Due to the epitaxial growth connection, NaREF4 can transfer energy through phonon-assisted pathway to TiO2, which is more efficient than the traditional indirect secondary photon excitation. Additionally, F doping brings oxygen vacancies in the TiO2 subunit, which further introduces new impurity energy levels in the intrinsic band gap of TiO2 subunit, and facilitates the energy transfer through phonon-assisted method from NaREF4 to TiO2. As a proof of concept, TiO2-NaGdF4 : Yb,Tm@NaYF4@NaGdF4 : Nd@NaYF4 HNCs were rationally constructed. Taking advantage of the dual-model up- and downconversion luminescence of the delicately designed multi-shell structured NaREF4 subunit, highly efficient photo-response capability of the F-doped TiO2 subunit and the efficient phonon-assisted energy transfer between them, the prepared HNCs provide a distinctive nanoplatform for bioimaging-guided NIR-triggered PDT.

Noble metal-free plasmonic Cu/WO3-x@ZNC bi-functional composite for ciprofloxacin photocatalytic degradation and photothermal water evaporation via visible-infrared exposure.

Herein, coupling of noble metal-free plasmonic copper nanoparticles with tungsten suboxide and supporting on zeolite nanoclay (Cu/WO3-x@ZNC) composite will be introduced for bi-functional photocatalytic ciprofloxacin (CIP) degradation and water photothermal evaporation under visible/infrared (Vis/IR) exposure. Reduced band-gap of WO3-x via oxygen vacancies creation and localized surface plasmon resonance (LSPR) formation by Cu nanoparticles contributed significantly the extension and intensification of composite's photo-absorption range. Furthermore, small mesoporous structure of ZNC enhanced CIP adsorption and charge carriers separation where the reported photocatalytic efficiencies were 88.3 and 81.7% upon IR and Vis light exposure respectively. It was evidenced that plasmonic hot electrons (e-.s) and hydroxyl radicals (OH•-) performed the basic functions of the photocatalytic process. At the other side, oxygen vacancies existence, plasmonic effect, and confining thermal characteristics of WO3-x, Cu, and ZNC correspondingly induced water photothermal evaporation with efficiencies up to 97.5 and 72.8% under IR and Vis illumination respectively. This work introduces synthesis of a novel bi-functional photocatalytic-photothermal composite by metal sub-oxide and non-noble metal plasmonic coupling and supporting on naturally-derived carrier for water restoration under broad spectral exposure.

Assessment of alternative metrics in the application of infrared thermography to detect muscle damage in sports.

Objective.The association between muscle damage and skin temperature is controversial. We hypothesize that including metrics that are more sensitive to individual responses by considering variability and regions representative of higher temperature could influence skin temperature outcomes. Here, the objective of the study was to determine whether using alternative metrics (TMAX, entropy, and pixelgraphy) leads to different results than mean, maximum, minimum, and standard deviation (SD) skin temperature when addressing muscle damage using infrared thermography.Approach.Thermal images from four previous investigations measuring skin temperature before and after muscle damage in the anterior thigh and the posterior lower leg were used. The TMAX, entropy, and pixelgraphy (percentage of pixels above 33 °C) metrics were applied.Main results.On 48 h after running a marathon or half-marathon, no differences were found in skin temperature when applying any metric. Mean, minimum, maximum, TMAX, and pixelgraphy were lower 48 h after than at basal condition following quadriceps muscle damage (p< 0.05). Maximum skin temperature and pixelgraphy were lower 48 h after than the basal condition following muscle damage to the triceps sural (p< 0.05). Overall, TMAX strongly correlated with mean (r= 0.85) and maximum temperatures (r= 0.99) and moderately with minimum (r= 0.66) and pixelgraphy parameter (r= 0.64). Entropy strongly correlates with SD (r= 0.94) and inversely moderately with minimum temperature (r= -0.53). The pixelgraphy moderately correlated with mean (r= 0.68), maximum (r= 0.62), minimum (r= 0.58), and TMAX (r= 0.64).Significance.Using alternative metrics does not change skin temperature outcomes following muscle damage of lower extremity muscle groups.

