A Hemoglobin Bionics-Based System for Combating Antibiotic Resistance in Chronic Diabetic Wounds via Iron Homeostasis Regulation.

Owing to the increased tissue iron accumulation in patients with diabetes, microorganisms may activate high expression of iron-involved metabolic pathways, leading to the exacerbation of bacterial infections and disruption of systemic glucose metabolism. Therefore, an on-demand transdermal dosing approach that utilizes iron homeostasis regulation to combat antimicrobial resistance is a promising strategy to address the challenges associated with low administration bioavailability and high antibiotic resistance in treating infected diabetic wounds. Here, it is aimed to propose an effective therapy based on hemoglobin bionics to induce disturbances in bacterial iron homeostasis. The preferred "iron cargo" is synthesized by protoporphyrin IX chelated with dopamine and gallium (PDGa), and is delivered via a glucose/pH-responsive microneedle bandage (PDGa@GMB). The PDGa@GMB downregulates the expression levels of the iron uptake regulator (Fur) and the peroxide response regulator (perR) in Staphylococcus aureus, leading to iron nutrient starvation and oxidative stress, ultimately suppressing iron-dependent bacterial activities. Consequently, PDGa@GMB demonstrates insusceptibility to genetic resistance while maintaining sustainable antimicrobial effects (>90%) against resistant strains of both S. aureus and E. coli, and accelerates tissue recovery (<20 d). Overall, PDGa@GMB not only counteracts antibiotic resistance but also holds tremendous potential in mediating microbial-host crosstalk, synergistically attenuating pathogen virulence and pathogenicity.

Culture-Delivery Live Probiotics Dressing for Accelerated Infected Wound Healing.

Probiotic therapy in infected wound healing is hindered by its low viability and colonization efficiency during treatments. Developing dressings that maintain metabolic activity and prevent the potential leakage of probiotics is imperative. Herein, a culture-delivery live probiotics hydrogel dressing is designed and synthesized, formed by gelatin modified with norbornene (GelNB) and sulfhydryl (GelSH), distributing Lactobacillus reuteri (L. reuteri)-laden alginate microspheres (AlgMPs). GelNB-GelSH hydrogel (GelNBSH) incorporating AlgMPs embedding L. reuteri (GelNBSH-L) possesses bioprintability and efficient polymerization that can maintain the activity of L. reuteri in situ, promote its proliferation, and limit its leakage. Thereby, GelNBSH-L achieved a sustainable antimicrobial effect against both S. aureus and E. coli (>90%). Above all, the results show that GelNBSH-L could ensure propitious viability and efficient antibacterial properties of probiotics, effectively inhibit the further development of bacterial infectious wounds and shorten the repair cycle, aiding in ameliorating future clinical probiotic biotherapy.

Flexible Transparent Hydrophobic Coating Films with Excellent Scratch Resistance Using Si-Doped Carbonized Polymer Dots as Building Blocks.

Flexible transparent hydrophobic coating films with excellent scratch resistance have important applications in many fields, especially for optical materials. Herein, a hydrophobic composite coating film was prepared and used as a polymer film protective material by combining 3-glycidyloxypropyltrimethoxysilane (GPTMS)-modified Si-doped carbonized polymer dots (Si-CPDs) with mono-trimethoxysilyl-terminated poly(dimethyl siloxane) (PDMS). The Si-CPDs derived from tetramethyl disiloxane propylamine tetraacetic acid and multi-amino oligosiloxanes were successfully prepared via one-step hydrothermal method and then grafted by GPTMS to obtain modified Si-CPDs (mSi-CPDs). Among them, mSi-CPDs act as a matrix layer, and PDMS acts as a low-surface energy layer. Cross-linking the Si-O-Si network of the coating film was formed through sol-gel chemistry. Driven by the hydrophilic-hydrophobic effect, PDMS trends to aggregate at the film surface, thus avoiding the phase separation which can affect transparency. The highly cross-linked network and the presence of hard silica core provide a high hardness to stand the steel-wool scratch. Flexible polymer chains impart the coating film an outstanding bendability. Introduction of PDMS makes the coating film possess hydrophobicity and anti-graffiti function.

Exploiting synergistic effect of CO/NO gases for soft tissue transplantation using a hydrogel patch.

