Elucidating osseointegration in vivo in 3D printed scaffolds eliciting different foreign body responses.

Osseointegration between biomaterial and bone is critical for the clinical success of many orthopaedic and dental implants. However, the mechanisms of in vivo interfacial bonding formation and the role of immune cells in this process remain unclear. In this study, we investigated the bone-scaffold material interfaces in two different 3D printed porous scaffolds (polymer/hydroxyapatite and sintered hydroxyapatite) that elicited different levels of foreign body response (FBR). The polymer/hydroxyapatite composite scaffolds elicited more intensive FBR, which was evidenced by more FBR components, such as macrophages/foreign body giant cells and fibrous tissue, surrounding the material surface. Sintered hydroxyapatite scaffolds showed less intensive FBR compared to the composite scaffolds. The interfacial bonding appeared to form via new bone first forming within the pores of the scaffolds followed by growing towards strut surfaces. In contrast, it was previously thought that bone regeneration starts at biomaterial surfaces via osteogenic stem/progenitor cells first attaching to them. The material-bone interface of the less immunogenic hydroxyapatite scaffolds was heterogenous across all samples, evidenced by the coexistence of osseointegration and FBR components. The presence of FBR components appeared to inhibit osseointegration. Where FBR components were present there was no osseointegration. Our results offer new insight on the in vivo formation of bone-material interface, which highlights the importance of minimizing FBR to facilitate osseointegration for the development of better orthopaedic and dental biomaterials.

Cobalt-containing borate bioactive glass fibers for treatment of diabetic wound.

Impaired angiogenesis is one of the predominant reasons for non-healing diabetic wounds. Cobalt is well known for its capacity to induce angiogenesis by stabilizing hypoxia-inducible factor-1α (HIF-1α) and subsequently inducing the production of vascular endothelial growth factor (VEGF). In this study, Co-containing borate bioactive glasses and their derived fibers were fabricated by partially replacing CaO in 1393B3 borate glass with CoO. Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR) analyses were performed to characterize the effect of Co incorporation on the glass structure, and the results showed that the substitution promoted the transformation of [BO3] into [BO4] units, which endow the glass with higher chemical durability and lower reaction rate with the simulated body fluid (SBF), thereby achieving sustained and controlled Co2+ ion release. In vitro biological assays were performed to assess the angiogenic potential of the Co-containing borate glass fibers. It was found that the released Co2+ ion significantly enhanced the proliferation, migration and tube formation of the Human Umbilical Vein Endothelial Cells (HUVECs) by upregulating the expression of angiogenesis-related proteins such as HIF-1α and VEGF. Finally. In vivo results demonstrated that the Co-containing fibers accelerated full-thickness skin wound healing in streptozotocin (STZ)-induced diabetic rat model by promoting angiogenesis and re-epithelialization.

An injectable MB/BG@LG sustained release lipid gel with antibacterial and osteogenic properties for efficient treatment of chronic periodontitis in rats.

Periodontitis is a chronic inflammatory disease characterized by the colonization of pathogenic microorganisms and the loss of periodontal supporting tissue. However, the existing local drug delivery system for periodontitis has some problems including subpar antibacterial impact, easy loss, and unsatisfactory periodontal regeneration. In this study, a multi-functional and sustained release drug delivery system (MB/BG@LG) was developed by encapsulating methylene blue (MB) and bioactive glass (BG) into the lipid gel (LG) precursor by Macrosol technology. The properties of MB/BG@LG were characterized using a scanning electron microscope, a dynamic shear rotation rheometer, and a release curve. The results showed that MB/BG@LG could not only sustained release for 16 days, but also quickly fill the irregular bone defect caused by periodontitis through in situ hydration. Under 660 â€‹nm light irradiation, methylene blue-produced reactive oxygen species (ROS) can reduce local inflammatory response by inhibiting bacterial growth. In addition, in vitro and vivo experiments have shown that MB/BG@LG can effectively promote periodontal tissue regeneration by reducing inflammatory response, promoting cell proliferation and osteogenic differentiation. In summary, MB/BG@LG exhibited excellent adhesion properties, self-assembly properties, and superior drug release control capabilities, which improved the clinical feasibility of its application in complex oral environments.

