GelMA-catechol coated FeHAp nanorods functionalized nanofibrous reinforced bio-instructive and mechanically robust composite hydrogel scaffold for bone tissue engineering.

Critical bone defects complicate tissue graft-based surgeries, raising healthcare expenditures and underscoring scaffold-based tissue-engineering strategies to support bone reconstruction. Our study highlighted that the phase-compatible combination of inorganic nanorods, nanofibers, and hydrogels is promising for developing biomimetic and cell-instructive scaffolds since the bone matrix is a porous organic/inorganic composite. In brief, methacrylated gelatin (GelMA) was reacted with dopamine to form catechol-modified GeLMA (GelMA-C). The GelMA-C was nanocoated onto an iron-doped hydroxyapatite (FeHAp) nanorod via metal-catechol network coordination. The modified nanorod (FeHAp@GelMA-C) was loaded onto GelMA-based nanofibers. The nanorods loaded pre-fibers were electrospun onto GelMA solution and photochemically crosslinked to fabricate a fiber-reinforced hydrogel. The structural, mechanical, physicochemical, biocompatibility, swelling properties, osteogenic potential, and bone remodelling potential (using rat femoral defect model) of modified nanorods, simple hydrogel, and nanorod-loaded fiber-reinforced hydrogel were studied. The results supported that the interface interaction between GelMA-C/nanorods, nanorods/nanofibers, nanorods/hydrogels, and nanofiber/hydrogels significantly improved the microstructural and mechanical properties of the scaffold. Compared to pristine hydrogel, the nanorod-loaded fiber-reinforced scaffold better supported cellular responses, osteogenic differentiation, matrix mineralization, and accelerated bone regeneration. The nanorod-loaded fiber-reinforced hydrogel proved more biomimetic and cell-instructive for guided bone reconstruction.

Mussel bioinspired, silver-coated and insulin-loaded mesoporous polydopamine nanoparticles reinforced hyaluronate-based fibrous hydrogel for potential diabetic wound healing.

Diabetes wounds take longer to heal due to extended inflammation, decreased angiogenesis, bacterial infection, and oxidative stress. These factors underscore the need for biocompatible and multifunctional dressings with appropriate physicochemical and swelling properties to accelerate wound healing. Herein, insulin (Ins)-loaded, and silver (Ag) coated mesoporous polydopamine (mPD) nanoparticles were synthesized (Ag@Ins-mPD). The nanoparticles were dispersed into polycaprolactone/methacrylated hyaluronate aldehyde dispersion, electrospun to form nanofibers, and then photochemically crosslinked to form a fibrous hydrogel. The nanoparticle, fibrous hydrogel, and nanoparticle-reinforced fibrous hydrogel were characterized for their morphological, mechanical, physicochemical, swelling, drug-release, antibacterial, antioxidant, and cytocompatibility properties. The diabetic wound reconstruction potential of nanoparticle-reinforced fibrous hydrogel was studied using BALB/c mice. The results indicated that Ins-mPD acted as a reductant to synthesize Ag nanoparticles on their surface, held antibacterial and antioxidant potential, and their mesoporous properties are crucial for insulin loading and sustained release. The nanoparticle-reinforced scaffolds were uniform in architecture, porous, mechanically stable, showed good swelling, and possessed superior antibacterial, and cell-responsive properties. Furthermore, the designed fibrous hydrogel scaffold demonstrated good angiogenic, anti-inflammatory, increased collagen deposition, and faster wound repair capabilities, therefore, it could be used as a potential candidate for diabetic wound treatment.

An osteogenic, antibacterial, and anti-inflammatory nanocomposite hydrogel platform to accelerate bone reconstruction.