Autologous skin flap transplantation is a common method for repairing complex soft tissue defects caused by cancer, trauma, and congenital malformations. Limited blood supply range and post-transplantation ischemia-reperfusion injury can lead to distal necrosis of the flap and long-term functional loss, which severely restricts the decision-making regarding the optimal surgical plan. To address this issue, we develop a hydrogel patch that releases carbon monoxide and nitric oxide gases on demand, to afford a timely blood supply for skin flap transplantation during surgery. Using an ischemia-reperfusion dorsal skin flap model in rats, we show that the hydrogel patch maintains the immediate opening of blood flow channels in transplanted tissue and effective blood perfusion throughout the perioperative period, activating perfusion of the hemodynamic donor site. We demonstrate that the hydrogel patch promotes distal vascularization and long-term functional reconstruction of transplanted tissues by inhibiting inflammatory damage and accelerating blood vessel formation.

Hierarchical hydrogel microarrays fabricated based on a microfluidic printing platform for high-throughput screening of stem cell lineage specification.

2D cell cultures are suitable for rapid exploration of the factors in the extracellular matrix affecting the development of cells. The technology of the micrometre-sized hydrogel array provides a feasible, miniaturized, and high-throughput strategy for the process. However, current microarray devices lack a handy and parallelized methodology in sample treatment, which makes the process of high-throughput cell screening (HTCS) expensive and inefficient. Here, based on the functionalization of micro-nano structures and the fluid control capability of microfluidic chips, we build a microfluidic spotting-screening platform (MSSP). The MSSP can print 20000 microdroplet spots within 5 min, coupled with a simple strategy for parallel addition of compound libraries. Compared with open microdroplet arrays, the MSSP can control the evaporation rate of nanoliter droplets, providing a stable fabrication platform for hydrogel-microarray-based materials. As a proof-of-concept demonstration, the MSSP successfully controlled the adhesion, adipogenic, and osteogenic differentiation behavior of mesenchymal stem cells by rationally designing the substrate stiffness, adhesion area, and cell density. We anticipate that the MSSP may provide an accessible and promising tool for hydrogel-based HTCS. STATEMENT OF SIGNIFICANCE: High-throughput screening of cells is a common approach to improve the efficiency of biological experiments, and one challenge of the existing technologies is to achieve rapid and precise cell screening with a low-cost and simple strategy. Through the integration of the microfluidic and micro-nanostructure technologies, we fabricated a microfluidic spotting-screening platforms. Benefiting from the flexible control of the fluids, the device can print 20000 microdroplet spots within 5 min, coupled with a simple procedure for parallel addition of compound libraries. High-throughput screening of stem cell lineage specification has also been achieved by the platform, which provides a high-throughput, high-content information extraction strategy for cell-biomaterial interaction research.

A multifunctional black phosphorus-based adhesive patch intrinsically induces partial EMT for effective burn wound healing.

The ultimate goal of cutaneous wound healing is to reform a stratified epithelium to restore the normal epidermal barrier, which involves the epithelial-to-mesenchymal transition (EMT) process. However, healing strategies based on EMT induction are immature and ambiguous to date. Excessive induction of EMT may cause fibrosis, hypertrophic scarring, and increased risk of malignancy. Here, we present a new EMT-inducing strategy for eliciting partial EMT to facilitate proper epithelial cell migration. The new EMT-inducing system integrates black phosphorus nanosheets (BPNSs), catechol-modified chitosan (CA-CS), and oxidized dextran (Odex) to engineer an adhesive hydrogel patch (C&BP-Patch) with remarkable efficacy on infectious burn wound healing. The C&BP-Patch can orchestrate key early skin wound healing processes including hemostasis, inflammation, and proliferation, which enable fast partial EMT induction to restore an intact epithelial barrier. The C&BP-Patch acts initially as a high-performance bio-sealant to create a moist and stable microenvironment for EMT. Moreover, the photothermal effects of the C&BP-Patch can eliminate bacteria, accelerate microcirculation and reduce inflammation to maintain a proper EMT. Most importantly, the BPNSs can intrinsically induce partial EMT of epithelial cells via a Snail1-mediated signaling pathway. Therefore, our study proposes a new strategy for effective infectious burn wound healing based on inducing partial EMT.

A sustained-release Trametinib bio-multifunction hydrogel inhibits orthodontically induced inflammatory root resorption.