Antibacterial, injectable, and adhesive hydrogel promotes skin healing.

With the development of material science, hydrogels with antibacterial and wound healing properties are becoming common. However, injectable hydrogels with simple synthetic methods, low cost, inherent antibacterial properties, and inherent promoting fibroblast growth are rare. In this paper, a novel injectable hydrogel wound dressing based on carboxymethyl chitosan (CMCS) and polyethylenimine (PEI) was discovered and constructed. Since CMCS is rich in -OH and -COOH and PEI is rich in -NH2, the two can interact through strong hydrogen bonds, and it is theoretically feasible to form a gel. By changing their ratio, a series of hydrogels can be obtained by stirring and mixing with 5 wt% CMCS aqueous solution and 5 wt% PEI aqueous solution at volume ratios of 7:3, 5:5, and 3:7. Characterized by morphology, swelling rate, adhesion, rheological properties, antibacterial properties, in vitro biocompatibility, and in vivo animal experiments, the hydrogel has good injectability, biocompatibility, antibacterial (Staphylococcus aureus: 56.7 × 107 CFU/mL in the blank group and 2.5 × 107 CFU/mL in the 5/5 CPH group; Escherichia coli: 66.0 × 107 CFU/mL in the blank group and 8.5 × 107 CFU/mL in the 5/5 CPH group), and certain adhesion (0.71 kPa in the 5/5 CPH group) properties which can promote wound healing (wound healing reached 98.02% within 14 days in the 5/5 CPH group) and repair of cells with broad application prospects.

Hydrophilic surface-modified 3D printed flexible scaffolds with high ceramic particle concentrations for immunopolarization-regulation and bone regeneration.

Bioceramic scaffolds used in bone tissue engineering suffer from a low concentration of ceramic particles (<50 wt%), because the high concentration of ceramic particles increases the brittleness of the composite. 3D printed flexible PCL/HA scaffolds with high ceramic particle concentrations (84 wt%) were successfully fabricated in this study. However, the hydrophobicity of PCL weakens the composite scaffold hydrophilicity, which may limit the osteogenic ability to some extent. Thus, as a less time-consuming, less labour intensive, and more cost-effective treatment method, alkali treatment (AT) was employed to modify the surface hydrophilicity of the PCL/HA scaffold, and its regulation of immune responses and bone regeneration were investigated in vivo and in vitro. Initially, several concentrations of NaOH (0.5, 1, 1.5, 2, 2.5, and 5 mol L-1) were employed in tests to determine the appropriate concentration for AT. Based on the comprehensive consideration of the results of mechanical experiments and hydrophilicity, 2 mol L-1 and 2.5 mol L-1 of NaOH were selected for further investigation in this study. The PCL/HA-AT-2 scaffold dramatically reduced foreign body reactions as compared to the PCL/HA and PCL/HA-AT-2.5 scaffolds, promoted macrophage polarization towards the M2 phenotype and enhanced new bone formation. The Wnt/ß-catenin pathway might participate in the signal transduction underlying hydrophilic surface-modified 3D printed scaffold-regulated osteogenesis, according to the results of immunohistochemical staining. In conclusion, hydrophilic surface-modified 3D printed flexible scaffolds with high ceramic particle concentrations can regulate the immune reactions and macrophage polarization to promote bone regeneration, and the PCL/HA-AT-2 scaffold is a potential candidate for bone tissue repair.

Reversing inflammatory microenvironment by a single intra-articular injection of multi-stimulus responsive lipogel to relieve rheumatoid arthritis and promote joint repair.