Fabricating an organic-inorganic nanocomposite hydrogel platform with antibacterial, anti-inflammatory, and osteoinductive properties that mimic bone extracellular matrix composition is decisive for guiding bone development in orthopedic practice. Despite significant progress in developing hydrogels for tissue repair, little attention has been paid to replicating the natural bone ECM microenvironments and addressing the importance of anti-inflammatory agents during osteogenesis. Herein, we developed ciprofloxacin and dexamethasone loaded strontium (Sr) and/or iron (Fe) substituted hydroxyapatite (HAp) nanomaterials precipitated in collagen (Col) to construct a multifunctional bioactive nanocomposite hydrogel platform to prevent inflammation and bacterial adhesion, leading to augmenting bone development in the defect site. The fabricated nanocomposite hydrogels (Sr:HAp-Col, Fe:HAp-Col, and Sr/Fe:HAp-Col) were physicochemically characterized and demonstrated high loading and prolonged drug release, and excellent antibacterial activity against Gram-positive and Gram-negative bacteria. In in vitro experiments, the Sr/Fe:HAp-Col sample exhibited enhanced bioactivity against the preosteoblast MC3T3-E1 cell line, with high alkaline phosphatase and bone-like inorganic calcium deposition, as well as increased gene expression of osteogenesis-related differentiation markers, including OPN, OCN, and RUNX2. Furthermore, in vivo experiments revealed that the Sr/Fe:HAp-Col matrix degraded over time by controlling the release of ions into the body, without causing acute inflammation at the implanted site or in the blood serum, or in the internal organs, including the heart, lungs, liver, and kidney of the Sprague-Dawley rat model. The micro-CT scan and histological examination showed high bone mineral density and more mature bone formation at the nanocomposite hydrogel implanted site associated with the ColMA hydrogel in the femur defect of the rat model. The strategy of applying collagen hydrogel supplemented with HAp to bone regeneration is promising due to its ability to mimic the natural bone ECM. Overall, the developed bioactive nanocomposite hydrogel may have great potential not only in bone regeneration but also in repairing nonunion-infected defects of other tissues.

Graphene Based Nanohybrid Aptasensors in Environmental Monitoring: Concepts, Design and Future Outlook.

In view of ever-increasing environmental pollution, there is an immediate requirement to promote cheap, multiplexed, sensitive and fast biosensing systems to monitor these pollutants or contaminants. Aptamers have shown numerous advantages in being used as molecular recognition elements in various biosensing devices. Graphene and graphene-based materials/nanohybrids combined with several detection methods exhibit great potential owing to their exceptional optical, electronic and physicochemical properties which can be employed extensively to monitor environmental contaminants. For environmental monitoring applications, aptamers have been successfully combined with graphene-based nanohybrids to produce a wide range of innovative methodologies. Aptamers are immobilized at the surface of graphene based nanohybrids via covalent and non-covalent strategies. This review highlights the design, working principle, recent developmental advances and applications of graphene based nanohybrid aptasensors (GNH-Apts) (since January 2014 to September 2021) with a special emphasis on two major signal-transduction methods, i.e., optical and electrochemical for the monitoring of pesticides, heavy metals, bacteria, antibiotics, and organic compounds from different environmental samples (e.g., water, soil and related). Lastly, the challenges confronted by scientists and the possible future outlook have also been addressed. It is expected that high-performance graphene-based nanohybrid aptasensors would find broad applications in the field of environmental monitoring.

Heavy Metal Ions Detection Using Nanomaterials-Based Aptasensors.

Heavy metals ions as metallic pollutants are a growing global issue due to their adverse effects on the aquatic ecosystem, and human health. Unfortunately, conventional detection methods such as atomic absorption spectrometry exhibit a relatively low limit of detection and hold numerous disadvantages, and therefore, the development of an efficient method for in-situ and real-time detection of heavy metal residues is of great importance. The aptamer-based sensors offer distinct advantages over antibodies and emerged as a robust sensing platform against various heavy metals due to their high sensitivity, ease of production, simple operations, excellent specificity, better stability, low immunogenicity, and cost-effectiveness. The nucleic acid aptamers in conjugation with nanomaterials can bind to the metal ions with good specificity/selectivity and can be used for on-site monitoring of metal ion residues. This review aimed to provide background information about nanomaterials-based aptasensor, recent advancements in aptamer conjunction on nanomaterials surface, the role of nanomaterials in improving signal transduction, recent progress of nanomaterials-based aptasening procedures (from 2010 to 2022), and future perspectives toward the practical applications of nanomaterials-based aptasensors against hazardous metal ions for food safety and environmental monitoring.