The use of infrared thermography as an indicator of methane production in hair sheep.

Infrared thermography may be an alternative technology for measuring the amount of CH4 produced and has the advantages of low cost, speed and efficiency in obtaining results. The study's objective was to determine if the infrared thermography is adequate for predicting the emission of CH4 in hair sheep and the best time after feeding to carry out the measurement. Twelve Santa Inês lambs (females, non-pregnant, with twelve months old and mean body weight of 39.3 ± 2.1 kg) remained for two days in respirometric chambers, in a semi-closed system, to determine the CH4 production. The animals were divided into two treatments, according to the diet provided. During this period, seven thermographic photographs were taken, at times - 1 h, -0.5 h, 0 h, 0.5 h, 1 h, 2 h, 3 h, 5 h, and 7 h, according to the feeding time, defined as 0 h. CH4 production was measured over 24 h. Thermographic images measured the maximum, minimum, average and point temperatures at the left and right flanks. The temperature difference between the left and right flanks (left minus right) was calculated each time. Pearson correlation coefficients, multiple regression and principal component analysis were carried out in SAS®. The best prediction of emission intensity of CH4 (kg of CH4 per dry matter intake) was obtained at 3 h after feeding: CH4/DMI = 13.9016-0,38673 * DifP2 + 3.39089 * DifMed2 (R² = 0.48), using the difference between left and right flanks for point and average temperature measures. Therefore, infrared thermography can be used as an indicator of CH4 production in hair sheep three hours after feeding.

Near-Infrared Emissive π-Conjugated Oligomer Nanoparticles for Three- and Four-Photon Deep-Brain Microscopic Imaging Beyond 1700 nm Excitation.

High-resolution visualization of the deep brain is still a challenging and very significant issue. Multiphoton microscopy (MPM) holds great promise for high-spatiotemporal deep-tissue imaging under NIR-III and NIR-IV excitation. However, thus far, their applications have been seriously restricted by the scarcity of efficient organic probes. Herein, we designed and synthesized two donor-acceptor-donor-type conjugated small molecules (TNT and TNS) for in vivo mouse deep-brain imaging with three- and four-photon microscopy under 1700 and 2200 nm excitation. With a selenium (Se) substitution, we synthesized two conjugated small molecules to promote their emission into the deep near-infrared region with high quantum yields of 55% and 20% in THF solvent, respectively, and their water-dispersive nanoparticles have relatively large absorption cross-sections in the 1700 and 2200 nm windows, respectively, with good biosafety. With these superiorities, these organic NPs achieve high-resolution deep-brain imaging via three-photon and four-photon microscopy with excitation at 1700 and 2200 nm windows, and 1620 µm deep in the brain vasculature can be visualized in vivo. This study demonstrates the efficiency of NIR-emissive conjugated small molecules for high-performance MPM imaging in the NIR-III and NIR-IV window and provides a route for the future design of organic MPM probes.

Potential of combined red and near-infrared photobiomodulation to mitigate pro-osteoclastic and inflammatory gene expression in human mandibular osteogenic cells.

Appropriate regeneration of jawbone after dental or surgical procedures relies on the recruitment of osteoprogenitor cells able to differentiate into matrix-producing osteoblasts. In this context, photobiomodulation (PBM) has emerged as promising therapy to improve tissue regeneration and to facilitate wound healing processes. The aim of this study was to determine the effect of PBM on human osteoprogenitor cells isolated from mandibular trabecular bone.Bone marrow stromal cell cultures were established from 4 donors and induced toward osteogenic differentiation for 14 days in a standard osteogenic assay. Cells were irradiated with a combined red/near-infrared (NIR) laser following different schedules and expression of osteogenic, matrix-related, osteoclastogenic and inflammatory genes was analyzed by quantitative PCR.Gene expression analysis revealed no overall effects of PBM on osteogenic differentiation. However, a statistically significant reduction was observed in the transcripts of COL1A1 and MMP13, two important genes involved in the bone matrix homeostasis. Most important, PBM significantly downregulated the expression of RANKL, IL6 and IL1B, three genes that are involved in both osteoclastogenesis and inflammation.In conclusion, PBM with a red/NIR laser did not modulate the osteogenic phenotype of mandibular osteoprogenitors but markedly reduced their expression of matrix-related genes and their pro-osteoclastogenic and pro-inflammatory profile.