Rheumatoid arthritis (RA) is a common chronic disease dominated by inflammatory synovitis, which is characterized with hyperplastic synovium, up-regulated matrix metalloproteinase (MMP) expression, hypoxic joint cavity and excessive reactive oxygen species (ROS) accumulation. Such local adverse microenvironment in RA joints further exacerbates the infiltration of synovial inflammatory cells, especially M1-type macrophages. Regulating intra-articular pathological conditions, eliminating excess M1 macrophages or converting them to an anti-inflammatory M2 phenotype may break the vicious progression circle. Herein, we develop a multi-stimulus responsive lipogel as effective platform to relieve RA symptoms and promote articular cartilage recovery via reversing its inflammatory microenvironment. The injectable lipogel is fabricated by loading polydopamine nanoparticles and methotrexate into a thermosensitive gel, and intra-articularly injected to form the therapeutic depot (PDA/MTX@TSG) in situ. The gel degrades slowly under esterase hydrolysis, and maintains sustained drug release in physiological conditions. Meanwhile, it can 1) induce a reversible gel-sol phase transition upon mild photothermal treatment (external NIR light control), and 2) specifically respond to MMP-rich RA microenvironment (internal enzymatic hydrolysis effect). Such stimulus-responsive system can deliver therapeutic components in a controllable manner, and significantly reverse adverse inflammatory microenvironment of RA joints through ROS eliminating, hypoxia alleviating, and M1-M2 macrophage polarization effects. Animal experiments indicate that observable RA relief and joint repair are realized after a single lipogel injection combined with NIR irradiation. Our study highlights the importance of altering local RA microenvironment via anti-inflammatory macrophage polarization, and therefore presents a potent therapeutic strategy for RA treatment in clinical intervention.

A novel fluorescent nanoprobe based on potassium permanganate-functionalized Ti3C2 QDs for the unique "turn-on" dual detection of Cr3+ and Hg2+ ions.

Titanium carbide quantum dots (Ti3C2 QDs) were synthesized by ammonia-assisted hydrothermal method. We also synthesized potassium permanganate (KMnO4)-functionalized Ti3C2 QDs (Mn-QDs) by modifying Ti3C2 nanosheets with KMnO4 and then cutting the functional nanosheets into Mn-QDs. The Ti3C2 QDs and Mn-QDs were characterized by fluorescence spectroscopy (FL), Fourier transform infrared spectroscopy (FTIR), UV-vis spectrophotometry (UV-vis), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). Furthermore, the modified Mn-QDs have strong luminescence ability and good dispersion stability, which can be used for Cr3+ and Hg2+ double ion detection with enhanced fluorescence specificity. Cr3+/Hg2+ and negatively charged Mn-QDs are bound together by electrostatic interactions. Meanwhile, the surface of Mn-QDs is rich in functional groups, which interacts with Cr3+/Hg2+ to modify the surface traps, leading to defect passivation and exhibiting photoluminescence enhancement. For the dynamic quenching produced by the interaction of Mn-QDs with Hg2+ within 50 µM, it may be caused by the complex formation of Hg2+ trapped by the amino group on the surface of Mn-QDs. The detection limits for Cr3+ and Hg2+ were 0.80 µM and 0.16 µM, respectively. The recoveries of Cr3+ and Hg2+ ions in real water samples were 93.79-105.10% and 93.91-102.05%, respectively, by standard addition recovery test. In this work, the application of Mn-QDs in Cr3+ and Hg2+ ion detection was researched, which opens a new way for its application in the field of detecting heavy metal ions.

Photo-crosslinked bioactive BG/BMSCs@GelMA hydrogels for bone-defect repairs.

The clinical treatments of bone defects remain a challenge. Hydrogels containing bone marrow mesenchymal stem cells (BMSCs) are extensively used to bone regeneration because of excellent biocompatibility and hydrophilicity. However, the insufficient osteo-induction capacity of the BMSC-loaded hydrogels limits their clinical applications. In this study, bio-active glass (BG) and BMSCs were combined with gelatin methacryloyl (GelMA) to fabricate composite hydrogels via photo-crosslinking, and the regulation of bone regeneration was investigated. In vitro experiments showed that the BG/BMSCs@GelMA hydrogel had excellent cytocompatibility and promoted osteogenic differentiation in BMSCs. Furthermore, the BG/BMSCs@GelMA hydrogel was injected into critical-sized calvarial defects, and the results further confirmed its excellent angiogenetic and bone regeneration capacity. In addition, BG/BMSCs@GelMA promoted the polarization of macrophages towards the M2 phenotype. In summary, this novel composite hydrogel demonstrated remarkable potential for application in bone regeneration due to its immunomodulatory, excellent angiogenetic as well as osteo-induction capacity.