Electrospun tannin-rich nanofibrous solid-state membrane for wastewater environmental monitoring and remediation.

Heavy metal, organic dyes, and bacterial contamination in water endanger human/animals' health, and therefore, the detection, adsorption, and capturing of contaminants are essential for environmental safety. Ligand-rich membranes are promising for sensors, adsorption, and bacterial decontamination. Herein, tannin (TA)-reinforced 3-aminopropyltriethoxysilane (APTES) crosslinked polycaprolactone (PCL) based nanofibrous membrane (PCL-TA-APTES) was fabricated via electrospinning. PCL-TA-APTES nanofibers possess superior thermal, mechanical, structural, chemical, and aqueous stability properties than the un-crosslinked membrane. It changed its color from yellowish to black in response to Fe2+/3+ ions due to supramolecular iron-tannin network (FeTA) interaction. Such selective sensing has been noticed after adsorption-desorption cycles. Fe3+ concentration, solution pH, contact time, and ligand concentration influence FeTA coordination. Under optimized conditions followed by image processing, the introduced membrane showed a colorimetric linear relationship against Fe3+ ions (16.58 µM-650 µM) with a limit of detection of 5.47 µM. The PCL-FeTA-APTES membrane could restrain phenolic group oxidation and result in a partial water-insoluble network. The adsorption filtration results showed that the PCL-FeTA-APTES membrane can be reused and had a higher methylene blue adsorption (32.04 mg/g) than the PCL-TA-APTES membrane (14.96 mg/g). The high capture efficiency of nanocomposite against Fe3+-based S. aureus suspension than Fe3+-free suspension demonstrated that Fe3+-bounded bacterium adhered to the nanocomposite through Fe3+/TA-dependent biointerface interactions. Overall, high surface area, rich phenolic ligand, porous microstructure, and super-wetting properties expedite FeTA coordination in the nanocomposite, crucial for Fe2+/3+ ions sensing, methylene blue adsorption-filtration, and capturing of Fe3+-bounded bacterium. These multifunctional properties could promise nanocomposite membrane practicability in wastewater and environmental protection.

Multifaceted tannin crosslinked bioinspired dECM decorated nanofibers modulating cell-scaffold biointerface for tympanic membrane perforation bioengineering.

Tympanic membrane (TM) perforation leads to persistent otitis media, conductive deafness, and affects life quality. Ointment medication may not be sufficient to treat TM perforation (TMP) due to the lack of an underlying tissue matrix and thus requiring a scaffold-based application. The engineering of scaffold biointerface close to the matrix via tissue-specific decellularized extracellular matrix (dECM) is crucial in instructing cell behaviour and regulating cell-material interaction in the bioengineering domain. Herein, polycaprolactone (PCL) and TM-dECM (from Sprague-Dawley rats) were combined in a different ratio in nanofibrous form using an electrospinning process and crosslinked via tannic acid. The histological and biochemical assays demonstrated that chemical and enzymatic decellularization steps removed cellular/immunogenic contents while retaining collagen and glycosaminoglycan. The morphological, physicochemical, thermomechanical, contact angle, and surface chemical studies demonstrated that the tannin crosslinked PCL/dECM nanofibers fine-tune biophysical and biochemical properties. The multifaceted crosslinked nanofibers hold the tunable distribution of dECM moieties, assembled into a spool-shaped membrane, and could easily insert into perforated sites. The dECM decorated fibers provide a preferable biomimetic matrix for L929 fibroblast adhesion, proliferation, matrix adsorption, and f-actin saturation, which could be crucial for bioengineering. Overall, dECM patterning, surface hydrophilicity, interconnected microporosities, and multifaceted nanofibrous biosystem modulate cell-scaffold performance and could open opportunities to reconstruct TMP in a biomimetic fashion.

Antidiabetic and Hypolipidemic Potential of Green AgNPs against Diabetic Mice.