Orthodontic tooth movement (OTM) is a bone reconstruction process. In most cases, OTM could induce root resorption as a common side effect, called orthodontically induced inflammatory root resorption (OIIRR). OIIRR affects tooth health and interferes with the stability of orthodontic treatment. Osteoclasts, which perform bone resorption in OTM, attack cementum, causing OIIRR. Many signaling pathways are involved in the maturation and differentiation of osteoclasts, among which the ERK1/2 is one of the important pathways. In this experiment, we added Trametinib (Tra), a specific inhibitor of ERK1/2, to catechol-modified chitosan (CHI-C) and oxidized dextran (ODex) to form a CCOD-Trametinib composite hydrogel (CCOD-Tra) to prevent OIIRR. CCOD-Tra exhibited good biocompatibility, injectability, strong adhesion, good hemostatic function and sustained release of Tra. We performed local injection of CCOD-Tra into the periodontal tissues of rats. CCOD-Tra firmly adhered to the periodontal tissues and then released Tra to establish a good biological environment and maintain a drug concentration at a high level around the roots for a long time. H&E, TRAP, immunochemistry staining and micro-CT indicated that CCOD-Tra had a good effect in terms of preventing OIIRR. Cell experiments showed that CCOD-Tra reduced the expression of TRAP, MMP-9 and C-FOS in osteoclast cells through the ERK1/2 signaling pathway to inhibit the differentiation and maturation of osteoclasts. Based on the above results, we concluded that CCOD-Tra had the ability to prevent OIIRR, the high adhesion and injectability of CCOD may provide better therapeutic ideas for clinical prevention of OIIRR.

Reinforced Blood-Derived Protein Hydrogels Enable Dual-Level Regulation of Bio-Physiochemical Microenvironments for Personalized Bone Regeneration with Remarkable Enhanced Efficacy.

Physiological microenvironment engineering has shown great promise in combating a variety of diseases. Herein, we present the rational design of reinforced and injectable blood-derived protein hydrogels (PDA@SiO2-PRF) composed of platelet-rich fibrin (PRF), polydopamine (PDA), and SiO2 nanofibers that can act as dual-level regulators to engineer the microenvironment for personalized bone regeneration with high efficacy. From the biophysical level, PDA@SiO2-PRF with high stiffness can withstand the external loading and maintaining the space for bone regeneration in bone defects. Particularly, the reinforced structure of PDA@SiO2-PRF provides bone extracellular matrix (ECM)-like functions to stimulate osteoblast differentiation via Yes-associated protein (YAP) signaling pathway. From the biochemical level, the PDA component in PDA@SiO2-PRF hinders the fast degradation of PRF to release autologous growth factors in a sustained manner, providing sustained osteogenesis capacity. Overall, the present study offers a dual-level strategy for personalized bone regeneration by engineering the biophysiochemical microenvironment to realize enhanced osteogenesis efficacy.

A Dual-Modal Magnetic Resonance/Photoacoustic Imaging Tracer for Long-Term High-Precision Tracking and Facilitating Repair of Peripheral Nerve Injuries.

Neuroanatomical tracing is considered a crucial technique to assess the axonal regeneration level after injury, but traditional tracers do not meet the needs of in vivo neural tracing in deep tissues. Magnetic resonance (MR) and photoacoustic (PA) imaging have high spatial resolution, great penetration depth, and rich contrast. Fe3 O4 nanoparticles may work well as a dual-modal diagnosis probe for neural tracers, with the potential to improve nerve regeneration. The present study combines antegrade neural tracing imaging therapy for the peripheral nervous system. Fe3 O4 @COOH nanoparticles are successfully conjugated with biotinylated dextran amine (BDA) to produce antegrade nano-neural tracers, which are encapsulated by microfluidic droplets to control leakage and allow sustained, slow release. They have many notable advantages over traditional tracers, including dual-modal real-time MR/PA imaging in vivo, long-duration release effect, and limitation of uncontrolled leakage. These multifunctional anterograde neural tracers have potential neurotherapeutic function, are reliable and may be used as a new platform for peripheral nerve injury imaging and treatment integration.

A Flexible Polymer Nanofiber-Gold Nanoparticle Composite Film for Solar-Thermal Seawater Desalination.

Interfacial solar-thermal conversion has broad application prospects in solar driven steam generation, seawater desalination, sewage purification, and other fields. For a wide range of applications, high-efficiency interfacial solar-thermal conversion materials with the feature of being lightweight, flexible, and easy to scale up at the same time are significantly valued. Herein, a strategy for the preparation of solar-thermal poly (4-vinylpyridine) (P4VP) nanofiber-gold nanoparticle (Au NP) composite film (PGCF) is reported. Combining with the flexible and lightweight P4VP nanofibers, these absorbed Au NPs enable better solar-thermal conversion efficiency. Accordingly, the PGCF provides high-performance interfacial solar-driven steam generation, with 77% solar-heat conversion efficiency under the power density of 3.4 kW m-2 , which shows stable output (3.4 kg m-2 h-1 ) in the application of solar-driven seawater desalination. In addition, PGCF is light in weight, flexible, and suitable for scalable commercial production, enabling PGCF broad application prospects in the field of light-to-heat conversion.