Vacuum sealing drainage system combined with an antibacterial jackfruit aerogel wound dressing and 3D printed fixation device for infections of skin soft tissue injuries.

Injuries and infections of skin and soft tissue are commonly encountered in primary health care and are challenging to manage. Vacuum sealing drainage (VSD) is generally used in clinical treatment, but current commercial methods of VSD have some disadvantages, such as easy blockage, nonantibacterial effects, and inconvenient curved surfaces. Herein, we report a functional zinc oxide/jackfruit aerogel (ZnO/JFA) composite material that is ultralight, superabsorbent and antibacterial as a new antibacterial VSD wound dressing. The JFA is carbonized from fresh jackfruit, and the JFA exhibits superhydrophilicity and superabsorbability. The water absorption rate of JFA was up to 1209.39%, and the SBF absorption rate was up to 1384.22%. The water absorption rate of ZnO/JFA was up to 494.47%, and the SBF absorption rate was up to 473.71%. The JFA and ZnO/JFA possess a pipeline structure, which is beneficial for absorbing wound exudates. In addition, surface modification of nanosized ZnO and its effects on antibacterial properties and biocompatibility were performed. When the concentration of ZnO/JFA was 3.125 mg/mL, the survival rate of human fibroblast cells was close to 80%, while the antibacterial rates against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli were up to 99.06%, 75.28% and 93.58%, respectively. Moreover, a 3D printed assisted device was introduced to make the ZnO/JFA wound dressing more attached to the bottom of the wound on a curved surface. An integrated device was formed under the printing mold, and then animal experiments were conducted in vivo. The results showed that a healing rate of almost 100% for infected skin wounds was obtained with this novel VSD device after 14 days, compared to only 79.65% without the VSD device. This novel VSD with a negative pressure suction dressing is beneficial for healing infectious wounds.

ZnO nanoparticle modified chitosan/borosilicate bioglass composite scaffold for inhibiting bacterial infection and promoting bone regeneration.

The treatment of implant-associated bone infection remains a significant clinical challenge. However, bone scaffolds with antimicrobial activity and osteoinductive properties can prevent these infections and improve clinical outcomes. In this study, borosilicate bioglass and chitosan composite scaffolds were prepared, and then the surface was modified with nano-zinc oxide.In vitroandin vivoexperiments showed that the chitosan/borosilicate bioglass scaffolds have good degradation and osteogenic properties, while the oxidized Zinc scaffolds have better antibacterial properties.

Evaluation of 'surgery-friendly' bone scaffold characteristics: 3D printed ductile BG/PCL scaffold with high inorganic content to repair critical bone defects.

The repair of irregular and complex critical bone defects remains a challenge in clinical practice. The application of 3D-printed bioceramics particle/polymer composite scaffolds in bone tissue engineering has been widely studied. At present, the inorganic particle content of the composite scaffolds is generally low, resulting in poor osteogenic activity. However, scaffold with high inorganic content are highly brittle, difficult to operate during surgery, and cannot be in close contact with surrounding bones. Therefore, it is of great significance to design a 'surgery-friendly' scaffold with high bioceramic content and good ductility. In this study, we used the solvent method to add high concentration (wt% 70%) bioglass (BG) into polycaprolactone (PCL), and polyethylene glycol was used as plasticizer to prepare 70% BG/PCL composite scaffolds with high ductility using 3D printing technology.In vitroexperiments showed that the scaffold had good mechanical properties: easy extension, easy folding and strong compressive resistance. It also showed good performance in biocompatibility and osteogenic activity. It was further observed that compared with pure BG or PCL implantation, the scaffold with higher BG content could have more new bone tissue appeared after 12 weeks. All these results indicate that 3D-printed 70% BG/PCL scaffolds have great potential for personalized repair of bone defects.

Self-Stirring Microcatalysts: Large-Scale, High-Throughput, and Controllable Preparation and Application.

