Postoperatively Noninvasive Optogenetic Stimulation via Upconversion Nanoparticles Enhancing Sciatic Nerve Repair.

The efficacy of electrical stimulation facilitating peripheral nerve regeneration is evidenced extensively, while the associated secondary damage resulting from repeated electrode invasion and indiscriminate stimulation is inevitable. Here, we present an optogenetics strategy that utilizes upconversion nanoparticles (UCNPs) to convert deeply penetrating near-infrared excitation into blue emission, which activates an adeno-associated virus-encoding ChR2 photoresponsive ion channel on cell membranes. The induced Ca2+ flux, similar to the ion flux in the electrical stimulation approach, efficiently regulates viability and proliferation, secretion of nerve growth factor, and neural function of RSC96 cells. Furthermore, deep near-infrared excitation is harnessed to stimulate autologous Schwann cells in situ via a UCNP-composited scaffold, which enhances nerve sprouting and myelination, consequently promoting functional recovery, electrophysiological restoration, and reinnervation of damaged nerves. This developed postoperatively noninvasive optogenetics strategy presents a novel, minimally traumatic, and enduring therapeutic stimulus to effectively promote peripheral nerve repair.

Integrated GelMA and interleukin 8-loaded liposome composite scaffold for endogenous BMSCs recruitment in bone repair.

Bone repair strategies, based on endogenous stem cell recruitment, can effectively avoid immune rejection and the low utilization of exogenous stem cells. Endogenous stem cells can be recruited to the implantation site by loading chemokines onto bone tissue-engineered scaffolds. However, challenges such as unstable chemokine activity and easy inactivation after implantation remain significant. In the present study, composite fiber scaffolds ((IL8@LIP)-GelMA) consisting of Interleukin 8 (IL8) -loaded liposomes and GelMA were constructed by electrospinning and photocrosslinking, and its ability to recruit bone marrow-derived mesenchymal stem cells (BMSCs) and immunomodulatory effect was investigated. Compared to GelMA loaded directly with IL8, scaffolds of (IL8@LIP)-GelMA demonstrated superior protection of IL8 activity, ensuring a slow and continuous release. Both in vivo and in vitro experiments demonstrated that the (IL8@LIP)-GelMA scaffolds effectively recruited BMSCs to the desired sites. Additionally, the (IL8@LIP)-GelMA scaffolds exhibited the capacity to recruit more macrophages to the implantation site. Importantly, they promoted the polarization of macrophages toward the M2 anti-inflammatory phenotype, facilitating the transition from the inflammatory stage to the tissue repair stage. Therefore, (IL8@LIP)-GelMA scaffolds show great potential for cell-free tissue engineering applications and provide insights into the loading mode of growth factors in scaffolds.

Conformal sulfidation of HKUST-1 for constructing porous Cu2S/CuO octahedrons realizing highly sensitive non-enzymatic glucose detection.

Metal-organic frameworks (MOFs) are believed to be promising precursors for constructing novel and efficient catalysts for glucose sensing. Herein, HKUST-1 precursors are first fabricated using a one-pot hydrothermal approach, and then HKUST-1 is converted into porous Cu2S/CuO octahedrons through conformal sulfidation with the help of OH-ions. The as-obtained Cu2S/CuO composite can provide rich electrochemical active sites and promoted electric transfer kinetics. Benefiting from these combined merits, the as-fabricated Cu2S/CuO composite is confirmed to be a high-performance catalyst, with high sensitivities of 8269.45 and 4140.82µA mM-1cm-2in the corresponding ranges of 0.05 ∼ 0.6 mM and 0.6 ∼ 1.2 mM, respectively. Moreover, the as-prepared electrode materials possess good anti-interference ability, reproducibility and long-term stability. This work opens up new avenues for the design and preparation of transition metal sulfide composites.

Ratiometric fluorescence detection of dopamine based on copper nanoclusters and carbon dots.

Nanoclusters for fluorescence detection are generally comprised of rare and expensive noble metals, and the nanoclusters based on more affordable transition metal have attracted increasing attention. This study designed a ratiometric fluorescent probe to detect dopamine (DA), an important neurotransmitter. With carbon dots encapsulated within silica (CDs@SiO2) as the reference, the emitted reference signal was almost unchanged due to the protection of inert silicon shell. Meanwhile, copper nanoclusters modified with 3-aminophenyl boronic acid (APBA-GSH-CuNCs) provided the sensing signal, in which the phenylboric acid could specifically recognize the cis-diol structure of DA, and caused the fluorescence quenching by photoinduced electron transfer. This dual emission ratiometric fluorescent probe exhibited high sensitivity and anti-interference, and was able to selectively responded to DA with a linear range of 0-1.4 mM, the detection limit of 5.6 nM, and the sensitivity of 815 mM-1. Furthermore, the probe successfully detected DA in human serum samples, yielding recoveries ranging from 92.5% to 102.7%. Overall, this study highlights the promising potential of this ratiometric probe for detecting DA.

Artificial periosteum promotes bone regeneration through synergistic immune regulation of aligned fibers and BMSC-recruiting phages.