Green nanotechnology-based approaches have been acquired as environmentally friendly and cost effective with many biomedical applications. The present study reports the synthesis of silver nanoparticles (AgNPs) from the leaves of Emblica phyllanthus, characterized by UV-Vis spectroscopy, EDX, SEM, AFM, and XRD. The acute and chronic antidiabetic and hypolipidemic potential of AgNPs was studied in alloxan-induced diabetic mice. A total of 11 groups (G1-G11, n = 6) of mice were treated with different concentrations (150 and 300 mM) and sizes of AgNPs and compared with those treated with standard glibenclamide. A significant decrease (P > 0.05) in the glucose level was achieved for 30, 45, and 65 nm after 15 days of treatment compared to the diabetic control. The oral administration of optimal AgNPs reduced the glucose level from 280.83 ± 4.17 to 151.17 ± 3.54 mg/dL, while the standard drug glibenclamide showed the reduction in glucose from 265.5 ± 1.43 to 192 ± 3.4 mg/dL. Histopathological studies were performed in dissected kidney and liver tissues of the treated mice, which revealed significant recovery in the liver and kidney after AgNP treatment. Acute toxicity study revealed that AgNPs were safe up to a size of 400 nm and the raw leaf extract of Emblica phyllanthus was safe up to 2500 mg/kg b.w. This study may help provide more effective and safe treatment options for diabetes compared to traditionally prescribed antidiabetic drugs.

Ni-Nitrilotriacetic Acid Affinity SELEX Method for Selection of DNA Aptamers Specific to the N-Cadherin Protein.

Nucleic acid aptamers are single-stranded oligonucleotides that may be evolved for affinity and specificity for their targets and can be easily produced, regenerated, and stabilized. In this study, we adapted Ni-NTA (nickle-charged nitrilotriacetic acid) affinity-chromatography in the development of single-stranded DNA aptamers against N-cadherin protein by systematic evolution of ligands by exponential enrichment (SELEX). After ten rounds of selection, two aptamers, designated NS13 and NC23, were selected, which showed low dissociation constants of 93 and 174 nM, respectively. The 5'-carboxyfluorescein-labeled NS13 was used for the sensitive detection of N-cadherin protein by the enzyme-linked oligonucleotide assay (ELONA) method.

Attenuation of vincristine-induced neuropathy by synthetic cyclohexenone-functionalized derivative in mice model.

Vincristine (VCR) is a well-known anticancer drug which frequently induced painful neuropathy and impairs the quality of life of patients. The present study was designed to investigate the alleviative potential of a novel cyclohexenone derivative (CHD), i.e., ethyl 6-(4-methoxyphenyl)-2-oxo-4-phenylcyclohexe-3-enecarboxylate, against VCR-induced neuropathic pain in mice model. VCR was administered intraperitoneally for 10 days in two cycles to induce neuropathic pain. Static and dynamic mechanical allodynia was evaluated using von Frey hair filaments and cotton buds, respectively. Paw thermal hyperalgesia was determined through a hot plate analgesiometer. The tail cold immersion hyperalgesia and paw cold allodynia were determined by available standard protocols. The formalin nociception was induced via subplantar injection of formalin. The antioxidant potential was evaluated via 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity. The outcome of this study revealed that CHD (30-45 mg/kg) and gabapentin (75 mg/kg) significantly enhanced the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in static and dynamic allodynia, respectively, and increased the PWL in thermal hyperalgesia and tail withdrawal latency (TWL) as compared to the VCR-treated group. CHD significantly augmented the paw withdrawal duration (PWD) in paw cold allodynia, while the same compound only increased the paw elevation and paw licking in the delayed phase of formalin nociception. Moreover, CHD significantly inhibited the DPPH free radical scavenging action (IC50 = 56), butylated hydroxytoluene (BHT) (IC50 = 39), and ascorbic acid (IC50 = 2.93). In conclusion, CHD exhibited a profile of potential attenuative effect against the VCR-induced neuropathic pain which might be attributed to its possible antinociceptive and antioxidant effect.