Herein, we introduce a strategy to develop a kind of unprecedented microcatalyst, which owns self-stirring and catalytic performance based on pneumatic printing and magnetic field induction technology. A spindle-shaped microcatalyst based on metal-organic frameworks (MOFs) with a certain aspect ratio and size can be obtained by tuning the printing parameters and the intensity of the magnetic field. One nozzle can print 18 000 microcatalysts per hour, which provides a prerequisite for the realization of large-scale production in the industrial field. Furthermore, this strategy can be widely applied to a variety of other heterogeneous catalysts, such as mesoporous SiO2, zeolite, metallic oxide, and so on. To demonstrate the superiority of the printed catalyst, the series of printed microcatalysts were evaluated by various catalytic reactions including liquid-phase hydrogenation, microdroplet dye-fading, and photocatalytic degradation in microreactor, all of which exhibited excellent catalytic performance.

Pore Size of 3D-Printed Polycaprolactone/Polyethylene Glycol/Hydroxyapatite Scaffolds Affects Bone Regeneration by Modulating Macrophage Polarization and the Foreign Body Response.

3D-printed porous bioactive ceramic scaffolds have been widely used in bone defect repair. However, material implantation is often accompanied by a foreign body response (FBR), which may affect host tissue regeneration. The physical properties of biomaterials, including shape, pore size, and porosity, control the relevant immune responses during tissue regeneration. To the best of our knowledge, the effect of the pore size of 3D-printed scaffolds on the immune response and bone-biomaterial integration has not been studied in vivo. Polycaprolactone/polyethylene glycol/hydroxyapatite (PCL/PEG/HA) bioactive scaffolds with different pore sizes, including 209.9 ± 77.1 µm (P200), 385.5 ± 28.6 µm (P400), and 582.1 ± 27.2 µm (P600), were prepared with a pneumatic extrusion 3D printer. Compared with other pore sizes, P600 significantly reduced the FBR and induced more M2 macrophage infiltration, vascular ingrowth, and new bone formation. Immunohistochemical staining revealed that the MyD88 protein might be involved in macrophage polarization-related signal transduction in response to the pore size. Based on these results, bone regeneration requires the active participation of the immune response, and the P600 PCL/PEG/HA scaffold is a preferable candidate for the repair of bone defects.

Tannic acid-reinforced zwitterionic hydrogels with multi-functionalities for diabetic wound treatment.

Diabetic wounds remain one of the most prevalent hard-to-heal wounds in the clinic. The causative factors impeding the wound healing process include not only the elevated oxidative stress and bacterial infections but also the high and repetitive plantar stress (including compressive pressure and shear stress). Conventional hydrogel dressings are mechanically weak and fragile, limiting their applications in the high stress-loading conditions of diabetic foot ulcers. As such, mechanically tough hydrogel dressings with appropriate bioactivities are highly desirable for diabetic wound treatment. In this study, a mechanically reinforced hydrogel with multiple biofunctionalities was developed via a facile and straightforward strategy of incorporation of tannic acid (TA) in zwitterionic poly(sulfobetaine methacrylate) (polySBMA) hydrogel. The polySBMA hydrogel reinforced by TA showed excellent mechanical property, with the tensile stress and compressive stress up to 93.7 kPa and 18.4 MPa, respectively, and it could resist cyclic compressive stress at ∼200 kPa (maximum in-shoe plantar pressure) for up to 3500 cycles. The TA-reinforced zwitterionic hydrogel exhibited strong adhesion to skin tissue (20.2 kPa), which was expected to reduce the shear stress on the foot. The plantar pressure on the foot was significantly reduced by the application of the resilient hydrogel. Attributed to the antioxidant and antibacterial properties of TA, the hydrogel showed rapid radical scavenging capability and strong bactericidal efficacy against Gram-positive and Gram-negative bacteria. In vitro and in vivo studies confirmed that the hydrogel has good cytocompatibility and negligible skin irritation, and promoted healing of diabetic wounds in mice. Such tough and effective hydrogel with a straightforward preparation strategy holds great promise as wound dressings for diabetic wound treatment.

Utilizing dual carriers assisted by enzyme digestion chemiluminescence signal enhancement strategy simultaneously detect tumor markers CEA and AFP.