BiVO4@Bi2S3 Heterojunction Nanorods with Enhanced Charge Separation Efficiency for Multimodal Imaging and Synergy Therapy of Tumor.

Despite malignant tumors being one of the most serious diseases threatening human health and living quality, exploring theranostic agents for highly effective tumor diagnosis and treatment is still full of challenges. Herein, we demonstrate the design and preparation of Tween-20-modified BiVO4@Bi2S3 heterojunction nanorods (HNRs) for multimodal computed tomography (CT)/photoacoustic (PA) imaging and radiotherapy (RT)/radiodynamic therapy (RDT)/photothermal therapy (PTT) synergistic therapy. Benefiting from the high X-ray attenuation coefficient of Bi, BiVO4@Bi2S3 HNRs exhibit a sensitive CT imaging capacity and radiation enhancement effect during RT. Meanwhile, the strong NIR absorption of Bi2S3 endows BiVO4@Bi2S3 HNRs with an excellent PA imaging and photothermal transformation capacity. More importantly, by taking advantage of the type II band alignment between BiVO4 and Bi2S3, an extra internal electric field is established to accelerate the separation of X-ray-induced electrons and holes in BiVO4@Bi2S3 HNRs, resulting in the realization of highly effective X-ray-induced RDT. Because the in vitro and in vivo experiments have verified that the RT/RDT/PTT synergistic therapeutic efficacy is greatly superior to any single treatment, it is believed that our BiVO4@Bi2S3 HNRs can be used as the multifunctional nanotheranostic platform for malignant tumor theranostics.

Ultrahigh-Sensitivity Sandwiched Plasmon Ruler for Label-Free Clinical Diagnosis.

Optical biosensors, especially those based on plasmonic structures, have emerged recently as a potential tool for disease diagnostics. Plasmonic biosensors have demonstrated impressive benefits for the label-free detection of trace biomarkers in human serum. However, widespread applications of these technologies are hindered because of their insufficient sensitivity, their relatively complex chemical immobilization processes, and the use of prism couplers. Accordingly, a sandwiched plasmon ruler (SW-PR) based on a Au nanohole array with ultrahigh sensitivity arising from the plasmonic coupling effect is developed. Highly confined surface charges caused by Bloch wave surface plasmon polarizations substantially increase the coupling efficiency. This platform exhibits thickness sensitivity as high as 61 nm nm-1 and can detect at least 200 000-fold lower analyte concentrations than a nanowell sensing platform with the same wavelength shift. Additionally, the sandwiched plasmonic biosensor allows precise and label-free testing of clinical biomarkers, namely C-reactive protein and procalcitonin, in patient serum samples without requiring a sophisticated prism coupler, extra antibodies, or a chemical immobilization technique. This study yields new insight into the structural design of plasmon rulers and will open exciting avenues for disease diagnosis and therapy follow-up at the point-of-care.

Pressure-controlled microfluidic sub-picoliter ultramicro-volume syringes based on integrated micro-nanostructure arrays.

Ultramicro-volume syringes were fabricated by integrating micro-nanostructure arrays in microchannels for quantitatively dispensing sub-picoliter volumes of liquids. Using this system, liquids were dispensed in volume increments as low as 0.5 pL with 96% accuracy. Specifically, the controllable synthesis of nanocrystals was achieved using a lab-on-chip platform that was integrated with the syringes.

Wrinkled single-layer graphenes fabricated by silicon nanopillar arrays.

The degree of crumpling affects the optoelectronic properties of graphene, which are very important for the performance of graphene-based devices and materials. In this article, we report an approach to tune the formation of wrinkles on single-layer graphene (SLG) by silicon nanopillar (SNP) arrays. By using gold nanoparticles as an etching mask, SNP arrays with different heights could be prepared by tuning the duration of etching. The formation of wrinkles on these SNP arrays was studied systematically. We found that thermal treatment could lead to a wrapping behavior of graphene around SNP arrays, which was accompanied by the emergence of many more wrinkles. Controllable wettability, conductivity and transmittance were demonstrated. This ability to tune wrinkles using SNP arrays can be employed to engineer the fabrication of graphene-related devices and other optoelectronic applications.