Structure Tailoring of Hemicyanine Dyes for In Vivo Shortwave Infrared Imaging.

In vivo bioimaging using shortwave infrared (SWIR) (1000-2000 nm) molecular dyes enables deeper penetration and higher contrast compared to visible and near-infrared-I (NIR-I, 700-900 nm) dyes. Developing new SWIR molecules is still quite challenging. This study developed SRHCYs, a panel of fluorescent dyes based on hemicyanine, with adjustable absorbance (830-1144 nm) and emission (886-1217 nm) wavelength. The photophysical attributes of these dyes are precisely tailored by strengthening the donor parts and extending polymethine chains. SRHCY-3, with its clickable azido group, was chosen for high-performance imaging of blood vessels in living mice, enabling the precise detection of brain and lung cancer. The combination of these probes achieved in vivo multicolor imaging with negligible optical crosstalk. This report presents a series of SWIR hemicyanine dyes with promising spectroscopic properties for high-contrast bioimaging and multiplexing detection.

Multi-effective nanoplatform with down/upconversion dual-mode emissions for NIR-II imaging and PDT/PTT synergistic therapy of early atherosclerosis.

We design a multi-effective nanoplatform (CeO2:Nd@SiO2@CeO2:Yb,Er@SiO2-RB/MB/CD36) with down/upconversion dual-mode emissions and targeting ability in foam macrophages. Under NIR excitation, this nanoplatform can realize in vivo NIR-II imaging and PDT/PTT coordinated therapy for early AS simultaneously.

Manipulating Charge Distribution of Graphitic Carbon Nitride for Boosting NIR-II Light-Activated Reactive Oxygen Species Generation.

Structure engineering is of great importance to enhance the carrier separation efficiency of multiphoton absorption (MPA) materials for near-infrared (NIR) light-driven reactive oxygen species (ROS) generation. In this study, the MPA-responsive potassium/cyano group-functionalized graphitic carbon nitride was investigated, demonstrating charge redistribution and improved carrier separation efficiency by density functional theory calculations and experimental results. With various types of boosted ROS generation under UV-vis or NIR-II light irradiation, the potassium/cyano group-functionalized graphitic carbon nitride could achieve efficient multiphoton photodynamic therapy after reducing the particle size. This study developed a simple strategy to manipulate charge distribution for booting NIR light-activated ROS generation in efficient multiphoton photodynamic therapy.

Visualization of Diabetes Progression by an Activatable NIR-IIb Luminescent Probe.

Developing NIR-IIb luminescence probes with rapid visualization and a high penetration depth is essential for diabetes research. Combining a sensitizing switch with lanthanide-doped nanoparticles (LnNPs) has been employed to fabricate the NIR-IIb probes. However, these probes mainly adopt heptamethine cyanine dye as the antenna, and the NIR-IIb signal is activated by inhibiting the photoinduced electron transfer (PET) of the dye. Due to limited recognition units, this strategy makes many biomolecules undetectable, such as cysteine (Cys), which is closely related to diabetes. Herein, in this article, hemicyanine dye, NFL-OH, was verified as a new antenna to sensitize NIR-IIb emission from LnNPs. Unlike traditional cyanine dyes, hemicyanine's fluorescence intensity can also be modulated by intramolecular charge transfer (ICT), thereby expanding the range of detectable targets for NIR-IIb probes based on sensitization mechanism. Through switching the hemicyanine-sensitized NIR-IIb emission, we successfully fabricated an NFL-Cys-LnNPs' nanoprobe, which can effectively monitor Cys concentration in the liver of diabetic mice during diabetes progression and evaluate the efficacy of diabetic drugs. Our work not only presents an excellent tool for Cys imaging but also introduces new concepts for designing NIR-IIb probes.