To measure two tumor biomarkers, alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA), a dual-carrier CL sensor with restriction enzyme digestion (Exo I) and aptamer technology utilizing gold nanoparticles (hydroxylamine amplification) and horseradish peroxidase (HRP) as the CL signal enhancement in the sensing strategy was formed. These nanoparticles and nano-enzyme were precisely detected and tagged to the appropriate position attributable to the particular recognition of biotin and streptavidin. In this sensing strategy, target markers were further enriched and recognized sensitively by CL following enrichment, and matching strong chemical signals were collected under luminol catalysis, allowing for marker identification. For CEA (0.1-80 ng/mL) and AFP (2-500 ng/mL), the proposed method has a large linear range, with detection limits of 36.6 pg/mL and 0.94 ng/mL, respectively.

Eu doped Ti3C2 quantum dots to form a ratiometric fluorescence platform for visual and quantitative point-of-care testing of tetracycline derivatives.

Antibiotic residues have become a public health issues, the fast detection of tetracycline (Tc) in the environment is urgently required. In this work, Ti3C2 quantum dots (Ti3C2 QDs) and Europium ions jointly constructed a ratiometric fluorescence (FL) platform for the detection of Tc, based on synergistic impact of the Foster Resonance Energy Transfer (FRET) from Ti3C2 QDs to Eu3+ ions and the Antenna Effect (AE) between Tc and Eu3+ ions. And we proposed a ratiometric FL platform for detecting Tc with good linear response range (100-1000 uM) and low detection limit (48.79 nM). Meanwhile, we applied this platform to detect a serious of ß-diketone ligands of Eu3+ ions, demonstrating the platform's versatility for this category of chemical. Furthermore, based on the color changes of QDs@Eu3+ from blue to red at 365 nm ultraviolet light, an intelligent detection smart device was built for the visual semi-quantitative detection of Tc in actual samples. We proved the applicability of the device in complicated samples and the potential for rapid, sensitive, intuitive and point-of-care detection in the field of environment, food, pharmaceutical and agriculture.

Characterisation of bone regeneration in 3D printed ductile PCL/PEG/hydroxyapatite scaffolds with high ceramic microparticle concentrations.

3D printed bioactive glass or bioceramic particle reinforced composite scaffolds for bone tissue engineering currently suffer from low particle concentration (<50 wt%) hence low osteoconductivity. Meanwhile, composites with very high inorganic particle concentrations are very brittle. Scaffolds combining high particle content and ductility are urgently required for bone tissue engineering. Herein, 3D printed PCL/hydroxyapatite (HA) scaffolds with high ceramic concentration (up to 90 wt%) are made ductile (>100% breaking strain) by adding poly(ethylene glycol) which is biocompatible and FDA approved. The scaffolds require no post-printing washing to remove hazardous components. More exposure of HA microparticles on strut surfaces is enabled by incorporating higher HA concentrations. Compared to scaffolds with 72 wt% HA, scaffolds with higher HA content (90 wt%) enhance matrix formation but not new bone volume after 12 weeks implantation in rat calvarial defects. Histological analyses demonstrate that bone regeneration within the 3D printed scaffolds is via intramembranous ossification and starts in the central region of pores. Fibrous tissue that resembles non-union tissue within bone fractures is formed within pores that do not have new bone. The amount of blood vessels is similar between scaffolds with mainly fibrous tissue and those with more bone tissue, suggesting vascularization is not a deciding factor for determining the type of tissues regenerated within the pores of 3D printed scaffolds. Multinucleated immune cells are commonly present in all scaffolds surrounding the struts, suggesting a role of managing inflammation in bone regeneration within 3D printed scaffolds.

Chemiluminescence "signal-on-off" dual signals ratio biosensor based on single-stranded DNA functions as guy wires to detect EcoR V.