Given the crucial role of periosteum in bone repair, the use of artificial periosteum to induce spontaneous bone healing instead of using bone substitutes has become a potential strategy. Also, the proper transition from pro-inflammatory signals to anti-inflammatory signals is pivotal for achieving optimal repair outcomes. Hence, we designed an artificial periosteum loaded with a filamentous bacteriophage clone named P11, featuring an aligned fiber morphology. P11 endowed the artificial periosteum with the capacity to recruit bone marrow mesenchymal stem cells (BMSCs). The artificial periosteum also regulated the immune microenvironment at the bone injury site through the synergistic effects of biochemical factors and topography. Specifically, the inclusion of P11 preserved inflammatory signaling in macrophages and additionally facilitated the migration of BMSCs. Subsequently, aligned fibers stimulated macrophages, inducing alterations in cytoskeletal and metabolic activities, resulting in the polarization into the M2 phenotype. This progression encouraged the osteogenic differentiation of BMSCs and promoted vascularization. In vivo experiments showed that the new bone generated in the AP group exhibited the most efficient healing pattern. Overall, the integration of biochemical factors with topographical considerations for sequential immunomodulation during bone repair indicates a promising approach for artificial periosteum development. STATEMENT OF SIGNIFICANCE: The appropriate transition of macrophages from a pro-inflammatory to an anti-inflammatory phenotype is pivotal for achieving optimal bone repair outcomes. Hence, we designed an artificial periosteum featuring an aligned fiber morphology and loaded with specific phage clones. The artificial periosteum not only fostered the recruitment of BMSCs but also achieved sequential regulation of the immune microenvironment through the synergistic effects of biochemical factors and topography, and improved the effect of bone repair. This study indicates that the integration of biochemical factors with topographical considerations for sequential immunomodulation during bone repair is a promising approach for artificial periosteum development.

Unveiling protein corona composition: predicting with resampling embedding and machine learning.

Biomaterials with surface nanostructures effectively enhance protein secretion and stimulate tissue regeneration. When nanoparticles (NPs) enter the living system, they quickly interact with proteins in the body fluid, forming the protein corona (PC). The accurate prediction of the PC composition is critical for analyzing the osteoinductivity of biomaterials and guiding the reverse design of NPs. However, achieving accurate predictions remains a significant challenge. Although several machine learning (ML) models like Random Forest (RF) have been used for PC prediction, they often fail to consider the extreme values in the abundance region of PC absorption and struggle to improve accuracy due to the imbalanced data distribution. In this study, resampling embedding was introduced to resolve the issue of imbalanced distribution in PC data. Various ML models were evaluated, and RF model was finally used for prediction, and good correlation coefficient (R2) and root-mean-square deviation (RMSE) values were obtained. Our ablation experiments demonstrated that the proposed method achieved an R2 of 0.68, indicating an improvement of approximately 10%, and an RMSE of 0.90, representing a reduction of approximately 10%. Furthermore, through the verification of label-free quantification of four NPs: hydroxyapatite (HA), titanium dioxide (TiO2), silicon dioxide (SiO2) and silver (Ag), and we achieved a prediction performance with an R2 value >0.70 using Random Oversampling. Additionally, the feature analysis revealed that the composition of the PC is most significantly influenced by the incubation plasma concentration, PDI and surface modification.

A H2S-Evolving Alternately-Catalytic Enzyme Bio-Heterojunction with Antibacterial and Macrophage-Reprogramming Activity for All-Stage Infectious Wound Regeneration.

The disorder of the macrophage phenotype and the hostile by-product of lactate evoked by pathogenic infection in hypoxic deep wound inevitably lead to the stagnant skin regeneration. In this study, hydrogen sulfide (H2S)-evolving alternately catalytic bio-heterojunction enzyme (AC-BioHJzyme) consisting of CuFe2S3 and lactate oxidase (LOD) named as CuFe2S3@LOD is developed. AC-BioHJzyme exhibits circular enzyme-mimetic antibacterial (EMA) activity and macrophage re-rousing capability, which can be activated by near-infrared-II (NIR-II) light. In this system, LOD exhausts lactate derived from bacterial anaerobic respiration and generated hydrogen peroxide (H2O2), which provides an abundant stock for the peroxidase-mimetic activity to convert the produced H2O2 into germicidal •OH. The GPx-mimetic activity endows AC-BioHJzyme with a glutathione consumption property to block the antioxidant systems in bacterial metabolism, while the O2 provided by the CAT-mimetic activity can generate 1O2 under the NIR-II irradiation. Synchronously, the H2S gas liberated from CuFe2S3@LOD under the infectious micromilieu allows the reduction of Fe(III)/Cu(II) to Fe(II)/Cu(І), resulting in sustained circular EMA activity. In vitro and in vivo assays indicate that the CuFe2S3@LOD AC-BioHJzyme significantly facilitates the infectious cutaneous regeneration by killing bacteria, facilitating epithelialization/collagen deposition, promoting angiogenesis, and reprogramming macrophages. This study provides a countermeasure for deep infectious wound healing via circular enzyme-mimetic antibiosis and macrophage re-rousing.