Bacteria-based cascade in situ near-infrared nano-optogenetically induced photothermal tumor therapy.

Rationale: Optogenetically engineered facultative anaerobic bacteria exhibit a favorable tendency to colonize at solid tumor sites and spatiotemporally-programmable therapeutics release abilities, attracting extensive attention in precision tumor therapy. However, their therapeutic efficacy is moderate. Conventional photothermal agents with high tumor ablation capabilities exhibit low tumor targeting efficiency, resulting in significant off-target side effects. The combination of optogenetics and photothermal therapy may offer both tumor-targeting and excellent tumor-elimination capabilities, which unfortunately has rarely been investigated. Herein, we construct a bacteria-based cascade near-infrared optogentical-photothermal system (EcNαHL-UCNPs) for enhanced tumor therapy. Methods: EcNαHL-UCNPs consists of an optogenetically engineered Escherichia coli Nissle 1917 (EcN) conjugated with lanthanide-doped upconversion nanoparticles (UCNPs), which are capable of locally secreting α-hemolysin (αHL), a pore-forming protein, in responsive to NIR irradiation. Anti-tumor effects of EcNαHL-UCNPs were determined in both H22 and 4T1 tumors. Results: The αHL not only eliminates tumor cells, but more importantly disrupts endothelium to form thrombosis as an in situ photothermal agent in tumors. The in situ formed thrombosis significantly potentiates the photothermic ablation of H22 tumors upon subsequent NIR light irradiation. Besides, αHL secreted by EcNαHL-UCNPs under NIR light irradiation not only inhibits 4T1 tumor growth, but also suppresses metastasis of 4T1 tumor via inducing the immune response. Conclusion: Our studies highlight bacteria-based cascade optogenetical-photothermal system for precise and effective tumor therapy.

SDAM: A dual attention mechanism for high-quality fusion of infrared and visible images.

Image fusion of infrared and visible images to obtain high-quality fusion images with prominent infrared targets has important applications in various engineering fields. However, current fusion processes encounter problems such as unclear texture details and imbalanced infrared targets and texture detailed information, which lead to information loss. To address these issues, this paper proposes a method for infrared and visible image fusion based on a specific dual-attention mechanism (SDAM). This method employs an end-to-end network structure, which includes the design of channel attention and spatial attention mechanisms. Through these mechanisms, the method can fully exploit the texture details in the visible images while preserving the salient information in the infrared images. Additionally, an optimized loss function is designed to combine content loss, edge loss, and structure loss to achieve better fusion effects. This approach can fully utilize the texture detailed information of visible images and prominent information in infrared images, while maintaining better brightness and contrast, which improves the visual effect of fusion images. Through conducted ablation experiments and comparative evaluations on public datasets, our research findings demonstrate that the SDAM method exhibits superior performance in both subjective and objective assessments compared to the current state-of-the-art fusion methods.

Phototherapeutic applications of benzophenone-containing NIR-emitting photosensitizers based on different receptor modulations.