Signal output mode is the important part of biosensor. In general, "signal on" and "signal off" are two common output modes. The development of dual signals-based ratio analysis as a powerful diagnostic tool has attracted widespread attention in the biosensor field in recent years. Dual signals ratio sensors with "signal on" and "signal off" are more favored because of their low background signal and better sensitivity and selectivity. In this study, inspired by the idea that EcoR V can cut specific sites of DNA to produce two corresponding fragments, and by using the capturing probe as guy wires, a reliable and sensitive method for EcoR V assay is developed based on the ratio of dual chemiluminescence (CL) signals for the first time. In particular, in the existence of the objective EcoR V, the substrate DNA would be degraded into two double stranded oligonucleotides with blunt ends which include the sequence I and the sequence II, then they can separately compete with two different corresponding capture probes on magnetic beads (MBs). One of capture probe hybridized with the sequence I containing more guanine (G) bases that reacted with the phenylglyoxal (PG) to produce chemical reaction which triggered a positive CL signal output I + CL as "signal-on"; another capture probe is priority to hybridize the sequence II, which triggered the weaker reporter DNA linked with horseradish peroxidase (HRP) probe to fall off the MBs, thereby outputting a negative CL signal I-CL as "signal-off". By comparing the linear relation and the correlation coefficient, the I-CL/I + CL ratio method has better linear relation (0.01-10 U/mL) and higher sensitivity (0.0045 U/mL). In addition, this developed strategy of high selectivity which can directly detect low concentration of target EcoR V in human serum, and thus this dual ratio biosensor might offer a promising detection approach for clinical diagnostics.

One-pot label-free dual-aptasensor as a chemiluminescent tool kit simultaneously detect adenosine triphosphate and chloramphenicol in foods.

The chemiluminescence (CL) analysis based on label-free dual-aptasensor was developed for simultaneous detection of adenosine triphosphate (ATP) and chloramphenicol (CAP) in food. Magnetic microspheres and polystyrene microspheres used as separating and immobilizing carriers which immobilized the two different captured DNA, respectively. Then these carriers were put in the mixture of ATPs, CAPs, ATP-binding aptamers and CAP-binding aptamers to make one-pot label-free recognized interaction. The more ATP or CAP molecules binding their aptamers, the less aptamers left on the surface of carriers reducing the CL signals. The proposed aptasensor exhibited high selectivity and sensitivity for ATP and CAP with the limits of detection of 3.76 × 10-8 moL/L and 2.48 × 10-8 moL/L, respectively. Finally, this method is further validated by measuring the recovery of ATP/CAP spiked in three different food samples.

Mechano-Responsive, Tough, and Antibacterial Zwitterionic Hydrogels with Controllable Drug Release for Wound Healing Applications.

Acute wounds subject to frequent deformations are difficult to be treated because the healing process was easily interfered by external mechanical forces. Traditional wound dressings have limited efficacy because of their poor mechanical properties and skin adhesiveness and difficulty in the delivery of therapeutic drugs effectively. As such, tough and skin-adhesive wound dressings with sustainable and stimuli-responsive drug release properties for treatment of those wounds are highly desirable. For this purpose, we have developed a mechano-responsive poly(sulfobetaine methacrylate) hydrogel which aims to control the delivery of antibiotic drug upon application of mechanical forces. Diacrylated Pluronic F127 micelles were used as a macro-cross-linker of the hydrogel and loaded with hydrophobic antimicrobial drugs. The micelle-cross-linked hydrogel has excellent mechanical properties, with the ultimate tensile strength and tensile strain of up to 112 kPa and 1420%, respectively, and compressive stress of up to 1.41 MPa. Adhesiveness of the hydrogel to the skin tissue was ∼6 kPa, and it did not decrease significantly after repetitive adhesion cycles. Protein adsorption on the hydrogel was significantly inhibited compared to that on commercial wound dressings. Because of the mechano-responsive deformation of micelles, the release of drug from the hydrogel could be precisely controlled by the extent and cycles of mechanical loading and unloading, endowing the hydrogel with superior antibacterial property against both Gram-positive and Gram-negative bacteria. In addition, drug penetration into the skin tissue was enhanced by mechanical stress applied to the hydrogel. The micelle-cross-linked zwitterionic hydrogel also showed good cell biocompatibility, negligible skin irritation, and healing capacity to acute skin wounds in mice. Such a tough mechano-responsive hydrogel holds great promise as wound dressings for acute wounds subjected to frequent movements.