Photodynamic therapy (PDT) plays a crucial role in treating cancer and major infectious diseases. However, the hypoxic microenvironment and deep-seated tumors often compromise the effectiveness of photosensitizers (PSs). PSs primarily generate type-II reactive oxygen species (ROS), which are limited under hypoxic conditions. Pyridinium salts frequently exhibit critical dark toxicity in vitro. Moreover, PDT alone often fails to achieve optimal anti-tumor effects compared to its combined application with photothermal therapy (PTT). To address these issues, we replaced pyridinium with quinolinium, significantly reducing dark toxicity. Additionally, the incorporation of benzophenone enhanced ROS generation, achieving a synergistic effect of type-I and type-II PDT. Fine-tuning the conjugated structure enhanced the donor-acceptor (D-A) intensity, while the stretching vibrations of carbon-carbon double bonds and carbon-nitrogen triple bonds red-shifted the excitation wavelength to the near-infrared (NIR) region and improved the photothermal conversion efficiency (PCE). This strategy provides a molecular design approach for achieving synergy between PDT and PTT. The synthesized four NIR-emitting aggregation-induced emission quinolinium salts exhibited mitochondrial targeting ability and low dark toxicity. Among them, FCN-TPAQ-BP showed excellent ROS generation capability, a PCE of 39.2%, good biocompatibility, and low dark toxicity, making it an ideal candidate for enhancing PDT's antitumor efficacy.

Infrared neuroglial modulation of spinal locomotor networks.

Infrared neural stimulation (INS) emerges as a promising tool for stimulating the nervous system by its high spatial precision and absence of the use of exogenous agents into the tissue, which led to the first successful proof of concept in human brain. While neural networks have been the focal point of INS research, this technique is also non cell type specific as it triggers activity in non electrically excitable cells. Despite increasing interest, there remains to demonstrate well defined simultaneous astrocytic and neuronal signals in response to INS. Using calcium imaging, we show that INS has the capacity to initiate calcium signaling in both astrocytes and neurons simultaneously from the rostral lumbar spinal cord, each exhibiting distinct temporal and amplitude characteristics. Importantly, the mechanism underlying infrared-induced neuronal and astrocytic calcium signaling differ, with neuronal activity relying on sodium channels, whereas induced astrocytic signaling is predominantly influenced by extracellular calcium and TRPV4 channels. Furthermore, our findings demonstrate the frequency shift of neuronal calcium oscillations through infrared stimulation. By deepening our understanding in INS fundamentals, this technique holds great promise for advancing neuroscience, deepening our understanding of pathologies, and potentially paving the way for future clinical applications.

Graphene Oxide/Black Phosphorus Functionalized Collagen Scaffolds with Enhanced Near-Infrared Controlled In Situ Biomineralization for Promoting Infectious Bone Defect Repair through PI3K/Akt Pathway.

Infectious bone defects resulting from surgery, infection, or trauma are a prevalent clinical issue. Current treatments commonly used include systemic antibiotics and autografts or allografts. Nevertheless, therapies come with various disadvantages, including multidrug-resistant bacteria, complications arising from the donor site, and immune rejection, which makes artificial implants desirable. However, artificial implants can fail due to bacterial infections and inadequate bone fusion after implantation. Thus, the development of multifunctional bone substitutes that are biocompatible, antibacterial, osteoconductive, and osteoinductive would be of great clinical importance. This study designs and prepares 2D graphene oxide (GO) and black phosphorus (BP) reinforced porous collagen (Col) scaffolds as a viable strategy for treating infectious bone defects. The fabricated Col-GO@BP scaffold exhibited an efficient photothermal antibacterial effect under near-infrared (NIR) irradiation. A further benefit of the NIR-controlled degradation of BP was to promote biomineralization by phosphorus-driven and calcium-extracted phosphorus in situ. The abundant functional groups in GO could synergistically capture the ions and enhance the in situ biomineralization. The Col-GO@BP scaffold facilitated osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSC) by leveraging its mild photothermal effect and biomineralization process, which upregulated heat shock proteins (HSPs) and activated PI3K/Akt pathways. Additionally, systematic in vivo experiments demonstrated that the Col-GO@BP scaffold obviously promotes infectious bone repair through admirable photothermal antibacterial performance and enhanced vascularization. As a result of this study, we provide new insights into the photothermal activity of GO@BP nanosheets, their degradation, and a new biological application for them.